SURGICAL INFECTIONS: Volume 11, Number 1, 2010, (© Mary Ann Lieber, in. 0}: 10.1088/sur-2008.8890 Surgical Infection Society Guidelines Diagnosis and Management of Complicated Intra-Abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America Joseph §. Solomkin! John E. Mazuski? John S. Bradley? Keith A. Rodvold’® Ellie J.C. Goldstein? Ellen J. Baron® Patrick J. O'Neill? Anthony W. Chow!® E. Patchen Dellinger! Soumitra R. Eachempati,’ ‘Sherwood Gorbach!® Mary Hilfiker Addison K. May? Avery B. Nathens)” Robert G. Sawyer'* and John G. Bartiett"® Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2008, The guidelines are intended for treating patients who either have these infections or may be at risk for them, New information, based on publications from the period 2003— 2008, is incorporated into this guideline document. The panel has also added recommendations for managing {intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates. Executive Summary ‘me 2009 UPDATE OF THE GUIDELINES contains evidence- based recommendations for the initial diagnosis and subsequent management of adult and pediatric patients with ‘complicated and uncomplicated intra-abdominal infection. ‘The multifaceted nature of these infections has led to collab oration and endorsement of these recommendations by the follovring organizations: American Society for Microbiology, ‘American Society of Health-System Pharmacists, Pediatric Infectious Diseases Society, and Society of Infectious Diseases Pharmacists. These guidelines make therapeutic recommendations on ‘the basis of the severity of infection, which is defined for ‘hese guidelines as a composite of patient age, physiologic derangements, and background medical conditions. These ‘values are captured by severity scoring systems, but for the individual patient, clinical judgment is at least as accurate ‘as a numerical score [1-4]. “High risk" is intended to de- scribe patients with a zange of reasons for increased rates of treatment failure in addition to a higher severity of in- fection, particularly patients with an anatomically uni ‘vorable infection or a health care-associated infection [5] (Table 1) "Department of Surgery, te Univesity of Gncianad College of Medicine, Gia, Ohio “Department of Susge, Washington Unie School of Medisine Sains Lis Missour Departments of Pedi: infoviow Diseases and “Suspery, Rady Chiers Hoop pi san Disgo San Diego, Calfora;"R M.alden Revnrh Laboratory, David Gefen Stool of Medicine at UCLA, Los Angels, Cabfomia ‘Si pavtent of Fatnology, Stanford Urvecsity Shoal of Medicine Palo Alo, Caforue; Departments of Pharmacy Prac and Medici, University of Minos at Chicago, Chicago, nol, "Department of Surgery, The Trauma Center st Maricope Medial Cente, Phoenix “Anzora: HDepartnent of Surgery, Uniesy of Washirgron Seat, Washington: Department of Surgery, Cosel Medic Cente, New ‘Yank, New York, “Department of Medicine, Tas Unversty School of Medicine, Besion, Massachusets; "Departnet of Surgery, ‘Vanderbilt University Medical Center, Nesvile, Tennestee, "Department of Surgery, Univesity of Virginia, Chasotevl, Vigna Deparment of Medicine, Jans Hopiin University Scheel of Madiine, Baltimore, Maryland, "Department of Mecicine, University of Butoh Columbia, Vancouver, Bash Columbia, Canada and "Se Michael's Hoopla, Toronn, nimo, Canada This guidcline might be updated pecodiily. To be sure you have the most secent version, check the website of the joural (ep bert com /sepelieions). Tis Important to vealze tat guidlines cannot always account for individual vaiston among patients. They ae nat intended to supplant phsicianjadgmene wit seaport to partial patente or epedal cine sutions. The infeciows Diseases Society of Amesca and the [Epil lfecton Society conde adherence to these guideines tobe voluntary, with he ultimate determination regarding thei application to be made by the plysican in height ofeach patiants individual crcustanees 79Initial Diagnostic Evaluation 1. Routine history, physical examination, and laboratory studies will identify most patients with suspected ine tra-abdominal infestion for whom further evaluation and management is warranted (A-I). 2, For selected patients with unreliable physical exani- nation findings, such as those with an obtunded rental status O° spinal cord injury or those immuno- suppressed by disease or therapy, intra-abdominal infection should be considered if the patient presents with evidence of infection from an undetermined source (BAN. 3, Further diagnostic imaging is unnecessary in patients with obvious signs of difise peritonitis and in whom ‘immediate surgical intervention is to be performed jam. 4 Tn adult patients not undergoing immediate laparot- omy, computed tomography (CT) scan isthe imaging modality of choice to determine the presence of an intra-abdominal infection and its source (AID Fluid Resuscitation 5. Patients should undergo rapid restoration of intra- vascular volume and additional measures as needed to promote physiological stability (A-T). 6. For patients with septic shock, such resuscitation should begin immediately when hypotension is identified (Ac. 7. For patients without evidence of volume depletion, Intravenous fluid therapy should begin when the diag nosis of intra-abdominal infection is first suspected (Bain, Timing of initiation of Antimicrobial Therapy 8. Antimicrobial therapy should be initiated once a patient receives a diagnosis of an intra-abdominal in- fection or once such an infection is considered likely. For patients with septic shock, antibiotics should be administered as soon as possible (A-IID, 9. For patients without septic shock antimicrobial therapy should be started in the emergency department (B-II). 10, Satisfactory antimicrobial drug levels should be ‘maintained during the intervention, which may ne- ‘Taste 1, Cumtcat Factors PREDICTING FAILURE ‘or Sounce CONTROL FOR INTRA-ABDOMINAL INFECTION Delay in the initial intervention (>24) High severity of iliness (APACHE Il score >15) Advanced age Comorbidity and degree of organ dysfunction Low albumin level Poor nutritional status Degree of peritoneal involvement or diffuse peritonitis Inability to achieve adequate debridement of control of drainage Presence of malignancy Note: APACHE, Acule Physiology and Chronic Health Bvalua- INTRA-ABDOMINAL INFECTIONS GUIDELINES cessitate additional edininstation of antimicrobials just before inittion of the procedure (AD Elements of Appropriate Intervention U1, An appropriate source control procedure to dain ine fected foci, control ongoing peritoneal contamination by diversion or resection, and restore anatomic and physiological function to the extent feasible is recom mended for nearly all patients with intra-abdominal infection (8-1). 12. Patients with diffuse peritonitis should undergo an ‘emergency surgical procedure as soon as is posible even if ongoing measures to restore physiologic sta- bility need tobe continued during the procedure (-). 13. Where feasible, percutaneous diainage of abscesses and other well-locaized fluid collections is preferable to surgical drainage (8-0). 14. For hemodynamically stable patients without evidence of acute organ failure, an urgent approach should be taken. Intervention may be delayed for a long as 26h 4 appropsiate antimicrobial therapy is given and careful clinial monitoring is provided (B-M), 15, In patients with severe peritonitis, mandatory ot scheduled relaparotomy is not recommended in the absence of intestinal discontinuity, abdominal fascial Joss that prevents abdominal wall closure, oF intra- abdominal hypertension (AI). 16, Highly selected patients with minimal physiological derangement and a wellcircumscribed focus of inec- tion, such as @ periappendiceal or pericolonic phleg- ‘mon, may be treated with antimicrobial therapy alone without a source control procedure, provided that very close clinical follow-up is possible (8-1). ‘Microbiologie Evaluation 17, Blood cultures do not provide additional clinically relevant information for patients with. community- acquired intre-abdominal infection and are therefore not routinely recommended for such patients (8-1). 18. If patient appears clinically toxic or is immunocom- promised, knowledge of bacteremia may be helpful in determining duration of antimicrobial therapy (BI), 19, For community-acquired infections, there is no proven value in obtaining @ routine gram stain of the infected ‘material (CI), 20. For health care-associated infections, gram stains may help define the presence of yeast (C-II). 21. Routine aerobic and anaerobic cultures from lovwer- risk patients with community-acquired infection are considered optional in the individual patient but may be of value in detecting epidemiological changes in the resistance patterns of pathogens associated with community-acquired intra-abdominal infection and in ‘guiding follow-up oral therapy (BD. 22. If there is significant resistance (Le, resistance in 10%- 20% of isolates) of a common community isolate (e., Escherichia col) to an antimicrobial regimen in wide- spreed local use, routine culture and susceptibility studies should be obtained for perforated appendicitis,INTRA-ABDOMINAL INFECTIONS GUIDELINES ‘and other community-acquited intra-abdominal in- fections (B-ID). 23, Anaerobic cultures are not necessary for patients with ‘community-acquired intra-abdominal infection if em- ppiric antimicrobial therapy active against common anaerobie pathogens is provided (B-Il). 24, For higher-risk patients, cultures from the site of infec- tion should be routinely obtained, particularly in pa- tients with prior antibiotic exposure, who are more likely than other patients to harbor resistant pathogens (acm. 25, The specimen collected from the intra-abdominal focus of infection should be representative of the material associated with the clinical infection (B-ID, 26. Cultures should be performed from one specimen, pro- vided itis of sufficient volume (at least 1m. of fluid or tissue, preferably more) and is transported to the lab- oratory in. an appropriate transport system. For optimal recovery of aerobic bacteria, 1-10 of fluid should be ‘inoculated directly into an aerobic blood culture bottle. In addition, 0.5m of fluid should be sent tothe labo- ratory for gram stain and, iFindicated, fungal cultures, If anaerobic cultures are requested, at least 0.5L of fluid or 0.5g of tissue should be transported in an an- ‘aerobic transport tube. Alternately, for recovery of an- aerobic bacteria, 1-10ml of fluid can be inoculated. directly into an anaerobic blood culture bottle (AI). 27. Susceptibility testing for Pseudomonas, Proteus, Acne tobaeter, Staphylococcus aureus, and predominant Entero- ‘acteriacece, as determined by moderate-to-heavy growth, should be performed, because these species are ‘more likely than others to yield resistant organisms (Ac 1). Recommended Antimicrobial Regimens ‘The antimiceobials and combinations of antimicrobials tailed in Tables 2-4 are considered adequate for treating 8 comununity- and health care-associated intra-abdominal in- fection as indicated. Community-Acquired Infection of Mild-to-Moderate Severity in Aduts 28. Antibioties used for empitic treatment of community- acquired intra-abdominal infection should be active against enteric graminegative aerobic and facuative baci and enteric gram-positive sreptococd (AD. 2. Coverage for obligate anaerobic bacili should be provided for distal small bowel, appendices, and color-desived infection and for more proximal gas- trointstinal perforations in the presence of obstruction or paralytic ileus (A. 30. For adult patients with mild-to-moderate community. acquired infection, the use of ticarcilinclavulanate, cefoxitin, erapenem, moxifloxacin, or tigecyeline 2s single-agent therapy or combinations of metronidazole with celazolin cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin are preferable 10 725i smens with substantial ant-Pscudomional activity (A). 31. Ampicilinsulbactam is not recommended for use ‘because of high rates of resistance to this agent among, community-acquized E.coli @-1). 22, Cefotetan and. clindamycin are not recommended for use because of increasing prevalence of resls- tance to thete agents among the Bacieroides fragilis group BID, 433, Because ofthe availability of les toxic agents demon- strated tobe at least equally effective, aminoglycosides axe not recommended for routine use in adults with comnmunty-acquired intreabdominal infection (BD) 34, Empirie coverage of Entercoeaus is not necessary in patients with community-acquired intra-abdominal infection (A-1). 35, Empirie antifungal therapy for Condide is not 2e- commended for adult and pediatric patients with community-acquired intra-abdominal infection (@-. ‘Tanu 2 AcaNts AND REGIMENS THAT May BE Usk ror THE INrTiAat, EMronic TREATMENT OF EXTRA-BICIARY (ConrnicaTeD INTRA ;DOMINAT. INFECTION ‘Milé-o-moderate severity: perforated or absessed ‘appendicitis and other infections of mild-to-moderate severity Commeurity-aquired Regimen Infection in pediatric patients Comma aguine netion in ads Tigh vi or sever: Sere Praise datshence advanced age or sneered state Single agent Erapenen, meopene imipenem-cilastatin, Cefoxitin, etapenem moxifloxacin, tigecycline, and Imipenem-cilastatin, ‘meropenem, doripenem, and ticarcilin-clavulanate, and ticarciln-clavulanie acid piperacillin-tazobactam piperacilin-tazobactam Combination Ceftriaxone, cefotaxime, Cefazolin, cefuroxime, Cefepime, ceftazidime, cefepime, or ceftazidime, each in combination with ‘metronidazole; gentamicin or tobramycin, each in combination with metronidazole or clindamycin, and with or without ampicili, ceftriaxone, cefotaxime, ciprofloxacin, or levofloxacin, tach in combination with metronidazole" ‘iprofloxacin, or levofloxacin, ‘each in combination with, ‘metronidazole* "Because of increasing resistance of Eskerichie cli to Auoroquinolones, loc population suscepablty profiles and, i avaiable conte suscapebllity shouldbe reviewed.INTRA-ABDOMINAL INFECTIONS GUIDELINES ‘Taste 3. AGEwts AND REGIMENS THAT May Be Usap ron ras [nertat Emratc TREATMENT (OF BILIARY INFECTION IN ADULTS Infection Regimen ‘Community acquired acute cholecystitis of mild-to-moderate Cefazolin, cefuroxime, or ceftriaxone severity Community-acquired acute cholecystitis of severe physiologic disturbance, advanced age, or immunocompromised state Acute cholangitis following bilio-enteric anastamosis of any severity Health care-associated biliary infection of any severity Tmipenen-15 or other variables listed in Table 1 39, Quinolone-esistant E. coli has become common in some communities, and quinolones should not be used. unless hospital surveys indicate >90% suscepsibility of E.coli to quinolones (AI). 40. Aztreonam plus metronidazole is an alternative, but addition of an agent effective against gram-positive coc is recommended (B-I), 41, In adulls, routine use of an aminoglycoside or another second agent effective against gram-negative faculta- ‘ive and aerobic bacilli is not recommended in the ‘absence of evidence thatthe patient is likely to harbor resistant organisms that require such therapy (A-D, 42, Bmpizic use of agents effective against enterococci is recommended (B-I). 43, Use of agents effective against methicilin-resistant S. aureus (MRSA) or yeast is not recommended in the absence of evidence of infection due to such organisms (emp. 44. In these hightisk patients, antimicrobial. regimens should be adjusted according to culture and suscepti- bility reports to ensure activity against the predomi nant pathogens isolated in culture (AcIID) Health Care-Associated infection in Adults: 45, Empiic antibiotic therapy for hospital-acquited intra- abdominal infection should be driven by local micro- biologic results (4-10, 46. To achieve empiric coverage of likely pathogens, rullicdrug regimens that include agents with ex- panded spectra of activity against gram-negative aet~ bie and facultative bacili may be needed. These ‘agents include meropenem, imipenemcilastatin, dor ipenem, piperacilln-tazobactam, ceftazidime, or cefe- pime plus metronidazole; aminoglycosides or colistin say be required (BI). 47. Broad-spectrum antimicrobial therapy should be tai- lored when culture and susceptibility reports become available, to reduce the number and spectra of ad- ministered agents (B-ID, Aniungal Therapy 48, Antifungal therapy for patients with severe commu ‘ity-acquired or health care-associated infection is re commended if Candida is grown from intr-abdominal ‘cultures (B-Il). 49, Fluconazole is an appropriate choice for treatment fC. albicans isolated (-1) 50, For fuconazole-resistant Candida species, therapy with an echinocandin (easpofungin, mieafungin oF anidu- Jafungin) is appropriate (B-). 1, For the ically ill patient, inital therapy with an cechinocandin instead of a tsazole is recommended eu,INTRA-ABDOMINAL INFECTIONS GUIDELINES: 83 52, Because of tonicity, amphotericin B isnot recommen: i! Gol aval Wert 3 53. In neonates, empinic antifungal therapy should be started if Candids suspected If C. lice is isoated, g fluconazole isan appropriate choice @. i t 5 Vancomycin AntEnterococcal Therapy 54, Antimicrobial therapy for enterococci should be given ‘when enterococe! are recovered from patents With health care-associated infection (B-II]). 