BacteriemiaTriPasCefNCT07186894
Cefazolin Versus Antistaphylococcal Penicillins for Methicillin Susceptible Staphylococcus Aureus Bacteremia
An observational study of Bacteriemia and Methicillin Susceptible Staphylococcus Aureus (MSSA) Infection, run by Central Hospital, Nancy, France.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Bacteriemia, Methicillin Susceptible Staphylococcus Aureus (MSSA) Infection
- What is being tested?
- Antistaphylococcal penicillins and Cefazolin
- Type of treatment
- Injection or infusion
- How many people
- 5,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2000to 1 Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Variables : age, sex, medical history, type of infection and antibiotic used. Variables will be described as number and percentage for categorical variables, and mean and standard-deviation for continuous ones. A propensity score matching method will be conducted including (i) variables significantly different between the two cohorts in the bivariate descriptive analyses between the patient birth and the index event date (standard difference < 0.10 ; appendix 1), and (ii) clinically relevant variables (known confusion factors linked to mortality and safety outcomes ; appendix 2) at the index event date. Variables related to patients will be described before and after propensity score matching.
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official 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
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.
Read the 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.
- Being tested
- Antistaphylococcal penicillins, Cefazolin
- Keywords
- Methicillin-susceptible Staphylococcus aureus, bacteremia, antistaphylococcal penicillins, cefazolin, real-word evaluation, TriNetX
- Medical subject headings
- Infections, Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antistaphylococcal penicillinsDrug
It in not an interventional study. This project is a phase IV, retrospective, descriptive, and multicentric study.
CefazolinDrug
It in not an interventional study. This project is a phase IV, retrospective, descriptive, and multicentric study.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Antistaphylococcal penicillins | |
| 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 Receives: Drug: Cefazolin |
What is being measured
The primary outcome is the main question the study is designed to answer.
90 days all-cause mortality
All-cause mortality, at day 90
Measured: 90 days after the inclusion
Secondary outcomes (2)
All-cause mortality measured at other timeframes
All-cause mortality, at day 7, day 30, and 1 year
Measured: day 7, day 30, and 1 year
Safety outcomes
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.
Measured: 30 or 90 days after the inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2025
- Study start1 Jan 2000
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BacteriemiaStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LEFEVRE Benjamin, Central Hospital, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07186894
- Sponsor's protocol ID
- TriPasCef
- Acronym
- TriPasCef
- Status last verified
- Sep 2025
- First submitted
- 16 Sep 2025
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data are available upon reasonable request. Researchers can request access to data from the TriNetX research network through the TriNetX platform (https://live.trinetx.com). However, this may involve associated costs, require a data-sharing agreement and no patient-identifiable information can be accessible.
Publications
Ramsamy N, Simon M, Adam I, Hernandez G, Williford S, Denquin O, Pulcini C, Thilly N, Lefevre B. Effectiveness and safety of cefazolin vs antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus bacteremia: a multicenter real-world evaluation using the international TriNetX database. Antimicrob Agents Chemother. 2026 Sep 11:e0176525. doi: 10.1128/aac.01765-25. Online ahead of print.
PubMed 42725960
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07186894
- Acronym / sponsor ID
- TriPasCef / TriPasCef
- Keywords
- Methicillin-susceptible Staphylococcus aureus, bacteremia, antistaphylococcal penicillins, cefazolin, real-word evaluation, TriNetX
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 5,000 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 1 Jan 2000 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 22 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Antistaphylococcal penicillins (ASPs) | – | Drug: Antistaphylococcal penicillinsASPs 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 |
| Cefazolin | – | Drug: CefazolinCefazolin 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Variables : age, sex, medical history, type of infection and antibiotic used. Variables will be described as number and percentage for categorical variables, and mean and standard-deviation for continuous ones. A propensity score matching method will be conducted including (i) variables significantly different between the two cohorts in the bivariate descriptive analyses between the patient birth and the index event date (standard difference < 0.10 ; appendix 1), and (ii) clinically relevant variables (known confusion factors linked to mortality and safety outcomes ; appendix 2) at the index event date. Variables related to patients will be described before and after propensity score matching.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antistaphylococcal penicillinsIt in not an interventional study. This project is a phase IV, retrospective, descriptive, and multicentric study. | Drug | Antistaphylococcal penicillins (ASPs) |
| CefazolinIt in not an interventional study. This project is a phase IV, retrospective, descriptive, and multicentric study. | Drug | Cefazolin |
Primary outcome
90 days all-cause mortality
Time frame: 90 days after the inclusion
All-cause mortality, at day 90
2 secondary outcomes
All-cause mortality measured at other timeframes
Time frame: day 7, day 30, and 1 year
Safety outcomes
Time frame: 30 or 90 days after the inclusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Derived from this study: PubMed 42725960Ramsamy N, Simon M, Adam I, Hernandez G, Williford S, Denquin O, Pulcini C, Thilly N, Lefevre B. Effectiveness and safety of cefazolin vs antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus bacteremia: a multicenter real-world evaluation using the international TriNetX database. Antimicrob Agents Chemother. 2026 Sep 11:e0176525. doi: 10.1128/aac.01765-25. Online ahead of print.
- Individual participant dataSharing planned: No. Data are available upon reasonable request. Researchers can request access to data from the TriNetX research network through the TriNetX platform (https://live.trinetx.com). However, this may involve associated costs, require a data-sharing agreement and no patient-identifiable information can be accessible.
Related trials for Bacteriemia
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Bacteremia Due to Staphylococcus Aureus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Bacteriemia and Methicillin Susceptible Staphylococcus Aureus (MSSA) Infection, run by Central Hospital, Nancy, France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90 days all-cause mortality (time frame: 90 days after the inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07186894, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025.