Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Bacteriemia Bacteremia Bacterial Infections Bacterial Infections and Mycoses Infections Inflammation Methicillin Susceptible Staphylococcus Aureus (MSSA) Infection Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Systemic Inflammatory Response Syndrome

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Monobacterial methicillin susceptible Staphylococcus aureus (MSSa) bacteremia
In the cefazolin group : Cefazolin injectable prescription in the week before or the week after MSSa bacteremia
In the ASPs group :ASPs injectable prescription (flucloxacillin, floxacillin, cloxacillin, oxacillin, nafcillin and dicloxacillin) in the week before or the week after MSSa bacteremia

Exclusion criteria

In the cefazolin group : ASP injectable prescription in the year before or the year after MSSa bacteremia
In the ASPs group : cefazolin injectable prescription in the year before or the year after MSSa bacteremia

Treatment and study plan

Antistaphylococcal penicillins

Drug

It in not an interventional study. This project is a phase IV, retrospective, descriptive, and multicentric study.

Cefazolin

Drug

It in not an interventional study. This project is a phase IV, retrospective, descriptive, and multicentric study.

Primary outcomes

90 days all-cause mortality

Time frame: 90 days after the inclusion

All-cause mortality, at day 90

Secondary outcomes

All-cause mortality measured at other timeframes

Time frame: day 7, day 30, and 1 year

All-cause mortality, at day 7, day 30, and 1 year
Safety outcomes

Time frame: 30 or 90 days after the inclusion

The definition of this event is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (published in November 27, 2017 by the U.S. department of health and human services)

Clostridioides difficile infection: Clostridioides difficile infection diagnosis, between one day and 90 days after the index event.

Nephrotoxicity: acute kidney injury diagnosis, between one day and 30 days after the index event.

Hepatotoxicity: hepatic failure or liver disease or elevation of liver enzymes, between one day and 30 days after the index event.

Allergy: skin eruption or anaphylactic reaction, between one day and 30 days after the index event.

Haematotoxicity: cytopenia or eosinophilia, between one day and 30 days after the index event.

Sponsors and collaborators

Lead sponsor

Central Hospital, Nancy, France

Other

Registry information

Official study title

Effectiveness and Safety of Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia: a Multicentre Real-world Evaluation Using the International TriNetX Database

Acronym: TriPasCef

Important dates

Study start: 2000
Primary completion: 2026
Study completion: 2026
First posted: Sep 22, 2025
Registry last updated: Sep 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Recruiting