IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. OBJECTIVE To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018.INTERVENTIONS Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days. MAIN OUTCOMES AND MEASURESThe primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. RESULTSThe data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, −4.2%; 95% CI, −14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, −3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, −8.9%; 95% CI, −16.6% to −1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%).CONCLUSIONS AND RELEVANCE Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings.

Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).

Resistance in virus-infected stem cell transplant recipients illustrates the need for surveillance.

To prevent respiratory virus (RV) infection after hematopoietic SCT (HSCT), patient and household members are advised to have annual influenza vaccinations and avoid symptomatic contacts. The object of this study was to measure and increase patient/household awareness of RV infection and preventive measures. We used a selfadministered questionnaire before/after a 5-min educational module (2006)(2007) and interviews with HSCT patients (2005with HSCT patients ( -2007. The subjects were patients and their households attending pre-HSCT education in an Australian HSCT Unit. Outcome measures were awareness of RV infection post-HSCT and effective prevention strategies; household influenza vaccination on admission for HSCT. In all, 139 out of 205 (68%) participants completed both questionnaires. Baseline knowledge of RV infection risk was high; knowledge of prevention was low. Intervention increased awareness that influenza post-HSCT could be fatal or require intensive care (68-87%, P ¼ 0.003), knowledge of effective prevention strategies (41-78%, Po0.0001) including vaccination (11-58%, Po0.0001), and belief among family/friends (but not patients) that household vaccination reduces influenza risk post-HSCT (57-97%, Po0.0001 and 76-81%, P ¼ 0.2, respectively). Household vaccination at HSCT admission was 71% for attenders and 30% for non-participants (RR 2.38, 95% confidence interval (CI) 1.49-3.80, Po0.0001). We concluded that patient and family pre-HSCT education increases awareness of RV prevention strategies and household influenza vaccination.