Tailored Antibiotic Therapy for Respiratory Tract Infections

Mary P. Ettari, MPH, PA-C

Medical Partners of Martin County

Respiratory Tract Infections (RTIs)

Community-acquired pneumonia (CAP)

56 million cases annually4 1.3 million hospitalizations/year5

Acute bacterial exacerbation of chronic bronchitis (AECB)3

17% of adults in the US

Many current or ex-smokers

Acute bacterial rhinosinusitis (ABRS)1,2

31 million US cases/year

Fifth most common diagnosis for which antibiotics are prescribed

AAPA Chapter Lecture Series Supported by an educational grant from Aventis Pharmaceuticals, a member of the sanofi-aventis group

1 Garau J, et al. Clin Microb Infect. 1998;4(suppl 2):S51-S58 2 Bishai WR. Otolaryngol Head Neck Surg. 2002;127: S3-S9 3 Ball P, Make B. Chest. 1998;113:199S-204S 4 Colice GL, et al. Chest. 2004;125:2140-2145 5 Hall MJ, Owings MF. 2000. Advance Data From Vital Health Statistics. June 19, 2002, 329:1-20.

Number of Visits to PAs in 2004 (in millions)

A. Phillips PA-C
Immunizations/vaccinations Contraception Congestive heart failure Gynecological disorders & infections COPD Urinary infections Headache (including migraine) Asthma Dermatitis/skin Gastrointestinal disorders & infections Depression/anxiety
5

Dyslipidemia Health Maintenance Diabetes Pain management Allergic disorders Hypertension Respiratory/ENT infections Musculoskeletal disorders/injuries
1,000,000 5,000,000 9,000,000 13,000,000 17,000,000 21,000,000 25,000,000

Source: AAPA 2004 Annual Conference Survey

Antibiotic Use for RTIs

90 80 70 60 50 40 30 20 10 0 1991-1992 1994-1995 1998-1999 1991-1992 1994-1995 1998-1999 1991-1992 1994-1995 1998-1999
Narrow Spectrum Broad Spectrum

Streptococcus pneumoniae

Most important RTI pathogen 1

Associated with high morbidity and mortality

20%60% CAP 2 15%25% AECB 3 20%43% ABRS 4

Streptococcus pneumoniae

Common Cold +URTI

Sinusitis

Acute Bronchitis

1 File TM Jr. Lancet. 2003;362:1991-2001; 2American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-1754; 3 Guthrie R. Chest. 2001;120:2021-2034; 4Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130: 1-45; 5Bartlett JG, et al. Clin Infect Dis. 2000;31:347-382

Steiman MA, et al. Ann Intern Med 2003;138:525-533

Respiratory Tract Pathogen

Pathogen AECB ABRS CAP

S pneumoniae: The Major

Haemophilus influenzae

S pneumoniae 15%25%1 20%43%2 20%60%3 H influenzae 30%59%1 22%35%2 3%10%3 3%22%1 2%10%2 1%2%4 M catarrhalis S pyogenes 3%7%2 0%8%2 3%5%4 S aureus 1%6%4 Mycoplasma spp 2%8%4 Legionella spp 4%6%4 Chlamydophila spp
1. Guthrie R. Chest. 2001;120:20212034; 2. Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:145; 3. American Thoracic Society. Am J Respir Crit Care Med. 2001;163:17301754; 4. Bartlett JG, Mundy LM. N Engl J Med. 1995;333:16181624.

An important pathogen in RTIs causing 1 3%10% CAP 30%59% AECB2 22%35% ABRS3 Over 30% -lactamase positive4

Haemophilus influenzae

1 American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-1754.; 2Guthrie R. Chest. 2001;120:20212034; 3Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:1-45; 4Hoban DJ, et al. Clin Infect Dis. 2001;32(suppl 2):S81-S93

Moraxella catarrhalis

Atypicals of Concern in RTIs

Moraxella catarrhalis

An important pathogen in RTIs causing: 1%2% CAP1 3%22% AECB2 2%10% ABRS3 Over 90% lactamase positive4
1 3

Atypicals common in patients with CAP1

Mycoplasma pneumoniae

May be a factor in 30% 40% of CAP cases1 Often undetected because of poor diagnostic tools1 IDSA and ATS treatment guidelines for CAP include the importance of atypical coverage2,3

Bartlett JG, Mundy LM. N Engl J Med. 1995;333:1618-1624; 2Guthrie R. Chest. 2001;120:2021-2034; 3Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:1-45; 4Hoban DJ, et al. Clin Infect Dis. 2001;32(suppl 2):S81-S93.

