The Journal of antimicrobial chemotherapy
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J. Antimicrob. Chemother. · Apr 2019
Pharmacokinetics/pharmacodynamics of lefamulin in a neutropenic murine pneumonia model with Staphylococcus aureus and Streptococcus pneumoniae.
To present results of preclinical studies that supported further development of lefamulin for treating patients with community-acquired bacterial pneumonia (CABP). ⋯ Overall, lefamulin displays desirable pharmacokinetic/pharmacodynamic relationships that are predictive of the clinical effectiveness of lefamulin and other antibacterial agents used to treat CABP.
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J. Antimicrob. Chemother. · Apr 2019
Introduction: lefamulin and pharmacokinetic/pharmacodynamic rationale to support the dose selection of lefamulin.
Lefamulin is the first semisynthetic pleuromutilin being developed for oral and intravenous administration. The drug selectively inhibits prokaryotic ribosomal protein synthesis by binding to the peptidyl transferase centre via four H-bonds and other interactions, resulting in an 'induced fit' that tightens the binding pocket around lefamulin. ⋯ This Supplement, entitled 'Pharmacokinetic and pharmacodynamic analyses and dose rationale for lefamulin, a novel pleuromutilin antibiotic, for the treatment of community-acquired bacterial pneumonia', is intended to be a valuable resource for both clinicians and researchers. It provides the essential pharmacokinetic and pharmacodynamic data on lefamulin that were used to support the optimal dose selection of lefamulin for the safe and effective treatment of CABP in adults.
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J. Antimicrob. Chemother. · Apr 2019
Single- and multiple-dose pharmacokinetics and total removal of colistin in critically ill patients with acute kidney injury undergoing prolonged intermittent renal replacement therapy.
Owing to the emerging problem of MDR bacteria, interest in 'old' antibiotics such as colistin has re-emerged. However, research on the dosing of colistin in patients undergoing renal replacement therapy (RRT), such as prolonged intermittent renal replacement therapy (PIRRT), is scarce. ⋯ PIRRT eliminates about half of the daily administered colistin dose. Even a 6 MIU loading dose of colistin methanesulfonate may not ensure immediate sufficient colistin plasma levels in all critically ill patients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity.
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J. Antimicrob. Chemother. · Mar 2019
Ciprofloxacin in critically ill subjects: considering hepatic function, age and sex to choose the optimal dose.
Pathophysiological changes often result in altered pharmacokinetics of ciprofloxacin in critically ill patients. Although ciprofloxacin clearance (CLCIP) substantially depends on kidney function in healthy volunteers, its relationship to measured creatinine clearance (CLCRM) is weak in critically ill patients. ⋯ Bilirubin, age and sex should be considered to assess the need for dose reductions. For MICs ≤0.25 mg/L, it might be appropriate to reduce the dose to 400 mg/day for elderly female subjects with high bilirubin.
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J. Antimicrob. Chemother. · Mar 2019
Antibiotic prescribing for the older adult: beliefs and practices in primary care.
Older adults suffer high morbidity and mortality following serious infections, and hospital admissions with these conditions are increasingly common. Antibiotic prescribing in the older adult population, especially in long-term care facilities, has been argued to be inappropriately high. In order to develop the evidence base and provide support to GPs in achieving antimicrobial stewardship in older adults it is important to understand their attitudes and beliefs toward antibiotic prescribing in this population. ⋯ Diagnosing serious infections in older adults is challenging and antibiotic prescribing practices reflect this challenge, but also reflect an absence of clear guidance or evidence. Research that can fill the gaps in the evidence base is required in order to support GPs with their critical antimicrobial stewardship role in this population.