{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:55:40Z","timestamp":1792104940066,"version":"4.4.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012 and 2017 through the Centers for Disease Control and Prevention's Emerging Infections Program.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MICs to 6 antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. Whole genome sequencing was performed on all isolates to detect the presence of genes or mutations previously associated with resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among all isolates, 98.5% displayed a vancomycin MIC \u22642 \u03bcg\/mL and 97.3% displayed a metronidazole MIC \u22642 \u03bcg\/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 \u03bcg\/mL; MIC90: 2 \u03bcg\/mL) than non-RT027 isolates (MIC50: 0.5 \u03bcg\/mL; MIC90: 1 \u03bcg\/mL) (P &amp;lt; .01). No vanA\/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Elevated MICs to antibiotics used for treatment of C. difficile infection were rare, and there was no increase in MICs over time. The lack of vanA\/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciac817","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T13:45:31Z","timestamp":1665236731000},"page":"890-896","source":"Crossref","is-referenced-by-count":34,"title":["Reference Susceptibility Testing and Genomic Surveillance of<i>Clostridioides difficile<\/i>, United States, 2012\u201317"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-2636","authenticated-orcid":false,"given":"Amy S","family":"Gargis","sequence":"first","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2463-0598","authenticated-orcid":false,"given":"Maria","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"},{"name":"Goldbelt C6, LLC, Chesapeake, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-4355","authenticated-orcid":false,"given":"Ashley L","family":"Paulick","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen F","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Adamczyk","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Vlachos","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4751-6218","authenticated-orcid":false,"given":"Alyssa G","family":"Kent","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"McAllister","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susannah L","family":"McKay","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1643-1617","authenticated-orcid":false,"given":"Alison L","family":"Halpin","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davina","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C","family":"Korhonen","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6029-9812","authenticated-orcid":false,"given":"Christopher A","family":"Elkins","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Kamile","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Y","family":"Guh","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3044-5572","authenticated-orcid":false,"given":"L Clifford","family":"McDonald","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5723-8317","authenticated-orcid":false,"given":"Joseph D","family":"Lutgring","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Emerging Infections Program C. difficile Infection Working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghinwa","family":"Dumyati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Fridkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Gerding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy M","family":"Holzbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyel M","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Perlmutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin C","family":"Phipps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Winston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"2023030705143481300_","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:82532"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"ITC49","DOI":"10.7326\/AITC201810020","article-title":"Clostridioides difficile infection","volume":"169","author":"Guh","year":"2018","journal-title":"Ann Intern Med"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1056\/NEJMoa1910215","article-title":"Trends in U.S. Burden of Clostridioides difficile infection and outcomes","volume":"382","author":"Guh","year":"2020","journal-title":"N Engl J Med"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"e1029","DOI":"10.1093\/cid\/ciab549","article-title":"Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults","volume":"73","author":"Johnson","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1093\/cid\/ciab898","article-title":"Medicare prescription plans limit access to recommended drugs for Clostridioides difficile infection","volume":"74","author":"Buehrle","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1086\/647952","article-title":"Antimicrobial susceptibility testing: a review of general principles and contemporary practices","volume":"49","author":"Jorgensen","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1128\/CMR.00016-13","article-title":"Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories","volume":"26","author":"Burnham","year":"2013","journal-title":"Clin Microbiol Rev"},{"key":"2023030705143481300_","volume-title":"CLSI M11","author":"Clinical and Laboratory Standards Institute","year":"2018","edition":"9th ed"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1056\/NEJMoa051590","article-title":"An epidemic, toxin gene-variant strain of Clostridium difficile","volume":"353","author":"McDonald","year":"2005","journal-title":"N Engl J Med"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/ng.2478","article-title":"Emergence and global spread of epidemic healthcare-associated Clostridium difficile","volume":"45","author":"He","year":"2013","journal-title":"Nat Genet"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/jac\/dkz513","article-title":"Constitutive expression of the cryptic vanGCd operon promotes vancomycin resistance in Clostridioides difficile clinical isolates","volume":"75","author":"Shen","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"e0118150","DOI":"10.1371\/journal.pone.0118150","article-title":"Development and validation of an internationally-standardized, high-resolution capillary gel-based electrophoresis PCR-ribotyping protocol for Clostridium difficile","volume":"10","author":"Fawley","year":"2015","journal-title":"PLoS One"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"e01011-20","DOI":"10.1128\/MRA.01011-20","article-title":"Characterization of Clostridioides difficile isolates available through the CDC & FDA antibiotic resistance isolate bank","volume":"10","author":"Paulick","year":"2021","journal-title":"Microbiol Resour