International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Jan 2012
ReviewUsing pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review.
The prevalence of invasive fungal infections (IFIs) caused by Candida spp. is increasing in critically ill patients. Recent development of new antifungal agents has significantly contributed to the successful treatment of IFIs. However, the pharmacokinetics of antifungal agents can be altered in a number of disease states, including critical illness. ⋯ This systematic review provides a critical analysis of the pharmacokinetics of antifungal agents in the critically ill and their relevance to dosing requirements in clinical practice. Based on the limited data available, dosing of some antifungal agents may have to be adjusted in critically ill patients with conserved renal function as well as in those requiring renal replacement therapy. Further research to confirm the appropriateness of current dosing strategies to attain the appropriate pharmacodynamic targets is recommended.
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Int. J. Antimicrob. Agents · Jan 2012
Characteristics of carbapenem-resistant Acinetobacter spp. other than Acinetobacter baumannii in South Korea.
Although many studies have been performed on carbapenem-resistant Acinetobacter baumannii, only a few studies have addressed carbapenem resistance in Acinetobacter spp. other than A. baumannii (non-baumannii Acinetobacter). Amongst 287 Acinetobacter spp. isolates from patients with bacteraemia in a South Korean hospital collected between 2003 and 2010, 160 (55.7%) were non-baumannii Acinetobacter spp. Antimicrobial susceptibility testing was performed and the effect of efflux pump inhibitors was examined. ⋯ Clonal spread of carbapenem-resistant A. pittii carrying bla(IMP-1), which contributes to a high resistance rate in this species, was identified. The bla(IMP-1) and bla(SIM-1) genes were first identified in A. bereziniae and A. nosocomialis, respectively. Since no carbapenem resistance mechanisms could be identified, further efforts to find the resistance mechanism should be made.
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Int. J. Antimicrob. Agents · Jan 2012
Improving vancomycin prescription in critical illness through a drug use evaluation process: a weight-based dosing intervention study.
Vancomycin is currently recommended as first-line therapy for many meticillin-resistant Staphylococcus aureus (MRSA) infections. Recent guidelines have advocated loading doses (25-30 mg/kg) in critically ill patients in order to achieve therapeutic concentrations rapidly. However, weight-based loading doses are still not widely practised. ⋯ Despite higher weight-based initial doses, only 32.3% of patients in the post-intervention group had achieved optimal vancomycin exposures (AUC/minimum inhibitory concentration ratio ≥400) in the first 24h of therapy. A vancomycin dosing protocol improved the initial dosing of vancomycin and the proportion of patients who rapidly achieved optimal vancomycin exposures. However, subtherapeutic exposures were still prevalent and may warrant more vigilant promotion of the dosing protocol to ensure that recommended vancomycin doses are used in this population.
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Int. J. Antimicrob. Agents · Jan 2012
In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae.
The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 β-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-β-lactamase and extended-spectrum β-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. ⋯ MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 β-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme.