Pharmacodynamics of Vancomycin Against Coagulase-Negative Staphylococci Bloodstream Infections

The recommended therapeutic target for vancomycin for serious methicillin-resistant S. aureus infections is an area under the concentration-time curve (AUC) over 24 h to a minimum inhibitory concentration (MIC) ratio of ≥ 400. Its applicability to coagulase-negative staphylococcal (CoNS) bloodstream infections is unclear. Our review aims to determine the pharmacodynamic target of vancomycin for CoNS bloodstream infections. In January 2025, MEDLINE, Embase, and PubMed were searched to identify manuscripts reporting the relationship between vancomycin drug exposure (AUC) and bactericidal activity or clinical response for CoNS. Studies of alternative drug delivery systems/formulations, combination therapy, prophylaxis, other infections, and static in vitro studies were excluded. Overall, six articles were included. One in vivo study in young infants found that an AUC_0-24 ≥ 300 mg/L·h and AUC₂₄ ≥ 424 mg/L·h were associated with a 7.8-fold and 7.3-fold increased likelihood of bacteriological cure, respectively. Two studies in adults showed that an AUC₂₄/MIC ratio ≥ 373 resulted in improved treatment success and microbiological eradication. An in vitro model demonstrated that a vancomycin AUC₂₄/MIC ratio ≥ 665 achieved maximal bacterial killing, while a rabbit model linked an AUC₂₄/MIC ≥ 520 to an 80% reduction in C-reactive protein. Early treatment within 24 h was associated with the greatest chance of bacteriological cure. Two studies of biofilm-embedded CoNS demonstrated inadequate bacterial killing at AUC₂₄/MIC ratios of 260 and 354. Overall, or CoNS bloodstream infections, an AUC₂₄ ≥ 424 mg/L·h (median MIC 1 mg/L) or AUC₂₄/MIC ≥ 373 improves clinical outcomes. This review highlights the need for early effective vancomycin treatment. Alternative antibiotic therapy should be considered for biofilm-embedded CoNS infections.