Langenbecks Arch Surg (2006) 391:473482 DOI 10.

1007/s00423-006-0071-3

ORIGINAL ARTICLE

Infectiological diagnostic problems in tertiary peritonitis

G. Weiss & F. Meyer & H. Lippert

Received: 16 November 2005 / Accepted: 27 April 2006 / Published online: 15 August 2006 # Springer-Verlag 2006

Abstract Background The tertiary peritonitis causes the highest mortality in intraabdominal infections. Surgical interventions and antibiotic therapy may only provide an incomplete impact on nosocomial infections acquired at an intensive care unit (ICU) [Nathens et al., World J Surg 22:158163, 28]. To open up new resources in the management, in particular, in the previous infectious diagnostic, the aim was to investigate the infectious course as well as the diagnostic value of laboratory parameters and microbiological monitoring. Materials and methods In this retrospective patient cohort study from the Surgical ICU of a University Hospital (capacity, n=12), overall, 60 patients with a tertiary peritonitis were enrolled. Results Approximately 20% of the patients with an intraabdominal infection developed a tertiary peritonitis. A tertiary peritonitis can more frequently develop in nosocomial intraabdominal infections, in particular, in case of necrotizing pancreatitis. The device-associated infection rate in the spectrum of nosocomial infections is sevenfold higher than in all ICU patients. Compared with the secondary peritonitis, its mortality is double as high: 35%. In the diagnostic characterizing the course of the nosocomial, prognosis-relevant infections, usual inflammatory parameters show a considerable loss of their sensitivity
G. Weiss : F. Meyer : H. Lippert Department of Surgery, University Hospital, Magdeburg, Germany G. Weiss (*) Department of Anesthesiology/Intensive Care Medicine, Stdtisches Klinikum Magdeburg, Birkenallee 34, 39130 Magdeburg, Germany e-mail: guenter.weiss@klinikum-magdeburg.de

with a range from 3557%. By the mean of a routine microbiological monitoring, 47.3% of the analysed subsequent infections could be identified at an early stage. Conclusion In patients with a severe infection, an early diagnostic and treatment of infectious second hits can improve the complication rate and prognosis. During the prolonged and complicated septic course of tertiary peritonitis, an additional routine microbiological monitoring contributed effectively to early detection and diagnostic of nosocomial infections. Further studies to investigate the value and efficacy of such monitoring, which have been abandoned, should be undertaken in infectious high-risk patients. Keywords Tertiary peritonitis . Nosocomial infection . Microbiological monitoring . Infection installment

Introduction Peritonitis at a surgical intensive care unit (ICU) is the most frequent infectious diagnosis at the time of admittance. The associated severe inflammatory response originating from the peritoneal damage causes a high percentage of septic courses. In approximately 80% of the patients with a secondary peritonitis, the initial surgical intervention may sanitize the abdominal cavity from the infectious lesion [3]. The remaining patients develop a persisting peritonitis with a considerable number of subsequent surgical interventions, infectious complications, a high rate of severe sepsis, and septic shock as well as a mortality double as high ranging between 30 and 63% [3, 27, 28]. This manifestation is named tertiary peritonitis [1, 3, 4, 20, 27, 28]. Because of a persisting multiorgan failure (MOV), repeating surgical interventions and

474

Langenbecks Arch Surg (2006) 391:473482

intermittent after infections, the value of clinical and laboratory parameters for a sufficient monitoring is limited [8]. An early finding of the correct diagnosis and the subsequent effective initiation of an appropriate treatment may help to lower the complication rate and to improve the prognosis. Therefore, the aim of the study was to investigate (1) the infectious course in patients with tertiary peritonitis and an associated high infectious risk and (2) the efficacy of the laboratory and microbiological diagnostic. From the results, conclusions should be derived to improve diagnostic and treatment. Materials and methods The records of all ICU patients (capacity, 12 places) of the Department of Surgery at the University Hospital, Magdeburg (Germany), were evaluated from 2000 to 2002. In particular, the cohort of patients with peritonitis was investigated. According to the definition of tertiary peritonitis, the following study parameters of adequate cases were compared with cases diagnosed with secondary peritonitis: number, cause and clinical course of peritonitis, and mortality. The tertiary peritonitis is defined as persisting intraabdominal infection after initial attempt of treatment of a secondary peritonitis and occurrence of nosocomial microbes in the abdominal cavity [4]. In addition, the patients with tertiary peritonitis (n=60) also underwent a retrospective cohort study. In these patients, the infectious course (subsequent infections, microbial spectrum, and resistogram) and the efficacy of the laboratory and microbiological monitoring were analyzed. An infection was defined according to the recommendations of the consensus conference of the American College of Chest Physician (ACCP) and Critical Care Medicine (SCCM) [4]. By the mean of patients records, the infections occurring during the postoperative course after initial surgical intervention were documented. For the most frequent nosocomial infections (pneumonia, abdominal infections, catheter-related infections), it was investigated on the day of finding the specific diagnosis, which criteria were crucial to initiate the search for the infectious lesion and/or led to the correct diagnosis. In addition to the clinical criteria (clinical signs and symptoms, the course of body temperature, drainage volumes, and radiological findings), laboratory parameters (white blood cell count, CRP, and PCT) were registered. Kinetics and value of the infectious parameters in the diagnostic were determined within a time frame of 48 h before the time point of finding the specific infectious diagnosis. Three categories were subdivided.