Announc"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13073-014-0090-6","article-title":"SRST2: rapid genomic surveillance for public health and hospital microbiology labs","volume":"6","author":"Inouye","year":"2014","journal-title":"Genome Med"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btab607","article-title":"GAMMA: a tool for the rapid identification, classification, and annotation of translated gene matches from sequencing data","author":"Stanton","year":"2022","journal-title":"Bioinformatics"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"Zankari","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1128\/AAC.01310-13","article-title":"ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes","volume":"58","author":"Gupta","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"e00483-19","DOI":"10.1128\/AAC.00483-19","article-title":"Validating the AMRFinder tool and resistance gene database by using antimicrobial resistance genotype-phenotype correlations in a collection of isolates","volume":"63","author":"Feldgarden","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s41467-020-14382-1","article-title":"Plasmid-mediated metronidazole resistance in Clostridioides difficile","volume":"11","author":"Boekhoud","year":"2020","journal-title":"Nat Commun"},{"key":"2023030705143481300_","volume-title":"Performance standards for antimicrobial susceptibility testing","author":"Clinical and Laboratory Standards Institute","year":"2021","edition":"31st ed"},{"key":"2023030705143481300_","author":"European Committee on Antimicrobial Susceptibility Testing"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1128\/AAC.31.7.1039","article-title":"Genetic characterization of a Clostridium difficile erythromycin-clindamycin resistance determinant that is transferable to Staphylococcus aureus","volume":"31","author":"H\u00e4chler","year":"1987","journal-title":"Antimicrob Agents Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"e01074-19","DOI":"10.1128\/AAC.01074-19","article-title":"Cfr(B), cfr(C), and a new cfr-like gene, cfr(E), in Clostridium difficile strains recovered across Latin America","volume":"64","author":"Stojkovi\u0107","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"e00391-19","DOI":"10.1128\/AAC.00391-19","article-title":"U.S.-based national surveillance for fidaxomicin susceptibility of Clostridioides difficile-associated diarrheal isolates from 2013 to 2016","volume":"63","author":"Thorpe","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1093\/jac\/dkaa118","article-title":"Antimicrobial susceptibility of Clostridioides difficile isolated from diarrheal stool specimens of Canadian patients: summary of results from the Canadian Clostridioides difficile (CAN-DIFF) surveillance study from 2013 to 2017","volume":"75","author":"Karlowsky","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.diagmicrobio.2018.01.017","article-title":"PCR ribotyping and antimicrobial susceptibility testing of isolates of Clostridium difficile cultured from toxin-positive diarrheal stools of patients receiving medical care in Canadian hospitals: the Canadian Clostridium difficile surveillance study (CAN-DIFF) 2013\u20132015","volume":"91","author":"Karlowsky","year":"2018","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1093\/jac\/dkab099","article-title":"Antimicrobial resistance surveillance of Clostridioides difficile in Australia, 2015\u201318","volume":"76","author":"Putsathit","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/cid\/ciaa912","article-title":"Emergence of clinical Clostridioides difficile isolates with decreased susceptibility to vancomycin","volume":"74","author":"Darkoh","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/cid\/ciac377","article-title":"Can Clostridium innocuum masquerade as Clostridioides difficile?","volume":"75","author":"Skinner","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2023030705143481300_","first-page":"1661","volume":"75","year":"2022"},{"key":"2023030705143481300_","first-page":"1677","volume":"75","author":"Lutgring","year":"2022"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.anaerobe.2017.02.006","article-title":"Comparison of Clostridium difficile minimum inhibitory concentrations obtained using agar dilution vs broth microdilution methods","volume":"44","author":"Hastey","year":"2017","journal-title":"Anaerobe"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"ofab365","DOI":"10.1093\/ofid\/ofab365","article-title":"Reduced susceptibility to metronidazole is associated with initial clinical failure in Clostridioides difficile infection","volume":"8","author":"Gonzales-Luna","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/1471-2334-10-363","article-title":"Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection","volume":"10","author":"Gonzales","year":"2010","journal-title":"BMC Infect Dis"},{"key":"2023030705143481300_","author":"United States Food and Drug Administration","year":"2022"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/mmi.12299","article-title":"The functional vanGCd cluster of Clostridium difficile does not confer vancomycin resistance","volume":"89","author":"Ammam","year":"2013","journal-title":"Mol Microbiol"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1099\/00221287-147-10-2717","article-title":"Genomic analysis of the erythromycin resistance element Tn5398 from Clostridium difficile","volume":"147","author":"Farrow","year":"2001","journal-title":"Microbiology (Reading)"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S1473-3099(16)30514-X","article-title":"Effects of control interventions on Clostridium difficile infection in England: an observational study","volume":"17","author":"Dingle","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2023030705143481300_","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cmi.2017.10.008","article-title":"The ClosER study: results from a three-year pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes, 2011\u20132014","volume":"24","author":"Freeman","year":"2018","journal-title":"Clin Microbiol Infect"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac817\/46955202\/ciac817.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/5\/890\/49424690\/ciac817.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/5\/890\/49424690\/ciac817.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T15:45:51Z","timestamp":1701186351000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/76\/5\/890\/6754176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,8]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,10,8]]},"published-print":{"date-parts":[[2023,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac817","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3,1]]},"published":{"date-parts":[[2022,10,8]]}}}