Thibodeau KP, Viera AJ. Am Fam Physician. 2004;69:1699-1706; 2Bernstein JM. Chest. 1999;115:9S-13S; American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-1754.

Coverage of Atypical Pathogens Is Important for Treatment of CAP

Agent Number of Cases 4432 272 507 41 833 781 6866

Rapid Emergence of Macrolide Resistance in Strep pneumoniae

Penicillin approved 1943 Azithromycin approved 1991 Levofloxacin approved 1996

S pneumoniae Legionella spp M pneumoniae C pneumoniae H influenzae

Other Total

1.4 2.8 7.4 061.1*

% Resistance

Mortality Rate (%)* 12.3 14.7

30
Penicillin Azithromycin Levofloxacin

20

10

0
a 19 92 -1 99 3 b, c g h h h 99 2 d, e e, f 19 98 -1 99 9 20 00 -2 00 1 19 94 -1 20 01 -2 00 2 19 96 -1 99 7 19 99 -2 00 0 19 91 -1 19 94 99 5 h

*Mortality rates depend on pathogen: P aeruginosa mortality was 61.1%, but that organism was isolated in only 18 cases; C psittaci mortality was 0 and was isolated in 32 cases.
Adapted from Fine MJ, et al. JAMA. 1996;275:134-141.

a Thornsberry et al, Suppl. Infect. Med. 1993, 93:15-24; Thornsberry et al, AAC 1999, 43:2612-2623; bBarry et al, AAC 1994, 38:2419-2425; cBarry & Fuchs, AAC 1995, 39:238-240; dGruneberg et al, DMID 1996, 25:169-181; e(Invasive isolates tested with erythromycin) Gay et al JID 2000, 182:1417-24; fDoern et al, AAC 1996, 40:1208-1213; g Thornsberry et al, DMID 1997, 29:249-257; hKarlowsky et al CID 2003, 36:963-70

Significant Increases in Penicillin-1-4 & Macrolide-Resistant S pneumoniae 3-6

Macrolide Resistance Is a Problem in the Community Setting

Streptococcus pneumoniae Isolates (20022003)
Community Surveillance In Vitro Data NW 23% NC 30% SW 20% SC 39% SE 33%

Penicillin-resistant 35 30 Macrolide-resistant

(MIC 2 mg/L)

Percentage

25 20 15 10 5 0 1979-87 1988-89 1990-91 1994-95 1997-98 19992000 20002001 20022003

NE 27%

1 Spika JS, et al. J Infect Dis. 1991;163:1273-1278. 2Jorgensen JH, et al. Antimicrob Agents Chemother. 1990;34:2075-2080. 3 Doern GV, et al. Antimicrob Agents Chemother. 2001;45:1721-1729. 4Doern GV, Brown SD. J Infect. 2004;48:56-65. 5Doern GV, et al. Antimicrob Agents Chemother. 1996;40:1208-1213. 6Doern GV, et al. Emerg Infect Dis. 1999;5:757-765.

National Macrolide Resistance Rate: 29%

PROTEKT US study report 20022003

Macrolide Resistance Is a Problem in the Southwest United States

Increased Quinolone Use and Decreased S. pneumo Susceptibility to Quinolones

Percentage of pneumococci isolates, by age group, US Nonsusceptible to ofloxacin (OFL), 19951997 Nonsusceptible to levofloxacin (LFX), 19981999 Fluoroquinolone prescriptions, by age group US, 19931998

Streptococcus pneumoniae Isolates (20022003)

Community Surveillance In Vitro Data

Southwest 20%

Arizona California Colorado Nevada New Mexico Utah

32% 18% 23% 17% 17% 16%

4 % 3 2 1 0
1995 1996 1997

OFL-Nonsusceptible Isolates: Persons <18 Y OFL-Nonsusceptible Isolates: Persons 18 Y LFX-Nonsusceptible Isolates: Persons 18 Y

