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Ceftobiprole Duployez et al. Ann Clin Microbiol Antimicrob (2020) 19:9 https://doi.org/10.1186/s12941-020-00351-5 Annals of Clinical Microbiology and Antimicrobials RESEARCH Open Access Ceftobiprole: a potential empirical post-operative monotherapy in prosthetic joint infections Claire Duployez1, Frédéric Wallet1, Henri Migaud2,4, Eric Senneville3,4 and Caroline Loiez1* Abstract Background: This study aimed to evaluate in vitro susceptibility to ceftobiprole of clinical strains identifed from prosthetic joint infections (PJIs) compared to that of the associations currently recommended for post-opera- tive empirical antibiotic therapy (PEAT) (vancomycin with either cefepime, third-generation cephalosporin or piperacillin–tazobactam). Methods: We performed a 1-year retrospective study on all the surgical procedures performed in our hospital for PJI. Susceptibility profles of all the strains cultured from surgical samples were reviewed to compare ceftobiprole to cur- rent used associations. Results: During the study period (from January 2018 to December 2018), we identifed 106 patients managed for PJI and a total of 216 surgical interventions. One hundred-ffty strains were identifed from intraoperative samples, excluding redundant strains. Staphylococcus spp. represented 52.7% of all strains and Enterobacteriales 13.3%. Twenty- three patients had polymicrobial infection (22%). Among 149 surgical procedures with positive culture results, cefto- biprole covered the bacterial strains in 138 (92.6%) cases. In comparison, this percentage was 94.6% for vancomycin plus cefepime (p 0.64), 92.6% for vancomycin plus a third-generation cephalosporin in 138 cases (p 1) and 94.6% for vancomycin plus= piperacillin–tazobactam) (p 0.64). = = Conclusion: Based on antimicrobial susceptibility testing, our results suggest that ceftobiprole could be an interest- ing option for PEAT in PJIs, allowing the use of a single agent. Keywords: Prosthetic joint infection, Ceftobiprole, Empirical antibiotic therapy, Bacterial resistance Background is usually administered to prevent the colonization of Prosthetic joint infections (PJI) require both surgical newly prosthesis or the prosthesis that has been cleaned intervention and antibiotic therapy conducted accord- but has been retained during the so-called debridement- ing to the most recent guidelines for the management of antibiotic and implant retention (DAIR). Given the these potentially life-threatening infections [1, 2]. important role of staphylococci in PJI, the PEAT needs Te results of the susceptibility profle of the bacteria to be active against most Gram-positive cocci including isolated from the intraoperative samples usually require methicillin-resistant staphylococci but also Gram-neg- at least 5 days to become available. During this period, an ative bacilli. Currently, there has been no consensus on initial post-operative empirical antibiotic therapy (PEAT) the optimal choice of this antibiotic therapy. In France, the combinations of vancomycin combined with either a third-generation cephalosporin or piperacillin–tazobac- *Correspondence: [email protected] 1 Institute of Microbiology, Lille University Hospital, 59037 Lille, France tam are proposed choices [3]. Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Duployez et al. Ann Clin Microbiol Antimicrob (2020) 19:9 Page 2 of 7 Ceftobiprole is a newly commercialized beta-lactam mL of sterile saline were added to each sample, and sam- antibiotic with a broad spectrum, equivalent to an asso- ples were vigorously shaked during 1 min using sterile ciation of a third-generation cephalosporin plus vanco- glass beads, in order to disrupt tissue and release bacte- mycin. Notably, it is active against methicillin-resistant ria. Ten, one drop was inoculated onto a Columbia agar staphylococci, Enterococcus faecalis, most extended spec- with blood 5% (incubation at 37 °C in air for 5 days), one trum beta-lactamase-non-producing Enterobacteriales drop onto a chocolate agar with polyvitex (incubation at and Pseudomonas aeruginosa. It may replace use of this 37 °C in CO2 for 5 days) and one-millilitre aliquots were associations for PEAT. inoculated into an Aerobic VIRTUO blood culture bottle, Te main