55. Empiric anti-enterococeal therapy is recommended for patients with health eare-associated intra-abdominal infection, particularly those with postoperative infec: tion, those who have previously received cephalo- sporins or other antimicrobial agants selecting for Enierocccus species, immunocompromised pater, and those with valvular heart disease or prosthetic intravascular materials (-0). 56, Initial empiric antventerococcal therapy should be directed against Enterococcus facalis. Antibiotics that can potentially be used against this organism, on the basis of susceptibility testing of the individual isolate, include ampicilin,piperacllin-tazabactam, and van. comycin (BD. 57, Empisie therapy directed against vancomyein-resistant Enlerococcus faecium is not recommended unless the Patient is at ‘very high risk for an infection due to this ‘organism, such as a liver transplant recipient with an intr abdominal infection originating in the hepato- biliary tree or a patient known to be colonized with vancomycin-resistant E,fecium (8 Aminoglycoside Not recommended Not recommended Recommended ‘Recommended metronidazole ‘Recommended ‘Regimen [Not recommended ‘Not recommended Not recommended Not recommended Not recommended Not recommended _ Recommended ‘Recommended, Anti MRSA Therapy 58 Empiric antimicrobial coverage directed against MRSA should be provided to patients with health care-associated intra-abdominal. infection who are known to be colonized with the organism or who are at risk of having an infection due to this organism because of prior treatment failure and significant an- thiotic exposure B-I). 59, Vancomycin is recommended for treatment of sus- pected or proven intra-abdominal infection due to MRSA (AAI. Carbapenen™ ‘<20% Resistant Pseudomonas aeruginosa, ESBL-producing Recommended Cholecystitis and Cholangitis in Adults 60. Ultrasonography is the first imaging technique used for suspected acute cholecystitis or cholangitis (AD 61. Patients with suspected infection and either acute cholecystitis or cholangitis should receive antimicro- bial therapy, as recommended in Table 3, although anaerobic therapy is not indicated unless a biliary- enteric anastamosis is present (B-I), 62, Patients undergoing cholecystectomy for acute chole- cystitis. should have antimicrobial therapy dis- continued within 24h unless there is evidence of infection outside the wall of the gallbladder (ET), 63, For community-acquired biliary infection, activity against enterococci is not required, because the ‘TABLE 4. RECOMMENDATIONS FOR EMPIRIC ANTIMICROBIAL THERAPY FOR HIRALTH CARR-ASSOCIATED COMPLICATED INTRA-ABDOMINAL INFECTION nasi vecommended for empiric use, before culture and susceptibility dala are available, at inatitutions that encounter these isolates from other it oF hospital pectic sen-lastatin, meropenem, or doripenem. "Note: SDL, extendes-pectrum fHactamase; GNB, gram-negative bcll: MR, mulldrug resistant MRSA, methiilin-esstant Stopiloaccs aureus, “Recommended” indicates thatthe sted Enterobecteriaceae, Acinetobacter, or other MDR GNB ESBL-producing Enterobacteracene tmlpa P. oorginosa >20% resistant to ceftazidime MRSA agent or say bepathogenicity of enterococci has not been demon- strated. For selected immunosuppressed patients, patticularly those with hepatic transplantation, en- terococcal infection may be significant and require treatrnent (B-ID. Padlatrc Infection 64, Routine use of broad-spectrum agents isnot indicated for all children with fever and abdominal pain for whom there is & low suspicion of complicated ap- pendicts or ather acute intra-abdominal infection (B- im, 65, Selection of speciic antimicrobial therapy for pediatric patients with complicated intra-abdominal infection should be based on considerations ofthe origin of in fection (comunurity vs health ente), severity of iliness, and safety of the antimicrobial agents in specific pe- ittic age groups (AD. 66, Acceptable broad-spectrum antimicrobial egimens for pediatric patients with complicated intra-abdominal Infection include an aminogljcoside-based regimen, a carbapenem (imipenem clastatin, meropenem, oF er tapenem), a Sactam/(Mactamase-inhbito: combina- tion (piperaclin-tezobactam or ticacilin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, of cefepime) with metronida- 2ole (Table 5) (A). INTRA-ABDOMINAL INFECTIONS GUIDELINES 67. For childsen with severe reactions to B-lactam ant tes, ciprofloxacin plus metronidazole or an ami- noglyconide-based zegimen are recommended (BI 68, Necrotizing enterocolitis in neonates is managed with {uid resuscitation, intravenous broad-spectrum ant- biotics (potentially including antifungal agents), and bowel decompression. Urgent or emergent operative interveation, consisting of either laparotomy or pet- cutaneous drainage, should be performed when there is evidence of bowel perforation Intra-operative gram stains and cultures should be obtained (6 68, Broad-spectrum antibiotics that may be useful in ne conates with this condition include arpicilin, genta- icin, and metronidazole; ampicillin, cefotaxime, and metronidazole; or meropenem. Vancomycin may be ted instead of ampicillin for suspected MRSA or ampieili-rsistantenterocoocl infection. Fluconazole for amphotericin B should be used ifthe gram stain or cultures of specimens obtained at operation are con- sistent with a fungal infection (B-M). ‘Pharmacokinetic Considerations 70, Empivic therapy of patients with complicated intra- slbdominal infection requires the use of antibiotics at optimal doses to ensure maximum efficacy and mini- mal toxiety and to reduce antimicrobial resistance (Tables 6 and 7) (BD, ‘Tante 5. Inrriat IivTRaVveNoUs Proraarc Dosaces oF ANTIBIOTICS FoR TREATMENT ‘OF COMPLICATED INTRA-ASDOMINAL INFECTION Antibiotic, ge range Dosage? Frepuency of dosing Amikacin® 15-225mg/kg/day Every 6.24h, ‘Ampiailln sodium 200mg /kg/day Every 6h “Ampicilin-sulbactan 200mg /kg/day of ampicilin component Every 6h ‘Aatreonam® do-120 mg/kg/day Every 68h Cetepime® Wooma/ke/day Every 12h Gefotaxime® 150-200mg/kg/day Every 6-8h Cefotetan® 40-80ma/kg/day Every 12h Cefontin® iedmg/keg/day Every &6h Ceftazidimet 150me/ka/day Every 8h Ceftiaxone® 50-75 mg/kg/day Every 12-24h Cefuroxime® 150mg/ke/day Every 68h Ciprofloxacin 20-30mg/kg/day Every 12h Clindarycin 20-40mp/kg/day Every 68h Ertapenemn ‘3 months to 12 years 15mg vice dally (nt exceed g/day) Every 12h 213 years Teg/day Every 24h Gentamicin® 2275mg/kg/day Every 2-4h Imipenenveilastatn® 60-100me/kg/day Every 6h ‘Meropenem cOma/kg/1 center); from multiple time series; or from dramatic results of uncontrolled experiments Level IL ‘Bvidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees Note: Adapted from the Canadian Task Force onthe Pesiodic Health Examination [11 ‘7. Individualized daily administration of aminoglycosides according to lean body mass and estimated extracel- Tular fluid volume is preferred for patients receiving ‘these agents for intra-abdominal infection (B-I}. Use of Microbiology Results to Guide Antimicrobial Therapy 72. Lower-isk patients with community-acquired intra- bdominal infection do not require alteration of ther- apy ifa satisfactory clinical response to source control and inital therapy occuss, even if unsuspected and ‘untreated pathogens are later reported (B-I. 73, resistant bacteria were identified at the time ofiitial intervention and ther are persistent signs of infection, pathogen-directed therapy is also recommended for patients with lower severity disease (-I} 74, Use of culture and susceptibility results to determine antimicrobial therapy in high-severity commurity-ac- quired or health care-associated infection should be based on pathogenic potential and density of idert- fied organisms (I. 75. Microbes recovered from blood cultures should be assumed to be significant if they have established pathogenic potential or are present in 22 blood cultures (AD or if they are recovered in moderate or heavy concentration from samples obtained fom drainage em. Duration of Therapy for Complicated intra-abdominal Infections in Adults 76. Antimicrobial therapy of established infection should bbe limited to no more than seven days, unless itis dificult to achieve adequate source control. Longer durations of therapy have not been assocsted with improved outcome (B-I. 77, For acute stomach and proximal jejunum perforations, inthe absence of acid-reducing therapy ot malignancy and when source control is achieved within 26h, prophylactic antvingecive therapy directed at aerobic gran: postive cocd for 24 is adequate (BHD. 78. In the presence of delayed operation for acute stomach and proximal jejunum perforations, the presence of gastic malignancy or the presence of therapy reducing gastric acdiy, antimicrobial therapy to cover mixed flora (eg, as seen in complicated colonic invection) should be provided (BID, 78, Bowel inries atsibutable to penetrating, blunt, or iatrogenic tauma that are reptired within 12h and any other intraoperative contamination of the opera- tive field by enteric contents should be tested with antibiotics for 224h (A-1). 80, Acute appendicis without evidence of perforation abscess, or local pestonts requires only prophylactic administration of narrow-specrum regimens active agains aerobic and facultative and obligate anaerobes: treatment should be discontinued within 24h (A-1). 61, The acminstration of prophylactic antibiotics 0 pa tients with severe necrotizing pancreatitis prior to the diagnosis of infection isnot recommended (A), Use of Oral or Outpatient intravenous Antimicrobial Therapy 82. For children and adults whose signs and symptoms of infection are resolved, no further antibiotic therapy is required (BN). 83, For adults recovering, from intra-abdominal infection, completion ofthe antimicrobial course with oral forms of moxifloxacin, ciprofloxacin plus metronidazole, le- vofloxacin plus metronidazole, an oral cephalosporin with metronidazole, or amoxicillinlavalanic acid (B- 1) is acceptable in patients able to tolerate an oral diet and in patients in whom susceptibility studies do not demonstrate resistance (B-). ‘A, Leculture and susceptibility testing identify organisms that are only susceptible to intravenous therapy, such therapy may be administered outside of the Hospital enn, 85, For children, outpatient parenteral antibiotic manage- ment may be considered when subsequent drainage procedures are not likely to be required but symptoms ‘of ongoing intra-abdominal inflammation persist in ‘the context of decreasing fever, controlled pain, ability to tolerate oral fluids, and ability to ambulate (B-). 86. For oral step-down therapy in children, intr-abdom- inal cultures atthe time of the drainage procedure are secommended to allow for the use of the narrowest spectrum, besttolerated, and safest oral therapy. APe INTRA-ABDOMINAL INFECTIONS GUIDELINES. ‘Tawue 7, INITIAL INTRAVENOUS ADULT DosAGES OF ANTIBIOTICS FoR EMpIRc TasaTMeNT Antibiotic OF ComPLicATED INTRA-ABDOMINAL INFECTION Adult dosage® Brlactam/ lactamase inhibitor combination Piperacllin-tazobactam 33758 ‘Ticarcilin-clavalanie acid every 6h 3i1g every 6h; FDA labeling indicates 200 mg/kg/day in divided doses every 6 for moderate i tion and 300mg/ke/day in divided doses every 4 for severe infection Carbapenems Dorpenemt s00mg every 8h, Enapenem Ig every 24h Imipenerellstatin sibing every 6h or 1g every 8h : Meropenem Igevery 8h Cephalosporins Eefazain L-2gevery 8h Cefepime 2g every 12h Cefotaxime Tag every 68h Cefoxiin 2g every oh Ceftazidime 2g every 8h Ceftiaxone Se every 12-28h Cefuroxime pg every 8h Tigecyeline odimg intial dose, then 50mg every 12h Fluoroquinolones Ciprofloxacin 00mg every 12h Tevorloxacin ToOmg every 24h Moxifoxacin a00mg every 24h Metronidazole 500mg every 8-12 ot 1500mg every 26h ‘Aminoglyeosides ‘Gentamicin or tobramycin S.7 mg/g every 24" ‘Amikacin 15-20mng/kg" every 24h ‘Aztreonam Eeag every 6-8h ‘Vancomyeln 15-do mg/kg? every 8-12h4 Note: FDA, United States Food and Drug Administration. ‘Dosages are based on normal renal and bepatic function. For Poeudononas aruginese infection, dosage may be increased to 3375, every 4h or 45g every 6h. ‘Initial dosage regimens for aminoglycosides shoul be based on adjusted body weight. “Serum crug-concentation mentoring should be conaldeved for dosage individuaization, “nial dosage regimens for vancomycin should be based on total body weight. second or third-generation cephalosporin in combi- ‘ation with metronidazole, or amoxiillin-clavulanate, may be options if the isolated organisms are suscep- tible to these agents. Fluoroquinalones, such as cipro- floxacin or levofloxacin, may be used to treat susceptible Pseudomonas, Enterobacter, Serratia, and Ci trobacter species (B-M). If ciprofioxacin or levofloxacin, {is used, metronidazole should be added. 87. Drug susceptibility results of isolated gram-negative aerobic and facultative organisms, if available, should be used as a guide to agent selection in children and adults (BIN), 88. The intravenous regimens recommended for patients ‘with complicated intra-abdominal infection (Tables 2- 4) are appropriate for patients with intra-abdominal infection who are being managed without a primary source control procedure (B-II) 89. Because many of the patients who are managed ‘without a primary souzce contral procedure may be tueated in the outpatient setting, the oral regimens recommended (Tables 2-4) can also be used as either primary therapy or step-down therapy, following ini- ‘al intravenous antimicrobial therapy (B-ID. Suspected Treatment Failure 90, In patents who have persistent or recurrent clinical evi- dence of intre-abdominal infection after 4-7 days of therapy, appropriate diagnestic investigation should be undertaken. This should inelude CT oF ultrasound im- aging, and antimicrobial therapy effective against the organisms initally identified shoul be continued (AI). 91. Extre-abdominal sources of infection and. noninfec ‘ious inflammatory conditions should also be investi- gated ifthe patient is not experiencing a satisfactory linical response toa microbiclogically adequate intial empiric antimicrobial regimen (4-1. 92, resistant bacteria were identified atthe time of initial intervention and there are persistent signs of infection, pathogen-drected therapy is also recomended for lowerrisk patients (BI) 88, For patienis who do not respond initially and for ‘whom 2 focus of infection remains, both aerobic and anaerobic cultures should be performed from 1 spec- ‘men, provided itis ofsufficent volume (at least 10m of uid cr tissue) and is transported to the laboratory inan anaerobic transport system (C-I). Inoculation ofINTRA-ABDOMINAL INFECTIONS GUIDELINES 110ml of fluid directly into an anaerobic Blood cul ture broth bottle may improve yield Pathways for the Diagnosis and Management of Patients with Suspected Acute Appendicitis 94, Local hospitals should establish clinical pathways to standardize diagnosis, in-hospital management, dis- charge, and outpatient management (B-). 95, Pathways should be designed by collaborating clini- cians involved in the care of these patients, including ‘but not limited to surgeons, infectious diseases spe- cialists, primary care practitioners, emergency medi- cine physicians, radiologists, nursing providers, and pharmacists, and should reflect local resources and local standards of care (B-1). 96, Although no clinical findings are unequivocal in identifying patients with appendicitis, «constellation of findings, inchuding characteristic abdominal pain, localized abdominal tenderness, and laboratory evi dence of acute inflammation, will generally identify ‘most patients with suspected appendicitis (AD). 97, Helical CT of the abdomen and pelvis with intrave- nous, but not oral or rectal, contrast is the recom- ‘mended imaging procedure for patien’s with suspected appendicitis (B-D). 98, All female patients should undergo disgnostic im- ‘aging. Those of child-bearing potential should un- ergo pregnancy testing pricr fo imaging and, if in the first trimester of pregnancy, should undergo ul- ‘asound or magnetic resonance instead of imaging ionizing radiation (B-D. If these studies do not define ‘the pathology present, laparoscopy or limited CT seanning may be considered (BD) 99, Imaging should be performed for all childven, par- ticularly those aged <3 years, when the diagnosis of appendicitis is not certain. CT imaging is preferred, although to avoid use of ionizing radiation in chil- dren, ultrasound is a reasonable alternative (8-1. 100. For pationts with imaging study findings negative for suspected appendicitis, followup at 24h is re commended to ensure resolution of signs and symptoms, because ofthe low but measurable risk of false-negative results (8). 4101. For patients with suspected appendicitis that can neither be confirmed nor excluded by diagnostic imaging, careful follow-up is recommended (A-I}. 