12 10 8 Rate* 6 4 2 0
1864 Years <18 Years 1993 1994 1995 1996 1997 1998 65 Years

1998

1999

Year
*Per 100 persons

Year

National Macrolide Resistance Rate: 29%

PROTEKT US study report 20022003

Daily et al. MMWR. 2001;50(37):800-804

Streptococcus pneumoniae in US
FQ Prescriptions per 1000 people 6 Percent FQ - resistant 5 4 3 2 1 0 1988-89 1994-95 1997-98 1999-00 2001-02 2002-03
497 45 1527 30 1601 34 1531 33 1925 45 1974 44

Fluoroquinolone-resistant

Multidrug-Resistant S. pneumoniae Is Increasing Dramatically

14 12 10 8 6 4 2 0
1997-1998 (TRUST 2) 1998-1999 (TRUST 3) 1999-2000 (TRUST 4) 2000-2001 (TRUST 5) 2001-2002 (TRUST 6)
6.2 11.0 12.2 13.5 14.5

120 100 80 60 40 20

Isolates Centers

Percent of isolates

TRUST Studies (1997-2002)

Doern et al. ICAAC 2003

US Sensitivity/Resistance Rates of Common Antibiotics to S pneumoniae

Antibiotic
Telithromycin (Ketek) Moxifloxacin (Avelox) Levofloxacin (Levaquin) Amox/Clav (Augmentin) Erythromycin Clarithromycin (Biaxin) Azithromycin (Zithromax)

Factors That Decrease Resistance

% Sensitive (NCCLS)
100 98.2 97.1 89.6 70 70 70

Vaccines, especially pneumococcal (Prevnar)

Has rapidly resulted in a shift away from S. pneumo to H. Influenzae in selected populations, diseases AAP, IDSA, ATS, WHO, etc.

Adhering to treatment guidelines

High dose, short-course antibiotic therapies Appropriate-spectrum antibiotics without collateral damage

NCCLS now is known as the National Clinical and Laboratories Standards Institute

Other Patient Risk Factors That Increase the Prevalence of Resistance

Time of previous antibiotic use and PCN-NS S. pneumo bacteremia

Antibiotic use -Lactams 1 month 6 months Sulfonamides 1 month 6 months Macrolides 1 month 6 months OR (95% CI) 3.34 (1.76-6.36) 6.44 (3.80-10.94) 2.66 (1.31-5.38) 1.99 (1.06-3.73) 3.25 (1.39-7.61) 4.16 (2.16-7.98) P value <0.001 <0.001 0.005 0.029 0.005 <0.001

Age Recent exposure to antibiotics Exposure to Day Care Immunologic status Socioeconomic status Local geographic factors Recent hospitalization
Wise R. A review of the mechanisms of action and resistance of antimicrobial agents. Can Respir J 1999;6(SupplA):A20-2.

Rube & Hasbun; Clin Inf Dis 2003; 36: 1132-8

Percent erythromycin resistant

Identification of patients at low risk for high-level S. pneumo bacteremia

Relative risk of infection with macrolide resistant pneumococci, by prior antibiotic use, TIBDN
40 35 30 25 20 15 10 5 0 Unknown No prior AB Prior AB - Prior AB Prior ? not MAC Macrolide

Cross sectional study of 303 adults/children with S. pneumo bacteremia 33 PNSP; 270 PS or PISP Risk factors for PNSP:

RTI in previous 12 mo - OR 5.0 (1.6-15.6) -lactam in previous 6 mo - OR 10.9 (2.4-49.9) Stay in high risk area OR 5.8 (1.8-19.3)

> 1 Risk factor - PPV 21%; NPV 99% for PNSP bacteremia
Ruhe et al; Clin Inf Dis 2004; 38: 508-14

Vanderkooi et al; Clin Inf Dis 2005; 40: 1288-97

Rate of macrolide resistance in infecting pneumococcal isolate, by prior macrolide use

Rate of macrolide resistance in infecting isolates 60 50 40 30 20 10 0 No macrolide Erythro Biaxin Zithromax

