ArticleThe Journal of infectious diseases2025
Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease.
Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic and quantitative analyses of hollow fiber model ofMicrobiology spectrum · 2026Pooled it
- Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens forAntimicrobial agents and chemotherapy · 2026Article
- The Role of β-Lactam Antibiotics in Treating Mycobacterium abscessus: From Laboratory Insights to Clinical Applications and the Case for Clinical Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Review
- Eravacycline pharmacokinetics/pharmacodynamics in the hollow fiber system model ofMicrobiology spectrum · 2026Article
- Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease.The Journal of antimicrobial chemotherapy · 2026Article
- Sulbactam-durlobactam improves cephalosporin and carbapenem susceptibility and time-kill effect againstMicrobiology spectrum · 2025Article
- Article
- Sulbactam-Durlobactam Plus Ceftriaxone Dosing and Novel Treatment Regimens forbioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundGuideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion (SCC) rates of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, its biologic effect, with or without β-lactamase inhibitors, is unproven.
methodsWe performed imipenem-relebactam minimum inhibitory concentration (MIC) in 122 Mab isolates, and an exposure-response study in the HFS-Mab using human intrapulmonary pharmacokinetics. The percentage of time that concentration persisted above the MIC (TMIC), mediating maximal effect in the HFS-Mab, was used as the exposure target for dose finding in a Monte Carlo experiment including 10 000 virtual patients. For real-world evidence, we performed a patient, intervention (imipenem), comparison (no β-lactam), and outcome (SCC) (PICO) analysis.
resultsImipenem killed 1.32 log10 colony-forming units/mL below the day 0 level in HFS-Mab. The average target exposure for imipenem was a TMIC of 47.9% (SD, 9.77%). Infusion of 1 g every 6 hours achieved the target in >90% of virtual patients in Monte Carlo experiments. The pharmacokinetic-pharmacodynamic MIC break point was 1 mg/L. In PICO analyses, the median time to SCC was 470 days in comparators, 311 days for imipenem added on to a failing regimen, and 37 days in newly treated patients (P = .049). The odds ratio for SCC when imipenem was part of the initial regimen, versus comparators, was 12.5 (95% confidence interval, 1.47--84.55). No patients receiving imipenem experienced treatment-limiting adverse events, compared with 2 of 7 comparators (P = .046). Middlebrook 7H9 broth MIC distribution, read at 24 hours, was better correlated with patient responses than cation-adjusted Mueller-Hinton broth.
conclusionsImipenem demonstrated biologic effect in the HFS-Mab and in patients. Imipenem-relebactam doses of 1 g every 6 hours are recommended.
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