{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:20:14Z","timestamp":1790713214561,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Pathology NSW"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>CoNS bacteraemia causes significant neonatal morbidity. Previous work has suggested that \u03b2-lactam antibiotics vary in their binding affinity to PBP2a (produced by the mecA gene) present in most CoNS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We evaluated cefazolin MICs for CoNS isolated in an Australian neonatal ICU (NICU) and correlated them with isolate genotype and phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Significant blood isolates from 2009 to 2017 were speciated and underwent broth microdilution testing for cefazolin, cefoxitin, oxacillin and flucloxacillin. Correlation with mecA presence and PBP2a expression was evaluated. A selection of Staphylococcus capitis isolates underwent WGS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The CoNS (n = 99) isolates were confirmed as S. capitis (n = 57), Staphylococcus epidermidis (n = 32), Staphylococcus haemolyticus (n = 2) and Staphylococcus warneri (n = 8). The MIC of cefazolin was \u22642 mg\/L for 30% of isolates and 75% had an MIC of \u22648 mg\/L (MIC90 = 16 mg\/L). This contrasted with MIC90s of cefoxitin, oxacillin and flucloxacillin, which were all \u226532 mg\/L. WGS found a number of S. capitis isolates closely related to the globally established NRCS-A clone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CoNS displayed distinctly lower MIC values of cefazolin than of other agents tested. MIC variation may be related to binding affinity of PBP2a or regulation of expression of mecA by mecR1-mecI functional genes. Further, NRCS-A S. capitis strains were present in this Australian NICU before and after the unit underwent physical relocation, which raised questions about a common environmental source. It is considered justified to conduct a randomized clinical trial that assesses cefazolin versus vancomycin for management of late-onset neonatal sepsis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab402","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T11:17:24Z","timestamp":1634901444000},"page":"338-344","source":"Crossref","is-referenced-by-count":10,"title":["Cefazolin susceptibility of coagulase-negative staphylococci (CoNS) causing late-onset neonatal bacteraemia"],"prefix":"10.1093","volume":"77","author":[{"given":"I.","family":"Marr","sequence":"first","affiliation":[{"name":"Infectious Disease Department, The Canberra Hospital, ACT, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Swe","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, John Hunter Hospital, Newcastle, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Henderson","sequence":"additional","affiliation":[{"name":"UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Lacey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. P.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. K.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, John Hunter Hospital, Newcastle, NSW, Australia"},{"name":"University of Newcastle, Newcastle, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"2022021008132725300_dkab402-B1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.cmi.2015.09.008","article-title":"Wide geographical dissemination of the multiresistant Staphylococcus capitis NRCS-A clone in neonatal intensive-care units","volume":"22","author":"Butin","year":"2016","journal-title":"Clin Microbiol Infect"},{"key":"2022021008132725300_dkab402-B2","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1128\/JCM.00592-08","article-title":"Vancomycin heteroresistance in bloodstream isolates of Staphylococcus capitis","volume":"46","author":"D\u2019mello","year":"2008","journal-title":"J Clin Microbiol"},{"key":"2022021008132725300_dkab402-B3","doi-asserted-by":"crossref","first-page":"e31548","DOI":"10.1371\/journal.pone.0031548","article-title":"Methicillin-resistant Staphylococcus capitis with reduced vancomycin susceptibility causes late-onset sepsis in intensive care neonates","volume":"7","author":"Rasigade","journal-title":"PLoS One"},{"key":"2022021008132725300_dkab402-B4","doi-asserted-by":"crossref","first-page":"e00898-18","DOI":"10.1128\/AAC.00898-18","article-title":"Genomic analysis of multiresistant Staphylococcus capitis associated with neonatal sepsis","volume":"62","author":"Carter","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2022021008132725300_dkab402-B5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.cmi.2017.03.022","article-title":"Vancomycin treatment is a risk factor for vancomycin-nonsusceptible Staphylococcus capitis sepsis in preterm neonates","volume":"23","author":"Butin","year":"2017","journal-title":"Clin Microbiol Infect"},{"key":"2022021008132725300_dkab402-B6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.5694\/j.1326-5377.2009.tb02841.x","article-title":"Staphylococcus aureus bacteraemia: a major cause of mortality in Australia and New Zealand","volume":"191","author":"Turnidge","year":"2009","journal-title":"Med J Aust"},{"key":"2022021008132725300_dkab402-B7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/jac\/23.suppl_D.13","article-title":"Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus","volume":"23 Suppl D","author":"Truesdell","year":"1989","journal-title":"J Antimicrob Chemother"},{"key":"2022021008132725300_dkab402-B8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2215\/CJN.03070707","article-title":"Coagulase negative staphylococcal peritonitis in peritoneal dialysis patients: review of 232 consecutive