102, Patients may be hospitalized ifthe index of suspicion is high (ALD. 103. Antimicrobial therapy should be administered to all patients who receive a diagnosis of appendicitis (A-D, 104. Appropriate antimicrobial therapy includes agents ef- fective against facultative and aerobic gram-negative organisms and anaerobic organisms, as detailed in Tables 2 and 3 for the treatment of pationts with community-acquized ints-ebdominal infection (AD, 105, For patients with suspected appendicitis whose dic agnostic imaging studies aze equivocal, antimicrobial therapy should be initiated along with appropriate pain medication and antipyretics, if indicated. For adults, antimicrobial therapy should be provided for minimum of tee days, until clinical symptoms and a7 signs of infection resolve ora definitive diagnosis is made (B-II). 108, Operative intervention for acute, nonperforated ap- pendicits may be performed a son ass reasonably feasible. Surgery may be defemed fora shore period of time as appropriate according to individual insti tutional circumstances (6). 107, Both laparoscopic and open appendectomy are ac ceptable procedures, and use of either approach should be dictated by the surgeon's expertise in performing that particular procedure (AD, 108, Nonoperative management of elected patents with acate, nanpecforaed appendicitis can be considered if there is'2 marked improvement in the patent's concition prior to operation (B 109, Nenoperstive management may also be considered as part ofa specific approach for male patients, pro- Vided that the patient is admitted to the hospital for 48h and shows sustained improvement in lnial symptoms and signs within 2¢h while receiving an- dimicrobial therapy (AD. 10, Patients with perforated appendicitis should undergo urgent intervention to provide adequate source con trl (Bt. 1, Patients with a wellcircumscrbed periappendioeal abaces can be managed with percutaneous drainage or operative drainage when necessary. Appendec amy is generally deferred in such patients (A-D, 122. Selected patents who present several days after de- velopment of an inflammatory process and have a esappendiceal phlegmon or @ small absoese not menable 10 pereutaneous drainage may delay or avoid a source contol procedure f0 avoid a poten- tially more morbid procedure than simple appen- dectomy. Such patients are treated with antimicrobial therapy and carefl inpatient fllowr-up, in a manner analogous to patients with acute diverticulitis (8-1, 113. The ue of interval appendectomy after percutaneous drainage or nonoperative management of perforated ppendictis fs controversial anc may not be neces- sary (Ad Introduction ‘Complicated intra-abdominal infection extends beyond the hollow viscus of origin into the peritoneal space and is asso- ciated with either abscess formation or peritonitis. These guidelines do not include management of nonperforated primary enteritis and or colitis or pecforations due to diseases that are raze in North America. This term is not meant to describe the infection’s severity or anatomy. Uncomplicated infection involves intramural inflammation of the gastroin- testinal tract and has a substantial probability of progressing to complicated infection if not adequately treated, Similaely, these guidelines do not address diseases that are uncommon in North America. Complicated intra-abdominal infection is a common prob- lem, with appendicitis alone affecting ~300,000 patients/ year and consuming >1 million hospital days (6). Intra- ‘abdominal infection is the second most common cause of infectious mortality in the intensive care unit [7]. Nonetheless, ‘this disease clasifcation encompasses a variety of processes88 that affect several different organs, The requirement for in- tervention in most cases and the controversies surrounding the choice andl nature of the procedure performed add another layer of complexity to the management of these patients. "Appropriate management of these infections has evolved considesably, because of advances in supportive intensive care, diagnostic imaging, minimally invasive intervention, and antimicrobial therapy. These guidelines are intended to provide a framework iavolving these various care measures. ‘Given the frequency of acute appendicitis, the information in this document is suitable for developing local management guidelines for pediatric and adult patients with suspected acute appendicitis. ‘The following clinical questions will be addressed in this guideline: 1. What Are the Appropriate Procedures for Initial Evaluation of Patients with Suspected Intra- abdominal Infection? IL When Should Fluid Resuscitation Be Started for Pas tients with Suspected Intra-abdominal Infection? IIL When Should Antimicrobial Therapy Be Initiated for Patients with Suspected or Confirmed Intra- abdominal Infection? IV. What Are the Proper Procedures for Obtaining Adequate Source Control? V. When and How Should Microbiological Specimens Be Obtained and Processed? ‘VI What Are Appropriate Antimicrobial Regimens for Patients with Community-Acquired Intrasabdominal Infection of Mild-to-Moderate Severity? ‘What Are Appropriate Antimicrobial Regimens for Patients with Community-Acquired Intracabdominal Infection of High Severity? What Antimicrobial Regimens Should Be Used in Patients with Health Care-Associated Intra-abdomi- nal Infection, Particularly with Regard to En terococcus, MRSA, and Cari? IX, What Are Appropriate Diagnostic andl Antimicrobial ‘Therapeutic Strategies for Acute Cholecystitis ond Cholangitis? X. What Are Appropriate Antimicrobial Regimens for Pediatric Patients with Community-Acquired Intra- abdominal Infection? XL What Constitutes Appropriate Antibiotic Dosing? XIL How Should Microbiological Culture Results Be Used to Adjust Antimicrobial Therapy? XIIL What Is the Appropriate Duration of Therapy for Patients with Complicated Intra-abdominal Infec- tion? What Patients Should Be Considered for Oral or Outpatient Antimicrobial Therapy and What Regi- ‘mens Should Be Used? How Should Suspected Treatment Failure Be Man- aged? XVL What Are the Key Elements that Should Be Con- sidered in Developing a Local Appendicitis Pathway? VIL vu xiv. Xv. Practice Guldelines “Practice guidelines are systematically developed state- ‘ments to assist practitioners and patients in making decisions INTRA-ABDOMINAL INFECTIONS GUIDELINES about appropriate health care for specific clinical circum- stances” (8, p 8]. Attebutes of good guidelines include va- lidity, reliability, reproducibility, elinieal applicability, clinical Aexibility, clarity, multiisciplinary process, review of evi- dence, and documentation [8] Update Methodology Panel composition. A panel of experts in infectious dis- eases, surgery, pharmacology and microbiology was assem- bled by the Infectious Diseases Society of America (IDSA) and the Surgical Infection Society (SIS) to prepare these fuidelines, The panelists had both clinical and labocatory experience. Literature review and analysis. The Panel reviewed studies on the site of origin of intra-abdominal infections their microbiology, the laboratory approach to diagnosis of infec- tion, the selection and duration of antibiotic therapy, and use ‘of ancillary therapeutic aids, The Panel further reviewed the initial diagnostic work-ups, resuscitations, timings of inter- vention, and source control elements for infection. Previous guidelines detail recommendations made in 2002 and 2003 1,10), ‘These guidelines are based on randomized clinical tials using antimicrobials for treatment of intra-abdominal infec- tion published from 2002 through December 2008. The 2002 cut-off was used because relevant literature available through, 2002 was used for the previous guidelines. The Medline da- tabase was searched using multiple strategies in which the names of specific antimicrobials or more general descriptors (e, cephalosporins) were paired with words and phrases in- ddicating an intra-abdominal infection (ie, peritonitis or ap- pendicitis) Articles were also retrieved for review by searches for resuscitation, septic shock, CT scan, imaging, appendicitis, diverticulitis, source control, wound closure, and drainage. ‘The Panel members contributed reference lists in these areas. This search included studies that were in the Medline data- base as of 1 January 2008, The Cochrane database was also searched for relevant trials. Process overview. In evaluating the information re- ‘garding the management of intra-abdominal infection, the Panel followed a process used to develop other IDSA guide- lines [11]. The published studies were first categorized ac- cording to study design and quality, and in tum, the recommendations developed from these studies were graded according to the strength of evidence behing them. The level of evidence and the strength of the recommendation for a pparticular point were defined as described elsewhere [11] Table 6) Consensus development on the basis of evidence. The Panel met on 4 occasions, 3 times via teleconference and once {in person, to complete the guideline, The meetings were held to discuss the questions to be addressed, to make writing assignments, and to discuss recommendations. There was & large volume of e-mail comments, because drafts were regu- larly circulated electronically. All panel members participated in the preparation and review of the draft guideline. Feedback rom external peer reviewers was obtained. The guideline was reviewed and endorsed by the Pediatric Infectious DiseasesINTRA-ABDOMINAL INFECTIONS GUIDELINES Society, the American Society for Microbiology, the American Society of Health-System Pharmacists, and the Society of In- fectious Disease Pharmacists. The guideline was also re- viewed and approved by the IDSA Standards and Practice Guidelines Committee, the IDSA Board of Directors, the SIS ‘Therapeutic Agents Committee, and the SIS Executive Couneil prior to dissemination Guidelines and conflict of interest. All members of the Expert Panel complied with the IDSA policy regarding con- Aicts of interest, which requires disclosure of any financial or other interest that might be construed as constituting an ac- tual, potential, or apparent conflict. Members of the Expert Panel were provided a conflict of interest disclosure statement from the IDSA. and were asked to identify tes to companies developing prodiucts that might be affected by promulgation of the guideline. Information was requested regarding em ployment, consultancies, stock ownership, honoraria, esearch funding, expect testimony, and membership on company advisory committees, The Panel made decisions on a case- by-case basis as to whether an individual's role should be limited as a result of a conflict. No limiting conflicts were identified, Revision dates. At annual intervals, the Panel Chair, the IDSA, and SIS will determine the need for revisions to the guideline on the basis of an examination of current literature. If necessary, the entize Panel willbe reconvened to discuss po- tential changes. When appropziate, the Panel will recommend revision of the guideline for approval by the IDSA and SIS. Recommendations for the Diagnosis ‘and Management of Complicated Intra-Abdominal Infection in Adults and Children |. What are the Appropriate Procedures for Initial Evaluation of Patients with Suspected Intra-Abdor Infection? Recommendations 1. Routine history, physical examination, and laboratory ‘studies will identify most patients with suspected intra- abdominal infection for whom further evaluation and ‘management is warranted (AID. 2, For selected patients with unreliable physical exami- nation findings, such as those with an obtunded mental status or spinal cord injury or those immunosuppressed by disease or therapy, intr-abdominal infection should ‘be considered if the patient presents with evidence of infection from an undetermined source (B-I). 3, Further diagnostic imaging is unnecessary in patients ‘with obvious signs of diffuse peritonitis and in whom im mediate surgical intervention is to be performed (B-I). 4. In adult patients not undergoing immediate laparot- ‘omy, CT scan is the imaging modality of choice to de- femmine the presence of an intra-abdominal infection and its source (4-1). Evidence Summary Patients with intra-abdominal infection typically present with rapid-onset abdominal pain and symptoms of gastroin- a9. testinal dysfunction: (loss of appetite, nausea, vomiting, Dlonting, and/or obstipation), with or without signs of in fiammation (pin, tendemess, fever, tachycardia, and/or ta- chypnea). Often, a careful history and physical examination will provide a limited differential diagnosis and a clear as- sessment of the degree of the patients physiologic distur bance. This assessment, in tum, allows for immediate decisions regarding the need for and intensity of resuscitation / rehydration, appropriate diagnostic testing, the need for and timing of initiation of antimicrobial therapy, and whether emergent intervention is required. On the basis of these findings, the timing and nature of operative or percutaneous intervention can be determined. The clinician must be alert to the fact that signs of sepsis may be minimal in elderly patients land in patients receiving corticosteroids or other immuno- ‘suppressive therapy. ‘The value of a range of symptoms, signs, and physical findings in the diagnostic work-up for intra-abdominal in- fection has been most fully studied in relation to acute ap- pendictis (12-14) The findings of several analyses involving both children and adults are that no scoring system provides greater diagnostic sensitivity or specificity than clinical im pression, although the analyses used to generate and then ‘Verify these systems have identified independent variables and their postive and negative predictive values, which may help focus the attention of treating clinicians [13,15] In general, CT isthe preferred imaging modality [26} helical scanning is prefered [17]. A recent meta-analysis found that pooled sensitivity and specificity for diagnosis of appendicitis in children were 88% and 94%, respectively, for ultrasound studies and 94% and 95%, respectively, for CT studies. Pooled sensitivity and specificity for diagnosis in adults were 63% and 98%, respectively, for ultrasound! studies and 94% and 94%, respectively, for CT studies (18). No such studies have been performed on other intra-abdominal processes. Blood cultures aze seldom useful adjuncts for diagnosing intra-abdominal infection, even in health care-associated or ‘complicated cases. Published rates of bacteremia related tothe organisms present in the infected abdominal site range from O2e in a lange appendicits series [19] to 5% in a percutaneous dtrainage series [20]. Bacteremia appears to be more common in patients inthe intensive care unit and is associated with fncreased mortality [2] ‘The organisms isolated in bacteremia that accompanied comamunity-aequited complicated intra-abdominal infection have low potential for forming endocarditis on normal valves, for metastatic abscesses. Positive blood cultures for the of ganisms that may do 80, including S. aureus, Candida species, and Streptococcus miler 22), are so rarely reported prior to therapy for these infections that blood cultures are not re- commended, I, When Should Fluid Resuscitation be Started for Patients with Suspected Intra-Abdominal Infection? Recommendations 5, Patients should undergo rapid restoration of intravas- cular volume and additional measures as needed to promote physiological stability (AI). 