Dataset Information

The Cost-effectiveness of Cefazolin Compared With Antistaphylococcal Penicillins for the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia

ABSTRACT: Abstract

Background

Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is associated with significant morbidity, mortality, and hospitalization costs. Cefazolin and antistaphylococcal penicillins (ASPs), such as nafcillin, are the preferred treatments for MSSA bacteremia. The aim of this study was to compare the cost-effectiveness of each approach.

Methods

We constructed a decision-analytic model comparing the use of cefazolin with ASPs for the treatment of MSSA bacteremia. Cost-effectiveness was determined by calculating deaths averted and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds.

Results

In the base-case analysis, the cost associated with the cefazolin strategy was $38 863.1, and the associated probability of survival was 0.91. For the ASP strategy, the cost was $48 578.8, and the probability of survival was 0.81. The incremental difference in cost between the 2 strategies was $9715.7, with hospital length of stay being the main driver of cost, and the incremental difference in effectiveness was 0.10. Overall, cefazolin results in savings of $97 156.8 per death averted (ICER, $–97 156.8/death averted). In the probabilistic analysis, at a willingness-to-pay of $50 000, cefazolin had a 68% chance of being cost-effective compared with ASPs. In cost-effectiveness acceptability curves, the cefazolin strategy was cost-effective in 73.5%–81.8% of simulations compared with ASP for a willingness-to-pay ranging up to $50 000.

Conclusions

The use of cefazolin is a cost-effective strategy for the treatment of MSSA bacteremia and, when clinically appropriate, this strategy results in considerable health care cost-savings.

SUBMITTER: Pliakos E

PROVIDER: S-EPMC8566905 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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: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).