Effectiveness and Safety of Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia: a Multicentre Real-world Evaluation Using the International TriNetX Database
Effectiveness and Safety of Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia: a Multicentre Real-world Evaluation Using the International TriNetX Database
Background Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a common and serious infection, associated with significant morbidity and high mortality rates. Antistaphylococcal penicillins (ASPs) have traditionally been recommended as the first-line treatment. However, this established position has recently been challenged by meta-analyses suggesting that cefazolin may provide comparable efficacy, along with a more favourable safety profile. Further clinical and real-world studies are warranted to substantiate these findings.
Objectives The aim of this study was to assess the effectiveness and safety of cefazolin compared with ASPs in the management of MSSA bacteraemia.
Staphylococcus aureus (SA) is a frequent cause of bacteraemia and is associated with high mortality rates. Several studies have reported an increasing incidence over recent decades, accompanied by a decline in the prevalence of methicillin-resistant strains. In a recent meta-analysis by Bai et al., mortality related to S. aureus bacteraemia (SAB) remained substantial: 18.1% at one month, 27.0% at three months, and 30.2% at one year.
In the absence of specific international guidelines supported by randomised controlled trials, the management of methicillin-susceptible S. aureus (MSSA) bloodstream infections largely relies on expert consensus and clinical experience. For several decades, antistaphylococcal penicillins (ASPs) have been regarded as the gold standard for treating MSSA bacteraemia. This preference was primarily based on concerns regarding the so-called "inoculum effect," whereby the efficacy of cefazolin might be reduced at high bacterial loads .
However, recurring global shortages of ASPs have led clinicians to consider cefazolin as a viable first-line alternative. In this context, several meta-analyses, albeit based on observational data, have suggested that cefazolin provides similar efficacy with a more favourable safety profile than ASPs . Nonetheless, these results remain subject to confounding and bias and must be confirmed through randomised controlled trials, two of which are currently ongoing.
Large, real-world evaluations are therefore needed to assess the comparative effectiveness and safety of cefazolin and ASPs in routine clinical settings. The TriNetX platform offers access to real-time, real-world global hospital data, thereby enabling large-scale comparative analyses in an international context. Against this background, the present study aimed to evaluate the effectiveness and tolerability of cefazolin versus ASPs in the treatment of MSSA bacteraemia using data from the TriNetX database.
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