I. Values with no hint for an infection (levels within the normal range and falling pathological levels) II. Values altered by previous (<48 h) surgical interventions and diagnosed acute infections-pathological range is considered the response to ongoing inflammatory stimuli III. Increasing or consistently elevated pathological values Values were considered pathologic if the value is above the upper or below the lower limit of normal range. Falling or increasing levels were defined as minimally 10% below or above the former control value (white blood cell count, CRP, and PCT). Increase or fall of the body temperature (daily highest temperature) was defined as 0.5C for 48 h above or below the former temperature. The microbiological monitoring was routinely performed only in ICU patients with severe sepsis. The microbiological specimens were obtained according to formerly recommended intervals of every 34 days [32, 36]. The interval was also chosen according to the time period necessary from obtaining the specimen to the definitive final microbiological finding, which took 3 days in average. Therefore, twice a week (on Monday and Thursday), the following specimen were obtained and investigated according to the usual standards: Tracheal secretion: Aspiration of tracheal secret obtained from the tube or tracheal canule via a sterile aspiration catheter into an aspiration device (Trachealsaugset, Dahlhausen, Cologne, Germany). Blood sample : Under sterile conditions, blood (25 ml each) was withdrawn from two different locations at the human body (mostly, puncture of a peripheral vein; as exception, blood withdrawal out of the arterial canule for blood pressure monitoring or out of the central venous line) for an aerobic culture (BD Bactec plus + Aerobic/F, Becton Dickinson, Shannon, Ireland) and 25 ml for an anaerobic culture (BD Bactec plus + Anaerobic/F, Becton Dickinson, Shannon, Ireland). Urine: An aliquot was obtained out of the patients closed system for urine collection.

Out of the routine microbiological investigations, the percentage of positive findings, the frequency of microbial colonization or infection, and the number of microbiological findings with diagnostic and therapeutic impact was determined, in particular, how often microbiological results obtained in routine investigations alone, without hints from laboratory parameters or clinical symptomatology, had led to the search for the infectious lesion and/or to finding the correct infectious diagnosis. If a microbiological finding was the basis for finding the specific diagnosis, the kinetics of the inflammatory parameters such as CRP, PCT, body

Langenbecks Arch Surg (2006) 391:473482

475

temperature, and white blood cell count on the day of obtaining the microbiological specimen were investigated to assess whether at this time point, there were already hints for an infection indicated by laboratory parameters. The categories were also subdivided as mentioned above. If the inflammatory parameters showed a variable tendency of change, the most pronounced altitude of pathological inflammatory parameters was used to determine the appropriate category. Independent of the routine microbiological monitoring, specimens were additionally obtained in case of a specific infectious suspect. For pneumonia and catheter infections, the device-associated infection rate was determined: Infection rate/days of artificial respiration or days of the catheter being in situ 1,000. Statistics Statistical analyses were performed using t test and 2 test as appropriate with SPSS for Windows (version 10.1).

Results Among the overall 2,676 patients treated at the Surgical ICU, University Hospital, Magdeburg (Germany) from 2000 to 2002, 356 cases with abdominal infections were detected. The mean stay at the ICU amounted 13.5 days for patients with peritonitis; the hospital mortality was 20.1%. The main causes of peritonitis were as follows with decreasing frequency: Secondary peritonitis after perforations/injuries of the gastrointestinal tract, Intraabdominal abscess, and Acute necrotizing pancreatitis

