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Session: P032 Drug resistance - miscellaneous pathogens and special populations

Category: 3a. Resistance surveillance & epidemiology: MRSA, VRE & other Gram- positives

23 April 2017, 12:30 - 13:30 P0723

Activity of ceftobiprole and comparators against hospital-acquired pneumonia pathogens from Italy, January-May 2016

Tommaso Giani*1, Alberto Antonelli2, Marco Coppi2, Olga Lorenza Colavecchio2, Viola Conte3, Anne Santerre Henriksen4, Gian Maria Rossolini5

1University of Siena; Medical Biotechnologies

2University of Florence; Department of Experimental and Clinical Medicine

3Department of Medical Biotechnologies, University of Siena

4Basilea Pharmaceutica International Ltd.; Development

5University of Florence; Forence Careggi University Hospital; Don Carlo Gnocchi Foundation; Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence

Background: Ceftobiprole is a 5th-generation with an expanded-spectrum and potent activity against Gram-positive and -negative bacteria. It is approved for marketing in various European and non-European countries for the treatment of hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia) and community-acquired pneumonia (CAP) in adults. Ceftobiprole has in vitro activity against -resistant Staphylococcus aureus (MRSA) and other common pathogens in pneumonia, e.g. Enterobacteriaceae not expressing extended spectrum β-lactamases (ESBLs) or carbapenemases and . The objective of this study was to investigate the in vitro activity of ceftobiprole and comparators against a collection of clinical isolates putatively responsible for HAP, representative of the contemporary Italian epidemiology.

Material/methods: During the period January-May 2016, up to 25 consecutive, non-replicate clinical isolates putatively responsible of HAP were collected by 13 different centres distributed across Italy. During the same period, the collecting centres also collected all MRSA isolates from HAP. Identification of all isolates was confirmed by the reference laboratory using the MALDI-TOF Vitek-MS system (bioMérieux, Marcy L’Etoile, France). Antimicrobial susceptibility testing of ceftobiprole and comparators was performed by reference broth microdilution using custom plates (Thermo Fisher Scientific), and the results were interpreted according to the EUCAST breakpoints. The MRSA phenotype was confirmed by broth microdilution and, in case of discrepancy between central- laboratory and collecting-centre results, a cefoxitin screen test using disk-diffusion following EUCAST rules, was performed.

Results: A total of 313 isolates of Gram-negatives and Gram-positives were collected. Of all the isolates, the most common species were P. aeruginosa (n=105, 33%), (n=63, 20%), S. aureus (n=42, 13%) and (n=26, 8%). In the same period, 65 MRSA strains were collected from 12/13 centres. Similar to and , ceftobiprole was active against 35% and 58% of K. pneumoniae and E. coli, respectively. MIC50 and MIC90 values of ceftobiprole for P. aeruginosa were 8 mg/L and >16 mg/L, respectively. All methicillin-susceptible S. aureus isolates were susceptible to ceftobiprole. All MRSA isolates were susceptible to , and ; ceftobiprole had activity against 95% of these isolates.

Conclusions: Ceftobiprole showed a broad spectrum of activity against a collection of contemporary Gram-negative and Gram-positive HAP isolates from Italy. A high prevalence of both ESBL- and carbapenemase-producing Enterobacteriaceae was observed in this panel, affecting susceptibility against all tested. This study confirmed that ceftobiprole could be a valid therapeutic option in case of HAP caused by MRSA.