Relative risk of infection with FQ resistant pneumococci, by prior antibiotic use, TIBDN
Percent ciprofloxacin resistant 20 18 16 14 12 10 8 6 4 2 0 Unknown No prior AB Prior AB - Prior AB ? not FQ Prior FQ

P=.01 P=.03 P=.33

Vanderkooi et al; Clin Inf Dis 2005; 40: 1288-97

Vanderkooi et al; Clin Inf Dis 2005; 40: 1288-97

FQ resistance in pneumococci, TIBDN by risk factor

25 Percent resistant 20 15 10 5 0 Community, No FQ Community, prior FQ Nursing home, Nursing home, no FQ prior FQ Levoflox Gatiflox Moxiflox

Relative Risk for Developing Macrolide Resistance

Relative risk (95% CL)
Year of infection Prior penicillin Prior TMP-SMX Prior clarithromycin Prior azithromycin 1.1 (1.0, 1.2) 2.0 (1.2, 3.2) 2.2 (1.1, 4.3) 3.8 (2.1,6.9) 11 (5.2, 22)

P value
.002 .006 .02 <.001 <.001

Vanderkooi et al; Clin Inf Dis 2005; 40: 1288-97

Vanderkooi et al; Clin Inf Dis 2005; 40: 1288-97

Impact of Drug Resistant Pathogens

Clinical Relevance of Resistance

Inappropriate therapy with worse outcomes Treatment failures: Outpatient failure commonly results in inpatient treatment Inpatient failure results in prolonged hospitalization

Increased difficulty with placement in extended care facilities Need for isolation precautions with a negatively impacted quality of patient care

Increased costs Increased mortality Defensive medicine

Increased mortality with S pneumoniae with penicillin MICs >2.0 g/mL or >4.0 g/mL and a statistically significant increase in complications13 High likelihood of failure to prevent S pneumoniae bacteremia with macrolide therapy for CAP caused by macrolide-resistant strains46
1. Feikin DR, et al. Am J Public Health. 2000;90:223229. 2. Metlay JP, et al. Clin Infect Dis. 2000;30:520527. 3. Klepser ME, et al. Pharmacotherapy. 2003;23:349359. 4. Kelley MA, et al. Clin Infect Dis. 2000;31:10081011. 5. Lonks JR, et al. 2002;35:556564. 6. Iannini PB, et al. Presented at: Infectious Diseases Society of America 2004 Annual Meeting. September 30 October 3, 2004, Boston, Ma.

Prescriber Practices Contributing to Antibiotic Resistance

Prescribing antibacterial drugs to treat likely viral infections Using improper diagnostic criteria in clinical decision making for infections that likely have viral etiologies Providing broad-spectrum agents when narrowspectrum agents are most suitable Prescribing antibiotics at improper doses or for improper durations

Mechanisms of Antibiotic Resistance

Acquired Resistance Is a Function Of

Intrinsic resistance Acquired resistance

Alterations/mutation of the microorganism as a result of:

Antibiotic modifying enzymes (e.g., penicillin resistance in S aureus) Target site alterations (e.g., methicillin resistance in S Aureus) Permeability barriers (e.g., vancomycin tolerance in VISA) Efflux pumps (e.g., erythromycin resistance in S pneumoniae)

overuse? not completing antibiotic course? incorrect antibiotic choice? organisms genetic adaptability?

Requirements: a host, a microorganism, and exposure to an antimicrobial agent

Ideal Goals of Empiric Therapy

What Is Meant by Tailored Coverage?

Treat bacterial infections only Tailor the spectrum of coverage to likely pathogens Do not over-treat with shotgun therapies Prevent emergence of resistant organisms

Comprehensive coverage of respiratory pathogens1,2

Use of very broad spectrum antibiotics is causing development of resistant gram-negative enteric pathogens1,3

Typical respiratory pathogens Resistant respiratory strains Atypical pathogens

Collateral damage

Pseudomonas aeruginosa Proteus mirabilis Escherichia coli

1 3

Doern GV, Brown SD. J Infect. 2004;48:56-65; 2Johnson DM, et al. Diagn Microbiol Infect Dis. 2003;47:373-376; Ball P, et al. J Antimicrob Chemother. 2002;49:31-40.