peritonitis during the patients stay at the ICU. Patients with liverish peritonitis, abdominal infectious complications in necrotizing pancreatitis, and duodenal stump insufficiency developed more frequently a tertiary peritonitis than patients with other causes for a secondary peritonitis: 1.5fold, 2.5-fold, and 3.5-fold, respectively. Patients with secondary peritonitis are relaparotomized on demand and do not undergo programmed lavage. Indications for relaparotomy were new or persisting infections of the abdominal cavity. In 34% of patients, microbiological findings, in 33% of cases, clinical signs and symptoms (drainage fluid, acute abdomen, and radiological findings among others), in 20.7% increasing inflammatory parameters, and in the remaining subjects (12.2%), a combination of various factors were crucial for the search of an infectious lesion and/or indication for surgical intervention (Table 1). In the patients with a tertiary peritonitis, there were substantial differences of the risk profile and through the treatment course (Table 2), which was already found in scoring the patients at the time of admittance to the ICU. Table 3 shows further treatment characteristics of the patients. In addition to a long treatment period at the ICU and the high frequency of multiorgan failure, in particular, 4.7 subsequent surgical interventions and 5.1 novel nosocomial infections in average marked a difficult surgical and infectious treatment course. The surgical interventions to clear the focus of tertiary peritonitis are shown in Table 4. The main percentages of the following infections were as follows (Fig. 1): Intraabdominal infections (34.2%), Catheter infections (28.2%), and Infections of the pulmonary tract (22.5%)

Approximately 71.3% of patients with peritonitis developed a severe sepsis or septic shock during the clinical course. The mortality of these patients was 26.7%. Overall, 60 patients fulfilled the criteria of a tertiary peritonitis. Tertiary peritonitis developed in all patients after previous surgical intervention for the cause of a secondary
Table 1 Division of the initial criterion for the focus search from infections (in percentage) Microbiological results Clinical symptoms Laboratory results Combination

For the evaluated patients, the device-associated infection rate for the most frequent nosocomial infections at the ICU was determined, which was distributed as follows: Artificial respiration-associated pneumonia, 34.0 Infections of the central venous line, 15.8, and Infection of the urinary tract, 23.1
Pneumonia Catheter-related infection 59.5 Urinary tract infection 78.7 Total

Intraabdominal infection 34.1 32.9 20.7 12.2

17.9 53.8 7.7 20.5

45.9 23.4

21.3 40.5

14.6 16.1

476 Table 2 Difference between secondary and tertiary peritonitis Secondary peritonitis (n=296) Number nosocomial Length of ICU stay Mannheim peritonitis index (MPI) APACHE II score SAPS score Goris score Number of multiorgan failure (MOF) Proportion of patients with severe sepsis/septic shock Hospital mortality 33.8% 7.4 days (221) 25.9 12.4 31.9 3.76 3.5 65.5% 17.6% Tertiary peritonitis (n=60) 70% 43 days (20170) 31.4 20.7 45.6 6.1 6.3 100% 35% P-value Surgical intervention

Langenbecks Arch Surg (2006) 391:473482 Table 4 Surgical interventions to clear the focus of tertiary peritonitis (n=225 numerous naming is possible) Number 80 16 12 21 39 18 12 8 6 4 3 2 2 2

P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001

Lavage (rinsing, drainage) Lavage (bleeding control/tamponade of bleeding Lavage with bowel resection Lavage (abscess revision) Pancreatic necrosectomy Revision of abd. wound rupture Drainage of abscess (interventional) Anus praeter Cholecystectomy Revision of bile duct Gastroenterostomy Partial resection of lung Partial resection of liver Biliodigestive anastomosis

Number in percentage or median value; value of scoring for the day of admission to ICU

The spectrum and distribution of the initial diagnostic criteria for diagnosing the subsequent nosocomial infections are depicted in Table 1. Initially, microbiological findings led most frequently to the search of an infectious lesion and finding of the specific diagnosis. Clinical symptoms predominated as initial infectious criteria in intraabdominal infections and pneumonia (33 and 54%, respectively). Laboratory monitoring For the clinician, only increasing or persistently elevated laboratory parameter levels above the normal range or the increase of the body temperature above 38C can be considered reliable markers of an inflammatory response
Table 3 Characteristics of patients with tertiary peritonitis (n=60) Treatment characteristics of the patients Median length of hospital stay before ICU stay Median length of hospital stay after ICU stay Number of nosocomial infections/patients Number of surgical interventions/patient No definite treatment Median duration/frequency of ventilation Median duration of antibiotic therapy Median duration/frequency of hemodialysis Need of norepinephrine/days (median) HLA-DRa (CD14) <30%; HLA-DR (CD 14) 3060%
a

