Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.

PURPOSE: Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation. METHODS: This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance. FINDINGS: A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P < 0.01) and ICU stay (odds ratio, 2.64; P = 0.03). Notable differences between treatment groups were seen with: (1) end of therapy failure rates (11% vs 24% for daptomycin vs vancomycin; P = 0.025); (2) acute kidney injury rates (9% vs 23% for daptomycin vs vancomycin; P = 0.043); and (3) day 4 bacteremia clearance rates for immunocompromised patients (n = 26) (94% vs 56% for daptomycin vs vancomycin; P = 0.035). IMPLICATIONS: Results from this multicenter study provide, for the first time, a geographically diverse evaluation of daptomycin versus vancomycin for patients with vancomycin-susceptible MRSA bacteremia with vancomycin MIC values >1 µg/mL. Although the overall composite failure rates did not differ between the vancomycin and daptomycin groups when intensively matched according to risks for failure, the rates of acute kidney injury were significantly lower in the daptomycin group. These findings suggest that daptomycin is a useful therapy for clinicians treating patients who have MRSA bacteremia. Prospective, randomized trials should be conducted to better assess the potential significance of elevated vancomycin MIC.

Review of rapid diagnostic tests used by antimicrobial stewardship programs.

Rapid microbiologic tests provide opportunities for antimicrobial stewardship programs to improve antimicrobial use and clinical and economic outcomes. Standard techniques for identification of organisms require at least 48-72 hours for final results, compared with rapid diagnostic tests that provide final organism identification within hours of growth. Importantly, rapid microbiologic tests are considered "game changers" and represent a significant advancement in the management of infectious diseases. This review focuses on currently available rapid diagnostic tests and, importantly, the impact of rapid testing in combination with antimicrobial stewardship on patient outcomes.

A stewardship program's retrospective evaluation of vancomycin AUC24/MIC and time to microbiological clearance in patients with methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis.

BACKGROUND: Current guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia recommend targeting a vancomycin AUC24/MIC ≥400. Data on the association between AUC24/MIC and microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis are limited. OBJECTIVE: The objective of this study is to evaluate the association between the vancomycin AUC24/MIC and time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis. METHODS: Adult inpatients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin from January 1, 2007, through December 31, 2011, were evaluated. Classification and regression tree analysis was used to identify the AUC24/MIC associated with time to microbiological clearance. RESULTS: Fifty-nine patients had complete data available for review and were included in the analysis. Classification and regression tree analysis identified an AUC/MIC of 293 as the breakpoint that provides the greatest difference in time to microbiological clearance. On univariate analysis, mean (SD) time to clearance was 2 days shorter when the AUC/MIC was >293 (4 [2] days vs 6 [3] days, P = 0.01). Mean (SD) infection-related length of stay was 13 (6) versus 18 (14) days in patients with an AUC24/MIC ratio >293 or ≤293, respectively (P = 0.25). In patients with an AUC24/MIC ≤293, 39% versus 17% (P = 0.09) had recurrent bacteremia and were readmitted compared with patients with an AUC/MIC >293. Only 9% were able to achieve an AUC24/MIC >293 when the vancomycin MIC was >1 µg/mL. CONCLUSIONS: We observed a >2.5-fold increase in time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis unable to achieve a vancomycin AUC24/MIC >293. A 5-day increase in hospital and infection-related length of stay was observed when this target was not achieved. Recurrence of bacteremia and hospital readmissions were higher in the cohort who did not achieve an AUC24/MIC >293. Only 9% of patients were able to achieve an AUC24/MIC >293 if the isolate MIC was >1 µg/mL. Trough concentration did not correlate with AUC24/MIC. In patients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin, stewardship programs should optimize pharmacodynamic parameters, specifically AUC24/MIC, or alternative therapies should be considered.

An antimicrobial stewardship program's impact with rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus/S. aureus blood culture test in patients with S. aureus bacteremia.

Rapid organism detection of Staphylococcus aureus bacteremia and communication to clinicians expedites antibiotic optimization. We evaluated clinical and economic outcomes of a rapid polymerase chain reaction methicillin­resistant S. aureus/S. aureus blood culture test (rPCR). This single­center study compared inpatients with S. aureus bacteremia admitted from 1 September 2008 through 31 December 2008 (pre­rPCR) and those admitted from 10 March 2009 through 30 June 2009 (post­rPCR). An infectious diseases pharmacist was contacted with results of the rPCR; effective antibiotics and an infectious diseases consult were recommended. Multivariable regression assessed clinical and economic outcomes of the 156 patients. Mean time to switch from empiric vancomycin to cefazolin or nafcillin in patients with methicillin­susceptible S. aureus bacteremia was 1.7 days shorter post­rPCR (P = .002). In the post­rPCR methicillin­susceptible and methicillin­resistant S. aureus groups, the mean length of stay was 6.2 days shorter (P = .07) and the mean hospital costs were $21,387 less (P = .02). rPCR allows rapid differentiation of S. aureus bacteremia, enabling timely, effective therapy and is associated with decreased length of stay and health care costs.