PMID- 29421316 OWN - NLM STAT- MEDLINE DCOM- 20190920 LR - 20231213 IS - 2213-7173 (Electronic) IS - 2213-7165 (Linking) VI - 13 DP - 2018 Jun TI - In vitro activity of novel anti-MRSA cephalosporins and comparator antimicrobial agents against staphylococci involved in prosthetic joint infections. PG - 221-225 LID - S2213-7165(18)30024-9 [pii] LID - 10.1016/j.jgar.2018.01.022 [doi] AB - OBJECTIVES: Ceftaroline and ceftobiprole are new parenteral cephalosporins with potent activity against methicillin-resistant (MR) staphylococci, which are the leading cause of prosthetic joint infections (PJIs). The aim of this study was to determine and compare the in vitro activities of both molecules against staphylococcal isolates recovered from clinically documented PJIs. METHODS: A collection of 200 non-duplicate clinical isolates [100 Staphylococcus aureus and 100 coagulase-negative staphylococci (CoNS), including 19 and 27 MR isolates, respectively] was studied. Minimum inhibitory concentrations (MICs) of oxacillin, ceftaroline, ceftobiprole, vancomycin, teicoplanin, clindamycin, levofloxacin, linezolid and daptomycin were determined by the broth microdilution method. Bactericidal activity (at 4x MIC) of ceftaroline, ceftobiprole, vancomycin, teicoplanin, linezolid and daptomycin was assessed by time-kill assay. RESULTS: Among the S. aureus isolates, 100% were susceptible to ceftaroline (MIC(50/90), 0.25/0.5mug/mL) and 98% were susceptible to ceftobiprole (MIC(50/90), 0.5/1mug/mL), regardless of their methicillin resistance. The two ceftobiprole-non-susceptible strains (including one MRSA) showed MICs at 4mg/L. Against CoNS isolates, ceftaroline and ceftobiprole exhibited in vitro potency with MIC(50/90) values at 0.06/0.25mug/mL and 0.25/1mug/mL, respectively. At 4x MIC, ceftaroline and ceftobiprole showed rapid and marked bactericidal activity against both S. aureus and CoNS (after 24/12h and 12/6h of incubation, respectively), whilst none of the other molecules tested had a bactericidal effect by 24h. CONCLUSIONS: This study showed that ceftaroline and ceftobiprole have excellent in vitro activity against clinical isolates of staphylococci involved in PJIs. These molecules may therefore represent promising alternatives for the treatment of such infections. CI - Copyright (c) 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved. FAU - Isnard, Christophe AU - Isnard C AD - CHU de Caen, Service de microbiologie, Caen, France; Universite de Caen Normandie, EA4655 U2RM (equipe 'Antibio-resistance'), Caen, France. FAU - Dhalluin, Anne AU - Dhalluin A AD - Universite de Caen Normandie, EA4655 U2RM (equipe 'Antibio-resistance'), Caen, France. FAU - Malandain, Damasie AU - Malandain D AD - CHU de Caen, Service de microbiologie, Caen, France. FAU - Bruey, Quentin AU - Bruey Q AD - Universite de Caen Normandie, EA4655 U2RM (equipe 'Antibio-resistance'), Caen, France. FAU - Auzou, Michel AU - Auzou M AD - CHU de Caen, Service de microbiologie, Caen, France. FAU - Michon, Jocelyn AU - Michon J AD - CHU de Caen, Service des maladies infectieuses, Caen, France. FAU - Giard, Jean-Christophe AU - Giard JC AD - Universite de Caen Normandie, EA4655 U2RM (equipe 'Antibio-resistance'), Caen, France. FAU - Guerin, Francois AU - Guerin F AD - CHU de Caen, Service de microbiologie, Caen, France; Universite de Caen Normandie, EA4655 U2RM (equipe 'Antibio-resistance'), Caen, France. FAU - Cattoir, Vincent AU - Cattoir V AD - CHU de Rennes, Service de bacteriologie-hygiene hospitaliere, Rennes, France; CNR de la resistance aux antibiotiques (laboratoire associe 'Enterocoques'), Rennes, France. Electronic address: vincent.cattoir@chu-rennes.fr. LA - eng PT - Journal Article DEP - 20180205 PL - Netherlands TA - J Glob Antimicrob Resist JT - Journal of global antimicrobial resistance JID - 101622459 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cephalosporins) RN - 5T97333YZK (ceftobiprole) RN - 6Q205EH1VU (Vancomycin) RN - NWQ5N31VKK (Daptomycin) SB - IM MH - Anti-Bacterial Agents/*pharmacology MH - Cephalosporins/*pharmacology MH - Daptomycin/pharmacology MH - Humans MH - Joint Diseases/*microbiology MH - Methicillin-Resistant Staphylococcus aureus/*drug effects/isolation & purification MH - Microbial Sensitivity Tests MH - Prosthesis-Related Infections/*microbiology MH - Staphylococcal Infections/microbiology MH - Staphylococcus/*drug effects MH - Staphylococcus aureus/drug effects MH - Vancomycin/pharmacology MH - Ceftaroline OTO - NOTNLM OT - Ceftaroline OT - Ceftobiprole OT - CoNS OT - PJI OT - Prosthetic joint infection OT - Staphylococcus aureus EDAT- 2018/02/09 06:00 MHDA- 2019/09/21 06:00 CRDT- 2018/02/09 06:00 PHST- 2017/08/07 00:00 [received] PHST- 2018/01/22 00:00 [revised] PHST- 2018/01/29 00:00 [accepted] PHST- 2018/02/09 06:00 [pubmed] PHST- 2019/09/21 06:00 [medline] PHST- 2018/02/09 06:00 [entrez] AID - S2213-7165(18)30024-9 [pii] AID - 10.1016/j.jgar.2018.01.022 [doi] PST - ppublish SO - J Glob Antimicrob Resist. 2018 Jun;13:221-225. doi: 10.1016/j.jgar.2018.01.022. Epub 2018 Feb 5.