Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease
Abstract Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral...
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| Veröffentlicht in: | The Journal of infectious diseases 2024-08, Vol.230 (2), p.e241-e246 |
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| container_title | The Journal of infectious diseases |
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| creator | Negatu, Dereje A Shin, Sung Jae Kim, Su-Young Jhun, Byung Woo Dartois, Véronique Dick, Thomas |
| description | Abstract
Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral β-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual β-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.
Graphical Abstract
Graphical Abstract
Oral β-lactam pairs combining tebipenem, sulopenem, or amoxicillin with cefuroxime achieve strong bactericidal activity at recommended doses against pulmonary disease caused by the Mycobacterium avium complex. |
| doi_str_mv | 10.1093/infdis/jiad591 |
| format | Article |
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Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral β-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual β-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.
Graphical Abstract
Graphical Abstract
Oral β-lactam pairs combining tebipenem, sulopenem, or amoxicillin with cefuroxime achieve strong bactericidal activity at recommended doses against pulmonary disease caused by the Mycobacterium avium complex.</description><identifier>ISSN: 0022-1899</identifier><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiad591</identifier><identifier>PMID: 38150401</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Administration, Oral ; Amoxicillin ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; beta-Lactams - administration & dosage ; beta-Lactams - therapeutic use ; Brief Report ; Bronchopulmonary infection ; Carbapenems ; Cefuroxime ; Clinical trials ; Humans ; Lung diseases ; Lung Diseases - drug therapy ; Lung Diseases - microbiology ; Microbial Sensitivity Tests ; Mycobacterium avium ; Mycobacterium avium Complex - drug effects ; Mycobacterium avium-intracellulare Infection - drug therapy ; Mycobacterium avium-intracellulare Infection - microbiology ; Penicillin ; β-Lactam antibiotics</subject><ispartof>The Journal of infectious diseases, 2024-08, Vol.230 (2), p.e241-e246</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-e8bbd289a7c5a07e89fe040dfbf2fcf76233ccf27616543e00d9f780f7bb991d3</citedby><cites>FETCH-LOGICAL-c453t-e8bbd289a7c5a07e89fe040dfbf2fcf76233ccf27616543e00d9f780f7bb991d3</cites><orcidid>0000-0001-9470-5009 ; 0000-0001-9205-6842</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38150401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Negatu, Dereje A</creatorcontrib><creatorcontrib>Shin, Sung Jae</creatorcontrib><creatorcontrib>Kim, Su-Young</creatorcontrib><creatorcontrib>Jhun, Byung Woo</creatorcontrib><creatorcontrib>Dartois, Véronique</creatorcontrib><creatorcontrib>Dick, Thomas</creatorcontrib><title>Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral β-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual β-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.
Graphical Abstract
Graphical Abstract
Oral β-lactam pairs combining tebipenem, sulopenem, or amoxicillin with cefuroxime achieve strong bactericidal activity at recommended doses against pulmonary disease caused by the Mycobacterium avium complex.</description><subject>Administration, Oral</subject><subject>Amoxicillin</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>beta-Lactams - administration & dosage</subject><subject>beta-Lactams - therapeutic use</subject><subject>Brief Report</subject><subject>Bronchopulmonary infection</subject><subject>Carbapenems</subject><subject>Cefuroxime</subject><subject>Clinical trials</subject><subject>Humans</subject><subject>Lung diseases</subject><subject>Lung Diseases - drug therapy</subject><subject>Lung Diseases - microbiology</subject><subject>Microbial Sensitivity Tests</subject><subject>Mycobacterium avium</subject><subject>Mycobacterium avium Complex - drug effects</subject><subject>Mycobacterium avium-intracellulare Infection - drug therapy</subject><subject>Mycobacterium avium-intracellulare Infection - microbiology</subject><subject>Penicillin</subject><subject>β-Lactam