objective of the present study was to assess and an anaerobic VIRTUO blood culture bottle (BioMé- the antibacterial in vitro activity of ceftobiprole on strains rieux, Marcy l’Etoile, France). All plates were examined recovered from PJI infections in order to enable or not its daily for 5 days. VIRTUO blood culture bottles were use as a single molecule in PEAT. We therefore compared placed on the VIRTUO system for 14 days and were sub- ceftobiprole to vancomycin plus cefepime, vancomycin cultured if they fagged positive.” Strains were identifed plus third generation cephalosporin (e.g. cefotaxime or using MALDI-TOF spectrometry mass (Bruker Dalton- ceftriaxone) and vancomycin plus piperacillin–tazobac- ics, Wissembourg, France) with a minimal score require- tam in this setting. ment of 2. Te antibiotic susceptibility profle of all pathogens Methods identifed from intraoperative samples was assessed Defnitions either by the Vitek 2 cards (BioMérieux, Marcy l’Etoile, PJIs were identifed according to the Infectious Diseases France) or by agar difusion technique using the proce- Society of America defnition [2]. dure and interpretation criteria proposed by the Comité de l’Antibiogramme de la Société Française de Micro- Study design and population biologie (CA-SFM EUCAST 2018) (http://www.sfm- Tis retrospective study was performed at the French micro biolo gie.org). Minimum inhibitory concentrations National Reference Centre for Complex Osteoarticular (MIC) of ceftobiprole were determined with the Etest Infections in the North West region of France (Roger (Lioflchem, Roseto degli Abruzzi, Italy). Methicillin Salengro Hospital, Lille, France). Medical charts of all resistance was confrmed by detection of mecA gene if adult patients with documented PJI who received PEAT required. from January 2018 to December 2018 were reviewed. All patients included in the study had surgical management Results including DAIR, one or two-step implant exchange. Patients During the study period, we identifed 106 patients Surgical management and curative antibiotic therapy managed for PJI (57 hip prosthesis, 39 knee prosthesis, All surgical procedures (i.e., implant retention, or one- 9 shoulder prosthesis, 4 elbow prosthesis and 4 other to two-step implant exchange) were performed without prosthesis, with sometimes more than one prosthesis by antibiotic prophylaxis. Ceftobiprole administered intra- patient). A total of 216 surgical interventions were identi- venously was begun intraoperatively immediately after fed from these 106 patients. Among these 216 surgical samples were taken. PEAT was continued until the results interventions, 67 remained negative for the three samples of intraoperative sample cultures were available and was (31%).Te demographic characteristics of the included then modifed in accordance with the culture results patients are reported in Table 1. (curative antibiotic therapy). Terapeutic strategies were decided for each patient during multidisciplinary meet- Microbiology ings of orthopaedic surgeons, infectious diseases consult- A total of 150 clinical strains were identifed from intra- ants, microbiologists and anaesthesiologists, based on the operative samples, excluding redundant strains taken in patient’s characteristics and were administered following diferent surgical interventions performed on the same the recommendations of Zimmerli et al. [4]. In each case, patient (Table 2). the patient was aware of the diferent therapeutic options Staphylococcus spp. accounted for 52.7% of all strains, and took part in the fnal decision. especially coagulase negative staphylococci (CoNS) (32.7% of all strains) with 53.1% of methicillin-resist- Microbiology ant and 20.4% of teicoplanin-resistant strains. S. aureus During surgical procedures, at least three tissue samples accounted for 20.0% of all strains including 2 methicil- were taken in diferent areas suspected of being afected lin-resistant S. aureus (MRSA). Streptococcus spp. and using a separate sterile instrument for each sample. Tree Enterococcus spp. accounted for 21.3% of all strains. Duployez et al. Ann Clin Microbiol Antimicrob (2020) 19:9 Page 3 of 7 Table 1 Characteristics of 106 patients (216 events) (patient C). Te
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