ArticleAntimicrobial agents and chemotherapy2010
Moxifloxacin pharmacokinetics/pharmacodynamics and optimal dose and susceptibility breakpoint identification for treatment of disseminated Mycobacterium avium infection.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 52 citations in OpenAlex.
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- Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses.The Journal of antimicrobial chemotherapy · 2022Article
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Drug Treatment of Non-Tuberculous Mycobacteria in Cystic Fibrosis.Clinical pharmacokinetics · 2021Review
- Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections.Clinical pharmacokinetics · 2021Review
- Comparison of Rifamycins for Efficacy AgainstFrontiers in pharmacology · 2021Article
- Feline mycobacterial disease in northern California: Epidemiology, clinical features, and antimicrobial susceptibility.Journal of veterinary internal medicine · 2021Article
- Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research.Pathogens (Basel, Switzerland) · 2020Review
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Authors and funding
6 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Organisms of the Mycobacterium avium-intracellulare complex (MAC) have been demonstrated to be susceptible to moxifloxacin. However, clinical data on how to utilize moxifloxacin to treat disseminated MAC are scanty. In addition, there have been no moxifloxacin pharmacokinetic-pharmacodynamic (PK/PD) studies performed for MAC infection. We utilized an in vitro PK/PD model of intracellular MAC to study moxifloxacin PK/PD for disseminated disease. Moxifloxacin doses, based on a serum half-life of 12 h, were administered, and the 0- to 24-h area under the concentration-time curve (AUC(0-24)) to MIC ratios associated with 1.0 log(10) CFU/ml per week kill and 90% of maximal kill (EC(90)) were identified. The AUC(0-24)/MIC ratio associated with 1.0 log(10) CFU/ml kill was 17.12, and that with EC(90) was 391.56 (r(2) = 0.97). Next, the moxifloxacin MIC distribution in 102 clinical isolates of MAC was identified. The median MIC was 1 to 2 mg/liter. Monte Carlo simulations of 10,000 patients with disseminated MAC were performed to determine the probability that daily moxifloxacin doses of 400 and 800 mg/day would achieve or exceed 1.0 log(10) CFU/ml per week kill or EC(90). Doses of 400 and 800 mg/day achieved the AUC(0-24)/MIC ratio of 17.12 in 64% and 92% of patients, respectively. The critical concentration of moxifloxacin against MAC was identified as 0.25 mg/liter in Middlebrook media. The proposed susceptibility breakpoint means that a larger proportion of clinical isolates is resistant to moxifloxacin prior to therapy. For patients infected with susceptible isolates, however, 800 mg a day should be examined for safety and efficacy for disseminated M. avium disease.
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