and/or infection (category III). In all evaluated cases of infection, the rate was, depending on the specific parameter, between 33.5 and 57.1% (mean, 42%). The rate of normal and falling pathological values ranged between 20 and 50% for the evaluated inflammatory parameters. Taking into account the values which were altered by other inflammatory responses within 48 h before the time point of finding the correct diagnosis, 58% of the infectious markers did not give any hint for a new infectious lesion (Table 5). In the infectious diagnostic during the clinical course as used in this investigation, CRP changes showed the highest and increasing body temperature the lowest sensitivity for the detection of new infectious lesions (Table 6). In addition to the analyses of the single inflammatory parameters, it was investigated how often none of the typical inflammatory parameters showed alterations indicating an infection (persistently elevated or increasing pathological values) at the time point of finding the specific diagnosis: in pneumonia, 66.6% of cases did not show any specific values (further infections, 21.2 to 35.1% of cases). Microbiological monitoring Overall, 3,924 routine microbiological specimens were obtained from the patients through the treatment period. Furthermore, 15 tracheal secretion specimens, three blood samples, and four urine aliquots were obtained for additional microbiological cultures externally of the routine microbiological monitoring, which aimed for a specific search of an infectious lesion. Out of the 42 patients who were artificially respirated for more than 3 days, the tracheal secretion specimens could be evaluated for the follow-up assessment. Out of the 429 samples, 385 (89.7%) were positive; 26% (n=100) of these specimens showed, despite previous negative microbiological test result, a new

19.1 days (157 days) 25.3 days (0120 days) 5.0 (315) 4.7 (324) 23.7% 21.8 days; 89.8% 30.6 days (9111) 12.9 days 30.5% 88% 12.7 days 45.7%; 54.3%

HLA-DR (CD 14), human leukocyte antigen presentation of monocyte

Langenbecks Arch Surg (2006) 391:473482 Fig. 1 Number of subsequent ICU acquired infections in patients with tertiary peritonitis
60

477

50

49 47

40

39

39 37 33

30

28

20

11 10 6 5 3 1 0

s iti ol C

Pl

En

Pn

Su

Ab

Tr

Ab

microbial colonization (55%) or a microbial change (45%). Twenty-two of these findings belong to patients who developed pneumonia during the time period of artificial respiration. In nine of these pneumonia cases, sterile tracheal secretion specimens were found before the time point of finding the specific diagnosis and in the remaining 13 patients, there were positive findings of the microbiological culture but these findings were interpreted as colonization. In seven cases with pneumonia (32%), the microbial change (n=3) or the newly detected microbes (n=4) led to the search of the infectious lesion and in case of infiltrate detection to the diagnosis pneumonia. At the time point when the sample was obtained, there was no hint

Table 5 Meaning of the inflammatory markera from all infections (in percentage)(temperature/CRP/leukocyte n=205 PCT/IL-6 n=90) Category I II III Temperature 47.8 15.6 36.6 CRP 20 22.9 57.1 Leukocyte count 49.1 12.7 38 PCT 44.4 20 35.5 IL-6 50 14.4 35.5 Total 40.9 17.1 42 Value for the diagnostic No evidence for new infections Interfered by ongoing inflammatory events Probable infection

I Within normal range and pathological levels but decreasingno evidence of infection, II pathological levels (with no tendency or increasing) but interfered by ongoing infections or operations, III pathological or normal levels and increasing (normal levels over normal range) a Results at the day of definite diagnosis of subsequent ICU acquired infections

Pe rit s iti on

rin ar y tra

at

l ho

eu

ac

sc

do

eu m on ia fe ct io n in ct

do

rg ic al w

he te r-r el ou nd in fe ct io n

ra

o he

g an

es s ed in fe ct io n at

ca

m in ch on iti s

le

rd

for a pulmonal infection. In the remaining pneumonia cases, changes of clinical symptoms, radiological findings, or laboratory parameters initially led to the correct diagnosis but in further five pneumonia cases, the specific microbe could be early identified in the previously obtained routine microbiological specimens. This resulted in the fact that in 12 pneumonia patients with artificial respiration (54.5%), a specific treatment with antibiotics could be initiated. The calculated headstart was 2.6 days in average. Twenty-eight further microbiological changes of tracheal secretion specimens were considered as tracheobronchitis with required treatment depending on the clinical parameters and the treatment course. Overall, 40 microbiological

br

iti

al fis tu la

iti

s a

py em

478 Table 6 Sensitivity at the day of definite diagnosis of subsequent ICU acquired infections CRP (%) Value with no infections Value with evidence of new infection (sensitivity) 42.9 57.1 PCT (%) 64.5 36.5 Leukocyte count (%) 62 38 Temperature (%) 63.4 36.6 IL-6 (%) 58 42

