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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials

IA Bliziotis, G Samonis, KZ Vardakas, S Chrysanthopoulou, and ME Falagas.

Review published: 2005.

Link to full article: [Journal publisher]

CRD summary

This review evaluated the effect of adding an aminoglycoside to β-lactam therapy on development of antimicrobial resistance among hospitalised, non-neutropenic patients with serious infections. The authors concluded that there was no protective effect for combination therapy. Limitations around the generalisability of this evidence and the robustness of the analysis mean these conclusions may not be entirely reliable.

Authors' objectives

To determine whether addition of an aminoglycoside to a β-lactam therapy regimen has an effect on the development of antimicrobial resistance among hospitalised, non-neutropenic patients with serious infections.

Searching

PubMed, Current Contents and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant English-language studies published after 1 January 1980. Search terms were reported, but the end date for searches was not. Reference lists of retrieved studies and review articles were examined to identify further relevant papers.

Study selection

Randomised controlled trials (RCTs) that compared β-lactam monotherapy with the combination of an aminoglycoside and a β-lactam for treatment of hospitalised adults were eligible for inclusion in the review. Eligible studies had to report emergence of resistance of bacterial isolates, effectiveness of therapy and mortality rate. Studies of patients with neutropenia and cystic fibrosis were excluded.

Patients in included trials had a range of serious infections, which included pneumonia, sepsis, peritonitis and cholangitis. β-lactam therapy agents included ceftazidime, imipenem, cefoperazone, imipenem/cilastatin, mezlocillin, piperacillin, ceftriaxone, cefotaxime, ampicillin, cefazolin, ticarcillin and carboxypenicillin. Aminoglycosides included gentamicin, netilmicin and tobramycin.

Two reviewers independently selected studies for inclusion in the review.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

For the primary outcome of emergence of antimicrobial resistance, data were extracted on the proportion of patients in whom bacterial isolates became resistant to drugs administered to them during treatment or follow-up. Data were extracted on rates of superinfection, treatment failure (all-cause, due to emergence of resistance and due to superinfection) and mortality (all-cause and due to infection).

Two reviewers independently extracted data from the included studies. Any disagreements resolved by consensus.

Methods of synthesis

Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using Mantel-Haenszel fixed-effect and DerSimonian and Laird random-effects models. Statistical heterogeneity was assessed using the Χ2 test. Publication bias was assessed using Egger's test. Results of the random-effects model were presented in the presence of statistical heterogeneity; otherwise, results of the fixed-effects model were reported.

Results of the review

Eight RCTs (1,394 clinically evaluable patients) were included in the review.

No statistically significant differences were found between β-lactam monotherapy and aminoglycoside/β-lactam combination therapy in terms of emergence of antimicrobial resistance, treatment failure due to resistance, all-cause mortality or mortality due to infection.

Treatment with monotherapy was associated with a statistically significant lower number of superinfections than combination therapy (OR 0.62, 95% CI 0.42 to 0.93).

Authors' conclusions

Compared to β-lactam monotherapy, the aminoglycoside/β-lactam combination was not associated with a beneficial effect on development of antimicrobial resistance among initially antimicrobial-susceptible isolates.

CRD commentary

The review question was clearly defined in terms of the participants, interventions, comparators, outcomes and study designs of interest. Attempts were made to minimise bias and errors in selection and extraction of data from studies. Multiple sources were searched to identify relevant studies, but search dates were not reported. All of the included studies were published prior to 1996. The included studies were clinically heterogeneous in terms of treatment regimens and this appeared to be reflected in some of the outcome estimates; no information on statistical heterogeneity was reported. Around 25% of patients were not microbiologically evaluable for the primary outcome, but the authors did not explore the impact of this loss to follow-up on outcomes. The authors' conclusions appeared to follow from the evidence presented, although limitations around the generalisability of this evidence and the robustness of the analysis mean these conclusions may not be entirely reliable.

Implications of the review for practice and research

The authors did not state any implications for practice or research.

Funding

Not stated.

Bibliographic details

Bliziotis IA, Samonis G, Vardakas KZ, Chrysanthopoulou S, Falagas ME. Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials. Clinical Infectious Diseases 2005; 41(2): 149-158. [PubMed: 15983909]

Indexing Status

Subject indexing assigned by NLM

MeSH

Aminoglycosides /administration & dosage /pharmacology; Anti-Bacterial Agents /administration & dosage /pharmacology; Bacterial Infections /drug therapy /mortality; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Superinfection; Treatment Failure; beta-Lactams /administration & dosage /pharmacology

AccessionNumber

12005000911

Database entry date

31/03/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 15983909

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