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

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

doi:10.1093/jac/dkq397

Cited by 24 publications

(15 citation statements)

References 25 publications

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“…The high rates of susceptibility to ceftobiprole among MSSA, MRSA, and S. pneumoniae isolates observed in this study are similar to ceftobiprole susceptibility rates reported in a previous study of 9,067 pathogens collected from hospitalized patients across the EU and Middle East in 2008 (CLASS study) 36. In the CLASS study, ceftobiprole susceptibility rates of 100%, 99.9%, and 100% were observed for MSSA, MRSA, and S. pneumoniae , respectively,36 which align very closely with the ceftobiprole susceptibility rates observed in the current study (100%, 100%, and 99.8% for MSSA, MRSA, and S. pneumoniae , respectively).…”

Section: Discussionsupporting

confidence: 89%

“…In the CLASS study, ceftobiprole susceptibility rates of 100%, 99.9%, and 100% were observed for MSSA, MRSA, and S. pneumoniae , respectively,36 which align very closely with the ceftobiprole susceptibility rates observed in the current study (100%, 100%, and 99.8% for MSSA, MRSA, and S. pneumoniae , respectively). This suggests that the in vitro activity of ceftobiprole against these prevalent Gram-positive pathogens has not changed in almost a decade.…”

Section: Discussionsupporting

confidence: 87%

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Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014–2015

Henriksen¹,

Smart²,

Hamed³

2018

IDR

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PurposeLower respiratory tract infections (LRTIs) can cause significant morbidity and mortality and are becoming increasingly difficult to treat because of the growing prevalence of resistance to conventional antimicrobial agents. This study aimed to assess the current in vitro susceptibility of respiratory tract pathogens collected from the UK and Ireland to ceftobiprole, an advanced-generation cephalosporin, as compared with other antibiotics.MethodsPathogens isolated from patients with LRTIs were analyzed as part of the British Society for Antimicrobial Chemotherapy Antimicrobial Resistance Surveillance Programme during 2014–2015. Antibiotic susceptibility was evaluated using European Committee on Antimicrobial Susceptibility Testing breakpoints, including the ceftobiprole pharmacokinetic/pharmacodynamic non-species-specific breakpoint when species-specific breakpoints were not available.ResultsOne thousand one hundred and sixty-eight isolates from community-onset LRTIs and 1,264 isolates from hospital-onset LRTIs were analyzed. The ceftobiprole susceptibility rate was 99.8% (428/429) for Streptococcus pneumoniae, 100% (502/502) for Haemophilus influenzae, and 99.6% (236/237) for Moraxella catarrhalis. All Staphylococcus aureus isolates, including methicillin-susceptible S. aureus (MSSA; N=181) and methicillin-resistant S. aureus (MRSA; N=35), were susceptible to ceftobiprole. Overall, ceftobiprole susceptibility was observed in 88.1% (215/244) of Escherichia coli isolates, 83.4% (156/187) of Klebsiella pneumoniae isolates and 86.7% (98/113) of Enterobacter spp. isolates.ConclusionCeftobiprole had in vitro activity against all S. aureus (both MSSA and MRSA) isolates, and almost all S. pneumoniae isolates, as well as against Gram-negative bacteria associated with community-onset or hospital-onset LRTIs. Based on this analysis, ceftobiprole is a good treatment option when broad-spectrum antibiotic coverage is needed for LRTIs.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 87%

Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014–2015

Henriksen¹,

Smart²,

Hamed³

2018

IDR

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“…In particular, for MRSA and pneumococci, MIC 90 values of 2 and 0.5 mg/L, respectively, have been reported, with susceptibility rates consistently exceeding 95% and 99%, respectively ( Table 1). Strains of MRSA resistant to ceftobiprole are uncommon, and usually exhibit an MIC of 4 mg/L, i. e. only two-fold higher than the EUCAST breakpoint for susceptibility (European Committee on Antimicrobial Susceptibility Testing [EUCAST] clinical breakpoint tables, version 9.0, 2019; http://www.eucast.org) [12][13][14][15][16]. Against Enterobacterales, MIC 90 values ≥16 mg/L have been reported, with variable susceptibility rates (Table 1) [12][13][14][15][16][17][18], depending on the prevalence of ESBL and carbapenemase producers.…”

