{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:29:43Z","timestamp":1793384983673,"version":"4.5.0"},"reference-count":38,"publisher":"The Pediatric Pharmacy Association","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014]]},"abstract":"The production of \u03b2-lactamase is the most common mechanism of resistance to \u03b2-lactam antibiotics among gram-negative bacteria. Extended-spectrum \u03b2-lactamases (ESBLs) are capable of hydrolyzing most penicillins, extended-spectrum cephalosporins, and aztreonam, but their activity is suppressed in the presence of a \u03b2-lactamase inhibitor. Serious infections with ESBL-producing isolates are associated with high rates of mortality, making early detection and adequate medical management essential to ensure optimal patient outcomes. Much controversy has centered on the recommendations for testing and reporting of antibiotic susceptibility of potential ESBL-producing organisms. The latest version of the Clinical Laboratory Standards Institute (CLSI) susceptibility reporting guidelines, published in 2010, no longer advocates for phenotypic testing of ESBL-producing isolates. From newer studies demonstrating a correlation between organism minimum inhibitory concentration (MIC) and clinical outcome, along with pharmacokinetic\/pharmacodynamic (PK\/PD) modeling demonstrating the importance of the MIC to achieving therapeutic targets, the CLSI has assigned lower susceptibility breakpoints for aztreonam and most cephalosporins. The new guidelines recommend using the lower MIC breakpoints to direct antibiotic selection. This article reviews the microbiology and epidemiology of ESBLs, the recent change in CLSI susceptibility reporting guidelines for ESBLs, and the clinical and PK\/PD data supporting the relationship between in vitro<\/jats:italic> susceptibility and clinical outcome. Finally, considerations for antimicrobial selection when treating patients with infections caused by ESBL-producing organisms from various sources are discussed.<\/jats:p>","DOI":"10.5863\/1551-6776-19.3.156","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T20:11:43Z","timestamp":1603829503000},"page":"156-164","source":"Crossref","is-referenced-by-count":13,"title":["Beyond Susceptible and Resistant, Part II: Treatment of Infections Due to Gram-Negative Organisms Producing Extended-Spectrum \u03b2-Lactamases"],"prefix":"10.5863","volume":"19","author":[{"given":"Jennifer","family":"Curello","sequence":"first","affiliation":[{"name":"1Department of Pharmaceutical Services, University of California Los Angeles Medical Center, Los Angeles, California,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conan","family":"MacDougall","sequence":"additional","affiliation":[{"name":"2Department of Clinical Pharmacy, University of California, San Francisco School of Pharmacy, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3883","reference":[{"issue":"6","key":"i1551-6776-19-3-156-b1","series-title":"Infect Control Hosp Epidemiol","first-page":"600","article-title":"Trends in antibacterial use in hospitalized pediatric patients in United States academic health centers","volume":"30","year":"2009","unstructured":"Pakyz\n AL\n , GurgleHE, IbrahimOM, et al. Trends in antibacterial use in hospitalized pediatric patients in United States academic health centers. Infect Control Hosp Epidemiol. 2009;30(6):600\u2013603."},{"issue":"4","key":"i1551-6776-19-3-156-b2","series-title":"Clin Microbiol Rev","first-page":"557","article-title":"Beta-lactamases in laboratory and clinical resistance","volume":"8","year":"1995","unstructured":"Livermore\n DM.\n \n \n Beta-lactamases in laboratory and clinical resistance. Clin Microbiol Rev. 1995;8(4):557\u2013584."},{"issue":"4","key":"i1551-6776-19-3-156-b3","series-title":"Clin Microbiol Rev","first-page":"657","article-title":"Extended-spectrum beta-lactamases: a clinical update","volume":"18","year":"2005","unstructured":"Paterson\n DL\n , BonomoRA.\n Extended-spectrum beta-lactamases: a clinical update. 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Are susceptibility tests enough, or should laboratories still seek ESBLs and carbapenemases directly?J Antimicrob Chemother. 2012;67(7):1569\u20131577."},{"issue":"9","key":"i1551-6776-19-3-156-b31","series-title":"J Clin Microbiol","first-page":"3127","article-title":"Susceptibility of extended-spectrum-β-lactamase-producing Enterobacteriaceae according to the mew CLSI breakpoints","volume":"49","year":"2011","unstructured":"Wang\n P\n , HuF, XiongZ, et al. Susceptibility of extended-spectrum-β-lactamase-producing Enterobacteriaceae according to the mew CLSI breakpoints. 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Infect Control Hosp Epidemiol. 2012;33(8):853\u2013855."},{"issue":"12","key":"i1551-6776-19-3-156-b33","series-title":"J Antimicrob Chemother","first-page":"2793","article-title":"Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis","volume":"67","year":"2012","unstructured":"Vardakas\n KZ\n , TansarliGS, RafailidisPI, FalagasME.\n Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother. 2012;67(12):2793\u20132803."},{"issue":"2","key":"i1551-6776-19-3-156-b34","series-title":"Clin Infect Dis","first-page":"167","article-title":"β-lactam\/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase\u2013producing Escherichia coli: a post hoc analysis of prospective cohorts","volume":"54","year":"2012","unstructured":"Rodr\u00edguez-Ba\u00f1o\n J\n , NavarroMD, RetamarP, et al; Extended-Spectrum Beta-Lactamases\u2013 Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa\/Grupo de Estudio de Infecci\u00f3n Hospitalaria Group. β-lactam\/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase\u2013producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012;54(2):167\u2013174."},{"issue":"7","key":"i1551-6776-19-3-156-b35","series-title":"Antimicrob Agents Chemother","first-page":"3402","article-title":"Impact of the MIC of piperacillintazobactam on the outcome of patients with bacteremia due to extended-spectrum-β-lactamase-producing Escherichia coli","volume":"57","year":"2013","unstructured":"Retamar\n P\n , L\u00f3pez-CereroL, MuniainMA, et al. Impact of the MIC of piperacillintazobactam on the outcome of patients with bacteremia due to extended-spectrum-β-lactamase-producing Escherichia coli. Antimicrob Agents Chemother. 2013;57(7):3402\u20133404."},{"issue":"4","key":"i1551-6776-19-3-156-b36","series-title":"Clin Infect Dis","first-page":"488","article-title":"Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase\u2013producing Enterobacteriaceae: MIC matters","volume":"56","year":"2013","unstructured":"Lee\n N-Y\n , LeeC-C, HuangW-H, et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase\u2013producing Enterobacteriaceae: MIC matters. Clin Infect Dis. 2013;56(4):488\u2013495."},{"issue":"7","key":"i1551-6776-19-3-156-b37","series-title":"Antimicrob Agents Chemother","first-page":"3936","article-title":"impact of cefepime therapy on mortality among patients with bloodstream infections caused by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and Escherichia coli","volume":"56","year":"2012","unstructured":"Chopra\n T\n , MarchaimD, VeltmanJ, et al. impact of cefepime therapy on mortality among patients with bloodstream infections caused by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother. 2012;56(7):3936\u20133942."},{"issue":"11","key":"i1551-6776-19-3-156-b38","series-title":"Pharmacotherapy","first-page":"1073","article-title":"Combination antibiotic therapy for empiric and definitive treatment of gram-negative infections: insights from the Society of Infectious Diseases Pharmacists","volume":"31","year":"2011","unstructured":"Boyd\n N\n , NailorMD.\n Combination antibiotic therapy for empiric and definitive treatment of gram-negative infections: insights from the Society of Infectious Diseases Pharmacists. 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