6. For patien’s with septic shock, such resuscitation should begin immediately when hypotension is ident- fied (AID,90 7. For patients without evidence of volume depletion, in- travenous fui therapy should begin when the diagnosis of intra-abdominal infection is first suspected (B-I). Evidence Summary Volume depletion is common in febrile patients and is worsened by poor fluid intake because of nausea and/or vomiting and in the presence of ileus induced by intra-ab- dominal inflammation, Much ofthe fluid loss is attributable to tachypnea. Commonly, patients experience a panting re- sponse through which tidal volume is minimized and breathing frequency is maximized (23,24). Blood-gas tensions and pH are maintained during this hyperventilation, and the associated heat loss by evaporation helps regulate body temperature. A second pattem of breathing adopted in hy- thermia, thermal hyperpnea, results in increased tidal volume as well as increased breathing frequency, resulting in a respiratory alkalosis and further evaporative water loss. ‘There is compelling historically controlled data that patients with perforated or abscessed appendicitis benefit from ad- ‘ministration of fluids even absent septic shock [25]. For patients with septic shock or organ failure, more-ag- ‘gressive fluid therapy should be provided. We recommend following the Surviving Sepsis Campaign guidelines for managing septic shock [26]. Key recommendations include carly goal-directed resuscitation during the first 6h after recognition (administration of either crystalloid or colloid fuid resuscitation, fluid challenge to restore mean circulating filling pressure, reduction in rate of uid administration with increasing filling pressures and no improvement in tissue perfusion, vasopressor preference for norepinephrine or do- ‘pamine to maintain an initial target of mean arterial pressure >65mmHg, dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and com- bined inotropic/vasopressor therapy, and stress-dose steroid therapy given only in septic shock after blood pressure is Identified to be poorly responsive to fluid and vasopressor therapy) Il, When Should Antimicrobial Therapy be Initiated for Patients with Suspected or Confirmed Intra-Abdominal Infection? Recommendations 8, Antimicrobial therapy should be initiated once a pa- tient receives a diagnosis of an intra-abdominal infec- tion or once such an infection is considered likely. For patients with septic shock, antibiotics should be ad- ministered as soon as possible (AID. 9. For patients without septic shock, antimicrobial therapy’ should be started in the emergency department (B-I1) 10. Satisfactory antimicrobial drug levels should be ‘maintained during the intervention, which may ne- cessitate additional administration of antimicrobials just before initiation of the procedure (A-1) Evidence Summary Delaying antimicrobial therapy has been associated with, poorer outcomes in patients with septic shock, including those with intrz-abdominal infection 27]; however, the study INTRA-ABDOMINAL INFECTIONS GUIDELINES [27] was oflow quality asjudged by the methodologic quality Score system presented by van Nieuwenhoven et al (25). On the basis of this study [28], sepsis guidelines have re commended that antibiotics be administered within 1h of recognition of septic shock [26]. In patents without hemo- dynamic or organ compromises, the Expert Pane] members agreed that antibacterials should be adiniistered within 8 alter presentation. In patients undergoing a source contol procedure, ant- microbial therapy provides for surgical wound prophylaxis and treatment of pathogens that aze potentially disseminated during. the procedure, in addition to providing ongoing therapy for the infection. Antimicrobial therapy is, therefore, also considered to be wound prophylaxis fr all patents un- dergoing intervention. The rules for prophylaxis in elective surgical procedure include use of agents tat are likely tobe effective against the contaminating organisms and adminis: tration within 1h before the operation [29,30 1V. What are the Proper Procedures for Obtaining ‘Adequate Source Control? Source control is defined as any procedure or series of procedutes that eliminate infectious foci, control factors that promote ongoing infection, and correct or control anatomic derangements to restore normal physiologie function. Recommendations 11, An appropriate source control procedure to drain ine fected foc, control ongoing peritoneal contamination by diversion or resection, and restore anatomic and physiological function to the extent feasible is re- commended for neal all patients with intra-sbdom inal infection (6-1 12, Patients with diffuse peritonitis should undergo an emergency surgical procedure as soon as is posible, even if ongoing measures t restore physiologic sta bility need to be continued during the procedure (BI. 15. Where feasible, percutaneous drainage of abscesses and other wel-localized fluid collections is preferable to surgical drainage (BD) 1s, For hemodynamically stable patients without evidence of acute organ failure, an urgent approach should be taken, Intervention may be delayed for as long as 24 if appropriate antimicrobial therapy is given and careful clinical monitoring is provided (B-, 15. In patients with severe. peritonitis, mandatory ot schedued relaparotomy is not recommended in the absence of intestinal discontinuity, abdominal fascial loss that prevents abdominal wall closure, or intra- abdominal hypertension (A-I. 16, Highly selected patients with minimal physiological derangement and a well-circumserbed focus of ifec- ton, such as a periappendiceal or pescolonic phieg- ‘mon, may be treated with antimicrobial therapy alone without 2 source conirol procedure, provided that very close clinical followup is possible (8-1) Evidence Summary The timing of intervention is a key decision, particularly in the presence of diffuse peritonitis. Patients with diffuse peri-INTRA-ABDOMINAL INFECTIONS GUIDELINES tonits from a perforated viscus cannot be full resuscitated ‘unt ongoing soiling has been controlled. In such patients, resuscitation should be continued intraoperatively. For he rodynamicelly table patents without peritonitis, delay of ‘uptoone day may be appropriate, The Expert Pane notes that this decision is a complex calculation based on a variety of patient, institation-, and surgeor-specic factors, and a greater or lesser delay may be appropriate, with most patients benefiting from a more urgent approach Source control is defined as any single procedure or series of procedures that eliminate infectious for, contro factors that promote ongoing infection, and corrector control ana~ tomic derangements to restore normal physiologic function [61] Source control failure i more likely o occu inpatients with delayed (>24h) procedutal intervention, higher seventy illness (APACHE I score >15), advanced age (>70 year), pre-existing chronic medical conditions, poor nutritional sta- fus, and a higher degree of peritoneal involvement and is heralded by persistent or recurrent intra-abdominal infection, anastomotic failure, or fistula formation [32-36] ‘Well localized fd collections of appropriate density may be drained percutaneously with acceptable morbidity and mortality (20, 37-29], Percutaneous drainage of appropriately selected infectious sources may result in significantly less physiologic alterations in patients and may eliminate Or re- Guce the need for open techniques, Open surgical tecaniques, are likely require for poorly localized loculated, complex, dfs fd colletions and necrotic issu, high density uid, or percutancously inaccessible collections. The majority of patients respond to a single intervention without significant complication Given the range of diseases and the various rsk factors for poor outcome in nonappendiceal disease, clinical practice has been driven by uncontzolled case series 40-46} Perewtaneous techniques have continued toevolve, and many abscesses that were previously considered tobe best approached by lapa- zoiomny axe nov often approached by interventional radiog- raphy 47} Tris important to discuss sadiographie findings with the surgeon to avoid inappropriate abscess drainage in the pres- ence of free hollow-organ perforation and acute peritonitis ‘Acute peritonitis is best treated surgically rather than with percutaneous drainage There are some patients in whom drainage catheter place- rent is not appropriate, and laparotomy isthe procedure of choice. If clinical evaluation suggests peritonitis, the patent should proceed to surgery even if imaging demonstrates, rainable collections, except in extreme cizcumstances in which a patient is deemed unit for surgical intervention. Eetrluminal air and fisid in a “contained” distribution im- mediately adjacent to underiying diseased bowel (eg, in di- verticulite of appendicitis) can be drained. However, @ patient with a simular abscess but with extensive and massive {ree air or fluid remote from the perforation site should wsu- ally undergo surgery for such an “uncontained” perforation, ‘There is only a limited role for catheter placement in some panereatitizeated collections ‘When laparotomy is undertaken fornoreappendicealintra- abdominal infection, range of factors will determine the extent (if any) of bovrel resection, whether an anastamosis or ostomy is created, what Hssue is debrided, what type of Grainage (i any) is necessary, and what wound management ” technique is used. These questions have not been adres: sed in controlled trials, and specific guidelines cannot be provided. ‘Three general strategies should be considered for critically il patients who are either physiologically unstable or at high risk of experiencing failed source control. These inctude (1) laparostomy or the “open abdomen,” (2) planned re-aparot- omy, and (3) on-demand redaparotomy [48) ‘Generally accepted indications for laparostomy in which neither the fascia nor skin are closed include severe physic logic derangements intraoperatively that predade comple- tion of the planned procedure, intra-abdominal hypertension, and loss of abdominal softssue preventing immediate fas- cial closure, Generally accepted indications for either lapar- ostomy or planned relaparotomy include settings in which adequate source control cannot be obtained at the index procedure, control or reestablishment of hollow viscus con tinuity eannot be safely performed, and possible ongoing in- testinal ischemia requiring a second-look operation to ensure enteric viability [48]. Unless clear indications for relaparot- ‘omy exis, relaparotomy on demand has been shown to re- ce use of health care services, costs, and laparotomies with similar outcomes, V. When and how should Microbiological Specimens be obtained and Processed? Gram Stain and Blood Cultures Recommendations 17, Blood cultures do not provide additional clinialy relevant information for patienss with commanity-ac- quired inteabdomina irvection and are therefore not routinely recommended for such patients (AD. 18. Ia patient appears clinically toxe ori mmenocom- promised, knowedge of bacteremia may be help in Selermining duration of antimicrobial therapy (HD 19, For commenity-acquired infections, there is no proven value in obtaining a routine Gram sain ofthe infected Inateral (CD. 20, For nenlthcare-assocated infections, Gram stains may help define the presence of yeast (Cl, 2, Routine aerobic and ancersbic cultures from lower- risk patents with community. acquired infection are considered optional in he individual patient but may be of value in detecting epidemiological changes inthe resistance pattems of pathogens associated with conmuity-cquired inteabdominal infection and in guiding follow-up oral therapy (BI), 22, I there is significant resistance (ie resistance in 10% 21% of isolates) of a common commit isolate (5, cn) toan animcrobial regimen in widespread local se routine culture and susceptibility studies should be sbtaines for perforated appendicitis and other com- ‘muruty-acquited intra-abdominal infections 1) 23, Anaerobic cltares are not necessary for patients with ‘communiy-acqured intra-abdominal invection if em- pine antimicrobial therapy active against common Inacrobie pathogens is provided (-IN) 24, For higherisk patients, cltares from the site of fn- fection should be routinely obtained, particularly in patents with prior antbiotc expomure, who are more2 likely than other patients to harbor resistant pathogens (aa. 25, The specimen collected from the intra-abdominal focus of infection should be representative of the material associated with the clinical infection (B-I). 25, Cultures should be performed from 1 specimen, pro- vided itis of sufficient volume (at least Im of fluid or tissue, preferably more) and is transported to the lab- ‘ratory in an appropriate transport system. For opti- mal recovery of aerobic bacteria, 1-10mL of fluid should be inoculated directiy into an aerobic blood culture bottle, In addition, 0.5m. of fluid should be sent to the laboratory for Gram stain and, if indicated, fungal cultures. If anaerobic cultures are requested, at least OSmL of fluid or 05g of tissue should be transported in an anaerobic transport tube. Alter nately, for recovery of anaerobic bacteria, 1-10mL of fluid can be inoculated directly into an anaerobic blood culture bottle (A-D, 27. Susceptibility testing for Pseudomonas, Proteus, Acine- lobacter, Stephylococcus aureus, and predominant En- terobacteriaceae, as determined by moderate-to-heavy growth, should be performed, because these, species are more likely than others to yield resistant organisms (am. Evidence Summary ‘There are few data indicating that gram stan, culture, and suscepetbiity data provide information ikelytoalte outcome in patients with a community-acqured complicated intze- abdominal infection. For palénts with perforated or gangze- nous appendicitis, many surgeons do not obtain cultures (50, Si], For patients with health care-asociated infection, antic rmicrobial therapy tha fast cover eventual pathogens has bean associated with higher rates of treatment failure and rorialit [52], Thus, gram stains may be of valuein detecting gram-positive coce! or yeast that would lead to additional empiric antimicrobial therapy before definitive culture results areavailable. Local susceptibility pattems for S. sureus and for entero- cocci might warrant addition ofan MRSA-active agent ut results of cultures and susceptibility teating are available [52] For enterococci, local susceptibilities should be monitored for penielin and vancomyein resistance If yeast ae identified ona gram stan, additional therapy for Candida species may be considered. ‘The major pathogens in community-acquited intre-ab- dominal infection are coliforms (Enterobacteriacee, especially E col) and anaerobes (especially B.frugis) (Table 8). Patho- gens are nearly always present in concentrations >1x10° or- ganisms/g of tissue or 1x10 organisms ml. of exudate. This ‘would correspond to moderate ot heavy growth on the sary isolation plates. The primary focus shoul, therefore, be on the predominant organisms isolated from these cultures, Most intra-abdominal infections involve anaerobic bacte- ria, but laboratories show great variation in reliably per- forming in vitro susceptibility tests, Sentinel studies of B ‘fugis, the major pathogen, show uniform susceptibility 10 ‘metronidazole, carbapenems, and some Placan/f-acta- ‘mate inhibitors [53-57] Studies ofthe activity of quinolones against Bfnglis isolates have yielded conflicting data, in part INTRA-ABDOMINAL INFECTIONS GUIDELINES ‘Tantus 8. ORGANISMS IDENTIFIED IN 3 RANDOMIZED Prospective TRtats OF INVESTIGATIONAL ANTIBIOTICS oR CompLicaTeD INTRA-ABDOMINAL INFECTION, INCLUDING 1237 MicRORIOLOGICALLY CONFIRMED INFECTIONS Patents, % Orgonism (a= 1237) Facultative and aerobie gram-negative Escienchincol n Kietsila species uM Pseudomontsaeraginon “4 Proteus mirabilis 5 Enterobacter species 5 ‘Anaerobic Bacteroides fags 35 Other Becteraces species 7 Clostridium species 29 Prevotla species 2 Peptosrepiccocus species y Fusobacterium species 8 Eubacterin species v Gram-positive aerobic cocci ‘Strepocoecs species 38 Eneocseus feecais 2 Enterococcus ecu 3 Enterococcus species 8 Staphylococus aureus 4 NOTE. Adapt fom (7, 166, 190, The Kequeny of specie Bacteroides Specs and other anaerobes is provided eswhere (3). because ofthe use of abdominal abscess versus bacteremic isolates [58-61]. Susceptibility testing of individual anaerobic isolates should be considered when there is persistent isoa- {Hon of te organism, bacteremia, or when prolonged therapy is needed because of immunosuppresion or prosthetic fection. Laboratories can purify and hold isolates for addi tional testing if requested by the clinician (62) Tn many locations there is increasing resistance to selected antibiotics among community-acquired strains of gram-neg- ative organisms. These include the widespread prevalence of ampiciln-sulbactamresistant E. coli worldwide, the high penetration of fuoroquinolone-resistant E. cal in Latin ‘America and East Asia, and locations with a high prevalence of ‘extended-spectrum [Haciamase-producing strains of Klebsiella species and coi [63], In some populations and communities, a relatively high prevalence of moreresistant nonenteric gram-negative organisms, such as Pseudomonas ‘eruginasa, will impact the selection of appropriate empire antibiotic therapy [64-66]. Routine cultures from patients ‘with community-acquired intra-abdominal infection may fa- clitate recognition of local changesin resistance and, hereby, optimal selection of antimicrobial agents for both definitive ‘treatment and oral step-down therapy. There axe marked differences in susceptibility pattems within and between liffeent communities and institutions. Taese epidemiologic Gata are of considerable value in defining the most suitable antimicrobial therapy for intra-abdominal infection. Te fail lure to provide adequate antimicrobial therapy in such pa- tients has been repeatedly associated with an increased incidence of therapeutic failure and, in some cases, increased mortality (52,67)INTRA-ABDOMINAL INFECTIONS GUIDELINES Certain communities and age groups have an inexplica- bly high incidence of P. aeruginosa infection associated with commmunity-acquired appendicitis (64-66, 68]. Even if ther- apy with a broader spectrum is used empirically, culture results may allow the dlinician to narrow the spectrum of therapy considerably for more-prolonged, definitive therapy. ‘Complete inoculation of all appropriate media (eight agar plates, a Gram stain, and a broth enrichment tube) for aerobic fand anaerobic bacterial cultures alone calls for 0.0SmL of tissue or uid per medium or slide, requiring a minimum of ‘LOmL o 10g of specimen. Fungal or acid-fast cultures will necessitate additional sample volume VL. What are Appropriate Antimicrobial Regimens {for Patients with Community-Acquired Intra-Abdominal Infection of Mild-to-Moderate Severity? Recommendations 28, Antibiotics used for empitic treatment of community- acquired intra-abdominal infection should be active against enteric gram-negative aerobic and faculta- tive bacili and enteric) gram-positive streptococci @D. 29, Coverage for obligate anaerobic bacilli should be provided for distal small bowel, appendiceal, and colon-derived infection and for more proximal gas- ‘trointestinal perforations in the presence of obstruction or paralytic ileus (A-D. 30. For adult patients with mild-to-moderate community- acquired infection, the use of ticarcillin-clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metranida~ zole with cefazolin, cefuroxime, ceftriaxone, cefotax- ime, levofloxacin, or ciprofloxacin are preferable to regimens with substantial anti-Pseudomonal activity (a. 31. Ampicilinsulbactam is not recommended for use ‘because of high rates of resistance to this agent among community-2equired E.coli (®-). 