Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia

NCT ID: NCT07186894

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 5000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2000-01-01
• Study Completion Date: 2026-09-01

Brief Summary

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.

Detailed Description

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.

Conditions

Bacteriemia; Methicillin Susceptible Staphylococcus Aureus (MSSA) Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Antistaphylococcal penicillins (ASPs)

ASPs group

Inclusion criteria

• Monobacterial methicillin susceptible Staphylococcus aureus (MSSa) bacteremia
• Antistaphylococcal penicillins (ASPs) injectable prescription (flucloxacillin, floxacillin, cloxacillin, oxacillin, nafcillin and dicloxacillin) in the week before or the week after MSSa bacteremia

Exclusion criteria : cefazolin injectable prescription in the year before or the year after MSSa bacteremia

Antistaphylococcal penicillins

Intervention Type: DRUG

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

Cefazolin

Cefazolin group

Inclusion criteria

• Monobacterial methicillin susceptible Staphylococcus aureus (MSSa) bacteremia
• Cefazolin injectable prescription in the week before or the week after MSSa bacteremia

Exclusion criteria : ASP injectable prescription in the year before or the year after MSSa bacteremia

Cefazolin

Intervention Type: DRUG

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

Interventions

Antistaphylococcal penicillins

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

Intervention Type: DRUG

Cefazolin

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

Intervention Type: DRUG

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: lead

Responsible Party

LEFEVRE Benjamin

Doctor (MD PhD)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

TriPasCef

Identifier Type: -

Identifier Source: org_study_id