International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Jan 2013
Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region.
Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated from hospitalised patients. MICs for carbapenems were determined for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii obtained from the COMPACT II programme conducted in the Asia-Pacific region. ⋯ Against A. baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens achieved optimal exposure in or outside the ICU. Owing to the high potency of carbapenems against these Enterobacteriaceae populations, standard regimens are likely to perform well in the Asia-Pacific region. However, larger doses combined with prolonged infusions will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa and A. baumannii that are prevalent in these countries.
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Int. J. Antimicrob. Agents · Dec 2012
Multicenter StudyEfficacy and safety of anidulafungin in elderly, critically ill patients with invasive Candida infections: a post hoc analysis.
Post hoc analysis of a non-comparative, prospective, multicentre, phase IIIb study was performed to compare efficacy and safety of anidulafungin in elderly (≥65 years) versus non-elderly (<65 years) Intensive Care Unit (ICU) patients with candidaemia/invasive candidiasis (C/IC). Adult ICU patients with confirmed C/IC meeting ≥1 of the following criteria were enrolled: post-abdominal surgery; solid tumour; renal/hepatic insufficiency; solid organ transplantation; neutropenia; age ≥65 years. Patients received anidulafungin (200 mg on Day 1, 100 mg/day thereafter) for ≥10 days followed by optional azole step-down therapy for a total treatment duration of 14-56 days. ⋯ Ninety-day survival was significantly lower (P=0.006) for elderly (42.8%) versus non-elderly patients (63.3%). The incidence and profile of adverse events were similar in elderly and non-elderly patients. Anidulafungin was effective and safe for treatment of C/IC in elderly ICU patients, despite higher baseline severity of illness scores.
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Int. J. Antimicrob. Agents · Dec 2012
Nitrofurantoin in the treatment of extended-spectrum β-lactamase-producing Escherichia coli-related lower urinary tract infection.
The aim of this study was to evaluate the effect of nitrofurantoin (NFT) in the treatment of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli-related lower urinary tract infection (LUTI). The hospital records of all patients aged >18 years with dysuria or problems with frequency or urgency in passing urine, >20 leukocytes/mm(3) in urine microscopy and culture-proven ESBL-producing NFT-sensitive E. coli in the urine (>10(5) CFU/mm(3)), no leukocytosis or fever and who were treated with NFT between January 2006 and May 2011 in our outpatient clinic or in the hospital were evaluated. All patients had received a NFT 50 mg capsule every 6 h for 14 days and had a control urine culture taken 7-9 days after therapy. ⋯ Re-infection and relapse rates were 6.5% (2/31) and 3.2% (1/31), respectively. In conclusion, these results suggest that NFT may be an alternative in the treatment of ESBL-producing E. coli-related LUTI. This is the first study in which NFT was used in the treatment of LUTI due to ESBL-producing E. coli as well as in patients with complicated UTI.
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Int. J. Antimicrob. Agents · Dec 2012
Comparative StudyEvaluation of benznidazole treatment combined with nifurtimox, posaconazole or AmBisome® in mice infected with Trypanosoma cruzi strains.
The present work aimed to investigate the curative effect of benznidazole (BZL) in combination with other patented drugs [nifurtimox (NFX), posaconazole (POS) or AmBisome(®) (AMB)] in mice acutely or chronically infected with either a BZL-susceptible (Tulahuen) or a BZL-partially-resistant (Y) strain of Trypanosoma cruzi. To appreciate the eventual advantage of such combinations, infected mice were treated for short durations (non-curative) of each individual treatment. Cure rates were determined by investigating blood parasites (microscopic examination) and parasite DNA (quantitative PCR) after submitting treated mice to immune suppression with cyclophosphamide. ⋯ Shortening the duration of treatment whilst keeping a complete curative effect deserves interest in limiting adverse reactions due to dose-cumulative toxic effects of long treatment. Genotyping of the T. cruzi strain(s) infecting patients might also allow a better adaptation of individual therapeutic schedules, improving both the efficiency and safety of trypanocidal treatment. This preliminary experimental study should encourage further investigations to find the best combination of adequate drug concentrations and timing of treatment.
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Int. J. Antimicrob. Agents · Nov 2012
Randomized Controlled TrialPharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia.
Several pathophysiological changes in critically ill patients are important in determining the therapeutic success of β-lactam antibiotics. The aim of this study was to assess the population pharmacokinetics and probabilities of target attainment (PTAs) of doripenem in patients with ventilator-associated pneumonia, comparing administration by 1-h and 4-h infusion. Patients were randomised into two groups: Group I received a 1-h infusion of 0.5 g every 8 h (q8h) for seven doses; and Group II received a 4-h infusion of 0.5 g q8h for seven doses. ⋯ For pathogens with a MIC of 1 μg/mL, the PTAs of achieving 40% T(>MIC) following administration of doripenem by a 1-h and 4-h infusion of 0.5 g q8h were 92.95% and 98.32%, respectively. For pathogens with a MIC of 2 μg/mL in immunocompromised hosts, the PTAs of achieving 80% T(>MIC) following administration of doripenem by 1-h and 4-h infusion of 2 g q8h were 56.57% and 91.21%, respectively. In conclusion, these findings indicated that higher than recommended doses in this patient population, particularly neutropenic patients, would be necessary to optimise the pharmacokinetics of doripenem.