32, Cefotetan and clindamycin are not recommended for use because of increasing prevalence of resistance to these agents among the Bacteroides fragilis group GD. 33, Because of the availabilty of less toxic agents dem- onstrated to be at least equally effective, atninogiyco- sides are not recommended for routine use in adults ‘with community-acquired intra-abdominal infection G2. 34. Empire coverage of Enterococcus is not necessary in patients with community-ecquired intra-abdominal infection (A-D. 35, Empirie antifungal therapy for Condit is not recommended for adult and pediatric patients ‘with community-acquired intra-abdominal infection GD. 36, The use of agents listed as appropriate for higher- severity community-acquired infection and health ‘care-associated infection is not recommended for pa~ tients with mild-to-moderate community-2cquixed in- fection, because such regimens may camry a greater 93 risk of toxicity and facilitate acquisition of morere- sistant organisms (B-I), 237. For those patients with intra-abdominal infection of mild-to-moderate severity, including acute divertcu- lit and various forms of appendicitis, who will not ‘undergo a source control procedure, regimens listed for treatment of mild-to-moderate-severity infection aze recommended, with a possibility of early oral therapy (BD. Evidence Summary Infections derived from the stomach, duodenum, biliary system, and proximal small bowel contain gram-positive and ‘gram-negative aerobic and facultative organisms. Infections derived from distal small bowel perforations contain gram- negative facultative and aerobic organisms with variable density. Perforations of this type often evolve into localized abscesses, with peritonitis developing only after rupture of the abscess. Anaerobes, such as B. fragilis, are commonly present, Colon-derived intra-abdominal infections harbor facultative and obligate anaerobic organisms. Streptococci, particularly the $, miller group, and enterococci are also commonly present. By far the most commonly detected gram- negative facultative organism is E.coli. ‘The efficacy and cost advantages of generic agents are no- ted elsewhere (69-72). ingle agents approved for use include ticarcllin-clavulanate, cefoxitin, moxifloxacin, ertaperem, and tigecycline [73-78]. Given the very broad spectrum of tigecycline, including activity against MRSA and a wide va- riety of other gram-positive and gram-negative organisms not ‘commonly seen in appendicdlerived infection, there is con- ccem for its use in mild-to-moderate complicated ini abdominal infection, The Expert Panel is also concerned that broad use of ertapenem may hasten the appearance of car bapenem-resistant Enterobucleiacae, Pseudomonas, and Acine- tobacler species. Quinolone-resisiant E. cali has become comnmon in some communities, and quinolones should not be ‘used unless hospital surveys indicate >90% susceptibility of E.coli to quinolone. 'A poorer outcome for patients with B. fragilis infection ‘treated with agents to which the organisms were resistant has been repeatedly demonstrated [79-81]. Given that no out come differences have been identified in randomized com- trolled trials, antimicrobial selection should be based on local microbiologic data, cost advantage, allergies, and formulary availability. ‘The occurrence of organisms in the community that have resistance to commonly prescribed agents is becoming a re- ality. I resistance to a given antibiotic is present in 10%-20% for more of isolates of a common intra-abdominal pathogen fn the community, use of that agent should be avoided. Because of widespread sesistance of E. coli to ampicillin sulbactam, that antibiotic is no longer recommended for routine empiric therapy of complicated intra-abdominal in- fection [63] Tnereasing antimicrobial resistance among B. fragilis 's0- lates is similarly of eancem, and there are data indicating Iigher failure rates if these oxganisms are treated with an inactive agent [79, 81]. No randomized clinical trials have ‘been performed with this agent since resistance was first re- ported. Similarly, use of moxifloxacin for the treatment of94 patients who are likely to harbor B, fragilis should be avoided if patients have received quinolone therapy within three ‘months, because organisms from such patients are likely to be quinolone resistant [82,83]. ‘The expanded gram-negative spectrum against which some agents have been shown tobe effective in clinical tials is not advantageous for patients with community-acquired in- fection, and their unnecessary use may contribute to the emergence of antimicrobial resistance (39, 47]. Hospitals should review local microbiologic findings, because use of broader-spectrum regimens may be required. Numerous prospective blinded and randomized trials have compared regimens active against routine isolates af Enterococcus for treatment of cornmunity-acquired infec: tion. In atleast six of these studies, the comparator regimen did not provide similar coverage (64, 84-88]. None of these trials demonstrated an advantage for treatment of entero- Patients with intra-abdominal infection, including acute diverticulitis and certain forms of acute appendicitis, may be ‘managed nonoperatively. The microbiology of patients ‘managed nonoperatively is likely similar to that of patients ‘managed operatively, and regimens recommended for pa- tients with complicated intra-abdominal infection are re commended (88), Vi What are Appropriate Antimicrobial Regimens for Patients with Community-Acquired Intra-Abdominal Infection of High Severity? Recommendations 28. The empiric use of antimicrobial egimens with broad- spectrum activity against graawnegative organisms, including meropenem, imipenemllastatin, dor ipenem, piperacilntazobactam, ciprofloxacin or le- vofloxacin in combination with metronidazole, of ceftazidime or cefepime in combination with mettoni- azole, is recommenced for patients with high-seveity community-acquired intra-abdominal infection, as de- fined by APACHE I scores >15 or other variables listed in Table 29. Quinolone-resistant E, coli has become common in some communities, and quinolones should not be used unless hospital surveys indicate >90% susceptibility of E. cal to quinolones (AI. 40. Aztreonam plus metronidazole isan alternative, but addition of an agent effective against gram-positive cocci is recommenced (BA). 41, Inadults, routine use ofan aminoglycoside or another second agent effective against gram-negative faculta- tive and aerobic bacilli is not recommended in the absence of evidence that the patient is likely to harbor resistant organisms that require such therapy (A-1) Empiric use of agents effective against enterococci is recommended (6-1). 48. Use of agents effective against MRSA or yeast is not recommended in the absence of evidence of infection due to such organisms (B-). 44, In these higherisk patients, antimicrobial regimens should be adjusted according to culture and suscepti- bility reports to ensure activity against the predomi- rant pathogens isolated in clture (A-I. 8 INTRA-ABDOMINAL INFECTIONS GUIDELINES. Evidence Summary Several attempts have been made to identify clinical fea- teres that incense the sk of averse oueomes in patients with complicated intte-abdominal infection. These analyses have identified parameters that are predictive of mostality rather thanf th sik of reruren infection. These rik factors include higher APACHE Ul sores, poor nutritional status, significant erdiovasula disease, and an inability to achieve adequate source contol (90-95), Similacy, patents who are immuno-suppresed by medical therapy for tansplantation, cancer of infanmatory disease are at higher tsk ofan 0 verte outcome, Prolonged hospital length of stay before the operation (25 days) and prolonged (22 days) preoperative sntimirobial therapy aesignfcant predictors of fale fom recurrent infection Patients with other acule and chronic Alseones may alo be iinmunowapprese, although ths is diffcutto define intrapertive cute, inching altars trom pereutancous drainage procedures, ave cena fo the prestbing of defniive therapeutic regimens for these pox tents and ay allow deecalation to less broad-spectrum therapy. , Inpatients wi higher every infection, he consequences of renee fthire may be more sgnfcat than they a in patients with infection of mildtonmoderate seventy. The se ofinal empiric ansiirbil regen that are subsequenty identified to lack in vio activity against the organisms so- inte from the nize abdomnnal infection hasbeen associated with an incrensed need for addtional source control proce ures and more aggresive antimicrobial therapy, ncressed hogptal lengths of say and costs, and increased mortalsy (67) Theretore wae of broaderspectrum agenis provi ing activity against some gram-negative facultative and ser bie organisms that ate occasionally isolated. from such Daten has the potential 9 improve outcomes, although {his hypotheis has not been sigorously examined in ciel tals Tn these cases, cultures and susceptibility tests are partic larly important The cationale forthe widening of coverage test common organs tha the rik of treatment are fm such patie is higher and the consequences potentally greater. “Aminoglycosdes have relatively nasrow therapeutic ra ges and asocated problems ofototbrcty and nephrotoxicity 186, 97, These agents shouldbe reserved for patients with allergies to acm agents and even en ate second choices to quinolonebased regimens. Aminoglycosides may be rea sonable choice for empire or defitive treatment of elected patients with health cce-asocatedinte-abdominal infec Eon, depending on loca susceptiity pattem of nosocomial aramnegative bac. A meternralyssof data from prospec five, randomized, controlled tals found that aminogiyeo- sidebased regimens appesred fo be inferior to many other reginens forthe teatment of patents with intre-abdominal infection [96]. There fs ro evidence tht routine use of agents effective against enterocoea improves outcome, but infection due fo {Ws organism has been associated with a poorer outcome Newly all enterococ isolate fom commit acquired in fection are E facie and are generally susceptible to amp cil, piperailin, and vancomycin. Ifthe regimen selected Tacks such coverage, selective ation ofan agent providingINTRA-ABDOMINAL INFECTIONS GUIDELINES such coverage can be considered. Isolation of staphylococct and yeast are quite uncommon in patients with community- acquired intra-abdominal infection, and use of agents effec- tive against MRSA and yeast is not recommended in the absence of evidence that Such organisms are involved in the infection. Vill, What Antimicrobial Regimens Should Be Used in Patients with Health Care-Associated Intra-Abdominal Infection, Particularly with Regard to Enterococcus, MRSA, and Candida? Recommendations 45, Empiric antibiotic therapy for hospitalacquired intra- sbdominal infection should be driven by local micro- biologic results (AD, 46. To achieve empiric coverage of likely pathogens, rutidrug regimens that include agents with ex panded spectra of activity against gram-negative aer- Obic and facultative bacilli may be needed. These agents include meropenem, imipenemcilastatin, do Spenem, piperacilin-tazobactam, ceftazidime, or ceft- ppime plus metronidazole; aminoglycosides or colistin may be required (-10), 47, Broad-speczum antimicrobial therapy should be tai Jored when culture and susceptibility reports become available, to reduce the number and spectra of ad- ministered agents (2-0) Antitungal Therapy Recommendations 48. Antifungal therapy for patients with severe commx nity-acquired or health caze-associated infection is recommended if Candid is grown from intra-abdom- inal cultures (B-). 49. Fluconazole is an appropriate choice for treatment if C. albicens is isolated (B-M). 50. For fhuconazole-resistant Candida species, therapy with fan echinocandin (caspofungin, micafungin, or anidu- Jfungin) is appropriate (B-I1}. S51, For the caitcaly ill patient, initial therapy with an echinocandin instead of a triazole is recommended om. 52, Because of toxicity, amphotericin B is not recommen- ded as initial therapy (B-M). 58. In neonates, empiric antifungal therapy should be started if Candida is suspected. If C. albicans is isolated, ‘uconazole is an appropriate choice (B-). Ant-Enterococcal Therapy Recommendations ‘54, Antimicrobial therapy for enterococci should be given when enterococci are recovered from patients with Jhealth care-associated infection (8-I} 155, Empiric ant-enterococcal therapy is recommenced for patients with health care-associated intra-abdominal infection, particularly those with postoperative infec- tion, those who have previously received cephalo- sporins or other antimicrobial agents selecting for 95 Enlerococeus species, immunocompromised patients, and those with valvular heart disease or prosthetic intravascular materials (B-I1). 56, Initial empiric antienterocoocal therapy should be directed against Enterococcus fecal, Antibiotics that can potentially be used against this organism, on the basis of susceptibility testing of the individual isolate, include ampieilin, piperaclir-tazobactam, and vane comycin (1) 57. Empiric therapy directed against vancomycin-resstant Enlerococes faecium is not recommended unless the patient is at very high risk for an infection due to this Organism, such asa ver transplant recipient with an intreabdominal infection originating in the hepato- biliary tee of a patient known to be colonized with vancomycin-zesstant E fazciums (I) AntiMRSA Therapy ‘Recommendations 58, Empitic antimicrobial coverage directed against MRSA should be provided to patients with health care-associated intra-abdominal infection who are mown to be colonized with the organism or who are at risk of having an infection due to this organism because of prior treatment failure and significant an- tibiotic exposure (B-I), 59, Vancomycin is recommended for treatment of sus- pected or proven intra-abdominal infection due to MRSA (A). Evidence Summary ‘Health care-associated infection is a relatively new term that includes a spectrum of adult patients who have close association with acute care hospitals or reside in chronic care settings [98]. These factors increase their risk of infection due to multidrug-resistant bacteria. The definitions for health ‘care-associated infections provided by Klevens et al. [98] are ‘used in this guideline. “Health care-associated infection” in- cludes “community-onset” and “hospital-onset.” Commu- nity-onset health care-associated infection includes cases involving patients with at least one of the following health care risk factors: (1) Presence of an invasive device at time of admission, (2) history of MRSA infection or colonization; or @)history of surgery, hospitalization dialysis, or residence in 2 long-term care facility in the 12 months preceding the cul- ture date. Hospital-onset infection includes cases involving patients with positive culture results from a normally sterile site obtained >48h after hospital admission. These patients ight also have >! of the comununity-onset risk factors, Recent data indicate that types of multidrug-resistant ‘pathogens may vary in different health care settings and that individuals infected with multidrug-resistant pathogens are more likely to receive inappropriate initial antibiotic therapy, which may result in poorer outcomes in texms of patient morbidity, mortality, and increased length of hospital stay. Infectionsin these patientsharbor the anaerobic flora described {or other comaunity-acquited intra-abdominal infections, “Health caze-assodated infection is commonly caused by a more resistant flora, which may include the nonfermenting96 gram-negative P. aeruginosa and Acinetobacter species, ex- tended spectrum f-lactamase-producing Klebsiella and E.coli, Enterobacter species, Proteus species, MRSA, enterococci, and Candide species (52, 99-101]. For these infections, complex rmultidrag regimens are recommended, because adequate empicic therapy appears to be important in determining postoperative complications and mortality 2]. Fallure to adequately treat resistant organisms has, in similar health cate-associated infections, been associated with increased death [102-204]. Local resistance patterns of nosocomial iso- lates observed in the specific hospital should dictate empiric treatment, and tentment should be altered on the bass ofa thorough microbiologie work-up of infected fui. In injection oacureing after elective or emergent operation, 1 more resistant flora is routinely encountered [52], The