Dataset Information

Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis.

ABSTRACT:

Background

Antistaphylococcal penicillins (ASPs) and cefazolin have become the most frequent choices for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, the best therapeutic agent to treat MSSA bacteremia remains to be established.

Methods

We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these two regimens for the treatment of MSSA bacteremia. PubMed, EMBASE and the Cochrane Library from inception to February 2018 were searched. The primary outcome was mortality. The secondary outcomes included treatment failure, recurrence of bacteremia, adverse effects (AEs) and discontinuation due to AEs. Data were extracted and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

A total of ten observational studies met the inclusion criteria. The results indicate that compared to ASPs, cefazolin was associated with significant reduction in mortality (OR, 0.69; 95% CI, 0.58 to 0.82; I²?=?3.4%) and clinical failure (OR, 0.56; 95% CI, 0.37 to 0.85; I²?=?44.9%) without increasing the recurrence of bacteremia (OR, 1.12; 95% CI, 0.94 to 1.34; I²?=?0%). There were no significant differences for the risk of anaphylaxis (OR, 0.91; 95% CI, 0.36 to 2.99; I²?=?0%) or hematotoxicity (OR, 0.56; 95% CI, 0.17 to 1.88; I²?=?0%). However, nephrotoxicity (OR, 0.36; 95% CI, 0.16 to 0.81; I²?=?0%) and hepatotoxicity (OR, 0.12; 95% CI, 0.04 to 0.41; I²?=?0%) were significantly lower in the cefazolin group. Moreover, cefazolin was associated with lower probability of discontinuation due to AEs compared with the ASPs (OR, 0.24; 95% CI, 0.12 to 0.48; I²?=?18%).

Conclusion

The results of present study favor the application of cefazolin and should be regarded as important evidence to help make clinical decisions in choosing a treatment option for treating MSSA bacteremia.

SUBMITTER: Shi C

PROVIDER: S-EPMC6180622 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis.

Shi Changcheng C Xiao Yubo Y Zhang Qi Q Li Qingyu Q Wang Fei F Wu Jing J Lin Nengming N

BMC infectious diseases 20181011 1

<h4>Background</h4>Antistaphylococcal penicillins (ASPs) and cefazolin have become the most frequent choices for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, the best therapeutic agent to treat MSSA bacteremia remains to be established.<h4>Methods</h4>We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these two regimens for the treatment of MSSA bacteremia. PubMed, EMBASE and the Cochrane Library from inception ...[more]

PMID: 30305037

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Project description:IntroductionMethicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of infection in humans. Beta-lactam antibiotics are the preferred agents, with anti-staphylococcal penicillins (ASPs) or the first-generation cephalosporin, cefazolin, favored by clinicians. Recent studies comparing the two strategies suggest similar outcomes between the agents. The purpose of this meta-analysis was to explore differences between cefazolin and ASPs for the treatment of MSSA infections.MethodsWe performed a meta-analysis with trial sequential analysis (TSA) of observational or cohort studies using a random-effects model. Two blinded reviewers independently assessed studies for inclusion, risk of bias, and data extraction. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, and antibiotic discontinuation due to adverse events. Subgroup analyses were conducted for the primary outcome by type of ASP, studies with a high percentage of deep-seated infections, and studies of low to moderate risk of bias.ResultsAfter performing a comprehensive search of the literature, and screening for study inclusion, 19 studies (13,390 patients) were included in the final meta-analysis. Fifteen of the 19 studies (79%) were judged as having a low or moderate risk of bias. Use of cefazolin was associated with lower all-cause mortality [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.56-0.91, p = 0.006, I2 = 28%], clinical failure (OR 0.55, 95% CI 0.41-0.74, p < 0.001, I2 = 0%), and antibiotic discontinuation due to adverse events (OR 0.25, 95% CI 0.16-0.39, p < 0.001, I2 = 23%). Infection recurrence was higher in the cefazolin patients (OR 1.41, 95% CI 1.04-1.93, p = 0.03, I2 = 0%).ConclusionThis meta-analysis demonstrated that the use of cefazolin was associated with significant reductions in all-cause mortality, clinical failure, and discontinuation due to adverse events, but was associated with an increased risk of infection recurrence.FundingUniversity of Florida Open Access Publishing Fund funded the Rapid Service Fees.Trial registrationPROSPERO International Prospective Register of Systematic Reviews (study ID: CRD42018106442).

Project description:Recent studies and experience suggest that cefazolin might be equally as effective as antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus (MSSA), with a better safety profile and lower cost. The objective of these meta-analyses was to compare the safeties of antistaphylococcal penicillins and cefazolin. The PubMed, Embase, and International Pharmaceutical Abstracts databases and websites for clinical trial registries through 23 June 2017 were searched. In addition, recent abstracts from infectious disease and pharmacy conferences were reviewed. We estimated Peto odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models. One analysis focused on hospitalized patients, and the other focused on outpatients. Eleven retrospective studies of hospitalized patients and three retrospective studies of outpatients were included. In hospitalized patients, lower rates of nephrotoxicity (Peto OR, 0.225; 95% CI, 0.127 to 0.513), acute interstitial nephritis (Peto OR, 0.189; 95% CI, 0.053 to 0.675), hepatotoxicity (Peto OR, 0.160; 95% CI, 0.066 to 0.387), and drug discontinuation due to adverse reactions (Peto OR, 0.192; 95% CI, 0.089 to 0.414) were found with cefazolin. In outpatients, lower rates of nephrotoxicity (Peto OR, 0.372; 95% CI, 0.192 to 0.722), hepatotoxicity (Peto OR, 0.313; 95% CI, 0.156 to 0.627), and hypersensitivity reactions (Peto OR, 0.372; 95% CI, 0.201 to 0.687) were observed with cefazolin. Compared to antistaphylococcal penicillins, cefazolin was associated with significant reductions in nephrotoxicity and hepatotoxicity in hospitalized patients and outpatients. Additionally, cefazolin was associated with lower likelihoods of discontinuation due to side effects in hospitalized patients and hypersensitivity reactions in outpatients. Cefazolin should be considered a first-line option for patients with MSSA infections for which efficacy is presumed to be similar to that of antistaphylococcal penicillin therapy.

Project description:Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Dataset Information

Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis.

Background

Methods

Results

Conclusion

Publications

Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis.

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