title: In vitro activity of ceftazidime/avibactam against Gram-negative pathogens isolated from pneumonia in hospitalised patients, including ventilated patients.
abstract: The activities of the novel β-lactam/non-β-lactam β-lactamase inhibitor combination ceftazidime/avibactam and comparators were evaluated against isolates from pneumonia in hospitalised patients including ventilated patients (PHP, pneumonia not designated as VABP; VABP, pneumonia in ventilated patients). Isolates were from the European-Mediterranean region (EuM), China and the USA collected in the SENTRY Antimicrobial Surveillance Program between 2009 and 2011 inclusive. A total of 2393 organisms from PHP were from the EuM, 888 from China and 3213 from the USA; from VABP patients there were 918, 97 and 692 organisms collected, respectively. Among Enterobacteriaceae from PHP, ceftazidime/avibactam MIC90 values against Escherichia coli ranged from 0.25-0.5mg/L and Klebsiella spp. MIC90 values were 0.5mg/L in each region. Among VABP isolates, MIC90 values for ceftazidime/avibactam against E. coli were 0.25mg/L; for Klebsiella spp. from VABP patients, MIC90 values were similar to those obtained against PHP isolates. The MIC of ceftazidime/avibactam was ≤8mg/L against 92-96% of Pseudomonas aeruginosa isolated from PHP patients. Isolates of P. aeruginosa from VABP patients were of lower susceptibility to all antibacterial agents (e.g. depending on region, meropenem susceptibilities were 51.2-69.4% in contrast to 68.3-76.7% among PHP patients). However, ceftazidime/avibactam inhibited 79.2-95.4% of VABP isolates at an MIC of ≤8mg/L. Acinetobacter spp. were resistant to many agents and only rates of susceptibility to colistin were >90% across all regions both for PHP and VABP isolates. Ceftazidime/avibactam was generally active against a high proportion of isolates resistant to ceftazidime from PHP and VAPB patients.
authors.affiliation: JMI Laboratories, Inc., 345 Beaver Kreek Center, Suite A, North Liberty, IA 52317, USA. Electronic address: robert-flamm@jmilabs.com.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: AstraZeneca Pharmaceuticals L.P., Waltham, MA 02451, USA.
authors.forename: Wright W
authors.initials: WW
authors.lastname: Nichols
authors.affiliation: JMI Laboratories, Inc., 345 Beaver Kreek Center, Suite A, North Liberty, IA 52317, USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, Inc., 345 Beaver Kreek Center, Suite A, North Liberty, IA 52317, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, Inc., 345 Beaver Kreek Center, Suite A, North Liberty, IA 52317, USA; Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D012121:Respiration, Artificial
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; C543519:avibactam; D002442:Ceftazidime
keywords: Ceftazidime/avibactam; Hospital-acquired pneumonia; Ventilator-associated pneumonia