or- genisms observed are similar to those seen in other nosoco- rial infections, and anaerobes are not frequently important sources of resistant organisms. The selection of antibiotics would be tailored according to the known nosocomial fora present at the institution where the patient developed the infection. Candida infection has been the subject of recent guidelines from the IDSA [105]. Candia albicans or oer Fungi aze cul- tured from ~20% of patients with acute perforations of the gastro-intestinal tract. Even when fungi are recovered, ant- fungal agents are unnecessary in adults unless the patent has recently received immunosuppressive therapy for neoplasm ‘or has a perforation of a gastric ulcer on acid suppression or malignancy, transplantation, or inflammatory disease or has postoperative or recurrent intra-abdominal infection [105— 107]. Inneonates with necrotiaing enterocolitis, Candida isnot ‘uncommon andl is more likely to represent a true pathogen in such patients than in previously healthy adults, In these settings, Candida is associated with increased ‘mortality [99]. Patents with health care-associsted intra- abdominal infection are at higher risk of Candida peritonit pavtcularly patients with recurrent gastrointestinal perfor tions and surgically treated pancreatic infection [105-107]. Preemptive antifungal therapy with fluconazole may de- ‘crease the incidence of Candida peritonitis in such high-isk patients (108, 109] ‘There has been an evolution of the species of Candida ob- served in candidemsia and Candida peritonitis [110] Because of its high susceptibility to fluconazole, C albicans has decreased in prevalence, and C. glabrata and other species have become somewhat more common. Tais observation, coupled with the ‘common use of fluconazole prophylaxis in the intensive care unit, suggests empiric use of echinocandins (caspofungin, anidulafungin, and micafungin) [111-115] Certain patient groups at particularly high risk of a poor outcome due to enterococcal infection include: (1) Imumuno- compromised patients; 2) patients with health care-assoc- ated postoperative peritonitis; (3) patients with severe sepsis of abdominal origin who have previously received cephalo- sporins and other broad-spectrum antibiotics selecting for Enterococcus species; and (4) patients with peritonitis and valvular heart disease or prosthetic intravascular material, ‘which place them at high risk of endocarditis [5, 100, 101, 116} Isolation of Enterococcus is more common among patients with nosocomial intra-abdominal infection, particularly those ‘with postoperative infections, and its isolation i a risk factor for treatment failure and death (117, 18). Thus, in patients INTRA-ABDOMINAL INFECTIONS GUIDELINES with health care-associated intra-abdominal infection, in- ‘cluding those with postoperative infection, a reasonable op- tion would be to include coverage of Enterococcus in the ‘empicic regimen until definitive culture results are available. Ampicilin’ and vancomycin are agents that have activity ‘against this organism and could be added to a regimen lack ing anticenterococcal activity. Specific risk factors for vanco- -mycin-resistant enterococci have been detailed [119-122] and ‘enter on transmission from other colonized or infected pa- tients in an epidemic manner. Isolates of MISA are recovered from patients with postop- trative infection, pancreatic infection, and tertiary peritonitis [123, 124], MRSA is not commonly isolated from patients with ‘community-acquired intta-abdominal infection. There are no specific data with regard to antibiotic preferences in treatment of intra-abdominal infections due to MRSA. In general, van comycin has been used to treat infections due to this organ- jsm. Other antibiotics, including quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline, have in vitro activity against MRSA, but there are few published data regarding their efficacy in the treatment of patients with intra-abdomi- nal infection. Thus, vancomycin should remain the first-line agent, with use of the other agents restricted to situations in ‘which vancomycin cannot be used because of severe adverse reactions or when intial therapy with vancomycin is thought to have failed, 1X, What are Appropriate Diagnostic and Antimicrobial ‘Therapeutic Strategies for Acute Cholecystitis and Cholangitis? Recommendations 60. Ultrsonography is the first imaging technique used for suspected acute cholecystitis or cholangitis (A. 61, Patients with suspected infection and either acute cholecystitis or cholangitis should receive antimicro- bial therapy, as recommended in Table 3, although anaerobic therapy is not indicated unless a biliay- enteric anastamosis is present (BI). (2. Patients undergoing cholecystectomy for acute chole- cysts should have antimicrobial therapy dix continued within 2¢h unless there is evidence of infection outside the wall of the gallbladder (8-0, 68. For community-acquired biliary infection, activity against enterococci isnot required, because the path- ogencity of enterococci has not been demonstrated. For selected immunosuppressed patients, particularly those with hepatic transplantation, enterococcal infec tion may be significant ancl require treatment (BI). Evidence Summary Recent guidelines have been published for the manage- ment of acute cholecystitis and acute cholangitis 125-129]. ‘These guidelines recommend use of abdominal ultrasanog- raphy and hepatobiliary scintigraphy. Ultrasonography de- tects cholelithiasis in ~98% of patients. Acute calculous cholecystitis is diagnosed radiologically by the concomitant presence of thickening of the galbladder wall (5mm), pericholecystic uid, or direct tenderness when the probe is pushed against the gallbladder (ultrasonographic Murphy sign).In a study involving 497 patients with suspected acuteINTRA-ABDOMINAL INFECTIONS GUIDELINES cholecystitis, the positive predictive value of the presence fof stones and @ positive ultrasonographic Murphy sign was 92%, and the positive predictive value of stones and thick- ening of the gallbladder wall was 95% [130]. The negative predictive value ofthe absence of stones combined with ether ‘a normal gallbladder wall or a negative Murphy sign was 95%, Hepatobiliary scintigraphy involves intravenous injec- tion of technetium-labeled analogues of iminodiacetic acid, ‘which are excreted into bile. The absence of gallbladder fling ‘within 60min after the administration of tracer indicates ob- struction of the eystie duct and has a sensitivity of 8%-90% for acute cholecystitis ‘A discussion of the timing of intervention for acute chole- cystitis or cholangitis is beyond the scope of these guidelines. ‘The exact timing should, however, depend on acuity and evidence of infection. In any case, there is no evidence sup- Porting improved outcomes from use of antibiotics that are ‘excreted by the liver X. What are Appropriate Antimicrobial Regimens {for Padiatrie Patients with Community-Acquired Intra-Abdominal Infection? Recommendations 64, Routine use of broad-spectrum agents is not indicated for all children with fever and abdominal pain for ‘whom there is a low suspicion of complicated ap- pendicitis or other acute intra-abdominal infection Gu. 65, Selection of specific antimicrobial therapy for pediatric patients with complicated intra-abdominal infection should be based on considerations of the origin of in- {fection (community vs health care), severity of ilness, and safety of the antimicrebial agents in specific pe- dliatric age groups (A-I). 66. Acceptable broad-spectrum antimicrobial regimens for pediatric patients with complicated intra-abdominal infection include an aminoglycoside-based regimen, 2 carbapenem (imipenem, meropenem, or ertapenetn, a Pelactam/f-lactamase-inhibitor combination (piper- acilintazobactam or tcarcilin-clavulzrate), or an advanced-generation cephalosporin (cefotaxime, cef- ‘wiaxone, ceftazidime, or cfepiane) with metronidazole (Table 5) B-D). 67, For childzen vrith severe reactions to lactam antibi- tics, ciprofloxacin plus metronidazole or an ami- noglycoside-based regimen aze recommended (B-ID} 68. Necrotizing enterocolitis in neonates is managed with fluid resuscitation, intravenous broad-spectrum anti- Diotics (potentially including antifungal agents), and ‘bowel decompression. Urgent or emergent operative intervention, consisting of either laparctomy or per- cutaneous drainage, should be performed when there is evidence of bowel perforation. Intra-operative Gram stains and cultures should be obtained (B-I). 69. Broad-spectrum antibiotics that may be useful in ne- conates with this condition include ampicilin, genta- micin, and metronidazole; ampicillin, cefotaxime, and metronidazole; or meropenem. Vancomycin may be used instead of ampicilin for suspected MRSA or ampicilln-resistant entecococeal infection. Fluconazole ‘or amphotericin B should be used if the Gram stain or a7 cultures of specimens obtained at operation are con sistent with a fungal infection (8-1). Evidence Summary ‘These guidelines do not deal with bility infections in children. Although enteric gram-negative bail and anzer- Obes, including B. fragilis, are most commonly isolated, an Increasing role of Pseudomonas has been documented in up f0 35% of children fom centers in North Amesia, Asia, and Europe [65, 66, 6]. Broad-spectrum empiric therapy for children with clinical or imaging evidence of a perforated appendix with peritonitis is approprine with carbapenems Giripenem-ciastatin or meropenem), piperacilintazobactam, ‘icarllin-clavulanate, or an extended-spetrumn cephalosporin (cefotaxime, cefsinxone, ceftazidime, or cefepime) with met ronidazole ‘Aminoglycosdecontaining regimens have been used successfully for decades to teat complicated intsabdominal infection in children. The three-drug regimen of gentamicin, ampicilin, and clindamycin (Che latter often replaced with retronidezoie) has been the most commonly weed regimen [131], This experience contrasts with that in adult, where difficulties in achieving therapeutic levels with use of dosing regimens of <5 to 7mg/kg (administered once daily) and aminoglycosidesnduced renal dysfunction have limited en ‘husiasm for thei se (96). ‘There is, however, an ongoing trend away from the use of aminoglycosidedbased regimens for pediatic appencicits 31). Thisis driven arglyby the fewer infusions required by ster regimens, Retrospective, historical, and. casecontol single-center reviews have examined altiple clinical nd costelated outcomes of traditional aminoglycoside based triple antibiotic therapy regimens, compared. with nom aminoglycosidebased regimens, and have demonstrated at least equivalent efficacy [132-134 A lage review of data on discharge diagnoses (x ~ 8555) from the Pediatric Helin Information database for 32 children’s hogptalsin the United States was recently compleed and found that there was sig- nificant and substantial improvement in tems of length af stay, pharmacy charges, and hospital charges, with no in- crease in hospital readmissions, among children receiving monotherapy, compared with those receiving traditional plesantibiotic therapy [11] For children, fever with abdominal pain is « common complaint and aggresive broad-spectrum antibiotic thempy {snot warranted for every chuld being evaluated for appen- dicts. In these situations, less broad-spectrum empicc agents, such as cefoxitin are appropriate uring the period of bservation and evahuation. Such therapy is sufcient for definitive treatment of confirmed perforated appendicis, particulary ifall oganisne are susceptible (131,135) ‘Therapy for pediatric patens with complisted inta-ab- dominal infection is constrained by safety concems, Teta: cyines, such as tigecycine, are contraindicated fr infections in children aged <8 yeas [136], Parenteral uoroquinclones ae not routinely recommended for treatment of infection in situations for whichanequalyefecivealiemativeexists(137) Some pediatic centers curently provide outpatient par- enteral convalescent therapy for children with compliceted appendicitis who, i the opinion of the treating physician, have significant sk forreidual infected collections (74). Ora98 convalescent therapy i less well described for children but is ‘an option for children who may benefit from anc can tolerete ‘ongoing oral antibiotic therapy [138]. An oral second-orthird- [generation cephalosporin in combination with an anaerobic gent such as metronidazole may be effective (65]. Because of increasing resistance of B. fragilis to clindamycin, this agent can no longer be routinely recommended for adults or chile dren, Oral ciprofloxacin may be used for convalescent trent ‘ment of children with infection due to Pseudomonns, Enterobacter, Serratia, and Citrobacter species if these organisms ae susceptible, because no other effective oral agents that have een investigated for intra-abdominal infection exist for these pathogens. [Necrotizing enterocolitis primarily affects premature in- fonts and full-term infants with an additional steessul illness [139]. The three components necessary for the disease are a substrate for bacterial growth (feedings), an infectious agent (usually bacterial), and an event causing bowel damage, such as decreased blood flow to the bowel ot bowel segment (vascular compromise secondary to decreased flow) (140) ‘This may result in mucosal injury, preumatosis intestinalis, bacterial overgrowth, and sepsis. More-extensive full thick ness hovel injury, as well as bowel perforation, may occu. ‘The general presentation involves increased episodes of apnea and bradycardia followed by abdominal distension, bloody stools, and bilious emesis [141]. Portal venous gas may also be present. The abdomen may become focally erythem- tous. Signs of sepsis, such as thrombocytopenia and neu- tropenia, may also be present; acidosis may also occur if there is bowel ischemia, In very low bieth weight neonates, peritoneal drainage may be used instead of immediate operation when bowel perfo- ration occurs {142]. Some pediatric surgeons advocate this as the only treatment option when combined with antibiotic administration. Other pediatric surgeons use drainage as a temporizing method or not at all. Operation generally in- volves bowel resection with the creation of stomas or re- anastomsis ‘The survival rate for necrotizing enterocolitis is close 10 95% unless necrotizing enterocolitis involves the entice bowel, which occurs ~25% of the time and is associated with a mortality rate of 40%-B0%. Nonoperative management of necrotizing enterocolitis is successful ~70% ofthe time (143). XI, What Constitutes Appropriate Antibiotic Dosing? Recommendations 70. Empitic therapy of patients with complicated intra- ‘abdominal infection requires the use of antibiotics at ‘optimal doses to ensure maximum efficacy and mini- nal toxicity and to reduce antimicrobial resistance (Tables 6 and 7) (6-0). ‘71. Individualized daily administration of aminoglyco- sides according to lean body mass and estimated extra- cellular Quid volume is preferred for patients receiving these agents for intra-abdominal infection (Bl). Evidence Summary Initia intravenous dosage regimens for adult and pediatric ppatients with normal renal and hepatic function are shovwn in ‘Tables 6 and 7, respectively. The recomunended regimens are INTRA-ABDOMINAL INFECTIONS GUIDELINES based on dosage ranges that have been shown to be effective in clinical trials and are applicable to patients with mild-to- moderate community-acguited infection, but they have not been well investigated in the treatment of severe and/or ‘nosocomial infection. Product package inserts and/or current published literature should be consulted for dosage adjust- ‘ments in patients with impaired renal or hepatic function. Pharmacokinetic-pharmacodynamic properties of specific antibiotics should be considered in selecting an adequate dosage regimen [144]. The f-lactam antibiotics have time- ‘dependent bactericidal activity and a minimal postantibiotic cllect, with the exception of carbapenems against P. eerugi- rosa, The best predictor of microbiological and clinical re- sponse to f-lactam antibiotics is the duration during which ‘unbound drug concentrations exceed the minimum inhibitory concentration (MIC) of the microorganism (T > MIC). Opti= mization of this parameter to treat severe infections or or- {ganism with higher MIC values may requive dosage strategies that incorporate more-frequent dosing interval, larger doses, or prolonged (including extended or continuous) intravenous infusion of (lactams with short elimination half-lives, com- pared with dosage and interval recommendations from the label (145). In contrast, agents such as fluoroquinolones, ‘minoglycosides, and metronidaaole have concentration-de- pendent bactericidal activity and a moderate to prolonged. postantibiotic effect. Parameters that incorporate the exposure of unbound drug concentrations, either the ratio of area under the concentration-time curve (AUC) or maximum drug con- centration (Css) to MIC of the microorganism (fAUC:MIC. and fCmex ‘MIC), are the best predictors of microbiological and clinical response for these agents [144] Large intravenous doses administered less frequently (eg, every 24h) can opti- mize