{"doi":"10.5588/ijtldopen.24.0238","title":"Antibacterial action of penicillin against <i>Mycobacterium avium complex</i>","abstract":"SUMMARY INTRODUCTION β-lactam antibiotics are promising treatments for Mycobacterium avium complex (MAC) lung disease. We hypothesized that benzylpenicillin has efficacy against MAC. METHODS Benzylpenicillin lung concentration–time profiles of seven doses in three dosing schedules were administered for 28 days using the hollow fiber system model of intracellular MAC (HFS-MAC). Data were analyzed using the inhibitory sigmoid maximal effect (E max ) model for each sampling day, while two ordinary differential equations (ODEs) were used for the wild-type and penicillin-resistant mutants. RESULTS Benzylpenicillin killed &gt;2.1 log 10 colony-forming unit (CFU)/mL below Day 0, better than azithromycin, ethambutol, and rifabutin. Efficacy was terminated by acquired resistance. Sigmoid E max parameter estimates significantly differed between sampling days and were a poor fit. However, ODE model parameter estimates vs. exposure were a better fit. The exposure mediating E max was 84.6% (95% CI 76.91–82.98) of time concentration exceeded the minimum inhibitory concentration (MIC). In Monte Carlo experiments, 24 million international units of benzylpenicillin continuous infusion achieved the target exposure in lungs of &gt;90% of 10,000 subjects until an MIC of 64 mg/L, designated the susceptibility breakpoint. CONCLUSIONS Benzylpenicillin demonstrated a better bactericidal effect against MAC than guideline-recommended drugs before the development of resistance. Its role in combination therapy with other drugs with better efficacy than guideline-recommended drugs should be explored.","journal":"IJTLD OPEN","year":2024,"id":456312,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267028,"name":"Gesham Magombedze","orcid":"0000-0003-2745-3475","position":1,"is_corresponding":false},{"id":267029,"name":"Shashikant Srivastava","orcid":"0000-0002-8786-8851","position":2,"is_corresponding":false},{"id":267039,"name":"Tawanda Gumbo","orcid":"0000-0001-7592-8012","position":3,"is_corresponding":false},{"id":1081692,"name":"Devyani Deshpande","orcid":"0000-0002-1665-7619","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:03:27.785212Z","pmid":"39131587","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}