Langenbecks Arch Surg (2006) 391:473482

findings obtained in the routine microbiological monitoring (9.3%) led to an early finding of the diagnosis of a nosocomial pulmonal infection and the subsequent initiation of a specific treatment with antibiotics (Table 7). Overall, 2,544 blood samples were withdrawn for microbiological test cultures at 636 time points of withdrawal, out of which 211 (8.3%) were positive. At 129 time points of withdrawal (20.3%), at least one positive microbiological culture result was found in 36 patients (61%). In 19 cases (14.7%), there was a bacterial contamination. Thirty-seven positive findings of microbiological blood culture as a result of a repeated microbiological test culture could be associated with an infection; 18 further positive results of microbiological blood culture were found immediately after a previously diagnosed infection with initiated treatment. Overall, 55 (42.6%) of the infectious episodes were the reason for initiating the search of an infectious lesion and subsequently led to the successful identification of such septic lesion as follows: Abdominal infections, n=28 (diffuse peritonitis, n=5; abscess, n=2), Catheter infections (central venous line), n=22, Infections of the urinary tract, n=2, Pneumonia, n=2, Endocarditis, n=1.

Twelve abdominal infections were sanitized with a surgical intervention, and in 16 further cases, a treatment with antibiotics was initiated. The result of the microbioTable 7 Results of routine microbiological monitoring (60 patients) Blood culture removal, n=636 Number/percentage of positive results Early diagnosis/ adequate therapy of subsequent ICU acquired infections 129 (20.3%) 55 (8.6%) Endotracheal aspirate cultures, n=429 385 (89.7%) 40 (9.3%) Urine cultures, n=628

logical blood culture in the cases with surgical intervention was identical to the microbiological test culture of the specimens obtained in the surgical intervention. The 27 further microbiological blood cultures in other infections led to a change of the treatment with antibiotics. One hundred eighty-six (29.6%) of the 628 urine samples showed a positive finding. Eighty-six positive microbiological test results (first or repeated culture) were found in 47 patients with infection of the urinary tract; in 12 cases, there was only a bacteriuria or a colonization with no required treatment. Adequate therapy with antibiotics was possible for 46 patients (Table 7). The microbial detection rate in the urine during an ongoing treatment with antibiotics was 2.2% whereas in the treatment-free intervals, it was 18.2%. The evaluation of the patients courses showed that except for the two patients with a positive microbiological test result of blood culture before the time point of finding the specific diagnosis, the specific treatment in all the remaining patients was only initiated after positive test results of microbiological culture had been found. The time interval between taking the microbiological samples, the positive results, and the initiation of a specific treatment was 2 to a maximum of 3 days (mean, 2.5 days). The analysis of the infectious laboratory parameters on the day of taking the microbiological culture samples showed only in 32% of patients minimally one infection-specific value vs in 78% of cases on the day of finding the specific diagnosis. At both time points, 22% of the values are overlapped by simultaneously occurring further infections, i.e., in 68% of cases, there was no specific suspect of a new infection. In the cases with routine microbiological blood culture and patients with infections of the central venous line, there was still a higher rate of unspecific inflammatory parameters on the day of taking the samples for microbiological test culture. It indicates the routine characteristic of taking microbiological samples. In the spectrum of microbiological culture results in abdominal infections, there were distinctly more Pseudomonas spp., Enterobacter spp., and Enterococcus faecium (Fig. 2). In these problematic microbes, there were two- to threefold increased rates of antibiotic resistance compared with the microbial spectrum found in secondary peritonitis.

Discussion The tertiary peritonitis belongs to the nosocomial infections with the highest mortality, which has been reported to range between 50 and 60% [3, 21, 27, 28]. An optimal treatment strategy has not yet established [1, 3, 27, 28]. In many cases, the surgical and antimicrobial treatment fails in this disease. Pathophysiologically, the tertiary

186 (29.6%) 46 (7.3%)

Langenbecks Arch Surg (2006) 391:473482 Fig. 2 Comparison of pathogen organism between tertiary and secondary peritonitis (in percentage)
25

479

20

Tertiary peritonitis Secundary peritonitis

15

10

0
s eu ot Pr s eb Kl c bi ro ae An as on m do eu p. Ps sp er ct ba ro te En p. sp lla C m iu li co ec fa E. us cc co is ro al te ec fa En us cc co ro . te ph En a t .S eg us .n re ag au ko us cc co lo hy ap St da di an

ie

peritonitis is characterized by a failure of the peritoneal inflammatory response. In addition, numerous infectious and noninfectious complications can develop through the treatment course. The invasive monitoring and treatment at the ICU, the recurrent surgical interventions, and the prolonged stay of the patients in an environment of threatening nosocomial infections as well as the altered immune response are relevant causes of particular importance for the infectious complications. The altered immune response is reflected by the high rate of patients with an immune paralysis (47.5%) indicated by the HLA-DR expression level. The scoring indicated higher values for patients with a later developing tertiary peritonitis. Thus, the development of a tertiary peritonitis is directly associated with the severity of the secondary peritonitis. Despite standardized and novel surgical techniques and technology as well as highly developed intensive care, the mortality of nosocomial abdominal infections could not be substantially improved through the last several years. Possible reserves may possibly lie in the early detection