Evaluation of Acute Cough

Cough < 3 weeks duration VS abnormality? Yes Yes No

Diagnosis of Pneumonia by History and Physical Exam

Lack of
Abnormal VS (HR > 100 b/min, RR > 24 b/min, oral temp > 38o C) Abnormal chest exam (consolidation)

No CXR Abnormal Pneumonia

Is influenza likely? Yes Normal AECB

PE abnormality? No

Yes

High risk

No Acute Bronchitis

makes

pneumonia unlikely

Elderly Immunosuppressed

Adapted from Gonzales R, Sande MA. Ann Int Med. 2000;133:981-991. Martinez, Comp Ther (in review)

Metlay et al. JAMA. 1997;278: 1440-5.

Bronchitis: Acute vs Chronic

Acute Cough is a predominant feature <3 weeks Usually viral in origin Antibiotics not recommended Chronic Persists for > 3 months each year for at least 2 years Acute exacerbations Increased dyspnea Increased sputum volume Increased sputum purulence

Azithromycin for Acute Bronchitis

Randomized trial of azithromycin vs Vitamin C Mean age ~45 yrs ~55% were ever smokers Trial stopped after 220 patients as there was no difference noted in any outcome
Evans AT, et al. Lancet. 2002;359:1648-1654.

Meta-analysis of trials with proportion of patients returning to usual activities

Ref Year 8 1984 11 1984 9 1987 10 1994 This study

*
-0.5 -0.3 -0.1 0 0.1 0.3
*DL pooled risk difference= -0.0167 (95% CI = -0.0591 to 0.0256)

Snow V, et al. Ann Intern Med. 2001;134:518-520.

Meta-Analysis of the Benefits of Antibiotics in AECB

Favors Placebo
Elmes, et al. 1957 Berry, et al. 1960 Fear, Edwards. 1962 Elmes, et al. 1965 Petersen, et al. 1967 Pines, et al. 1972 Nicotra, et al. 1982 Anthonisen, et al. 1987 Jorgensen, et al. 1992 Overall 1.0
Saint S, et al. JAMA. 1995;274:1131-1132.

Recent Guideline Recommendations for Antibiotic Therapy in AECOPD1-4

Favors Antibiotic

CTS: "antibiotics should only be considered for use in patients with purulent exacerbations1 GOLD: "Antibiotics are only effectivewith worsening dyspnea and cough also have increased sputum volume and purulence2 ATS/ERS: "May be initiated in patients with altered sputum characteristics3 NICE: "Antibiotics should be used to treat exacerbations of COPD associated with a history of more purulent sputum4

0.5

0.5

1.0

1.5
1 Balter, et al. Can Respir J. 2003;10(suppl B):3B-32B; 2Global Initiative for Chronic Obstructive Lung Disease. Executive Summary 2004; 3Celli BR, et al. Eur Respir J. 2004;23:932-946; 4National Institute for Clinical Excellence. Clinical Guideline 12, February 2004.

Effect Size

Duration of Symptoms in Rhinovirus Upper Respiratory Tract Infections (URTIs)

% of Patients With Symptoms 70 60 50 40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Day of Illness ABS diagnosis may be made in a patient with a viral URTI that is not better after 10d or worsens after 57d and is accompanied by associated symptoms.
Adapted from SAHP. Otolaryngol Head Neck Surg. 2004;130:1-45 and Gwaltney JM. JAMA. 1967;202:158-164.

Nasal Discharge Cough

Sore Throat Fever Worsening of symptoms at 57d in pts with ABS complicating a viral URTI

Significance of Rhinovirus Infection in Rhinosinusitis

Seasonal prevalence of ABRS correlates with common cold 0.5%2% of common colds complicated by ABRS infection 87% of patients with viral respiratory infections (common colds) have sinus cavity inflammation
Gwaltney et al. N Engl J Med 1994;330:2530. Pitkaranta et al. J Clin Microbiol 1997;35:17913.

Viral URI

Viral URI Resolved

Gwaltney. Clin Infect Dis 1996;23:120925. Osguthorpe et al. Med Clin North Am 1999;83:2741.

