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Updated: Jan 27, 2026
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia
S Weis1, M Kesselmeier2, J S Davis3
1Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Department of Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
Background:
For patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect.
Objectives:
To perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB).
Methods:
We searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I2. The primary endpoint was 90-day all-cause mortality. The Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment.
Results:
Fourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence).
Conclusions:
Cefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.
Insights
Cefazolin may be as effective as anti-staphylococcal penicillins (ASPs) for Staphylococcus aureus bacteraemia (SAB), with potentially lower mortality and nephrotoxicity. Further research is needed for treatment failure and relapse comparisons.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Medicine
Background:
- Methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia (SAB) treatment typically involves anti-staphylococcal penicillins (ASPs) or cefazolin.
- ASPs carry a risk of nephrotoxicity, while cefazolin may face reduced efficacy due to inoculum effect in some S. aureus strains.
Purpose of the Study:
- To systematically review and meta-analyze evidence comparing cefazolin and ASPs for patients with SAB.
- To assess the comparative efficacy and safety of cefazolin versus ASPs in treating SAB.
Main Methods:
- Systematic literature search of MEDLINE, Web of Science, Cochrane Database, and clinicaltrials.gov up to June 2018.
- Inclusion of 14 non-randomized studies comparing cefazolin and ASPs for methicillin-sensitive SAB, regardless of publication status.
- Meta-analysis of 90-day all-cause mortality, 30-day mortality, nephrotoxicity, and treatment failure/relapse, with quality assessed by NOS and GRADE.
Main Results:
- Cefazolin showed a potential association with lower 30-day mortality (RR 0.70; 95% CI 0.54-0.91) and significantly less nephrotoxicity (RR 0.36; 95% CI 0.21-0.59), based on low-quality evidence.
- Evidence regarding treatment failure/relapse was very low quality (RR 0.84; 95% CI 0.59-1.18), indicating uncertainty in comparative effectiveness.
- For specific conditions like endocarditis and abscesses, cefazolin may be associated with similar mortality rates compared to ASPs.
Conclusions:
- Cefazolin appears to be at least as effective as ASPs for SAB.
- Cefazolin is associated with a reduced risk of nephrotoxicity compared to ASPs.
- Further high-quality studies are needed to clarify comparative effectiveness regarding treatment failure and relapse.
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