these parameters and ease administration by decreasing, the number of infusions required per day. ‘Antimicrobial dosage considerations are also important in critically il patients and obese adult patients. Physiological changes can occur in both of these patient populations and. may alter the apparent volume of distribution and/or clear ance of commanly used antibiotics. In addition, i the estimate fof a dosage regimen is dependent on renal function, an ac- ‘curate estimate of creatinine clearance on the basis of serum creatinine values and body weight may be difficult with ‘commonly used equations, and direct measurement of creat- jnine clearance may be required. For lactams and ami- noglycosides,a critically ill patient in the early stages of sepsis may have shifts in body fluid and be in a hypermetabolic slate, resulting in an increase in both volume of distribution and clearance and lower serum antibiotic concentrations [146, 147, Similarly, lower serum concentrations of cephalosporins and cazhapenems have been observed in obese patients. Lower tissue concentrations of cephalosporins have also been reported in obese patients following perioperative surgical antibiotic prophylaxis (148, 149]. These studies suggest that higher doses and/or more frequent administration of frlac- ams may be needed in selected patients who are obese or ‘tically il with altered distribution and increased clearance of renally excreted antibiotics. Initial dosage regimens for aminoglycosides and vancomycin should be based on ad- justed body weight and total body weight, respectively. Ser- tum drug concentration monitoring is recommended for dosage individualization of aminoglycosides and vancomy- cin in these patient populations.INTRA-ABDOMINAL INFECTIONS GUIDELINES. ‘There is considerable evidence that less frequent dosing of ‘metronidazole, in particular, is effective. The nitroimidazoles are bactericidal through toxic metabolites that cause DNA strand breakage. Resistance, both clinical and microbiologi- cal, has been described only rarely. Liver disease leads to a decreased clearance of metronidazole, and dosage reduction is recommended [150-153] Xil. How Should Microbiological Culture Results Be Used To Adjust Antimicrobial Therapy? Recommendations 72. Lowersisk patients with community-acquiced intra- abdominal infection do not requite alteration of therapy if a satisfactory clinical response to source control and initial therapy occurs, even if unsus- pected and untreated pathogens are later reported Gu, 73, Ifresistant bacteria were identified at the time of initial intervention and there are persistent signs of infection, pathogen-directed therapy is also recommencied for patients with lower severity disease (B-ID. 74. Use of culture and susceptibility results to determine antimicrobial therapy in high-severity community- acquired or health care-associated infection should be ‘based on pathogenic potential and density of ident- fed organisms (8-11) 75. Microbes recovered from blood cultures should be assumed to be significant if they have established ‘pathogenic potential or are present in 22 blood cul- tures (Al) or if they are recovered in moderate or heavy concentrationg from samples obtained from drainage (BL). Evidence Summary ‘The major pathogens in intra-abdominal infection are Ex- terobacteriacee, especially F. coli and anaerobes (notably B. ‘fingilis). Pathogens are nearly always present in concentra- tions of 1x10 organisms/g of tissue or 110° organisms/mL, of exadate, corresponding to modezate or heavy growth on the primary isolation plates. There should be attention paid to the predominant pathogens, because many of these cultures yield mixed flora, and itis difficult to distinguish pathogens {rom commensal organisms. In patients with community-acquired intra-abdominal in- fection, empiric antimicrobial therapy directed against these predominant pathogens is likely to be associated with a suc- cessful outcome, However, ifthe initial antimicrobial regimen, does not cover the eventual isolates, itis more likely hat the ‘patient will perience a treatment failure. Nonetheless, zmany ‘Patients are sill successfully treated with an adequate source contol procedure and an empiric regimen directed against colifonms and anaerobes. There are no prospective data in- dicating that alteration of the regimen on the basis of culture xesults will improve outcome in patients who have unsus- ‘pected pathogens or more-resistant pathogens. However, it ‘would seem prudent to adjust the antimicrobial regimen in hhigher-risk patients for whom the consequences of treatment failure may be of greater significance and in lower-isk pa tients who have persistent signs of infection 99 Xill, What is the Appropriate Duration of Therapy for Patients with Complicated Intra-Abdominal Infection? Recommendations 176. Antimicrobial therapy of established infection should be limited to no more than seven days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome (B-II). 177. For acute stomach and proximal jejunum perforations, in the absence of acid-reducing therapy or malignancy and when source control is achieved within 24h, prophylactic anti-nfective therapy directed at aerobic {gram-positive cocci for 24h is adequate (BT). 78, In the presence of delayed operation for acute stomach and proximal jejunum perforations, the presence of {gastric malignancy or the presence of therapy reducing gastric acidity, antimicrobial therapy to cover mixed flora (eg, as Seen in complicated. colonic infection) should be provided (B-II), 79, Bowel injuries atteibutable to penetrating, blunt, or iatrogenic trauma that are repaired within 12h and any other intraoperative contamination of the opera- tive field by enteric contents should be treated with antibiotics for <24h (AD. 80, Acute appendicitis without evidence of perforation, abscess, oF local peritonitis requires only prophylactic administration of narrow spectrum regimens active against acrobic and facultative and obligate anaerobes; treatment should be discontinued within 24h (AD, 81. The administration of prophylactic antibiotics to pa- tients with severe necrotizing pancreatitis prior to the diagnosis of infection is not recommended (4-1, Evidence Summary ‘There is a wide range of individual antimicrobial agents and combinations of agents available for use in complicated intra-abdominal infection. There are convincing data th absent or inadequate empiric and definitive antibiotic therapy results in both increased treatment failure rates and increased morality (64, 67, 154-158]. Conversely, unnecessary and needlessly broad coverage or prolonged therapy cares its own problems, including cost. Patient and agent-speciic toxicities of therapy may occur, including superinfection, Clostridium dificil colitis, andl organ injury [158]. Acquisition of intrinsically resistant organisms and selective pressure for resistance within the unit, hospital, or community is of in- creasing concem [32, 160) Evidence presented in the previous guidelines suggested thata duration of therapy no greater than one week was ap- propriate for most patients with intra-abdominal infection, with the exception of those who had inadequate source con- trol [8, 10, 161]. Within this window, resolution of clinical signs of infection should be used to judge the termination point for antimicrobial therapy. The risk of subsequent treatment failure appears to be quite low in patients who have no clinical evidence of infection at the time of cessation of antimicrobial therapy {162, 16]. This usually implies thatthe patients are afebrile, haveniormal white blood cel counts, and are tolerating an oral diet100 ‘The previous guidelines also outlined a number of con: 24h was not believed to benecessary. In such patients, the primary goa of therapy i prophylaxis agninst a surgical ste infection, as opposed to treatment of an established infection. These conditions in- cluded traumatic or iatrogenic bowel injures operated on within 12h, upper gastrointestinal perforations operated on within 24h, and localized processes, such as nonperforated appendicitis, cholecystitis, bowel obstruction, and bowel ine faretion, in which the focus of inlammation or infection is ‘completely eliminated by a surgical procedure an there is no extension of infection beyond the organ in question. Broad-specteum antibiotic therapy has been used by some clinicians fr the treatment of patients with necrotizing pan- creatt, in an effort prevent an infection in the inflamma- tory phlegmon and thereby improve patient outcome, In a {guideline on the management of severe pancreatitis, however, the authors concluded that this approach was not justified on the basis of available data [4], A meta-analysis of tials per- formed in this area have shown that positive results were attributable to poor study design and that welldesigned studies did not demonstrate benefit 164]. Tis practice is not recommended without clinical or culture evidence of an es- tablished infection in patients with necrotizing pancreatitis.In those patients with established pancreatic infection, the agents recommended for use with community-acquired in- {ection of higher severity and health care-associated infection (Tables 2 and 4) are the preferred agents, Because ofthe dif- Fculty of achieving adequate source control in patients with infected pancreatic and peripancreatic phelgma, » longer duration of therapy may be needed. XIV, What Patients Should Be Considered for Oral ‘or Outpatient Antimicrobial Therapy and What Regimens Should Be Used? Recommendations 82, For children and adults whose signs and symptoms of infection are zesolved, no further antibiotic therapy is required (BID, 88, For adults recovering from intra-abdominal infection, completion of the antimicrobial course with oral forms of moxifloxacin, ciprofloxacin plus metronidazole, e- vyofloxacin plus metronidazole, an oral cephalosporin ‘with metronidazole, or amoxicillin-clavulanic acid (B- T) is acceptable in patients able to tolerate an oral diet and in patients in whom susceptibility studies do not demonstrate resistance (B-I). 84. Tfculture and susceptibility testing identify organisms that ave only susceptible to intravenous therapy, such therapy may be administered outside of the hospital (uD. 85, For children, outpatient parenteral antibiotic manage ment may be considered when subsequent drainage procedures are not likely to be required but symp- toms of ongoing intra-abdominal inflammation persist in the context of decreasing fever, controlled pain, abil- ity to tolerate oral fluids, and ability to ambulate (B-). 86. For oral step-down therapy in children, intra-abdom- inal cultures at the time of the drainage procedure are recommended to allow for the use of the narrowest spectrum, besttolerated, and safest oral therapy. A. INTRA-ABDOMINAL INFECTIONS GUIDELINES second- or third-generation cephalosporin in combi nation with metronidazole, or amoxiellinclavulanate, may be options if the isolated organisms are suscep- tible to these agents. Fluoroquinolone, such as cipro- floxacin or levofloxacin, may be used to treat susceptible Pseudomonas, Enterobacter, Serratia, and Ci trabacter species (B-I), If ciprofloxacin or levofloxacin is used, metronidazole should be added. 87. Drug susceptibility results of isolated gram-negative aerobic and facultative organisms, if available, should bbe used as a guide to agent selection in children and ‘adults (8-1). 188, The intravenous regimens recommenced for patients with complicated intra-abdominal infection (Tables 2-4) are appropriate for patients with int-abdominal infection who are being managed without a primary source control procedure (B-I). 89. Because many of the patients who are managed without @ primary source control procedure may be treated in the outpatient setting, the oral regimens recommended (Tables 2-4) can also be used as either primazy therapy o: step-down therapy, folowing ini- al intravenous antimicrobial therapy (B-ID, Evidence Summary Patients who are convalescing from complicated intra- abdominal infection may be treated with oral antibiotic ther- apy {165}. Such therapy should be included as part of the brief treatment intervals recommended, which in total should rarely exceed 5-7 days. Providing antimicrobial therapy for patients who are afebrile, with normal peripheral leuko- cyte counts and with return of bowel function, is rarely indi cated. Oral therapy is selected on the basis of susceptibilities ‘of the identified primary isolates or in the absence of cultures, ‘commonly isolated pathogens that include E.coli, stepto- cocci, and B. fragilis. Most of those regimens have not been formally studied but provide anticipated activity against the ‘major coliforms and anaerobes encountered in these infec- tions. Increasing resistance of E, coli to amoxicillin clavulanic acid may limit the continued use ofthis regimen (84, 166). XV. How Should Suspected Treatment Failure Be Managed? Recommendations 90, In patients who have persistent or recurrent clinical evidence of intra-abdominal infection after 4-7 days of therapy, appropriate diagnostic investigation should bbe undertaken. This should include CT or ultrasound imaging, and antimicrobial therapy effective against the organisms initially identified should be continued (acu, 91. Extra-abdominal sources of infection and noninfec- tious inflammatory conditions should also be investi gated if the patient is not experiencing a satisfactory. clinical response toa microbioiogically adequate initial empiric antimicrobial regimen (A-I), 92. Ifresistant bacteria were identified atthe time of initial {intervention and there are persistent signs of infection, pathogendirected therapy is also recommended for Jower-risk patients (B-IM).INTRA-ABDOMINAL INFECTIONS GUIDELINES * 93. For patients who do not respond initially and for ‘whom a focus of infection remains, both aerobic and anaerebic cultures should be performed from 1 speci- men provided itis of suficient volume (at least 1.0mL_ of fluid or tissue) and is transported to the laboratory. {n an anaerobic transport system (C-I). Inoculation of 110ml of uid directly into an anaerobic blood cul- ‘sure broth bottle may improve yield, Evidence Summary Patients with persistent or recurrent signs of peritoneal it- ritation, failure of bowel function to return to normal, or continued fever or leukocytosis are at high risk of an intra- abdominal or other infection that may require additional in- ‘tervention to achieve source control. In general, patients with ‘a persistent or new intra-abdominal infection, a deep organ- space infection, or'a superficial or deep surgical site infection ‘aan be identified through a careful physical examination supplemented by appropriated laboratory and imaging in- ‘vestigations, CT of the abdomen is usually the most accurate ‘method by which to diagnose an ongoing or recurrent intra- abdominal infection. The possibility of an extra abdominal infection, such as nosocomial pneumonia or urinary tract in- fection or a non-infectious cause of fever or leukocytosis (te, ‘venous thrombosis or a pulmonary embolism) and C. dficle disease, even without diarchea, should also be considered, ‘Appropriate antimicrobial therapy should be continued while the investigation proceeds, particularly if the patient mani- fests signs of sepsis, such as organ dysfunction. Antimicrobial regimens should be adjusted according to the results of the diagnostic investigations, For patients with a congirmed intra- abdominal infection, this may require broadening the regimen to include agents with activity against health care associated organisms typically isolated with this type of in- fection. For patients with persistent clinical symptoms and signs but in whom no evidence of a new or persistent infection is uncovered after a careful investigation, termination of an- ‘microbial therapy is warranted. XVL What Are the Key Elements that Should Be Considered in Developing a Local Appendicitis Pathway? Recommendations 94, Local hospitals should establish clinical pathways to standardize diagnosis, in-hospital management, dis- charge, and outpatient management (B-I} 95. Pathways should be designed by collaborating clii- cians involved inthe care ofthese patents, including Dut not limited to surgeons, infectious diseases spe- cialists, primary care practitioners, emergency medi- cine physicians, radiologists, nursing providers, and pharmacists, and should reflect local resources and local standards of care (BI). 96. Although no clinical findings are unequivocal in identifying patients with appendicitis, a conselation of findings, Including characteristic abdominal pain, localized abdominal tenderness, and laboratory evi= ence of acute inflammation, will generally identify most patients with suspected appendicitis (AI). 7, 98. 99, 100. 101. 102. 108. 104. 10s. 106. 07. 108. 108. 