Analysis of 42 Cases of Septicemia Caused by an Epidemic Strain of Methicillin-Resistant Staphylococcus aureus: Evidence of Resistance to Vancomycin

Abstract

Recent case reports of vancomycin treatment failures in the United States, Japan, and France have prompted a retrospective analysis of 42 cases of septicemia caused by epidemic methicillin-resistant Staphylococcus aureus strain 15 (EMRSA-15), which is the most prevalent epidemic strain of methicillin-resistant S. aureus in the United Kingdom; all cases occurred in a teaching hospital in Manchester, United Kingdom, between 1994 and 1998. Mortality was lowest (4%) in patients with rifampin-susceptible isolates treated with vancomycin and rifampin. It rose to 38% in patients who were treated with both antibiotics but in whom the organism became resistant to rifampin during therapy, and it reached 78% in patients who had rifampin-resistant isolates or in whom rifampin was contraindicated (P<.0001; Fisher exact test, 2-tailed). All isolates were susceptible to vancomycin by conventional laboratory testing, but susceptibility was lost by growth in vancomycin in vitro, becoming resistant at a minimum inhibitory concentration of 8 mg/L. This was associated with accumulation of cell-wall material. The deoxyribonucleic acid fingerprint remained unchanged. This study suggests that rifampin played a key role in the prevention of deaths caused by an epidemic strain of methicillin-resistant S. aureus that readily gave rise to a subpopulation with reduced susceptibility to vancomycin.

Combination of Quinupristin-Dalfopristin (Synercid) and Rifampin Is Highly Synergistic in Experimental Staphylococcus aureus Joint Prosthesis Infection

“…The efficacy of rifampin as monotherapy for an active infection is limited by the emergence of resistant mutants, especially during long-term therapy (18). The emergence of rifampin resistance during combination therapy with rifampin and vancomycin has been reported clinically (4,8) and was observed in 5 of 11 animals treated with rifampin plus vancomycin in the present study. By contrast, resistance to rifampin did not emerge in any of the 10 animals treated with rifampin plus Q-D.…”

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…In a few cases, therapy with oral rifampin and fusidic acid was an important component of therapy for the successful treatment of hVISA and VISA infections in patients who had failed vancomycin therapy (124). Importantly, it appears that vancomycin does not adequately protect against the development of rifampin resistance when this combination alone is used to treat serious MRSA infections (35,150). In addition, fusidic acid monotherapy should not be used because of the frequent development of fusidic acid resistance in S. aureus (120).…”

Unstable Vancomycin Heteroresistance Is Common among Clinical Isolates of Methiciliin-Resistant Staphylococcus aureus

“…While some microbiology, infectious disease, and public health personnel have focused concern on VISA and vancomycin-resistant S. aureus characterized as such by conventional test methods, others consider the in vitro phenomenon of unstable vancomycin heteroresistance an explanation for the therapeutic failure of vancomycin in humans (1,3,4,7,11,14,17). Further evidence is needed to confirm this association, since not all patients harboring unstably hetero-VISA strains fail therapy.…”