Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jan 2013
Population pharmacokinetic-pharmacodynamic analysis of anidulafungin in adult patients with fungal infections.
To evaluate the exposure-response relationships for efficacy and safety of intravenous anidulafungin in adult patients with fungal infections, a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from 262 patients in four phase 2/3 studies. The plasma concentration data were fitted with a previously developed population PK model. Anidulafungin exposures in patients with weight extremities (e.g., 40 kg and 150 kg) were simulated based on the final PK model. ⋯ There was a trend of positive association between anidulafungin exposure and efficacy in patients with esophageal candidiasis or invasive candidiasis, including candidemia (ICC); however, adequate characterization of the effect of anidulafungin exposure on response could not be established due to the relatively small sample size. No threshold value for exposure could be established, since patients with low exposure also achieved successful outcomes (e.g., area under the curve < 40 mg · h/liter in ICC patients). There was no association between anidulafungin exposure and the treatment-related adverse events or all-causality hepatic laboratory abnormalities.
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Antimicrob. Agents Chemother. · Jan 2013
Chlorhexidine and mupirocin susceptibilities of methicillin-resistant staphylococcus aureus from colonized nursing home residents.
Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. ⋯ Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.
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Antimicrob. Agents Chemother. · Dec 2012
Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in the mouse intestine.
In vivo bacteriophage targeting of enteroaggregative Escherichia coli (EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. ⋯ These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophages in vivo for the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.
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Antimicrob. Agents Chemother. · Dec 2012
Effect of continuous venovenous hemofiltration dose on achievement of adequate vancomycin trough concentrations.
The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (≤30 ml/kg/h; n = 10) or high (>30 ml/kg/h; n = 77) CVVH hemofiltration rate (HFR) for analysis. ⋯ Mortality at 28 days was unrelated to trough achievement in both the overall sample (P = 0.516) and in culture-positive MRSA patients (P = 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.