101 Helical CT of the abdomen and pelvis with intrave- nous, but not oral or rectal, contrast is the recom- mended imaging procedure for patients with suspected appendicitis (B-I), Al female patients should undergo diagnostic im- aging. Those of child-bearing potential should un- dergo pregnancy testing prior to imaging and, if in the fist trimester of pregnancy, should undergo ul- trasound or magnetic resonance instead of imaging ionizing radiation (B-U). If these studies do not define the pathology present, laparoscopy or limited CT scanning may be considered (B0). Imaging should be performed for all children, par- ticularly those aged <3 years, when the diagnosis of appendicitis not certain. CT imaging is pre- ferred, although to avoid use of ionizing radiation in children, ultrasound is a reasonable alternative om. For patients with imaging study findings negative for suspected appendicitis, follow-up ath isrecom- ‘mended to ensure resolution of signs and symptoms, because of the low but measurable risk of false negative results (BD). For patients with suspected appendicitis that can neither be confirmed nor excluded by diagnostic imaging, careful follow-up is recommended (AI. Patients may be hospitalized ifthe index of suspicion is high (AID). ‘Antimicrobial therapy should be administered to all patients who receive a diagnosis of appendicitis (aa, Appropsiate antimicrobial therapy includes agents cfiectve against facultative and aerobic gram- negative organisms and anaerobic organisms, a5 de- tailed in Tables 2 and 3 for the treatment of patients ‘with community-acquited intra-abdominal infection, (we. For patients with suspected appendicitis whose di- agnostic imaging stadies are equivocal, antimicrobial therapy should be initiated along with appropriate ppain medication and antipyretics, if indicated. For adults, antimicrobial therapy should be providea for a minimum of 3 days, until clinical symptoms and signs of infection resolve or a definitive diagnosis is made BI). Operative intervention for acute, nonperforated ap- ‘pendicitis may be performed as soon as is reasonably feasible. Surgery may be deferred fora short period of time as appropriate according to individual insti- tutional czcumstances (6-1). Both laparoscopic and open appendectomy are ac- ceptable procedures, and use of either approach should be dictated by the surgeon's expertise in ‘performing that particalar procedure (AD Nonoperative management of selected patients with acute, nonperforated appendicitis can be considered if there is @ marked improvement in the patient's condition prior to operation (B-). Nonoperative management may also be considered as part of a specific approach for male patents, pro- vided thatthe patient is admitted to the hospital for 48h and shows sustained improvement in clinical102 symptoms and signs within 24h while receiving antimicrobial therapy (Al), 110, Patients with perforated appendicitis should undergo urgent intervention to provide adequate source cor- ‘trol (B-IM). 111, Patients with a swll-circumscribed peiappendiceal abscess can be managed with percutaneous drainage for operative deainage when necessary. Append omy is generally deferred in such patients (A). 112, Selected patients who present several days afer de- velopment of an inflammatory process and have © peniappenciceal phlegmon or @ small abscess not fmenable to percutaneous drainage may delay or avoid a source control procedure to avoid @ poten- tally more morbid procedure than simple epper- decfomy. Such patients ate rented with antimicrobial therapy and cateul inpatient follow-up, ina manner analogous to patents with ate diverts (Bl) 113. The ase of interval appendectomy after percutaneous drainage or nonoperative management of prforted appendicitis is controversial and may not be neces- sary (A, Evidence Summary ‘There is now compelling evidence that the use of protocols for patient care management improves both the process of, care and patient outcomes, Locally adapted guidelines should, be implemented to improve process of care variables and relevant clinical outcomes. The guideline should address a ‘comprehensive set of elements in the process of care rather than a single element in isolation. Benefits accrue through diminished use of limited resources outside of the protocol, reduced demand for hospital beds for observation, stan- dardized documentation of follow-up fro diagnosis is made, Jess measurable but highly likely decreases in infectious and. other postoperative complications, likely decreases in length. of stay, and decreases in antibiotic usage. Locally developed clinical pathways have been established in appendicitis and other disease states to standardize the diagnosis and management of patients with suspicion of a specific disease state (65, 167, 168]. To be effective, these de. vices should act as a cohesive unit to ensure that all steps of ‘care are reliably delivered and documented. This approach reduces unwarranted clinical variation, prevents avoidable patient morbidity, reduces hospital stays, and improves pa- tient outcomes. In general, pathways that provide for evalu- ation by clinical judgment, are supported by appropriate laboratory tests and imaging, and are coupled with stan- dazdized approaches to management lead to fewer unneces- sary operations, less antibiotic use, and shorter hospital stays (68. ‘Tris section will identify elements for the construction of local pathways regarding evaluation, antimicrobial treat- ment, and surgical management of patients with non- perforated apperdicits. These pathways should emphasize comprehensive patient management from the time of first presentation to a health care provider ‘The symptoms and signs that suggest appendicitis, as well as their sensitivities and specificities, have been well described [070]. Scoring systems have been developed toad in decision- ‘making for immediate operation, diagnostic imaging, or ob- INTRA-ABDOMINAL INFECTIONS GUIDELINES servation in or out of the hospital [15]. These systems appear to be useful as documentary devices but should not replace clinical suspicion Diagnostic imaging is now the standard for most patients ‘with suspected acute appendicitis. Imaging is recommended for all individuals presenting with acute abdominal pain consistent with appendicitis, except for male patients aged <40 years with classical history and physical findings [16,171, {72}, Recent guidelines have been published for imaging in women {173} If appendicitis is excluded by diagnostic imaging and no other diagnosis is confirmed, further management is based on a range of clinical and socal factors. When clinical suspicion zemains, ongoing observation ofthe patient in the hospital or emergency department allows for an evaluation of the evo- lution of symptoms over time. Observation may also be latranted for patients if obtaining further follow-up i ikaly to be problematic. Patients discharged from the hospital should have follow-up within 24h, even ifthe follow-up must be performed by telephone. There remains a measurable false- negative rate with imaging, and other conditions requiring inedical inservention may become manifest during this in- ferval. An absence of improvement may require reexamina- fion and possibly reimaging or consideration of diagnostic laparoscopy. ‘The evidence supporting the importance of rehydration in ‘appendicitis comes from observational studies anteceding blood:-baniking [25] in which six-fold reduction in mortality dttsioutable to perforated appendicitis was observed fllow- fag the increased awareness of resuscitation. Other support comes from the Sueviving Sepsis Campaign [13,26] 1 Clinical trials demonstrating the efficacy of antimicrobial {herapy alone in male patents without appendiceal mass but ‘with clinically suspected appendicitis support antimicrobial therapy without intervention for patents with equivocal im- aging studies asa possible alterative to operative manage rent and as « means of converting appendectomy from an emetgency to an urgent surgical procedure (174). Farther support fr a less emergent approach comes from other clin: jeal trials analyzing time to perforation, which indicate this to bea unusual easly event [175, 176} 1 Observation of patients with ultrasound or CT evaluation of appendiceal masses is time-honored (175, 177-181]. A re- ent meta-analysis found that appendiceal abscess or phleg mon) was found in 4% of patients with appendicitis ‘Nonsurgical teatment failed in 7.2% of patients (95% conli- dence interval [CI], 4.0%-105%). Drainage of an abscess oc- curred eery in the course of illness in 20% of patients (95% CI, 11.0%- 28.3%) [182] Immediate surgery was associated witha higher morbidity, compared with nonsurgical treatment (odds ratio, 33; 95% Cl, 19-56; P<.001) After succesful nonsurgical treatment, ducing follow-up, a malignant disease ‘was detected in 1.2% (85% CI, 0.6%-1.7%) and an benign disease in 0.7% of patients (95% CI, 02%-11.9%). The Fisk of returrence was 74% (95% CL, 37%-11.1%) (183) Tes ngt apparent whether interval appendectomy is nec- essary following successful conservative treatment of ap- endiceal mass. The main debate centers on the recurrence ate, the complication rate of interval appendicectomy, and the potential for underlying malignancy. Two reviews have suggested that interval appendectomy is unnccessary in 75% 90% of cases [184,185].INTRA-ABDOMINAL INFECTIONS GUIDELINES Antimicrobial Stewardship ‘he role of antimicrobial stewardship programs in im- plementing these guidelines is emphasized. There is strong ‘evidence that all patients undergoing operation for appendix citis should receive brief antimicrobial therapy [186]. Ifsuch a rogram exists within a hospital, specific regimens should be ‘identified for each of the four categories of infections defined in these guidelines: (1) mild-to-moderate-soverty infection, (@) high-severity community acquired infection, (3) hospital: acquired infection, and (6) health eare-assodated infection. These locally determined regimens should be used preferen- ‘ally Performance Measures Given the emphasis placed on development of appendicitis pathways in these guidelines, the Expert Panel recomunends ‘that the following performance messures be focused on this disease: ‘+ Determine the time from admission to emergency facil ity to diagnosis for those patients not undergoing di- agnostic imaging. + Determine the interval from emergency contact to per~ formance of diagnostic imaging for patients not receiv- ing a diagnosis of appendicitis on the basis of history and physical examination findings who require opera~ tion, + Determine the interval from diagnosis of appendicitis to ‘administration of antimicrobial therapy. + Determine the interval from diagnosis to time of inter- vention. + Determine the negative appendectomy rate for patients admitted through the emergency department with acute appendicitis. For patients with nonperforated appendicitis, determine the duration of prophylactic antimicrobial therapy. For patients with perforated or abscessed appendicitis, determine the duration of both intravenous and oral antimicrobial therapy and determine the incidence of ssurgical-ite infection, ‘Areas for Future Research Several areas require further study. The issue of appropsi- ate specimen processing, including the role of routine anti- sicrobial susceptibility testing, requires close study. This say best be performed by prospective observational studies. This type of study would also generate epidemiological data on community resistance patterns and community-specific microbiologic findings (eg., an unanticipated incidence of rmultidrug-resistant organism). ‘Bvaluation of the effects of delaying appendectomy, as re- commended in these guidelines, is recommended. Review of Gata from large multi-hospital databases is one approach to this problem. ‘There is a pressing need for the study of appropriate du ration af antimicrobial therapy. The impact of prolonged therapy, driven by the availabilty of potent oral regimens, may have a significant impact on the incidence of resistant organisms in the community or in intermediate or chronic- care facilities. However, the duration of therapy is largely 103, dependent on adeqiate source control. The range of intra- abdominal inoculation varies from none to multiple, wide- spread intra-abdominal abscesses that may not all be drained ‘well with one procedure ‘With regard to higher-isk patients, particularly those with hhealth care-essociated infection, poor clinical outcomes are still common. Given the infrequency of such patients, pro- spective comparative randomized trials are unlikely to be performed; therefore, other methodologies, including pro- spective observational studies, may be useful. The pattem of infecting organisms needs to be confirmed, and the impact of empiric therapy should be examined. The hypothesis that broader-spectrum antimicrobial therapy is beneficial in such patients should be critically examined. Additionally, duration Of therapy in postoperative infection is an important variable ‘that requires study. ‘The pharmacokinetics of antimicrobial therapy in severely ill patients with sepsis syndrome is an urgent need. Few anti- ‘icrobialshave been studied in severely ill patients, and these shudies have suggested that current package insert dosage ecommendations may not be sufficient for such patients, Acknowledgments We thank Paul Auwaerter, John Bohnen, Ronald V. Maier, and David R Saydman for their thoughtful reviews of earlier eats. Financial support ‘The Infectious Diseases Society of America and the Surgical Infections Society. Potential Conflots of Interest JSS. has received honoraria for lectures in China from ‘Merck; financial support as consultant and principal investi- {gator ofa clinical research project in China andl honoraria for Tectures from Bayer; financial support as consultant, advisory board member, and lecturer from Johnson and Johnson; re- search support for a project on the interaction of PVL and neutrophils from Pfizer; financial support as consultant, ad- visory board member, and lecturer from Shering-Plough: and financial support as advisory board member from Optimer. JIEM. received research support form Artisan Pharmaceu- ticals, Eli Lilly, Ortho Biotech, Pennisula Pharmaceuticals, Phizer Pharmaceuticals, and Theravance and has served as 2 paid consultant, advisory board member, or speaker for Eli ‘Lily, Merck, Ortho-MeNell Pharmaceuticals, Plizer Pharma- ceuticals, Schering-Plough, and Wyeth Pharmaceuticals JIG, has served on the advisory boards of Abbott Labore- tories, Bristol, Pfizer Pharmaceuticals, Tibotee, Glaxo- SmithKline and served on the policy board of Johnson & Johnson. JSB. has served as a consultant to and received re- search funding from AstrsZeneca, Wyeth Pharmaceutical, and Johnson & Johnson. A.W.C. served as a speaker for Wyeth Pharmaceuticals and Bayer, is a member of the guideline committee of the Association of Medical Micro- biology and Infectious Diseases Canada, and is coauthor of the Canadian Practice Guidelines for Surgical Inra-abdom ral Infections, ABN. has served as a speaker for Bayer, Schering-Plough, and Wyeth Pharmaceuticals. KAR. re ceived research grants and contracts from Sanofi-Aventis and104 Roche Laboratories; has served 25a consultant to Johnson & Johnson, Ortho-McNeil Pharmaceuticals, anc GlaxoSmith- Kline; serves on the speakers bureau or advisory board of [Abbot Laboratories, Astellas Pharmaceuticals, AstraZeneca Pharmaceuticals, Daiichi Pharmaceuticals, Ortho-McNeil Pharmaceuticals, Pfizer Pharmaceuticals, Schering-Plough, Targanta, Theravance, and Wyeth Pharmaceuticals; and isa shareholder of Pizer Pharmaceuticals. RG Shas served as a consultant to Pfizer Pharmaceuticals, Merck, Wyeth Phar- maceuticals, and Schering-Plough. B,.B. has received hono- raria or served on advisory panels for Ortho-McNeil, GlaxoSmithKline, Aventis, Cepheid, Bector-Dickinson, bio- Merieux, Cubist, Wyeth-Ayerst, Johnson & Johnson, Asta Zenecs, and, Oxonia; received research support from Roche Molecular Diagnostics; and own shares of Cepheid and Merck. E.C.G. has served on advisory boards for Merck, Schering Plough Pharmaceuticals, Optimer Pharmaceuticals, ‘Theravance, Ocalus Innovative Sciences, and Viropharma; has been on speakers bureaus for Ortho-McNeil, Merck, Schering-Plough, Theravance, and Bayes; has received re- search grants from Merck, Schering-Plough, Cubist, Ther- avance, Optimer, Replidyne, Oculus Innovative Sciences, Pfizer, Astell, Cerexa, Impex pharmaceuticals, and Optimer Pharmaceuticals. PD. has gen lectures for honoraria and/ or served on advisory boards for Bayer, Merck, Wyeth “Ayerst, AstraZeneca, Pizer, Ortho-McNeil, Cubist, Vicuron, InterMune, Peninsula, Johnson & Johnson, Cepheid, Re- plidyne, Kimbesley-Ciat, Targanie, Schering-Plough, En- turia, Optimer, and BD-GeneOhm. P.O. serves on the speakers bureat for Pfizer Pharmaceuticals and is a member ofthe Surgery National Advisory Board. SE. serves on ad~ visory boards an the speakers bureau for Pizer, Cubist, and ‘Wyeth. All other authors: no conics References 1. Knaus WA, Wagner DP, Draper EA, et al. The APACHE IIL ‘prognostic system. Risk prediction of hospital morality for ‘cteally ill hospitalized adults [see comments). Chest 1991; 100:1619-36 2 Le Gall JR, Lemeshow 8, Sauinier F. A new Simplified ‘Acute Physiology Score (SAPS I) based on a Buropean/ North American multicenter study. JAMA 1993; 270:2957— (68 (erratum: JAMA 1996; 2711321). 3. Lemeshow 8, Le Gall JR. 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