The Journal of antimicrobial chemotherapy
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J. Antimicrob. Chemother. · Apr 2019
Randomized Controlled TrialPrediction of lefamulin epithelial lining fluid penetration after intravenous and oral administration using Phase 1 data and population pharmacokinetics methods.
Lefamulin is a semi-synthetic intravenous and oral pleuromutilin antibiotic with activity against pathogens commonly associated with community-acquired bacterial pneumonia. Using data from two Phase 1 studies, a population pharmacokinetics (PPK) model for lefamulin in plasma and epithelial lining fluid (ELF) was constructed. ⋯ The final PPK model allowed precise characterization of plasma and ELF exposures after intravenous and oral administration. The high ELF penetration ratio suggests that the penetration of lefamulin into the effect site is rapid and extensive, irrespective of route of administration.
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J. Antimicrob. Chemother. · Apr 2019
Pharmacokinetic/pharmacodynamic target attainment analyses to support intravenous and oral lefamulin dose selection for the treatment of patients with community-acquired bacterial pneumonia.
Lefamulin is a semi-synthetic intravenous (iv) and oral pleuromutilin antibiotic active against community-acquired bacterial pneumonia (CABP) pathogens. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment analyses were carried out to evaluate lefamulin 150 mg iv q12h and 600 mg orally q12h under fed and fasted conditions for the treatment of patients with CABP. ⋯ These data provide support for lefamulin 150 mg iv q12h and 600 mg orally q12h for the treatment of patients with CABP and suggest that doses may not need to be taken under fasted conditions.
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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. · 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.