and treatment of recurrent severe subsequent infections. Additional infections can further complicate the clinical course as so-called second hits and lead to a higher complication rate and mortality because of the imbalanced immune response [7]. In addition to the surgical and interventional sanitation of, in particular, abdominal infections, the antimicrobial treatment is essential. Through the last several years, the advantage of an initially adequate treatment with antibiotics has been shown in bacteriemia, pneumonia, and abdominal infections. In all infections, the inadequate treatment leads to a higher complication rate and mortality. A later change of the antibiotic treatment in case of initially inadequate treatment with antibiotics cannot significantly improve the prognosis of the patients [10, 13, 1619, 22, 23, 25, 26, 30, 37]. While in an isolated infection, clinical signs and laboratory parameters indicating an infection may provide a relatively high specificity and sensitivity for the diagnostic, there are considerable problems in patients with sepsis and persisting multiorgan failure as well as recurrent inflammatory responses. Because of the artificial respiration and analgosedation,

p. sp

480

Langenbecks Arch Surg (2006) 391:473482

(1) there can be a lack of valuable clinical signs for the diagnostic of abdominal disorders and (2) typical changes of laboratory parameters can be altered by inflammatory responses of the nonseptic type such as surgical intervention, reperfusion, dialysis, steroid therapy, and others. Crabtree et al. [6] has found a sensitivity of 55% for fever and leukocytosis in surgical patients with infections. Knowing these problems in the infectious diagnostic and treatment of nosocomial infections, the presented study aimed to investigate the infectious course of patients with severe abdominal infections and to determine the infectious parameters leading to the diagnosis of subsequent or further infections. Simultaneously, the impact of a simultaneous microbiological monitoring on the infectious diagnostic was studied. The data show that patients with a tertiary peritonitis have a high infectious risk profile. This is impressively indicated by the facts that, in average, five further nosocomial infections occurred during the hospital stay and there was a 1.5- to 6.6-fold higher deviceassociated infection rate compared with the great number of control patients with no abdominal infections. In agreement with Cabtree et al. [6] we found a low sensitivity of inflammatory parameters. Only 15% of these parameters could early identify new infections. The lowest sensitivity in the infectious diagnostic provided the change of the body temperature. In patients with a tertiary peritonitis, a body temperature of at least 38C was documented on 60.8% of the hospital days through the clinical course. On further 12% of treatment days, a continuous dialysis caused a cooling effect onto the patients body temperature via the extra corporal circulation and, thus, led to a nonvaluable course of the body temperature. This clearly demonstrates the limited value of fever in the infectious diagnostic. Taking the inflammatory parameters into account, which are overlapped by other inflammatory responses than caused by infections, this study resulted in a lower sensitivity than 40% of all usual inflammatory parameters except CRP. In one third of the infections, all usual and available infectious parameters failed to indicate an infection at the time point of finding the specific infection diagnosis. While only 15% of infections were identified by initially altered inflammatory parameters specific for an infection, the rate found by the microbiological monitoring (46%) was more promising. The established and standard routine monitoring of patients at the ICU for surveillance of infection and colonization [32, 36] has been increasingly questioned and subsequently given up because of the lacking detection of its efficacy [2, 12, 14, 24, 29, 32 34]. In patients with severe sepsis, infectious patients of high risk, it has been maintained as additional diagnostic tool at our ICU. In case of a limited value of typical and usual inflammatory parameters, a persisting multiorgan

failure, overlapping and simultaneously existing inflammatory responses, microbiological findings justified the initiation of the search for an infectious lesion in 46% of the subsequent nosocomial infections. In particular, the blood culture results were effective: rate of test results with diagnostic and therapeutic consequences, 8.6%. Beside the high incidence of 61% of positive test results of blood cultures, a positive test result of blood cultures was found on every fifth time point of taking microbiological samples. In the literature, taking routine microbiological samples for blood culture was considered unnecessary because of: A low incidence of 2.74.9%, A low microbial yield of up to 4.3%, A high contamination rate of up to 64%, and A low number of therapeutic consequences of 1:99 in intensive care patients [12, 13, 16, 24, 30, 33, 34, 38].

Even for continuously taking tracheal secretion samples, there is only little support from the literature because of: A low frequency of the early detection of the microbial pneumonia cause (approximately 20%), and The absent therapeutic consequences [15, 33].

