{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:19:15Z","timestamp":1789820355451,"version":"4.0.1"},"reference-count":13,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T00:00:00Z","timestamp":1439856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Allecra Therapeutics SAS (St-Louis, France)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We evaluated the in vitro potency of cefepime combined with AAI101, a novel extended-spectrum \u03b2-lactamase inhibitor, against a population of clinical Escherichia coli and Klebsiella pneumoniae collected from USA hospitals. Of the 223 cefepime non-susceptible isolates, 95% were ceftazidime non-susceptible, 49% ertapenem non-susceptible, 57% piperacillin\/tazobactam non-susceptible, 90% were multidrug-resistant (resistant to \u22653 drug classes), 22% produced carbapenemases, and 67% produced ESBLs. Addition of AAI101 restored the activity of cefepime such that the MIC50 was reduced from &gt;64 mg\/L for cefepime to 0.13 mg\/L for cefepime\/AAI101, supporting its continued development treatment for infections caused by these organisms.<\/jats:p>","DOI":"10.3390\/pathogens4030620","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T10:31:11Z","timestamp":1439893871000},"page":"620-625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["In Vitro Activity of Cefepime\/AAI101 and Comparators against Cefepime Non-susceptible Enterobacteriaceae"],"prefix":"10.3390","volume":"4","author":[{"given":"Jared","family":"Crandon","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, CT 06102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/cid\/cir202","article-title":"Carbapenem-resistant Enterobacteriaceae: Epidemiology and prevention","volume":"53","author":"Gupta","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1517\/14656566.2013.763030","article-title":"Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum beta-lactamases and carbapenemases)","volume":"14","author":"Lynch","year":"2013","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_3","unstructured":"Mushtaq, S., Chaudhry, A., Adkin, R., Woodford, N., Benedict, N., Pypstra, R., and Shapiro, S. (2014, January 10\u201313). In-vitro activity of diverse \u03b2-lactam\/aai101 combinations vs. Multidrug-resistant gram-negative clinical strains. Proceedings of the 24th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, Spain. Abstract eP452."},{"key":"ref_4","unstructured":"Nordmann, P., Girlich, D., Benedict, N., Pypstra, R., and Shapiro, S. (2014, January 10\u201313). Characterization of b-lactamase inhibition by aai101. Proceedings of the 24th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, Spain. Abstract eP451."},{"key":"ref_5","unstructured":"Clinical Laboratory Standard Institute (2014). Performance Standards for Antimicrobial Suceptibility Testing; Twenty-Fourth Informational Supplement, CLSI publication. M100-S24."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1128\/AAC.01989-12","article-title":"Human simulated studies of aztreonam and aztreonam-avibactam to evaluate activity against challenging gram-negative organisms, including metallo-beta-lactamase producers","volume":"57","author":"Crandon","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1128\/AAC.00851-12","article-title":"Comparative in vitro and in vivo efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa","volume":"56","author":"Crandon","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1128\/AAC.02513-12","article-title":"Pharmacokinetics-pharmacodynamics of tazobactam in combination with ceftolozane in an in vitro infection model","volume":"57","author":"VanScoy","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1093\/ajhp\/52.6_Suppl_2.S23","article-title":"Combination beta-lactam and beta-lactamase-inhibitor therapy: Pharmacokinetic and pharmacodynamic considerations","volume":"52","author":"Dudley","year":"1995","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_10","unstructured":"Sutherland, C., and Nicolau, D. (2014, January 5\u20139). Susceptibility profile of commonly utilized parenteral antimicrobials against E. coli, K. pneumoniae and P. aeruginosa from us hospitals. Proceedings of the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, USA. Abstract C119."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ijantimicag.2014.01.007","article-title":"Antimicrobial susceptibility of gram-negative organisms isolated from patients hospitalised with pneumonia in us and european hospitals: Results from the sentry antimicrobial surveillance program, 2009\u20132012","volume":"43","author":"Sader","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1128\/AAC.00033-15","article-title":"In vivo activities of simulated human doses of cefepime and cefepime-aai101 against multidrug-resistant gram-negative Enterobacteriaceae","volume":"59","author":"Crandon","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1128\/AAC.01395-12","article-title":"Rapid identification of carbapenemase types in Enterobacteriaceae and Pseudomonas spp. By using a biochemical test","volume":"56","author":"Dortet","year":"2012","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/4\/3\/620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:46:56Z","timestamp":1760215616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/4\/3\/620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,18]]},"references-count":13,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["pathogens4030620"],"URL":"https:\/\/doi.org\/10.3390\/pathogens4030620","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,18]]}}}