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However, ethambutol pharmacokinetics\/pharmacodynamics (PK\/PD) studies to inform on optimal exposure target and clinical dose for MKC are lacking. We performed studies to determine ethambutol minimum inhibitory concentration (MIC), mutation frequency (3\u00d7 MIC), a PK\/PD study using the hollow fiber system model of MKC (HFS-MKC) using the reference ATCC#12478 strain, and Monte Carlo simulation experiments for clinical dose selection and susceptibility breakpoint. We also performed a literature search to generate ethambutol MIC distribution for MKC. First, nine studies were identified with MIC of 587 isolates, and MIC\n                      <jats:sub>50<\/jats:sub>\n                      and MIC\n                      <jats:sub>90<\/jats:sub>\n                      identified as 4 and 16 mg\/L, respectively. Second, the ethambutol MIC of the ATCC strain was 8 mg\/L, and the mutation frequency was 4.23 \u00d7 10\n                      <jats:sup>\u22122<\/jats:sup>\n                      CFU\/mL. Third, in the HFS-MKC, ethambutol failed to kill\n                      <jats:italic toggle=\"yes\">M. kansasii<\/jats:italic>\n                      below stasis (\n                      <jats:italic toggle=\"yes\">B<\/jats:italic>\n                      <jats:sub>0<\/jats:sub>\n                      ), and resistance emerged rapidly. The target exposure was an AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      \/MIC of 5.47 (95% confidence interval: 1.17\u20139.77). Fourth, Monte Carlo experiments of 10,000 virtual subjects identified doses of 1,200 and 3,000 mg to achieve or exceed target exposure in 18.21% and 58.57% of patients; and PK\/PD MIC susceptibility breakpoints were determined as 2 and 4 mg\/L, respectively. Doses &gt;1,200 mg\/day may have a higher likelihood of ocular toxicity. The risk of toxicity versus no microbial kill benefit in HFS-MKC suggests the need for better drugs compared to ethambutol in the treatment of MKC lung disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01447-25","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:01:39Z","timestamp":1766152899000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical pharmacokinetics\/pharmacodynamics studies defining the role of ethambutol in\n                    <i>Mycobacterium kansasii<\/i>\n                    lung disease"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-8012","authenticated-orcid":true,"given":"Tawanda","family":"Gumbo","sequence":"first","affiliation":[{"name":"NASOS Biotech","place":["Dallas, USA"]},{"name":"IMPI Group","place":["Tateguru, Zimbabwe"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunavanthi D.","family":"Boorgula","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01azfw069","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, The University of Texas at Tyler School of Medicine","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-8851","authenticated-orcid":true,"given":"Shashikant","family":"Srivastava","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01azfw069","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, The University of Texas at Tyler School of Medicine","place":["Tyler, USA"]},{"id":[{"id":"https:\/\/ror.org\/01sps7q28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa241"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02320-21"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2022.102289"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01553-20"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00687-22"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00810-20"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04441-14"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00248-18"},{"key":"e_1_3_3_10_2","volume-title":"Goodman & Gilman\u2019s the pharmacological basis of therapeutics","author":"Gumbo T","year":"2018","unstructured":"Gumbo T. 2018. 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