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Impact of definitive therapy with beta-lactam monotherapy or combination with an aminoglycoside or a quinolone for Pseudomonas aeruginosa bacteremia.

ABSTRACT: BACKGROUND: Bacteremia by Pseudomonas aeruginosa represents one severe infection. It is not clear whether beta-lactam monotherapy leads to similar rates of treatment success compared to combinations of beta-lactams with aminoglycosides or quinolones. METHODS: Retrospective cohort study from 3 tertiary hospitals (2 in Greece and 1 in Italy). Pseudomonas aeruginosa isolates were susceptible to a beta-lactam and an aminoglycoside or a quinolone. Patients received appropriate therapy for at least 48 hours. Primary outcome of interest was treatment success in patients with definitive beta-lactam combination therapy compared to monotherapy. Secondary outcomes were treatment success keeping the same empirical and definitive regimen, mortality, and toxicity. RESULTS: Out of 92 bacteremias there were 54 evaluable episodes for the primary outcome (20 received monotherapy). Treatment success was higher with combination therapy (85%) compared to beta-lactam monotherapy (65%), however not statistically significantly [Odds ratio (OR) 3.1; 95% Confidence Interval (CI) 0.69-14.7, p = 0.1]. Very long (>2 months) hospitalisation before bacteremia was the only factor independently associated with treatment success (OR 0.73; 95% CI 0.01-0.95, p = 0.046), however this result entailed few episodes. All-cause mortality did not differ significantly between combination therapy [6/31 (19%)] and monotherapy [8/19 (42%)], p = 0.11. Only Charlson comorbidity index was associated with excess mortality (p = 0.03). CONCLUSION: Our study, in accordance with previous ones, indicates that the choice between monotherapy and combination therapy may not affect treatment success significantly. However, our study does not have statistical power to identify small or moderate differences. A large randomized controlled trial evaluating this issue is justified.

SUBMITTER: Bliziotis IA

PROVIDER: S-EPMC3202542 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Project description:Pseudomonas aeruginosa (PA) is a leading cause of healthcare-associated infections. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs) and fluoroquinolones (FQs), given either together in combination therapy or alone in monotherapy. A systematic review and meta-analysis were performed to evaluate the therapeutic efficacy of BL agents versus FQ agents as active, definitive monotherapy in PA infections in adults. Comprehensive literature searches of the Medline and Scopus electronic databases, alongside hand searches of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar, were performed without a time restriction to identify studies published in English comparing BL and FQ agents given as monotherapy for PA infection in hospitalized adults for which mortality, bacteriological eradication, or clinical response was evaluated. One reviewer screened search results based on pre-defined selection criteria. Two reviewers independently assessed included studies for methodological quality using NIH assessment tools. Two fixed-effects meta-analyses were performed. A total of 368 articles were screened, and six studies involving 338 total patients were included in the meta-analysis. Upon evaluation of methodological quality, two studies were rated good, three fair, and one poor. A meta-analysis of three studies demonstrates FQ monotherapy is associated with significantly improved survival compared to BL monotherapy for patients with PA bacteremia (OR, 3.65; 95% CI, 1.27-10.44; p = 0.02). A meta-analysis of three studies demonstrates FQ monotherapy is associated with equivalent bacteriological eradication compared to BL monotherapy for PA pneumonia or skin and soft tissue infection (RD, 0.07; 95% CI, -0.09 to 0.24; p = 0.39). The meta-analyses demonstrate FQ monotherapy significantly improves survival in PA bacteremia and is associated with similar rates of bacteriological eradication in pneumonia and skin and soft tissue infection caused by PA compared to BL monotherapy. However, more research is needed to make meaningful clinical recommendations.

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Impact of definitive therapy with beta-lactam monotherapy or combination with an aminoglycoside or a quinolone for Pseudomonas aeruginosa bacteremia.

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