Christophe Isnard1, Anne Dhalluin2, Damasie Malandain3, Quentin Bruey2, Michel Auzou3, Jocelyn Michon4, Jean-Christophe Giard2, François Guérin1, Vincent Cattoir5. 1. CHU de Caen, Service de microbiologie, Caen, France; Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France. 2. Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France. 3. CHU de Caen, Service de microbiologie, Caen, France. 4. CHU de Caen, Service des maladies infectieuses, Caen, France. 5. CHU de Rennes, Service de bactériologie-hygiène hospitalière, Rennes, France; CNR de la résistance aux antibiotiques (laboratoire associé 'Entérocoques'), Rennes, France. Electronic address: vincent.cattoir@chu-rennes.fr.
Abstract
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 4× 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 (MIC50/90, 0.25/0.5μg/mL) and 98% were susceptible to ceftobiprole (MIC50/90, 0.5/1μg/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 MIC50/90 values at 0.06/0.25μg/mL and 0.25/1μg/mL, respectively. At 4× 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.
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 4× 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 (MIC50/90, 0.25/0.5μg/mL) and 98% were susceptible to ceftobiprole (MIC50/90, 0.5/1μg/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 MIC50/90 values at 0.06/0.25μg/mL and 0.25/1μg/mL, respectively. At 4× 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.