In contrast, several authors such as Ewig, GarrousteOregas, and Cendrero have reported on a more frequent previous detection of a microbial pneumonia cause in 47 88% of cases [5, 9, 11]. Because of the microbiological monitoring of tracheal secretion specimens, 32% of the pneumonia cases were early identified and 9.3% of the obtained tracheal secretion samples allowed thus an early specific initiation of treatment with antibiotics. Taking the pathogenic microbes previously identified within the tracheal secretion into account, the initiation rate of an inadequate treatment with antibiotics was 0%. Data from the literature range between 16 and 30% for the inadequate administration of antibiotics in nosocomial pneumonia [17, 23, 30, 31, 35]. Samples for microbiological test culture of urine regularly led to the initiation of a specific treatment with antibiotics but they were only reasonable through nontreatment time intervals. While under ongoing treatment with antibiotics, only every 50th microbiological test culture revealed an infection, during nontreatment intervals, it was the case in every fifth test culture. The frequently found pathogenic microbes within the abdominal cavity such as Pseudomonas spp., Enterobacter spp., Enterococcus faecium, and Candida are identical with those reported in the literature in patients with tertiary peritonitis [20, 27, 28]. The microbial resistograms of these microbes revealed two- to threefold higher resistance rates compared with those in secondary peritonitis leading to a challenge in the initiation of an adequate and specific antibiotic treatment.

Langenbecks Arch Surg (2006) 391:473482

481 admitted to the intensive care unit with sepsis. Crit Care Med 31:27422752 Garrouste-Oregas M, Chevret S, Arlet G, Marie O, Rouveau M, Popoff N, Schlemmer B (1997) Oropharngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. Am J Respir Crit Care Med 56:16471655 Graevenitz A (1995) Bakteriologisch-mykologisches Monitoring auf Intensivstationen. Intensivmed 32:547551 Harbarth S, Ferriere K, Hugonnet S, Ricou B, Suter P, Pittet D (2002) Epidemiology and prognostic determinants of bloodstream infections in surgical intensive care. Arch Surg 137:13531359 Hauer T, Dziekan G, Krger WA, Rden H, Daschner F (2000) Sinnvolle und nich sinn-volle Hygienemassnahmen in der Ansthesie und auf Intensivstation. Anesthesist 49:96101 Hayon J, Figliolini C, Combers A, Trouillet JL, Kassis N, Dombert MC, Gibert C, Chastre J (2002) Role of serial routine microbiologic culture results in the initial management of ventilator-associated pneumonia. Am J Respir Crit Care Med 165:4146 Hoste E, Blot S, Lameire N, Vanholder R, De Bacquer D, Colardyn F (2004) Effect of nosocomial bloodstream infection on the outcome of critically ill patients with acute renal failure treated with renal replacement therapy. J Am Soc Nephrol 15:454462 Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH (2002) Clinical importance of delays in the initiation of appropriate treatment for ventilator-associated pneumonia. Chest 122:262 268 Kollef MH, Sherman G, Ward S, Fraser V (1999) Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115:462474 Kollef MH (2000) Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 31:131138 Kujath P, Rodloff AC (eds) (2003) Therapie chirurgischer InfektionenAktuelle Aspekte zur Dia-gnostik und Therapie, 1st edn. UNI-MED SCIENCE, Bremen, London, Boston:63 67 Kujath P, Rodloff AC (eds) (2001) PeritonitisGrundlagen der Therapie der Peritonitis, 1st edn. UNI-MED SCIENCE, Bremen, London, Boston:5669 Leone M, Bourgoin A, Cambon S, Dubue M, Albanese J, Claude M (2003) Empirical anti-microbial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med 31:462467 Leroy O, Meybeck A, Escrivan T, Devos P, Kipnis E, Georges H (2003) Impact of adequacy of initial antimicrobial therapy on the prognosis of patients with ventilator-associated pneumonia. Intensive Care Med 29:21702173 Levin PD, Hersch M, Rudensky B, Yinnon AM (1997) Routine surveillance blood cultures: their place in the management of critically ill patients. J Infect 35:125128 Luna CM, Vujacich P, Niederman MS, Vay C, Gherardi C, Matera J, Jolly EC (1997) Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 111:676685 Mac Arthur R, Miller M, Albertson T, Panacek E, Johnson D, Teoh L, Barchuk W (2004) Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial. Clin Infect Dis 38:284288 Marshall JC, Innes M (2003) Intensive care unit management of intraabdominal infection. Crit Care Med 31:22282237 Nathens AB, Rotstein O, Marshall JC (1998) Tertiary peritonitis: clinical features of a complex nosocomial infection. World J Surg 22:158163