antibiotics</subject><issn>0022-1899</issn><issn>1537-6613</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvLlSOyxAUOacdxHMenCi1tQdqqPRRxtBxnTL1K4sVOKvq3-kP6m-pqlwp64TJzmG-e3tMj5B2DQwaKH_nRdT4drb3phGIvyIIJLou6ZvwlWQCUZcEapfbIm5TWAFDxWr4me7xhAipgC_LjIpqe3t8VK2MnM9BL42OiLkQ6XSO9imimAceJBkfPb21oM4XRzwM1N49zGYZNj7_p5dwPYTTxln7xCU3CA_LKmT7h293eJ99PT66WX4vVxdm35edVYSvBpwKbtu3KRhlphQGJjXKYjXWudaWzTtYl59a6UtasFhVHgE452YCTbasU6_g-Od7qbuZ2wM5mrzmQ3kQ_ZDc6GK__vYz-Wv8MN5oxXtYNq7LCx51CDL9mTJMefLLY92bEMCddKpBMCclZRj88Q9dhjmPOpzkDDkKCFJk63FI2hpQiuic3DPRjaXpbmt6Vlh_e_53hCf_TUgY-bYEwb_4n9gAePqUM</recordid><startdate>20240816</startdate><enddate>20240816</enddate><creator>Negatu, Dereje A</creator><creator>Shin, Sung Jae</creator><creator>Kim, Su-Young</creator><creator>Jhun, Byung Woo</creator><creator>Dartois, Véronique</creator><creator>Dick, Thomas</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9470-5009</orcidid><orcidid>https://orcid.org/0000-0001-9205-6842</orcidid></search><sort><creationdate>20240816</creationdate><title>Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease</title><author>Negatu, Dereje A ; Shin, Sung Jae ; Kim, Su-Young ; Jhun, Byung Woo ; Dartois, Véronique ; Dick, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-e8bbd289a7c5a07e89fe040dfbf2fcf76233ccf27616543e00d9f780f7bb991d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Administration, Oral</topic><topic>Amoxicillin</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>beta-Lactams - administration & dosage</topic><topic>beta-Lactams - therapeutic use</topic><topic>Brief Report</topic><topic>Bronchopulmonary infection</topic><topic>Carbapenems</topic><topic>Cefuroxime</topic><topic>Clinical trials</topic><topic>Humans</topic><topic>Lung diseases</topic><topic>Lung Diseases - drug therapy</topic><topic>Lung Diseases - microbiology</topic><topic>Microbial Sensitivity Tests</topic><topic>Mycobacterium avium</topic><topic>Mycobacterium avium Complex - drug effects</topic><topic>Mycobacterium avium-intracellulare Infection - drug therapy</topic><topic>Mycobacterium avium-intracellulare Infection - microbiology</topic><topic>Penicillin</topic><topic>β-Lactam antibiotics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Negatu, Dereje A</creatorcontrib><creatorcontrib>Shin, Sung Jae</creatorcontrib><creatorcontrib>Kim, Su-Young</creatorcontrib><creatorcontrib>Jhun, Byung Woo</creatorcontrib><creatorcontrib>Dartois, Véronique</creatorcontrib><creatorcontrib>Dick, Thomas</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Negatu, Dereje A</au><au>Shin, Sung Jae</au><au>Kim, Su-Young</au><au>Jhun, Byung Woo</au><au>Dartois, Véronique</au><au>Dick, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2024-08-16</date><risdate>2024</risdate><volume>230</volume><issue>2</issue><spage>e241</spage><epage>e246</epage><pages>e241-e246</pages><issn>0022-1899</issn><issn>1537-6613</issn><eissn>1537-6613</eissn><abstract>Abstract
Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral β-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual β-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.
Graphical Abstract
Graphical Abstract
Oral β-lactam pairs combining tebipenem, sulopenem, or amoxicillin with cefuroxime achieve strong bactericidal activity at recommended doses against pulmonary disease caused by the Mycobacterium avium complex.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>38150401</pmid><doi>10.1093/infdis/jiad591</doi><orcidid>https://orcid.org/0000-0001-9470-5009</orcidid><orcidid>https://orcid.org/0000-0001-9205-6842</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE |
| subjects | Administration, Oral Amoxicillin Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - therapeutic use Antibiotics beta-Lactams - administration & dosage beta-Lactams - therapeutic use Brief Report Bronchopulmonary infection Carbapenems Cefuroxime Clinical trials Humans Lung diseases Lung Diseases - drug therapy Lung Diseases - microbiology Microbial Sensitivity Tests Mycobacterium avium Mycobacterium avium Complex - drug effects Mycobacterium avium-intracellulare Infection - drug therapy Mycobacterium avium-intracellulare Infection - microbiology Penicillin β-Lactam antibiotics |
| title | Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease |
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