Management of ABRS
Discolored nasal drainage, nasal congestion, facial pain (viz. upper teeth pain)
Sx worsening after 4 days, Sx persisting > 7 days (adults), > 10 days (children) YES NO Probably viral and no antibiotic is warranted. Rx decongestants, rest, hydration call if symptoms worsen or if persists > 10 days

Symptoms worsening after 4 days, persistence of major symptom 10d, or symptoms out of proportion to typical VRI

Presumptive Diagnosis of ABRS

Prior antibiotic recently YES NO

Switch class from prior antibiotic and consider: High dose amox/clav Moxifloxacin Consider ENT referral for endoscopic culture NO

Can afford to wait 48 hours to switch therapy because of impending complication, comorbidity

YES

Amoxicillin High potency cephalosporin: cefdinir, cefpodoxime, cefuroxime Clarithyromycin Doxycycline TMP/SMX Telithromycin

Major Factors Discolored Nasal / Post-nasal drainage Nasal obstruction / congestion Facial pain / pressure Cough not due to asthma (in children) Hyposmia / anosmia

Minor Factors Fever Cough Fatigue Maxillary dental pain Ear fullness/pressure Headache

Adapted from SAHP. Oto HNS 2004.

Adapted from Lanza DC et al. Otolaryngol Head Neck Surg. 1997;117(suppl):S1-S7. SAHP. Otolaryngol Head Neck Surg. 2004;130:1-45.

Our Antimicrobial World Is Changing Rapidly

Why Consider Collateral Damage?

Collateral damage refers to the ecological adverse effects of antibiotic therapy and includes1
Selection of non-respiratory drug-resistant organisms Unwanted development of colonization or infection with multidrug-resistant organisms

Antibiotic resistance is common Only prescribe antibiotic therapy when appropriate Use a antibiotic targeted to likely pathogensand nothing else! New treatment options should minimize resistant pathogens

Broad-spectrum antibiotics may cause development of resistance in key enteric gram-negative pathogens Development of resistance in other pathogens limits available treatment options A tailored-spectrum antibiotic in the treatment of RTIs may help prevent collateral damage
1 Paterson DL. Clin Infect Dis. 2004;38(suppl 4):S341-S345.

Tailored Coverage

1 Barman Balfour JA, Figgitt DP. Drugs. 2001;61:815-829; 2Lonks JR, et al. Clin Infect Dis. 2002; 35:556-564; 3Gleason PP. Pharmacotherapy. 2002;22:2s-11s; 4Neuhauser MM, et al. JAMA. 2003;289:885-888.

Why Choose an Antibiotic With a Tailored Spectrum?

The First Ketolide

The majority of RTIs are caused by three major pathogens: S pneumoniae, H influenzae, and M These major pathogens exhibit high antibiotic resistance levels; these levels are increasing Atypical pathogens have a significant mortality burden, especially in CAP Use of very broad spectrum antibiotics selects for resistance among non-respiratory bacteria, resulting in collateral damage

Telithromycin has an innovative molecular design

catarrhalis

Tailored coverage of common pathogens involved in AECB, ABRS, and mild to moderate CAP without collateral enteric gram-negative damage Low potential to induce macrolide type (ermB) resistance in vitro Rapid bactericidal activity against S pneumoniae in vitro Worldwide patient experience with more than 10 million prescriptions Convenient once-daily dosing

Ketolides: Overcome Macrolide Type ermB Resistance

Macrolide

Algorithm for Managing Patients with Bronchitis vs AECB

Acute bronchitis patient
No

CH3
Ribosome Domain II Domain V

Macrolide affinity for domain V is lost by methylation

Chronic bronchitis?
Yes

No antibiotics necessary
Uncomplicated

Disease severity?*

Complicated

Telithromycin

Active smoker?
CH3
Telithromycin maintains binding to domain V despite methylation

At risk for pseudomonas?

No Respiratory fluoroquinolones Amoxicillin/ clavulanate Yes Ciprofloxacin or levofloxacin based on sputum culture

Telithromycin maintains high affinity for domain II

Ribosome Domain II

No Macrolides Cephalosporins Ketolides Doxycycline

Yes Advanced generation macrolides Ketolides Respiratory fluoroquinolones

Domain V

*If antibiotic in previous 3 months, change class

Waites K, et al. J Clin Microbiol. 2000;38:1731-1734.

