{beta} lactam monotherapy versus {beta} lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

doi:10.1136/bmj.38028.520995.63

BMJ, doi: 10.1136/bmj.38028.520995.63, (Published 2 March 2004)

PAPERS

${beta}$ lactam monotherapy versus ${beta}$ lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

Mical Paul ¹, Ishay Benuri-Silbiger ², Karla Soares-Weiser ², Leonard Leibovici ²

¹ Department of Medicine E and Infectious Diseases Unit, Rabin Medical Centre, Beilinson Campus, Petah-Tikva 49100, Israel
² Department of Medicine E, Rabin Medical Centre, Beilinson Campus, Petah-Tikva

Objective To compare ${beta}$ lactam monotherapy with ${beta}$ lactam-aminoglycosidecombination therapy for severe infections.

Data sources Medline,Embase, Lilacs, Cochrane Library, and conference proceedings,to 2003; references of included studies; contact with all authors.No restrictions, such as language, year of publication, or publicationstatus.

Study selection All randomised trials of ${beta}$ lactam monotherapycompared with ${beta}$ lactam-aminoglycoside combination therapy forpatients without neutropenia who fulfilled criteria for sepsis.

Dataselection Two reviewers independently applied selection criteria,performed quality assessment, and extracted the data. The primaryoutcome assessed was all cause fatality by intention to treat.Relative risks were pooled with the random effect model (relativerisk <1 favours monotherapy).

Results 64 trials with 7586patients were included. There was no difference in all causefatality (relative risk 0.90, 95% confidence interval 0.77 to1.06). 12 studies compared the same ${beta}$ lactam (1.02, 0.76 to 1.38),and 31 studies compared different ${beta}$ lactams (0.85, 0.69 to 1.05).Clinical failure was more common with combination treatmentoverall (0.87, 0.78 to 0.97) and among studies comparing different ${beta}$ lactams (0.76, 0.68 to 0.86). There was no advantage to combinationtherapy among patients with Gram negative infections (1835 patients)or Pseudomonas aeruginosa infections (426 patients). There wasno difference in the rate of development of resistance. Nephrotoxicitywas significantly more common with combination therapy (0.36,0.28 to 0.47). Heterogeneity was not significant for these comparisons.

ConclusionsIn the treatment of sepsis the addition of an aminoglycosideto ${beta}$ lactams should be discouraged. Fatality remains unchanged,while the risk for adverse events is increased.

(Accepted 22 December 2003)

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

StumbleUpon Add to Technorati

Technorati What's this?

Relevant Article

Adding amynoglycoside to ${beta}$ lactam does not improve results
BMJ 2004 328: 0. [Full Text]

This article has been cited by other articles:

Leibovici, L., Vidal, L., Paul, M. (2009). Aminoglycoside drugs in clinical practice: an evidence-based approach--authors' response. J Antimicrob Chemother 63: 1082-1083 [Full text]
Williams, K. J. (2009). Why monotherapy?. J Antimicrob Chemother 63: i18-i20 [Abstract] [Full text]
Leibovici, L., Vidal, L., Paul, M. (2009). Aminoglycoside drugs in clinical practice: an evidence-based approach. J Antimicrob Chemother 63: 246-251 [Abstract] [Full text]
Cairns, B. J., Payne, R. J. H. (2008). Bacteriophage Therapy and the Mutant Selection Window. Antimicrob. Agents Chemother. 52: 4344-4350 [Abstract] [Full text]
Gupta, R., Wargo, K. A. (2008). An Update on the Management of Nosocomial Pneumonia. Journal of Pharmacy Practice 21: 380-389 [Abstract]
Masterton, R. G., Galloway, A., French, G., Street, M., Armstrong, J., Brown, E., Cleverley, J., Dilworth, P., Fry, C., Gascoigne, A. D., Knox, A., Nathwani, D., Spencer, R., Wilcox, M. (2008). Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 62: 5-34 [Abstract] [Full text]
Leibovici, L., Paul, M. (2007). Aminoglycoside/{beta}-lactam combinations in clinical practice. J Antimicrob Chemother 60: 911-912 [Abstract] [Full text]
Freundlich, M., Thomsen, R. W., Pedersen, L., West, H., Schonheyder, H. C. (2007). Aminoglycoside treatment and mortality after bacteraemia in patients given appropriate empirical therapy: a Danish hospital-based cohort study. J Antimicrob Chemother 60: 1115-1123 [Abstract] [Full text]
Vidal, L., Gafter-Gvili, A., Borok, S., Fraser, A., Leibovici, L., Paul, M. (2007). Efficacy and safety of aminoglycoside monotherapy: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 60: 247-257 [Abstract] [Full text]
Goldin, A. B., Sawin, R. S., Garrison, M. M., Zerr, D. M., Christakis, D. A. (2007). Aminoglycoside-Based Triple-Antibiotic Therapy Versus Monotherapy for Children With Ruptured Appendicitis. Pediatrics 119: 905-911 [Abstract] [Full text]
Beardsley, J. R., Williamson, J. C., Johnson, J. W., Ohl, C. A., Karchmer, T. B., Bowton, D. L. (2006). Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.. Chest 130: 787-793 [Abstract] [Full text]
Porzecanski, I., Bowton, D. L. (2006). Diagnosis and treatment of ventilator-associated pneumonia.. Chest 130: 597-604 [Abstract] [Full text]
Micek, S. T., Lloyd, A. E., Ritchie, D. J., Reichley, R. M., Fraser, V. J., Kollef, M. H. (2005). Pseudomonas aeruginosa Bloodstream Infection: Importance of Appropriate Initial Antimicrobial Treatment. Antimicrob. Agents Chemother. 49: 1306-1311 [Abstract] [Full text]

Rapid Responses:

Read all Rapid Responses

Neutropenic or not?: Robert Townsend
bmj.com, 19 Mar 2004 [Full text]
Re: Neutropenic or not?: Mical Paul, et al.
bmj.com, 22 Mar 2004 [Full text]
severe sepsis versus patients at lower risk of death?: Joseph C Watine
bmj.com, 23 Mar 2004 [Full text]
Are children, sometimes, little adults as well ?: Jean-francois Hartmann
bmj.com, 24 Mar 2004 [Full text]
Beta-lactam and aminoglycoside combination therapy. The role of different aminoglycoside dosing regimens.: Peter A Riley
bmj.com, 25 Mar 2004 [Full text]
A case for antibiotic combination therapy against pseudomonas infection remains: RICHARD P COOKE, et al.
bmj.com, 2 Apr 2004 [Full text]
Beta-lactam/aminoglycoside combination therapy should still be considered for patients with severe sepsis: Gavin D Barlow
bmj.com, 7 Apr 2004 [Full text]
Beta-lactam/ aminoglycoside combination therapy in severe P. aeruginosa infections?: Bart J.M. Vlaminckx, et al.
bmj.com, 22 Apr 2004 [Full text]
Use of aminoglycosides with beta-lactams: Christopher D Settle
bmj.com, 23 Apr 2004 [Full text]
Simplistic and inaccurate about anitbiotics: Gunnar S Simonsen, et al.
bmj.com, 28 Jun 2004 [Full text]
Is combination therapy with betalactam plus aminoglycoside (AGL) improving the outcome of nosocomial meningitis in children? (letter): Vladimir Krcmery, et al.
bmj.com, 1 Apr 2005 [Full text]