cases","volume":"3","author":"Szeto","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022021008132725300_dkab402-B9","author":"Australian and New Zealand Neonatal Network","year":"2021"},{"key":"2022021008132725300_dkab402-B10","author":"CLSI","year":"2015"},{"key":"2022021008132725300_dkab402-B11","doi-asserted-by":"crossref","first-page":"e01417-18","DOI":"10.1128\/JCM.01417-18","article-title":"Improved performance of a rapid immunochromatographic assay for detection of PBP2a in non-Staphylococcus aureus staphylococcal species","volume":"57","author":"Canver","year":"2019","journal-title":"J Clin Microbiol"},{"key":"2022021008132725300_dkab402-B12","author":"EUCAST","year":"2019"},{"key":"2022021008132725300_dkab402-B13","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1128\/AAC.40.9.2075","article-title":"Specific interaction between \u03b2-lactams and soluble penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus: development of a chromogenic assay","volume":"40","author":"Roychoudhury","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"key":"2022021008132725300_dkab402-B14","doi-asserted-by":"crossref","first-page":"e1002816","DOI":"10.1371\/journal.ppat.1002816","article-title":"The anti-repressor MecR2 promotes the proteolysis of the mecA repressor and enables optimal expression of \u03b2-lactam resistance in MRSA","volume":"8","author":"Ar\u00eade","year":"2012","journal-title":"PLoS Pathog"},{"key":"2022021008132725300_dkab402-B15","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1128\/AAC.42.3.717","article-title":"Analysis of diversity of mutations in the mecI gene and mecA promoter\/operator region of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis","volume":"42","author":"Kobayashi","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"2022021008132725300_dkab402-B16","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0966-842X(00)01762-5","article-title":"The bactericidal action of penicillin: new clues to an unsolved mystery","volume":"8","author":"Bayles","year":"2000","journal-title":"Trends Microbiol"},{"key":"2022021008132725300_dkab402-B17","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.cell.2014.11.017","article-title":"\u03b2-Lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery","volume":"159","author":"Cho","year":"2014","journal-title":"Cell"},{"key":"2022021008132725300_dkab402-B18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1128\/AAC.34.1.33","article-title":"Two bactericidal targets for penicillin in pneumococci: autolysis-dependent and autolysis-independent killing mechanisms","volume":"34","author":"Moreillon","year":"1990","journal-title":"Antimicrob Agents Chemother"},{"key":"2022021008132725300_dkab402-B19","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrmicro2333","article-title":"How antibiotics kill bacteria: from targets to networks","volume":"8","author":"Kohanski","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"2022021008132725300_dkab402-B20","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1093\/jac\/dkt527","article-title":"Population pharmacokinetic modelling of total and unbound cefazolin plasma concentrations as a guide for dosing in preterm and term neonates","volume":"69","author":"De Cock","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2022021008132725300_dkab402-B21","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000324852","article-title":"A seven-year survey of management of coagulase-negative staphylococcal sepsis in the neonatal intensive care unit: vancomycin may not be necessary as empiric therapy","volume":"100","author":"Hemels","year":"2011","journal-title":"Neonatology"},{"key":"2022021008132725300_dkab402-B22","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1093\/jac\/dks092","article-title":"Reduced expression of PBP-2A by neonatal mecA-positive coagulase-negative staphylococci (CoNS) blood isolates: \u03b2-lactams are useful first-line agents for the treatment of neonatal CoNS sepsis, restricting the use of vancomycin","volume":"67","author":"Fleer","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2022021008132725300_dkab402-B23","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3201\/eid2303.160833","article-title":"Worldwide endemicity of a multidrug-resistant Staphylococcus capitis clone involved in neonatal sepsis","volume":"23","author":"Butin","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2022021008132725300_dkab402-B24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13756-019-0512-8","article-title":"Successful implementation of infection control measure in a neonatal intensive care unit to combat the spread of pathogenic multidrug resistant Staphylococcus capitis","volume":"8","author":"Ory","year":"2019","journal-title":"Antimicrob Resist Infect Control"},{"key":"2022021008132725300_dkab402-B25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13756-019-0616-1","article-title":"Sources and reservoirs of Staphylococcus capitis NRCS-A inside a NICU","volume":"8","author":"Butin","year":"2019","journal-title":"Antimicrob Resist Infect Control"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/2\/338\/42466753\/dkab402.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/2\/338\/42466753\/dkab402.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T08:13:56Z","timestamp":1644480836000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/77\/2\/338\/6427455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,11,13]]},"published-print":{"date-parts":[[2022,2,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab402","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2,1]]},"published":{"date-parts":[[2021,11,13]]}}}