Susan L. Davis

Impact of Vancomycin Exposure on Outcomes in Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia: Support for Consensus Guidelines Suggested Targets

BACKGROUND High rates of vancomycin failure in methicillin-resistant Staphylococcus aureus (MRSA) infections have been increasingly reported over time. The primary objective of our study was to determine the impact of vancomycin exposure and outcomes in patients with MRSA bacteremia initially treated with vancomycin. METHODS This was a single-center retrospective analysis of 320 patients with documented MRSA bacteremia initially treated with vancomycin from January 2005 through April 2010. Two methods of susceptibility, Etest and broth microdilution, were performed for all isolates to determine the correlation of susceptibility testing to patient outcomes. RESULTS Among a cohort of 320 patients, more than half (52.5%) experienced vancomycin failure. Independent predictors of vancomycin failure in logistic regression included infective endocarditis (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 2.26-9.15), nosocomial-acquired infection (AOR, 2.19; 95% CI, 1.21-3.97), initial vancomycin trough <15 mg/L (AOR, 2.00; 95% CI, 1.25-3.22), and vancomycin minimum inhibitory concentration (MIC) >1 mg/L by Etest (AOR, 1.52; 95% CI, 1.09-2.49). With use of Classification and Regression Tree (CART) analysis, patients with vancomycin area under the curve at 24 h (AUC(24h)) to MIC ratios <421 were found to have significantly higher rates of failure, compared with patients with AUC(24h) to MIC ratios >421 (61.2% vs 48.6%; P = .038). CONCLUSIONS In light of the high failure rates associated with this antimicrobial, optimizing the pharmacokinetic/pharmacodynamic properties of vancomycin by targeting higher trough values of 15-20 mg/L and AUC(24h)/MIC ratios ≥400 in selected patients should be considered.

Early Use of Daptomycin Versus Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia With Vancomycin Minimum Inhibitory Concentration >1 mg/L: A Matched Cohort Study

BACKGROUND Recent reports have described decreased effectiveness with vancomycin treatment for methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) when the vancomycin minimum inhibitory concentration (MIC) is >1 µg/mL. METHODS This matched, retrospective cohort study compared the clinical effectiveness of daptomycin with that of vancomycin for the treatment of MRSAB with vancomycin MICs >1 µg/mL. The primary outcome was clinical failure, defined as a composite of 30-day mortality or bacteremia persisting for ≥7 days. RESULTS One hundred seventy patients were matched 1:1 with respect to the antimicrobial administered. In the daptomycin group, all patients received <72 hours of vancomycin (median, 1.7 days [interquartile range, 1.1-2.3 days]) prior to switching to daptomycin. The rate of clinical failure at 30 days was significantly lower in the daptomycin arm compared to the vancomycin arm (20.0% vs 48.2%; P < 0.001). Both 30-day mortality and persistent bacteremia were significantly lower in the daptomycin group compared to the vancomycin group (3.5% vs 12.9% [P = .047] and 18.8% vs 42.4% [P = .001], respectively). Logistic regression confirmed the association between vancomycin treatment and increased risk of clinical failure (adjusted odds ratio, 4.5; 95% confidence interval, 2.1-9.8). CONCLUSIONS This is the first matched study comparing early daptomycin versus vancomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL. Treatment with daptomycin resulted in significantly improved outcomes, including decreased 30-day mortality and persistent bacteremia. These results support the practice of switching early from vancomycin to daptomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL.

High-dose daptomycin for treatment of complicated gram-positive infections: A large, multicenter, retrospective study

Study Objective. To evaluate the clinical response and safety of high‐dose daptomycin for treatment of complicated gram‐positive infections.

Daptomycin versus Vancomycin for Complicated Skin and Skin Structure Infections: Clinical and Economic Outcomes

Study Objective. To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections.

