VRE bacteraemia has a high mortality and continues to defy control. Antibiotic risk factors for VRE bacteraemia have not been adequately defined. We aimed to determine the risk factors for VRE bacteraemia focusing on duration of antibiotic exposure.
A retrospective matched nested case-control study was conducted amongst hospitalized patients at Cambridge University Hospitals NHS Foundation Trust (CUH) from 1 January 2006 to 31 December 2012. Cases who developed a first episode of VRE bacteraemia were matched 1:1 to controls by length of stay, year, specialty and ward type. Independent risk factors for VRE bacteraemia were evaluated using conditional logistic regression.
Two hundred and thirty-five cases were compared with 220 controls. Duration of exposure to parenteral vancomycin, fluoroquinolones and meropenem was independently associated with VRE bacteraemia. Compared with patients with no exposure to vancomycin, those who received courses of 1–3 days, 4–7 days or >7 days had a stepwise increase in risk of VRE bacteraemia [conditional OR (cOR) 1.2 (95% CI 0.4–3.8), 3.8 (95% CI 1.2–11.7) and 6.6 (95% CI 1.9–22.8), respectively]. Other risk factors were: presence of a central venous catheter (CVC) [cOR 8.7 (95% CI 2.6–29.5)]; neutropenia [cOR 15.5 (95% CI 4.2–57.0)]; hypoalbuminaemia [cOR 8.5 (95% CI 2.4–29.5)]; malignancy [cOR 4.4 (95% CI 1.6–12.0)]; gastrointestinal disease [cOR 12.4 (95% CI 4.2–36.8)]; and hepatobiliary disease [cOR 7.9 (95% CI 2.1–29.9)].
Longer exposure to vancomycin, fluoroquinolones or meropenem was associated with VRE bacteraemia. Antimicrobial stewardship interventions targeting high-risk antibiotics are required to complement infection control procedures against VRE bacteraemia.
VRE are associated with ∼1300 deaths per year in the USA. Recent literature suggests that daptomycin, a cyclic lipopeptide antibiotic with concentration-dependent bactericidal activity, is the preferred treatment option for VRE bacteraemia, yet the optimal dosing strategy for this indication has not been established. In vitro evidence suggests that higher-than-labelled doses of daptomycin are required to optimally treat VRE bacteraemia and to inhibit the development of resistance. However, concern of dose-dependent toxicities, notably increases in creatine phosphokinase and the development of rhabdomyolysis, are a barrier to initiating high-dose schemes in clinical practice. Thus, the effectiveness and safety of high-dose daptomycin regimens in clinical practice have remained unclear. While early studies failed to identify differences in mortality, newer, larger investigations suggest high-dose (≥9 mg/kg) daptomycin is associated with reduced mortality in patients with VRE bacteraemia compared with standard (6 mg/kg) dosing regimens. Additionally, the high-dose regimens appear to be safe and may be associated with improved microbiological outcomes. The purpose of this review is to examine the published evidence on the effectiveness and safety of high-dose daptomycin compared with standard dosing regimens for VRE bacteraemia.