Section: Antimicrobial Properties Of Ceftobiprolementioning

confidence: 99%

Ceftobiprole: drug evaluation and place in therapy

Giacobbe

Rosa

Bono

et al. 2019

Expert Review of Anti-infective Therapy

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Introduction: Ceftobiprole is a fifth-generation cephalosporin with a broad spectrum of antimicrobial activity, including also methicillin-resistant Staphylococcus aureus (MRSA). Ceftobiprole is approved for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia, in several European and non-European countries. Areas covered: In this narrative review, we discuss the current place in therapy of ceftobiprole, both within and outside approved indications. An inductive MEDLINE/PubMed search of the available literature was conducted. Expert opinion: There are three main reasons which render ceftobiprole an attractive option for the empirical and targeted treatment of CAP and HAP: (i) its broad spectrum of activity; (ii) its activity against MRSA; (iii) its good safety profile. For these indications, ceftobiprole should be employed thoughtfully, in those scenarios in which its intrinsic advantages could be maximized. The use of ceftobiprole outside approved indications could be justified in specific scenarios, such as when other approved alternatives are ineffective, when the risk of toxicity due to other agents is unacceptable, and for salvage therapy. In the near future, ongoing phase 3 studies and further observational experiences could both enlarge the current panel of approved indications and enrich our knowledge on the use of ceftobiprole for off-label indications. ARTICLE HISTORY

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“…Ceftobiprole also displays potent activity against Enterobacteriaceae and Pseudomonas aeruginosa isolates that is similar to those of advanced-generation cephalosporins such as cefepime (10)(11)(12)(13).…”

mentioning

confidence: 92%

Ceftobiprole Activity against over 60,000 Clinical Bacterial Pathogens Isolated in Europe, Turkey, and Israel from 2005 to 2010

Farrell

Flamm

Sader

et al. 2014

Antimicrob Agents Chemother

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Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC 90 values of 0.25, 0.12, <0.06, and 0.5 g/ml, respectively. Ceftobiprole was active against methicillin-resistant S. aureus (MRSA) (98.3% susceptible) and methicillin-resistant CoNS, having a MIC 90 of 2 g/ml. Ceftobiprole was active against Enterococcus faecalis (MIC 50/90 , 0.5/4 g/ml) but not against most Enterococcus faecium isolates. Ceftobiprole was very potent against the majority of Enterobacteriaceae (87.3% susceptible), with >80% inhibited at <0.12 g/ml. The potency of ceftobiprole against Pseudomonas aeruginosa (MIC 50/90 , 2/>8 g/ml; 64.6% at MIC values of <4 g/ml) was similar to that of ceftazidime (MIC 50/90 , 2/>16 g/ml; 75.4% susceptible), but limited activity was observed against Acinetobacter spp. and Stenotrophomonas maltophilia. High activity was also observed against all Haemophilus influenzae (MIC 90 , <0.06 g/ml) and Moraxella catarrhalis (MIC 50/90 , <0.06/0.25 g/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens. C eftobiprole medocaril (BAL5788, formerly Ro-65-5788) is the prodrug form of ceftobiprole (BAL9141, formerly Ro-63-9141), which is an extended-spectrum anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) parenteral cephalosporin with potent activity against Gram-positive and -negative bacterial pathogens. Ceftobiprole has been evaluated in several phase III clinical trials focusing on skin and skin structure infections (SSSI) (1, 2), community-acquired pneumonia (CAP) requiring hospitalization (3), and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) (4), and has recently obtained regulatory approval in Europe for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) and community-acquired pneumonia in adults. Ceftobiprole is relatively stable toward AmpC ␤-lactamases and has a strong affinity for penicillin binding proteins (PBPs), including PBP 2A, which mediates resistance to ␤-lactams in MRSA and methicillin (oxacillin)-resistant co...

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

Abstract: 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.

Cited by 24 publications

References 25 publications

Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014–2015

Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014–2015

Ceftobiprole: drug evaluation and place in therapy

Ceftobiprole Activity against over 60,000 Clinical Bacterial Pathogens Isolated in Europe, Turkey, and Israel from 2005 to 2010

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

Abstract: 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.

Cited by 24 publications

References 25 publications

Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014&ndash;2015

Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014&ndash;2015

Ceftobiprole: drug evaluation and place in therapy

Ceftobiprole Activity against over 60,000 Clinical Bacterial Pathogens Isolated in Europe, Turkey, and Israel from 2005 to 2010

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Product

Resources

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Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014–2015

Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the United Kingdom and Ireland during 2014–2015