Comparison of 8 vs 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults: A Randomized Trial | Critical Care Medicine | JAMA | JAMA Network
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1.
 National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1990-May 1999, issued June 1999.  Am J Infect Control.1999;27:520-532.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10586157&dopt=AbstractGoogle Scholar
2.
Fridkin SK, Steward CD, Edwards JR.  et al.  Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2: Project Intensive Care Antimicrobial Resistance Epidemiology (ICARE) hospitals.  Clin Infect Dis.1999;29:245-252.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10476720&dopt=AbstractGoogle Scholar
3.
Kollef MH, Fraser VJ. Antibiotic resistance in the intensive care unit.  Ann Intern Med.2001;134:298-314.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11182841&dopt=AbstractGoogle Scholar
4.
Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use.  JAMA.2003;289:885-888.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12588273&dopt=AbstractGoogle Scholar
5.
Neu HC. The crisis in antibiotic resistance.  Science.1992;257:1064-1073.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1509257&dopt=AbstractGoogle Scholar
6.
Landman D, Quale JM, Mayorga D.  et al.  Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned.  Arch Intern Med.2002;162:1515-1520.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12090889&dopt=AbstractGoogle Scholar
7.
Mahgoub S, Ahmed J, Glatt AE. Completely resistant Acinetobacter baumannii strains.  Infect Control Hosp Epidemiol.2002;23:477-479.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12186218&dopt=AbstractGoogle Scholar
8.
 Staphylococcus aureus resistant to vancomycin — United States, 2002.  MMWR Morb Mortal Weekly Rep.2002;51:565-567.Google Scholar
9.
Goldmann DA, Weinstein RA, Wenzel RP.  et al.  Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals: a challenge to hospital leadership.  JAMA.1996;275:234-240.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8604178&dopt=AbstractGoogle Scholar
10.
Shlaes DM, Gerding DN, John Jr JF.  et al.  Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.  Clin Infect Dis.1997;25:584-599.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9314444&dopt=AbstractGoogle Scholar
11.
Lipsitch M, Bergstrom CT, Levin BR. The epidemiology of antibiotic resistance in hospitals: paradoxes and prescriptions.  Proc Natl Acad Sci U S A.2000;97:1938-1943.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10677558&dopt=AbstractGoogle Scholar
12.
Lawton RM, Fridkin SK, Gaynes RP, McGowan Jr JE. Practices to improve antimicrobial use at 47 US hospitals: the status of the 1997 SHEA/IDSA position paper recommendations: Society for Healthcare Epidemiology of America/Infectious Diseases Society of America.  Infect Control Hosp Epidemiol.2000;21:256-259.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10782587&dopt=AbstractGoogle Scholar
13.
Fagon JY, Chastre J, Vuagnat A, Trouillet JL, Novara A, Gibert C. Nosocomial pneumonia and mortality among patients in intensive care units.  JAMA.1996;275:866-869.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8596225&dopt=AbstractGoogle Scholar
14.
Vincent JL, Bihari DJ, Suter PM.  et al.  The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study.  JAMA.1995;274:639-644.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7637145&dopt=AbstractGoogle Scholar
15.
Bergmans DC, Bonten MJ, Gaillard CA.  et al.  Indications for antibiotic use in ICU patients: a one-year prospective surveillance.  J Antimicrob Chemother.1997;39:527-535.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9145828&dopt=AbstractGoogle Scholar
16.
 Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies: a consensus statement, American Thoracic Society, November 1995.  Am J Respir Crit Care Med.1996;153:1711-1725.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8630626&dopt=AbstractGoogle Scholar
17.
Chastre J, Fagon JY. Ventilator-associated pneumonia.  Am J Respir Crit Care Med.2002;165:867-903.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11934711&dopt=AbstractGoogle Scholar
18.
Fink MP, Snydman DR, Niederman MS.  et al.  Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin.  Antimicrob Agents Chemother.1994;38:547-557.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8203853&dopt=AbstractGoogle Scholar
19.
Rello J, Mariscal D, March F.  et al.  Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: relapse or reinfection?  Am J Respir Crit Care Med.1998;157:912-916.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9517611&dopt=AbstractGoogle Scholar
20.
Pingleton SK, Fagon JY, Leeper Jr KV. Patient selection for clinical investigation of ventilator-associated pneumonia: criteria for evaluating diagnostic techniques.  Chest.1992;102(suppl 5):553S-556S.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1424929&dopt=AbstractGoogle Scholar
21.
Wunderink RG, Mayhall CG, Gibert C. Methodology for clinical investigation of ventilator-associated pneumonia: epidemiology and therapeutic intervention.  Chest.1992;102(suppl 1):580S-588S.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1424933&dopt=AbstractGoogle Scholar
22.
Chastre J, Fagon JY, Bornet-Lecso M.  et al.  Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia.  Am J Respir Crit Care Med.1995;152:231-240.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7599829&dopt=AbstractGoogle Scholar
23.
Baselski VS, Wunderink RG. Bronchoscopic diagnosis of pneumonia.  Clin Microbiol Rev.1994;7:533-558.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7834604&dopt=AbstractGoogle Scholar
24.
Ibrahim EH, Ward S, Sherman G, Schaiff R, Fraser VJ, Kollef MH. Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.  Crit Care Med.2001;29:1109-1115.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11395584&dopt=AbstractGoogle Scholar
25.
Trouillet JL, Chastre J, Vuagnat A.  et al.  Ventilator-associated pneumonia caused by potentially drug-resistant bacteria.  Am J Respir Crit Care Med.1998;157:531-539.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9476869&dopt=AbstractGoogle Scholar
26.
McCabe WR, Jackson GJ. Gram-negative bacteremia, 1: etiology and ecology.  Arch Intern Med.1962;110:847-864.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6987871&dopt=AbstractGoogle Scholar
27.
Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study.  JAMA.1993;270:2957-2963.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8254858&dopt=AbstractGoogle Scholar
28.
Vincent JL, Moreno R, Takala J.  et al. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure.  Intensive Care Med.1996;22:707-710.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8844239&dopt=AbstractGoogle Scholar
29.
Fagon JY, Chastre J, Novara A, Medioni P, Gibert C. Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model.  Intensive Care Med.1993;19:137-144.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8315120&dopt=AbstractGoogle Scholar
30.
Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure.  Chest.1992;101:1481-1483.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1600757&dopt=AbstractGoogle Scholar
31.
Bernard GR, Artigas A, Brigham KL.  et al. The American–European Consensus Conference on ARDS.  Definitions, mechanisms, relevant outcomes, and clinical trial coordination.  Am J Respir Crit Care Med.1994;149:818-824.Google Scholar
32.
Fagon JY, Chastre J, Wolff M.  et al.  Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia: a randomized trial.  Ann Intern Med.2000;132:621-630.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10766680&dopt=AbstractGoogle Scholar
33.
Durrleman S, Simon R. Planning and monitoring of equivalence studies.  Biometrics.1990;46:329-336.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2194579&dopt=AbstractGoogle Scholar
34.
Jennison C, Turnbull BW. Repeated confidence intervals for group sequential clinical trials.  Control Clin Trials.1984;5:33-45.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6713906&dopt=AbstractGoogle Scholar
35.
Fleming TR, Harrington DP, O'Brien PC. Designs for group sequential tests.  Control Clin Trials.1984;5:348-361.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6518769&dopt=AbstractGoogle Scholar
36.
Gail M, Simon R. Testing for qualitative interactions between treatment effects and patient subsets.  Biometrics.1985;41:361-372.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4027319&dopt=AbstractGoogle Scholar
37.
Lepper PM, Grusa E, Reichl H, Hogel J, Trautmann M. Consumption of imipenem correlates with beta-lactam resistance in Pseudomonas aeruginosa Antimicrob Agents Chemother.2002;46:2920-2925.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183248&dopt=AbstractGoogle Scholar
38.
Meyer KS, Urban C, Eagan JA, Berger BJ, Rahal JJ. Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins.  Ann Intern Med.1993;119:353-358.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8135915&dopt=AbstractGoogle Scholar
39.
Combes A, Figliolini C, Trouillet JL.  et al.  Factors predicting ventilator-associated pneumonia recurrence.  Crit Care Med.2003;31:1102-1107.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12682479&dopt=AbstractGoogle Scholar
40.
Dennesen PJ, van Der VA, Kessels AG, Ramsay G, Bonten MJ. Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia.  Am J Respir Crit Care Med.2001;163:1371-1375.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11371403&dopt=AbstractGoogle Scholar
41.
Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit: a proposed solution for indiscriminate antibiotic prescription.  Am J Respir Crit Care Med.2000;162:505-511.http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10934078&dopt=AbstractGoogle Scholar
Caring for the Critically Ill Patient
November 19, 2003

