S Weis1, M Kesselmeier2, J S Davis3, A M Morris4, S Lee5, A Scherag6, S Hagel7, M W Pletz8. 1. Institute 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. Electronic address: sebastian.weis@med.uni-jena.de. 2. Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Research Group Clinical Epidemiology, CSCC, Jena University Hospital, Jena, Germany. 3. Global and Tropical Health Division, Menzies School of Health Research, Darwin, NT, Australia; Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia. 4. Department of Medicine, Division of Infectious Diseases, Sinai Health System, University Health Network, University of Toronto, Canada. 5. Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. 6. Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Research Group Clinical Epidemiology, CSCC, Jena University Hospital, Jena, Germany; Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany. 7. Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany. 8. Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.
Abstract
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.
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.
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