{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:46:34Z","timestamp":1785851194895,"version":"3.56.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1129600"],"award-info":[{"award-number":["OPP1129600"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Safe and effective treatment options for tuberculosis (TB) are urgently needed for pregnant and lactating women due to the adverse maternal and neonatal outcomes associated with TB disease. Pretomanid is recommended by the World Health Organization for treatment of multidrug-resistant pulmonary TB in combination with bedaquiline and linezolid. However, this regimen is not recommended during pregnancy or breastfeeding due to the absence of clinical safety and efficacy data of pretomanid in these populations. This manuscript presents the nonclinical developmental and reproductive toxicology profile of pretomanid and clinical outcomes of pregnancies in women known to have been exposed to pretomanid. In nonclinical studies, pretomanid did not have a direct effect on fertility and reproductive function in female rats, and no adverse maternal or developmental effects were seen in rats or rabbits up to two times the clinical exposure during organogenesis. Additionally, no adverse developmental effects were observed in pups of pregnant rats orally dosed throughout gestation and lactation at approximately 1.5-fold clinical exposure. In the rat pre- and postnatal development study at 4.4-fold clinical exposure, there was maternal toxicity, lower pup body weights, and a delay in attaining the righting reflex, but no effects on fertility were seen in the male or female rat offspring. Clinically, 11 women became pregnant during pretomanid treatment: 5 had healthy babies, 5 had elective abortions, and 1 had a spontaneous abortion. The weight of evidence from preclinical studies and limited clinical outcomes supports further evaluation of pretomanid use in pregnant or lactating women.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>CLINICAL TRIALS<\/jats:title>\n                      <jats:p>\n                        This study is registered with ClinicalTrials.gov as\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03086486\" xlink:type=\"simple\">NCT03086486.<\/jats:ext-link>\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00343-26","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:56:36Z","timestamp":1783695396000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Safety evaluation of pretomanid, an anti-tuberculosis drug, for the treatment of pregnant and lactating women"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1229-247X","authenticated-orcid":true,"given":"R.","family":"Bruning-Barry","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052tfza37","id-type":"ROR","asserted-by":"publisher"}],"name":"RTI International","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-6034","authenticated-orcid":true,"given":"J. L.","family":"Ambroso","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052tfza37","id-type":"ROR","asserted-by":"publisher"}],"name":"RTI International","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3427-0565","authenticated-orcid":true,"given":"X.","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052tfza37","id-type":"ROR","asserted-by":"publisher"}],"name":"RTI International","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6761-9764","authenticated-orcid":true,"given":"D.","family":"Hickman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Harkins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Noble","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Paris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1151-0049","authenticated-orcid":true,"given":"S.","family":"Foraida","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2326-0570","authenticated-orcid":true,"given":"E.","family":"Sun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-2482","authenticated-orcid":true,"given":"M.","family":"Beumont","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ms7cf36","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Alliance for TB Drug Development","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO. 2025. 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World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad445"},{"key":"e_1_3_4_10_2","volume-title":"Key updates to the treatment of drug-resistant tuberculosis: rapid communication","author":"WHO","year":"2024","unstructured":"WHO. 2024. Key updates to the treatment of drug-resistant tuberculosis: rapid communication. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","unstructured":"Conradie F Badat T Poswa A Rajaram S Kooverjee S Maartens G Meintjes G Ndjeka N Schaaf HS Hughes J et al.. 2025. BEAT Tuberculosis: a randomized controlled trial of a 6-month strategy for rifampicin-resistant tuberculosis. medRxiv. doi:10.1101\/2025.05.04.25326549","DOI":"10.1101\/2025.05.04.25326549"},{"key":"e_1_3_4_12_2","unstructured":"WHO. 2024. Global tuberculosis report 2024. World Health Organization Geneva Switzerland"},{"key":"e_1_3_4_13_2","unstructured":"International Council for Harmonisation (ICH. 2021. S5(R3) detection of reproductive and developmental toxicity for human pharmaceuticals. Food and Drug Administration. Available from: https:\/\/www.fda.gov\/media\/148475\/download"},{"key":"e_1_3_4_14_2","unstructured":"International Council for Harmonisation (ICH). 2010. M3(R2) nonclinical safety studies for the conduct of human clinical trials and marketing authorization of pharmaceuticals. Food and Drug Administration. Available from: https:\/\/www.fda.gov\/media\/71542\/download"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00907-19"},{"key":"e_1_3_4_16_2","unstructured":"Mylan. 2024. Pretomanid [package insert]"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2022.04.021"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623312466452"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad767"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002882"},{"key":"e_1_3_4_21_2","unstructured":"Otsuka. 2023. Delamanid (Deltyba) summary of product characteristics. European Medicines Agency. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/deltyba-epar-product-information_en.pdf"},{"key":"e_1_3_4_22_2","unstructured":"Mylan. 2023. Pretomanid (dovprela) summary of product characteristics. European Medicines Agency. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/dovprela-epar-product-information_en.pdf"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.70363"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.21.0654"},{"key":"e_1_3_4_25_2","unstructured":"WHO. 2025. WHO TB knowledge sharing platform operational handbooks module 4: treatment drug-resistant tuberculosis treatment 2022 update 6. the longer regimens 6.3 key subgroups 6.3.3 pregnant and lactating women. Geneva Switzerland"},{"key":"e_1_3_4_26_2","volume-title":"Early pregnancy loss (spontaneous abortion)","author":"Alves C","year":"2025","unstructured":"Alves C, Jenkins SM, Rapp A. 2025. Early pregnancy loss (spontaneous abortion). StatPearls Publishing, Treasure Island, Florida."},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000003069"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00343-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00343-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:02:17Z","timestamp":1785848537000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00343-26"}},"subtitle":[],"editor":[{"given":"Sean","family":"Wasserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,5]]}},"alternative-id":["10.1128\/aac.00343-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00343-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"assertion":[{"value":"2026-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00343-26"}}