Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Mar 2013
Pharmacokinetics of intravenous linezolid in moderately to morbidly obese adults.
The pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m(2) receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (±standard deviation) age, height, and weight were 42.2 ± 12.2 years, 64.8 ± 3.5 in, and 109.5 ± 18.2 kg (range, 78.2 to 143.1 kg), respectively. ⋯ The areas under the curve for the 12-h dosing interval (AUCτ) were similar between moderately obese and morbidly obese groups: 130.3 ± 60.1 versus 109.2 ± 25.5 μg · h/ml (P = 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (r(2) = 0.524), adjusted body weight (r(2) = 0.587), lean body weight (r(2) = 0.495), and ideal body weight (r(2) = 0.398), but not with BMI (r(2) = 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUCτ values similar to those seen in nonobese participants.
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Antimicrob. Agents Chemother. · Mar 2013
Multicenter StudyOutcomes of appropriate empiric combination versus monotherapy for Pseudomonas aeruginosa bacteremia.
Pseudomonas aeruginosa bacteremia is associated with high hospital mortality. Empirical combination therapy is commonly used to increase the likelihood of appropriate therapy, but the benefits of employing >1 active agent have yet to be established. The purpose of this study was to compare outcomes of patients receiving appropriate empirical combination versus monotherapy for P. aeruginosa bacteremia. ⋯ After adjusting for baseline APACHE II scores, the relationship between time to mortality and combination therapy was not statistically significant (P = 0.59). Overall, no significant differences were observed for 30-day mortality, hospital mortality, and time to mortality between combination and monotherapy for P. aeruginosa bacteremia. Empirical combination therapy did not appear to offer an additional benefit, as long as the isolate was susceptible to at least one antimicrobial agent.
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Antimicrob. Agents Chemother. · Mar 2013
Treatment duration for uncomplicated Staphylococcus aureus bacteremia to prevent relapse: analysis of a prospective observational cohort study.
Practice guidelines recommend at least 14 days of antibiotic therapy for uncomplicated Staphylococcus aureus bacteremia (SAB). However, these recommendations have not been formally evaluated in clinical studies. To evaluate the duration of therapy for uncomplicated SAB, we analyzed data from our prospective cohort of patients with SAB. ⋯ In multivariate analysis, primary bacteremia was associated with a trend toward increased treatment failure (P = 0.06). Therefore, in the treatment of uncomplicated SAB, it seems reasonable to consider at least 14 days of antibiotic therapy to prevent relapse, as practice guidelines recommend. Because of its poor prognosis, primary bacteremia, even with a low risk of complication, should not be treated with short-course therapy.
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Antimicrob. Agents Chemother. · Mar 2013
Pharmacokinetic and pharmacodynamic modeling to determine the dose of ST-246 to protect against smallpox in humans.
Although smallpox has been eradicated, the United States government considers it a "material threat" and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. ⋯ The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.
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Antimicrob. Agents Chemother. · Mar 2013
Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.
Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 μg/ml). ⋯ All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.