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Double-\u03b2-lactam combinations have been proposed to improve cure based on time-kill curves. We tested MICs followed by hollow fiber system model of MAB (HFS-MAB) exposure-effect studies with sulbactam-durlobactam administered every 8 h (q8h), q12h, and q24h, to identify target exposures. Next, the sulbactam-durlobactam target exposure plus ceftriaxone was administered in the HFS-MAB inoculated with three different MAB isolates, as was the sulbactam-durlobactam-ceftriaxone combination with epetraborole and omadacycline (SDCEO).\n                      <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                      -slopes (kill-speed) were calculated for all regimens. The minimal sulbactam-durlobactam clinical doses that achieved target exposure were identified using Monte Carlo experiments. Ceftriaxone reduced sulbactam-durlobactam MICs by eight-tube dilutions. In the HFS-MAB, sulbactam-durlobactam microbial kill and antimicrobial resistance were linked to % time concentration persists above MIC (%T\n                      <jats:sub>MIC<\/jats:sub>\n                      ), with target exposure of 50%T\n                      <jats:sub>MIC<\/jats:sub>\n                      . Sulbactam-durlobactam killed 3.85 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL below day 0 burden (\n                      <jats:italic toggle=\"yes\">\n                        B\n                        <jats:sub>0<\/jats:sub>\n                      <\/jats:italic>\n                      ) with regrowth. Sulbactam-durlobactam plus ceftriaxone killed without regrowth and demonstrated Bliss additivity. The kill slope of bacterial population in &gt;95% of virtual subjects was 2.28 (0.97\u20134.80) log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL\/day for sulbactam-durlobactam-ceftriaxone and 2.91 (1.65\u20134.93) log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL\/day for SDCEO. The optimal sulbactam-durlobactam dose co-administered with ceftriaxone was 2G q8h for creatinine clearance &gt;90 mL\/min (or 4G q12h for outpatients), 2G q12h for 60\u201390 mL\/min, 1G q12h for \u226530 to &lt;60 mL\/min, and 1G q24h for &lt;30 mL\/min. Sulbactam-durlobactam-ceftriaxone achieved the highest microbial kill encountered so far in the HFS-MAB. Sulbactam-durlobactam-ceftriaxone should be tested as the backbone for novel treatment shortening regimens.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01437-25","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:00:11Z","timestamp":1775739611000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens for\n                    <i>Mycobacterium abscessus<\/i>\n                    lung disease"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4601-5673","authenticated-orcid":true,"given":"Sanjay","family":"Singh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01azfw069","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas at Tyler","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avneesh","family":"Shrivastava","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01azfw069","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas at Tyler","place":["Tyler, USA"]}],"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, School of Medicine, University of Texas at Tyler","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C.","family":"Long","sequence":"additional","affiliation":[{"name":"Advanta Genetics","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Robbins","sequence":"additional","affiliation":[{"name":"Advanta Genetics","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J.","family":"McShane","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01azfw069","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Pulmonary and Critical Care, Department of Medicine, School of Medicine, University of Texas at Tyler","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-8012","authenticated-orcid":true,"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[{"name":"IMPI Group of Companies","place":["Mt. 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