Comparative activity of ceftobiprole against Gram-positive and Gram-negative isolates from Europe and the Middle East: the CLASS study

G M Rossolini ,Pascual ,Sevim Ünal ,Gül Durmaz ,M Morgan ,J.a.j.w Kluijtmans ,Ayşe Yüce ,T Fosse ,Michele Li Bergoli ,Günther ,F Giacomo ,D Alos ,H Akdeniz ,Pierre-Yves Donnio ,Concha Gimeno ,Erwin Brown ,D M J Espinar ,Vincent Jarlier ,Julie Cremniter ,Dimitra Petropoulou ,J Papaparaskevas ,Mireille Van Westreenen ,Perez-Trallero ,Nikolaos Vakalis ,Hélène Marchandin ,Pierangelo Clerici ,Vittorio Sambri ,P Lannote ,J.m Läuffer ,Marianne Abele‐Horn ,Fernando Cháves ,E Inci Tuncer ,Ayşe Willke Topçu ,Sb Cohen ,Gaye Usluer ,E.g Smyth ,Matthew Dryden ,D A Repetto ,A Sawicka-Grzelak ,Ian Morrissey ,Mario Sarti ,Yeşim Taşova ,D L Rubattu ,Piotr B Heczko ,Jean-Louis Pons ,Javier Aznar ,Bilgül Mete ,B.a Besirbellioglu ,M Cristino ,Jhosep Blanco ,D Kotulová ,Max Maurin ,Mustafa Berktaş ,Ezra A Jacobs ,Manfred Fille ,Katherine A Gould ,R Koslov ,Filiz Kibar ,Mario Recker ,Olga Paniara ,Reto Frei ,Helena Žemličková ,Achyut Guleri ,M Łuczak ,Marco Marco ,Rohinton Mulla ,Casal ,Claude-James Soussy ,Linares ,Jean-Louis Fauchère ,De João Victor De Oliveira Santos ,Reyhan Öztürk ,Nicholas Brown ,Laurent Gutmann ,Kathrin Mühlemann ,Alvaro Quintana ,Giuseppe Nicoletti ,Robert K Flamm ,Colin R Mackenzie ,Picazo ,Garcia-Rodriguez ,P Nicoletti ,E Lee ,Rafael Cantón ,Jacques Schrenzel ,Reinhard Zbinden ,As Moses ,Emilio Bouza ,H Malamou-Lada ,Anna Przondo−Mordarska ,Ch Schoerner ,Antonio Goglio ,Galia Rahav ,A G M Buiting ,D M Da Graca Ribeiro ,Zeynep Gülay ,Claudio Scarparo ,Harald Seifert ,Jacques Tankovic ,Antonio Spanò ,W Pfister ,Ahmet Başustaoğlu ,Waleria Hryniewicz ,Sören Gatermann ,Johan W Mouton ,Segovia ,Encho Savov ,Brea ,Guillem Prats ,Serhat Birengel ,Roman Kozlov ,Sabine Schubert ,J Bille ,Reinier Mutters ,Giovanni Gesu ,Onur Ural ,Devrim Dündar ,Tzvetan Velinov ,Uwe Mai ,F.-J Schmitz ,Deniz Gür ,İsmail Balık ,D Revillo ,F Ghaly ,A Swann

doi:10.1093/jac/dkq397

Abstract

to assess the in vitro activity of ceftobiprole and comparators against a recent collection of Gram-positive and Gram-negative pathogens, in order to detect potential changes in susceptibility patterns, and to evaluate the Etest assay for ceftobiprole susceptibility testing. contemporary Gram-positive and Gram-negative isolates (excluding extended-spectrum β-lactamase-producing isolates) from across Europe and the Middle East were collected, and their susceptibility to ceftobiprole, vancomycin, teicoplanin, linezolid, ceftazidime and cefepime was assessed using the Etest method. Quality testing [using Etest and broth microdilution (BMD)] was conducted at a central reference laboratory. some 5041 Gram-positive and 4026 Gram-negative isolates were included. Against Gram-positive isolates overall, ceftobiprole had the lowest MIC50 (0.5 mg/L), compared with 1 mg/L for its comparators (vancomycin, teicoplanin and linezolid). Against methicillin-resistant Staphylococcus aureus, all four agents had a similar MIC90 (2 mg/L), but ceftobiprole had a 4-fold better MIC90 (0.5 mg/L) against methicillin-susceptible strains. Only 38 Gram-positive isolates were confirmed as ceftobiprole resistant. Among Gram-negative strains, 86.9%, 91.7% and 95.2% were susceptible to ceftobiprole, ceftazidime and cefepime, respectively. Pseudomonas aeruginosa was less susceptible to all three antimicrobials than any other Gram-negative pathogen. There was generally good agreement between local Etest results and those obtained at the reference laboratory (for ceftobiprole: 86.8% with Gram-negatives; and 94.7% with Gram-positives), as well as between results obtained by BMD and Etest methods (for ceftobiprole: 98.2% with Gram-negatives; and 98.4% with Gram-positives). ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.

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