{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T09:50:15Z","timestamp":1775382615548,"version":"3.50.1"},"reference-count":29,"publisher":"International Union Against Tuberculosis and Lung Disease","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJTLD Open"],"accepted":{"date-parts":[[2024,7,11]]},"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      \u03b2-lactam antibiotics are promising treatments for\n                      <jats:italic>Mycobacterium avium<\/jats:italic>\n                      complex (MAC) lung disease. We hypothesized that benzylpenicillin has efficacy against MAC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Benzylpenicillin lung concentration\u2013time 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\n                      <jats:sub>max<\/jats:sub>\n                      ) model for each sampling day, while two ordinary differential equations (ODEs) were used for the wild-type and penicillin-resistant mutants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Benzylpenicillin killed &gt;2.1 log\n                      <jats:sub>10<\/jats:sub>\n                      colony-forming unit (CFU)\/mL below Day 0, better than azithromycin, ethambutol, and rifabutin. Efficacy was terminated by acquired resistance. Sigmoid E\n                      <jats:sub>max<\/jats:sub>\n                      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\n                      <jats:sub>max<\/jats:sub>\n                      was 84.6% (95% CI 76.91\u201382.98) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5588\/ijtldopen.24.0238","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:51:13Z","timestamp":1723078273000},"page":"362-368","source":"Crossref","is-referenced-by-count":7,"title":["Antibacterial action of penicillin against\n                    <i>Mycobacterium avium complex<\/i>"],"prefix":"10.5588","volume":"1","author":[{"given":"D.","family":"Deshpande","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Magombedze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Gumbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3554","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"2026011502101269000_1.8.362.1","first-page":"226","article-title":"On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae","volume":"10","author":"Fleming","year":"1929","journal-title":"Br J Exp Pathol"},{"key":"2026011502101269000_1.8.362.2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700580321"},{"key":"2026011502101269000_1.8.362.3","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700580320"},{"issue":"2","key":"2026011502101269000_1.8.362.4","doi-asserted-by":"crossref","first-page":"e02246","DOI":"10.1128\/AAC.02232-17","article-title":"Antibacterial and sterilizing effect of benzylpenicillin in tuberculosis","volume":"62","author":"Deshpande","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011502101269000_1.8.362.5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad545"},{"key":"2026011502101269000_1.8.362.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2024.107204"},{"key":"2026011502101269000_1.8.362.7","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx030"},{"key":"2026011502101269000_1.8.362.8","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix517"},{"issue":"12","key":"2026011502101269000_1.8.362.9","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.5588\/ijtld.18.0171","article-title":"Adverse reactions associated with long-term drug administration in Mycobacterium avium complex lung disease","volume":"22","author":"Kamii","year":"2018","journal-title":"Int J Tuberc Lung Dis"},{"issue":"Suppl_2","key":"2026011502101269000_1.8.362.10","doi-asserted-by":"crossref","first-page":"i60","DOI":"10.1093\/jac\/dkx309","article-title":"A programme to create short-course chemotherapy for pulmonary Mycobacterium avium disease based on pharmacokinetics\/pharmacodynamics and mathematical forecasting","volume":"72","author":"Deshpande","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2026011502101269000_1.8.362.11","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01761-09"},{"issue":"Suppl_2","key":"2026011502101269000_1.8.362.12","doi-asserted-by":"crossref","first-page":"i53","DOI":"10.1093\/jac\/dkx307","article-title":"A novel ceftazidime\/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM) regimen for pulmonary Mycobacterium avium disease","volume":"72","author":"Deshpande","year":"2017","journal-title":"J Antimicrob Chemother"},{"issue":"593","key":"2026011502101269000_1.8.362.13","doi-asserted-by":"crossref","first-page":"645264","DOI":"10.3389\/fphar.2021.645264","article-title":"Comparison of rifamycins for efficacy against Mycobacterium avium complex and resistance emergence in the hollow fiber model system","volume":"12","author":"Boorgula","year":"2021","journal-title":"Front Pharmacol"},{"issue":"suppl_2","key":"2026011502101269000_1.8.362.14","doi-asserted-by":"crossref","first-page":"i23","DOI":"10.1093\/jac\/dkx303","article-title":"Failure of the azithromycin and ethambutol combination regimen in the hollow-fibre system model of pulmonary Mycobacterium avium infection is due to acquired resistance","volume":"72","author":"Srivastava","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2026011502101269000_1.8.362.15","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05546-11"},{"key":"2026011502101269000_1.8.362.16","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.50.5034"},{"key":"2026011502101269000_1.8.362.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2011.10.001"},{"issue":"Suppl_3","key":"2026011502101269000_1.8.362.18","doi-asserted-by":"crossref","first-page":"S358","DOI":"10.1093\/cid\/ciy623","article-title":"Transformation morphisms and time to extinction analysis that map therapy duration from pre-clinical models to patients with tuberculosis: translating from apples to oranges","volume":"67","author":"Magombedze","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2026011502101269000_1.8.362.19","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac068"},{"key":"2026011502101269000_1.8.362.20","unstructured":"Clinical & Laboratory Standards Institute . Susceptibility testing of mycobacteria, nocardia spp., and other aerobic actinomycetes. 3rd ed. CLSI Standard M24. Malvern, PA, USA: CLSI, 2018."},{"issue":"2","key":"2026011502101269000_1.8.362.21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1128\/AAC.02232-17","article-title":"Antibacterial and sterilizing effect of benzylpenicillin in tuberculosis","volume":"62","author":"Deshpande","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011502101269000_1.8.362.22","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01355-09"},{"key":"2026011502101269000_1.8.362.23","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4770.1211"},{"issue":"6667","key":"2026011502101269000_1.8.362.24","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0140-6736(51)92756-0","article-title":"Concentration of penicillin in the lungs. Effects of two penicillin esters in chronic pulmonary infections","volume":"1","author":"Heathcote","year":"1951","journal-title":"Lancet"},{"key":"2026011502101269000_1.8.362.25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40780-016-0043-x","article-title":"Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis","volume":"2","author":"Komatsu","year":"2016","journal-title":"J Pharm Health Care Sci"},{"issue":"suppl_2","key":"2026011502101269000_1.8.362.26","doi-asserted-by":"crossref","first-page":"i42","DOI":"10.1093\/jac\/dkx306","article-title":"The discovery of ceftazidime\/avibactam as an anti-Mycobacterium avium agent","volume":"72","author":"Deshpande","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2026011502101269000_1.8.362.27","doi-asserted-by":"publisher","DOI":"10.1086\/510079"},{"key":"2026011502101269000_1.8.362.28","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00829-13"},{"key":"2026011502101269000_1.8.362.29","doi-asserted-by":"crossref","unstructured":"Shah RV , . Population pharmacokinetic study of benzylpenicillin in critically unwell adults. Antibiotics (Basel). 2023;12(4).","DOI":"10.3390\/antibiotics12040643"}],"container-title":["IJTLD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.5588\/ijtldopen.24.0238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:16:51Z","timestamp":1768472211000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.theunion.org\/lookup\/doi\/10.5588\/ijtldopen.24.0238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,1]]},"published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.5588\/ijtldopen.24.0238"],"URL":"https:\/\/doi.org\/10.5588\/ijtldopen.24.0238","relation":{},"ISSN":["3005-7590"],"issn-type":[{"value":"3005-7590","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]}}}