{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:24:07Z","timestamp":1792610647275,"version":"4.5.0"},"reference-count":63,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antimicrobial resistance poses a significant public health challenge, particularly with the rise of gram\u2010negative hospital\u2010acquired infections resistant to carbapenems. Aztreonam\u2013avibactam (ATM\u2013AVI) is a promising new combination therapy designed to combat multidrug\u2010resistant (MDR) gram\u2010negative bacteria, including those producing metallo\u2010\u03b2\u2010lactamases (MBLs). Aztreonam, a monobactam antibiotic, is resistant to hydrolysis by MBLs but can be degraded by other \u03b2\u2010lactamases. Avibactam, a novel non\u2010\u03b2\u2010lactam \u03b2\u2010lactamase inhibitor, effectively neutralizes extended\u2010spectrum \u03b2\u2010lactamases (ESBLs) and AmpC \u03b2\u2010lactamases, restoring aztreonam's efficacy against resistant pathogens. This review covers the chemistry, mechanisms of action, spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical efficacy of ATM\u2013AVI. ATM\u2013AVI combination has shown efficacy against a wide range of resistant Enterobacterales and other gram\u2010negative bacteria in both in\u00a0vitro and clinical studies. Pharmacokinetic and pharmacodynamic analyses demonstrate that ATM\u2013AVI maintains effective drug concentrations in the body, with dose adjustments recommended for patients with renal impairment. Clinical trials, including the REVISIT and ASSEMBLE studies, have demonstrated the safety and efficacy of ATM\u2013AVI in treating complicated intra\u2010abdominal infections (cIAI), urinary tract infections (UTIs), and hospital\u2010acquired pneumonia (HAP) caused by MDR gram\u2010negative pathogens. The European Medicines Agency (EMA) has approved ATM\u2013AVI for these indications, and further research is ongoing to optimize dosing regimens and expand its clinical use. This combination represents a critical advancement in the fight against antimicrobial resistance, offering a new therapeutic option for treating severe infections caused by MDR gram\u2010negative, including MBL\u2010producing, bacteria.<\/jats:p>","DOI":"10.1002\/phar.4629","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T06:45:03Z","timestamp":1732689903000},"page":"927-938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Aztreonam\u2013avibactam: The dynamic duo against multidrug\u2010resistant gram\u2010negative pathogens"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-9725","authenticated-orcid":false,"given":"Mohammed","family":"Al Musawa","sequence":"first","affiliation":[{"name":"Anti\u2010Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6232-6804","authenticated-orcid":false,"given":"Callan R.","family":"Bleick","sequence":"additional","affiliation":[{"name":"Anti\u2010Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-6159","authenticated-orcid":false,"given":"Shelbye R.","family":"Herbin","sequence":"additional","affiliation":[{"name":"John D. Dingell VA Medical Center  Detroit Michigan USA"},{"name":"Department of Pharmacy Services Detroit Receiving Hospital, Detroit Medical Center  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1468-8267","authenticated-orcid":false,"given":"Kaylee E.","family":"Caniff","sequence":"additional","affiliation":[{"name":"Anti\u2010Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2277-7089","authenticated-orcid":false,"given":"Sean R.","family":"Van Helden","sequence":"additional","affiliation":[{"name":"Anti\u2010Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0081","authenticated-orcid":false,"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti\u2010Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University  Detroit Michigan USA"},{"name":"Department of Pharmacy Services Detroit Receiving Hospital, Detroit Medical Center  Detroit Michigan USA"},{"name":"Division of Infectious Diseases, School of Medicine Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:82532"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:117915"},{"key":"e_1_2_11_4_1","volume-title":"Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022","year":"2022"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01076-18"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0159-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlab092"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025239"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab757"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10111341"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1622"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-021-00507-6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02603-21"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01008-17"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa586"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/7.Supplement_4.S579"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(16)30036-0"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(93)90568-u"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000238431"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.06.089"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00826-13"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9OB02605C"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00897-16"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","unstructured":"O'BrienS.A phase I 3\u2010part placebo\u2010controlled randomised trial to evaluate the safety tolerability and pharmacokinetics of aztreonam\u2010avibactam in healthy subjects. doi:10.26226\/morressier.56d5ba2ed462b80296c95132","DOI":"10.26226\/morressier.56d5ba2ed462b80296c95132"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-023-03609-x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz497"},{"key":"e_1_2_11_27_1","unstructured":"Emblaveo|European Medicines Agency2024. 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