Early response assessment to guide management of methicillin-resistant Staphylococcus aureus bloodstream infections with vancomycin therapy.

BACKGROUND: A subset of vancomycin-treated patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) developed persistent positive blood cultures. Treatment eventually failed. METHODS: A retrospective study was conducted to determine whether early response on day 3 after initiation of vancomycin therapy for MRSA BSI was associated with reduced rates of persistent bacteremia, end-of-treatment failure, and infection-related mortality. Patients' medical charts were reviewed. Susceptibility testing and molecular characterization of bacterial isolates were performed. RESULTS: In this elderly cohort (n = 111; median age 70 years, interquartile range: 57-80 years), early response was observed in 62% of patients and was significantly (P < 0.0001) associated with lower rates of end-of-treatment failure (19% vs 57%) and infection-related death (1% vs 29%), but not with persistent bacteremia (17% vs 29%, P = 0.23). Nearly half (46%; 46 of 100 patients) remained on vancomycin therapy for the entire treatment course; those who continued despite lack of early response had a trend toward a higher risk of death than those who were switched to alternative therapy (38% vs 10%, P = NS). Most (68%) isolates had vancomycin MIC of >1 µg/mL, whereas 10% showed heterogeneous glycopeptide-intermediate Staph aureus (hGISA) phenotype. Nearly half (47%) were typed with staphylococcal cassette chromosome mec IV or V. In a multivariate logistic regression model, lack of response at day 3 was the strongest predictor for end-of-treatment failure, after adjustment for confounders such as age, Acute Physiology And Chronic Health Evaluation II score, intensive care unit admission, vancomycin MIC >1 µg/mL, unbound trough concentration <4 to 5× MIC, and continued vancomycin therapy without change. CONCLUSIONS: Early response assessment after initiation of vancomycin therapy appeared to be useful for considering further diagnostic workup or a switch to alternative therapy to affect a positive outcome in patients with MRSA BSI.

Can clinical and molecular epidemiologic parameters guide empiric treatment with vancomycin for methicillin-resistant Staphylococcus aureus infections?

Reports of vancomycin treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with elevated minimum inhibitory concentration (MIC) has prompted use of high-dose therapy, but nephrotoxicity is a concern. We determined whether clinical and molecular epidemiologic parameters can be used to guide empiric vancomycin therapy and strain susceptibility to alternative agents. Medical charts of 180 hospitalized adults with MRSA infections were reviewed. MICs of vancomycin, daptomycin, linezolid, and tigecycline were determined by Etest. Patient isolates were assayed for genes encoding Panton-Valentine leukocidin (PVL) and SCCmec type. High vancomycin MIC did not correlate with place of acquisition, invasiveness of infection, or history of health care exposure. High MIC was present in 32% of strains overall and in 23% of PVL+, SCCmec IV strains; all were susceptible to alternative agents. Clinicians should not make empiric treatment decisions related to vancomycin use based on history of healthcare exposure risk or residence at onset of infection for patients hospitalized with MRSA infections.

Regulatory oversight and safety of probiotic use.

Depending on intended use of a probiotic (drug vs. dietary supplement), regulatory requirements differ greatly. For dietary supplements, premarketing demonstration of safety and efficacy and approval by the Food and Drug Administration are not required; only premarket notification is required. Saccharomyces boulardii is a probiotic regulated as a dietary supplement intended for use by the general healthy population, not as a drug to prevent, treat, or mitigate disease. However, since recent increases in incidence and severity of Clostridium difficile infection, probiotics have been used to treat recurrent and/or refractory disease in hospitalized patients. Saccharomyces fungemia secondary to use of the probiotic has been described for patients who are critically ill, are receiving nutrition enterally, or have a central venous catheter. Before use of a probiotic is considered for hospitalized patients, careful assessment of risk versus benefit must be made. To ensure patient safety, probiotics should be properly handled during administration.

An antimicrobial stewardship program with a focus on reducing fluoroquinolone overuse.

The fluoroquinolones have become the leading class of antimicrobial agents prescribed to adults in the United States. Resistance of key pathogens to fluoroquinolones has developed rapidly in parallel with increased prescribing of these drugs. We describe our pharmacist-led antimicrobial stewardship program that focused on reducing inappropriate prescribing of fluoroquinolones, with the goals of limiting the development of resistance and improving patient outcomes. Core strategies were regular monitoring and reporting of resistance trends observed on institutional antibiograms, performing drug audits and related studies with intervention and feedback to prescribers, implementing an automatic parenteral-to-oral conversion program, establishing and implementing a beta-lactam-based institutional guideline for empiric therapy, and educating prescribers. This successful program reduced empiric prescribing of fluoroquinolones by 30%, improved susceptibility for all antipseudomonal agents against Pseudomonas aeruginosa overall by 10%, and decreased mortality associated with P. aeruginosa infections by 2-fold. Our stewardship program clearly demonstrated that pharmacists can take on leadership roles to positively change antimicrobial prescribing at the institutional level and improve patient outcomes.

High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity.

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.