Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Aug 2010
Targeted surveillance of methicillin-resistant Staphylococcus aureus and its potential use to guide empiric antibiotic therapy.
The present study aimed to determine the frequency of methicillin-resistant Staphylococcus aureus (MRSA)-positive clinical culture among hospitalized adults in different risk categories of a targeted MRSA active surveillance screening program and to assess the utility of screening in guiding empiric antibiotic therapy. We completed a prospective cohort study in which all adults admitted to non-intensive-care-unit locations who had no history of MRSA colonization or infection received targeted screening for MRSA colonization upon hospital admission. Anterior nares swab specimens were obtained from all high-risk patients, defined as those who self-reported admission to a health care facility within the previous 12 months or who had an active skin infection on admission. ⋯ Only 2.4% of patients deemed to be at high risk but found to be screening negative had a sample positive for MRSA by clinical culture, and 1.6% of patients deemed to be at low risk had a sample positive for MRSA by clinical culture. The risk of MRSA infection was far higher in those who were deemed to be at high risk and who were surveillance culture positive. Targeted MRSA active surveillance may be beneficial in guiding empiric anti-MRSA therapy.
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Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. ⋯ Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.
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Antimicrob. Agents Chemother. · Jun 2010
Pharmacokinetic-pharmacodynamic-model-guided doripenem dosing in critically ill patients.
The growing number of infections caused by multidrug-resistant pathogens has prompted a more rational use of available antibiotics given the paucity of new, effective agents. Monte Carlo simulations were utilized to determine the appropriateness of several doripenem dosing regimens based on the probability of attaining the critical drug exposure metric of time that drug concentrations remain above the drug MIC (T>MIC) for 35% (and lower thresholds) of the dosing interval in >80 to 90% of the population (T>MIC 35% target). This exposure level generally correlates with in vivo efficacy for carbapenems. ⋯ A longer, 4-hour infusion time improved target attainment in most cases, such that the T>MIC was adequate for pathogens with doripenem MICs as high as 4 microg/ml. Efficacy is expected for infections caused by pathogens with doripenem MICs of < or =2 microg/ml in patients with moderate renal impairment (creatinine clearance, 30 to 50 ml/min) who receive doripenem at 250 mg infused over 1 h every 8 h and in patients with severe impairment (creatinine clearance between 10 and 29 ml/min) who receive doripenem at 250 mg, infused over 1 h or 4 h, every 12 h. Results of pharmacokinetics/pharmacodynamics (PK/PD) modeling can guide dose optimization, thereby potentially increasing the clinical efficacy of doripenem against serious Gram-negative bacterial infections.
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Antimicrob. Agents Chemother. · Jun 2010
Population pharmacokinetics of doripenem based on data from phase 1 studies with healthy volunteers and phase 2 and 3 studies with critically ill patients.
A population pharmacokinetic model of doripenem was constructed using data pooled from phase 1, 2, and 3 studies utilizing nonlinear mixed effects modeling. A 2-compartment model with zero-order input and first-order elimination best described the log-transformed concentration-versus-time profile of doripenem. The model was parameterized in terms of total clearance (CL), central volume of distribution (V(c)), peripheral volume of distribution (V(p)), and distribution clearance between the central and peripheral compartments (Q). ⋯ Creatinine clearance was the most significant predictor of doripenem clearance. Mean Bayesian clearance was approximately 33%, 55%, and 76% lower for individuals with mild, moderate, or severe renal impairment, respectively, than for those with normal renal function. The population pharmacokinetic model based on healthy volunteer data and patient data informs us of doripenem disposition in a more general population as well as of the important measurable intrinsic and extrinsic factors that significantly influence interindividual pharmacokinetic differences.
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Antimicrob. Agents Chemother. · Jun 2010
Randomized Controlled Trial Multicenter Study Comparative StudyLong-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection.
We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. ⋯ Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.