Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Apr 2013
Randomized Controlled TrialPharmacokinetics of anidulafungin in critically ill patients with candidemia/invasive candidiasis.
The pharmacokinetics of intravenous anidulafungin in adult intensive care unit (ICU) patients were assessed in this study and compared with historical data from a general patient population and healthy subjects. Intensive plasma sampling was performed over a dosing interval at steady state from 21 ICU patients with candidemia/invasive candidiasis. All patients received the recommended dosing regimen (a 200-mg loading dose on day 1, followed by a daily 100-mg maintenance dose), except for a 54-year-old 240-kg female patient (who received a daily 150-mg maintenance dose instead). ⋯ The exposure in the 240-kg patient at a daily 150-mg dose was within the range observed in ICU patients overall. The average AUC(0-24) and Cmax in the general patient population and healthy subjects were 110.3 and 105.9 mg · h/liter and 7.2 and 7.0 mg/liter, respectively. The pharmacokinetics of anidulafungin in ICU patients appeared to be comparable to those in the general patient population and healthy subjects at the same dosing regimen.
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Antimicrob. Agents Chemother. · Apr 2013
In vivo activities of ceftolozane, a new cephalosporin, with and without tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, including strains with extended-spectrum β-lactamases, in the thighs of neutropenic mice.
Ceftolozane is a new cephalosporin with potent activity against Pseudomonas aeruginosa and Enterobacteriaceae. A neutropenic murine thigh infection model was used to determine which pharmacokinetic/pharmacodynamic index and magnitude drives the efficacy of ceftolozane with Gram-negative bacilli, to compare the rates of in vivo killing of P. aeruginosa by ceftolozane and ceftazidime, and to determine the impact of different ratios of ceftolozane plus tazobactam on Enterobacteriaceae containing extended-spectrum β-lactamases (ESBLs). Neutropenic mice had 10(6.2-7.1) CFU/thigh when treated with ceftolozane for 24 h with (i) various doses (3.12 to 1,600 mg/kg) and dosage intervals (3, 6, 12, and 24 h) against two Enterobacteriaceae strains, (ii) 0.39 to 800 mg/kg every 6 h for four Enterobacteriaceae and four P. aeruginosa strains, and (iii) 400 or 800 mg/kg with 2:1. 4:1, and 8:1 ratios of tazobactam against five Enterobacteriaceae strains with ESBLs. ⋯ At 200 mg/kg every 3 h, the rate of in vivo killing of P. aeruginosa was faster with ceftolozane than with ceftazidime (-0.34 to -0.41 log10 CFU/thigh/h versus -0.21 to -0.24 log10 CFU/thigh/h). The 2:1 ratio of ceftolozane with tazobactam was the most potent combination studied. The T>MIC required for ceftolozane is less than with other cephalosporins and may be due to more rapid killing.
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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.