Validation of the Effectiveness of a Vancomycin Nomogram in Achieving Target Trough Concentrations of 15–20 mg/L Suggested by the Vancomycin Consensus Guidelines

Study Objective. To assess and validate the effectiveness of a newly constructed vancomycin dosing nomogram in achieving target trough serum concentrations of 15–20 mg/L.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates in Urban Detroit

ABSTRACT To gain a better understanding of epidemiology of resistance in Staphylococcus aureus, we describe the molecular epidemiology of methicillin-resistant Staphylococcus aureus bloodstream isolates in urban Detroit. Bloodstream isolates from July 2005 to February 2007 were characterized. Two hundred ten bloodstream isolates from 201 patients were evaluated. Patient characteristics were as follows: median age, 54 years; 56% male; and 71% African-American. Seventy-six percent of infections were health care associated, with 55% being community-onset infections and 21% hospital acquired, and 24% were community associated. The most common sources were skin/wound (25%), central venous catheters (24%), unknown source (20%), and endocarditis (9%). Ninety percent and 5% of isolates had a MIC of vancomycin of ≤1.0 mg/liter, using automated dilution testing and E-test, respectively. Six percent of isolates showed heteroresistance to vancomycin, all occurring with isolates having a vancomycin E-test MIC of ≥1.5 mg/liter. Results of pulsed-field gel electrophoresis showed 17 strain types. The predominant strains were USA100 (104 isolates) and USA300 (74 isolates). Forty-nine percent of the isolates had staphylococcal cassette chromosome mec II, and 56% had agr II. All USA300 isolates were positive for the Panton-Valentine leukocidin toxin genes and agr I. Forty-seven percent of USA300 bloodstream infections were health care associated (35% community onset and 12% hospital onset). USA300 strains were more common in injection drug users with skin/wound as the predominant source of infection. Thirty percent of the USA100 strains were closely related to vancomycin-resistant Staphylococcus aureus isolates. The results of this study show that vancomycin MICs using automated dilution testing with Vitek-2 and E-test were highly discordant. Most methicillin-resistant S. aureus strains causing bacteremia are health care associated, commonly have MICs of vancomycin that are high within the susceptible range are not detected by routine automated dilution testing, and have significant diversity of molecular characteristics. USA100 strains that are closely related to vancomycin-resistant S. aureus (VRSA) isolates and USA300 strains are common as causes of both hospital and community-onset infection. Infection control measures should focus not only on prevention of the spread of community strains in the hospital but also prevention of the spread of hospital strains associated with VRSA into the community.

Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort

To compare clinical outcomes and costs in patients treated with the new vancomycin guidelines recommending goal serum trough concentrations of 15–20 mg/L versus patients treated with vancomycin doses targeting trough concentrations 5–20 mg/L prior to the new guidelines.

Epidemiology, Risk Factors, and Outcomes of Candida albicans Versus Non-albicans Candidemia in Nonneutropenic Patients

Background: Candidemia is a major cause of morbidity and mortality in hospitalized patients. Objectives: To describe the epidemiology of and risk factors for non-albicans candidemia (NAC) in nonneutropenic adults and the impact of NAC on patient outcomes and treatment cost. Methods: We conducted a retrospective cohort analysis comparing demographics and risk factors for Candida albicans candidemia (CAC) versus NAC in 144 nonneutropenic patients with candidemia over a 6 year period (1997–2002) at Detroit Receiving Hospital. Results: Candida species distribution included albicans (50%), parapsilosis (13%), tropicalis (10%), and glabrata (13%). Predominant species varied by patient care unit, with C. glabrata more common in the medical intensive care unit (ICU) and C. parapsilosis in the burn ICU. In multivariate analysis, NAC was associated with the absence of antibiotic use at the onset of candidemia, recent history of solid tumor, and male sex, NAC was not associated with an increase in mortality or length of stay compared with CAC, but was found to have a higher cost of antifungal therapy (

Large Retrospective Evaluation of the Effectiveness and Safety of Ceftaroline Fosamil Therapy

2030 vs

Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

780; p = 0.05). Conclusions: The epidemiology of candidemia is complex and varies among the different patient care units. Specifically, patients appear less likely to develop NAC if they are receiving antibiotics at the onset of candidemia. Increased awareness of risk factors for NAC can be used to guide adequate initial antifungal therapy.