Martinez FJ. J Clin Outcomes Med. 2004;11:659-673.

Current N. American Treatment Guidelines for Outpatient CAP

Uncomplicated
Macrolide Recent ABX Doxycycline

Proposed N. American Treatment Guidelines for Outpatient CAP

(CDC/ATS/IDSA 2005)

Complicated
Macrolide Fluoroquinolone

Uncomplicated

Risk Factors or Recent Antibiotic Macrolide + -lactam Telithromycin Fluoroquinolone

Recent ABX

Macrolide + Amox Macrolide + -lactam Macrolide + Amox/Clav Fluoroquinolone Fluoroquinolone

Macrolide Doxycycline

1. Heffelfinger JD et al. Arch Intern Med. 2000;160:1399. 3. Niederman MS et al. Am J Respir Crit Care Med. 2001;163:1730.

2. Bartlett JG et al. Clin Infect Dis. 2000;31:347-82. 4. Mandell LA et al. Clin Infect Dis. 2003; 37:1405.

1. Heffelfinger JD et al. Arch Intern Med. 2000;160:1399. 3. Niederman MS et al. Am J Respir Crit Care Med. 2001;163:1730.

2. Bartlett JG et al. Clin Infect Dis. 2000;31:347-82. 4. Mandell LA et al. Clin Infect Dis. 2003; 37:1405.

In Vitro Quinolone Activity: S pneumoniae

AUC0-24 (gh/mL) 0.03 gemifloxacin 0.25 moxifloxacin 0.5 gatifloxacin 1.0 levofloxacin

Case Study

9.9 48.0 34.4 47.5

0.0

8882 Isolates

0.2

0.4

0.6
MIC 90 (g/mL)

0.8

1.0

1.2

Increasing Potency AUC0-24/MIC90: gemifloxacin=330; moxifloxacin=192; gatifloxacin=69; levofloxacin=48. AUC data from manufacturers product prescribing information.
Jacobs MR, et al. J Antimicrob Chemother 2003;52:229-246.

62-year-old man with a longstanding history of Class II COPD He presents with a complaint of just feeling bad He is usually managed on tiotropium bromide (Spiriva) q.d. and salmeterol (Serevent) b.i.d. PMhX is significant for dyslipidemia (rosouvastatin [Crestor] 10 mg q.d.) and HTN (lisinopril [Zestril] 10 mg q.d.)

62-yo With COPD

62-yo With COPD

Yesterday he began his usual routine of going out for newspaper, breakfast, coffee, but upon returning home he had to sit and rest for an extended period of time to catch his breath As the day progressed, he felt increasingly fatigued, and his daily cough worsened and developed an increased sputum Otherwise, he says everything is fine and specifically denies other symptoms when questioned

On PE he appears older than his stated age, sitting on exam table in NAD but fatigued; 5 6, 140 lbs. V/S: Temp 100.2o F oral, P 104, RR 24, 140/96 mmHg, SaO2 92% RA Cardiac: Tachy, + S1/S2, RRR, M/G/R, S3/S4 Pulm: Diminished BS bilat, scant upper airway rhonchi GI: Benign Ext: Pale, hair growth, cool, DP +1 B/L, edema

10

62-yo With COPD

Antibiotic Stewardship: Tailored Antibiotic Selections

Dx: AECB Common RX Choices:

Amoxicillin-Clavulanate misses atypical pathogens Azithromycin high resistance rate Levofloxacin broad spectrum with significant collateral damage Telithromycin tailored spectrum providing appropriate empiric coverage

Prevent or at least slow the emergence of antimicrobial resistance Optimize selection, duration, and dose of antibiotic selections Reduce mortality and morbidity Reduce length of stay/time off from ADLs Reduce global healthcare expenditures Reduce adverse drug events

Key Interventions for Antibiotic Use

Use evidence-based medicine

Dont treat non-bacterial infections or noninfectious diseases with antibiotics Dont prolong duration beyond what is needed Avoid prophylactic antibiotics unless the benefit has been demonstrated When given the choice, opt for bactericidal not bacteristatic antibiotics Use the narrowest spectrum agent available

11