Comparison of 8 vs 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults: A Randomized Trial

Author Affiliations

Author Affiliations: Service de RÉanimation MÉdicale, Hôpital PitiÉ-Salpêtrière, AP-HP (Dr Chastre), Service de RÉanimation MÉdicale, Hôpital Bichat-Claude-Bernard, AP-HP (Dr Wolff), Service de RÉanimation MÉdicale, Hôpital EuropÉen Georges-Pompidou, AP-HP (Dr Fagon), DÉpartement de Biostatistique et Informatique MÉdicale, Hôpital Saint-Louis, AP-HP (Dr Chevret), and Service de RÉanimation, Hôpital des Diaconesses, Paris (Dr Thomas); Service de RÉanimation MÉdicale, Hôpital Kremlin-Bicêtre, AP-HP, Le Kremlin-Bicêtre (Dr Wermert); Service de RÉanimation, Hôpital Les Audaries, La-Roche-sur-Yon (Dr Clementi); Service de RÉanimation MÉdicale, Hôpital Raymond-PoincarÉ, AP-HP, Garches (Dr Gonzalez); DÉpartement d'AnesthÉsie et de RÉanimation, CHU de Rouen, Rouen (Dr Jusserand); Service de RÉanimation MÉdicale, CHU d'Angers, Angers (Dr Asfar); Service de RÉanimation, Hôpital Courcouronne, Évry (Dr Perrin); Service de RÉanimation MÉdicale, Hôpital Saint-Louis, AP-HP, Paris (Dr Fieux); and DÉpartement d'AnesthÉsie et de RÉanimation, CHU de Montpellier, Montpellier (Dr Aubas), France.

 

Caring for the Critically Ill Patient Section Editor: Deborah J. Cook, MD, Consulting Editor, JAMA.

JAMA. 2003;290(19):2588-2598. doi:10.1001/jama.290.19.2588
Abstract

Context The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU).

Objective To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP.

Design, Setting, and Participants Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002.

Intervention A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician.

Main Outcome Measures Primary outcome measures—death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days—were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis.

Results Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], −3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, −3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation–free days, the number of organ failure–free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P = .04).

Conclusions Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.

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