In the patients with tertiary peritonitis and a severe septic clinical course, the high infectious risk and the problems of an adequate infectious diagnostic could be demonstrated. The low sensitivity of clinical and laboratory parameters specific for subsequent infections could be distinctly improved by the routine microbiological monitoring, which led to an early detection of nosocomial infections and an increased rate of an adequately initiated antibiotic treatment (47.3% of all subsequent infections) in the patients with a high infectious risk (Table 7). This improvement of the infectious management is associated with beneficial consequences such as a significant decrease of the infectious complication rate and mortality as various authors confirm. The low mortality in our study (35 vs 5060% reported in the literature) can be substantially caused by the favorable effect of the microbiological monitoring. Further prospective studies in patients with a high infectious risk are required to show statistical evidence for the efficacy with regard to a beneficial outcome and to justify the 5% of total costs in patients with a severe sepsis.
Acknowledgements The authors are grateful to the collaborators of the Institute of Microbiology (Head, Prof. W. Koenig, MD) at the University Hospital, Magdeburg (Germany) for routine microbiological test cultures and providing test results.

11.

12. 13.

14.

15.

16.

17.

18.

19.

References
20. 1. Bosscha K, van Vroonhoven Th, van der Werken Ch (1999) Surgical management of secondary peritonitis. Br J Surg 86:1371 1377 2. Brnnler T, Langgartner J, Klebl F, Salzberger B, Schlmerich J (2004) Mikrobiologische Routinediagnostik auf der Intensivstationein Update. Intensivmed 41:248254 3. Buijk SE, Bruining HA (2002) Future directions in the management of tertiary peritonitis. Intensive Care Med 28:10241029 4. Calandra T, Cohen J (2005) The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 33:15381548 5. Cendrero JAC, Violan JS, Benitez AB, Catalan JN, Fernandez JA, Santana PS, de Castro FR (1999) Role of different routes of tracheal colonization in the development of pneumonia in patients receiving mechanical ventilation. Chest 116:462470 6. Crabtree TD, Pelletier SJ, Antevil JL, et al (2001) Cohort study of fever and leukocytosis as diagnostic and prognostic indicators in infected surgical patients. World J Surg 25:739744 7. Engelmann L (2003) Patienten mit Sepsis versterben am second hit. Intensiv-News 5:12 8. Evans HL, Raymond DP, Shawn JP et al (2001) Diagnosis of intraabdominal infection in critically ill patient. Curr Opin Crit Care 7:117121 9. Ewig S, Torres A, Elebiary M, Fabregas N, Hernandez C, Gonzalez J, Nicolas JM, Soto L (1999) Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Am J Respir Crit Care Med 159:188198 10. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez F, Perez-Paredes C, Ortiz-Leyba C (2003) Impact of adequate empirical antibiotic therapy on the outcome of patients

21.

22.

23.

24.

25.

26.

27. 28.

482 29. Ortiz E, Sande MA (2000) Routine use of anaerobic blood cultures: are they still indicated? Am J Med 108:445447 30. Rello J, Ausina V, Ricart M, Castella J, Prats G (1993) Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 104:12301235 31. Rello J, Gallego M, Mariscal D, Sonora R, Valles J (1997) The value of routine microbial investigation in ventilator associated pneumonia. Am J Respir Crit Care Med 156:196200 32. Ruef CH, Francioli P (1997) Mikrobiologisches Monitoring auf der Intensivstation. Swiss-NOSO 4:17 33. Scheidegger C, Zimmerli (1997) Routinemige bakteriologische Kontrollunter-suchungen bei Intensivpatienten: Contra. Ansthes Intensivmed Notfallmed Schmerzther 32:115116 34. Strouhal Um, Byhahn C, Martens S, Albert S, Mierdl S, WimmerGreinecker G, Westphal K, Kessler P (2000) Stellenwert bakter-

Langenbecks Arch Surg (2006) 391:473482 iologischer Screeninguntersuchungen bei Patienten mit Sepsis auf einer herzchirurgischen Intensivstation. Z Herz-Thorax-Gefsschir 14:137142 Timothy CF (2000) Empiric therapy for pneumonia in the surgical intensive care unit. Am J Surg 179:18S25S Thlig B, v. Saene HKF, Hartenauer U (1994) Mikrobiologische berwachung. In: Praxis der Intensivbehandlung, 6th edn. Georg Thieme Verlag, Stuttgart, New York:121 147 Valles J, Leon C, Alvarez-Lerma F (1992) Nosocomial bacteremia in critically ill patients: a multicenter study evaluating epidemiology and prognosis. Clin Infect Dis 15:866873 Wichelhaus TA, Schfer V, Brade (1999) Keimnachweis in der Blutkultur. Zentralbl Chir 124:699702

35. 36.

37.

38.