In vitro activity of ceftazidime, ceftaroline and aztreonam alone and in combination with avibactam against European Gram-negative and Gram-positive clinical isolates.
Recent clinical isolates of key Gram-negative and Gram-positive bacteria were collected in 2012 from hospitalised patients in medical centres in four European countries (France, Germany, Italy and Spain) and were tested using standard broth microdilution methodology to assess the impact of 4 mg/L avibactam on the in vitro activities of ceftazidime, ceftaroline and aztreonam. Against Enterobacteriaceae, addition of avibactam significantly enhanced the level of activity of these antimicrobials. MIC(90) values (minimum inhibitory concentration that inhibits 90% of the isolates) of ceftazidime, ceftaroline and aztreonam for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii and Morganella morganii were reduced up to 128-fold or greater when combined with avibactam. A two-fold reduction in the MIC(90) of ceftazidime to 8 mg/L was noted in Pseudomonas aeruginosa isolates when combined with avibactam, whereas little effect of avibactam was noted on the MIC values of the test compounds when tested against Acinetobacter baumannii isolates. Avibactam had little effect on the excellent activity of ceftazidime, ceftaroline and aztreonam against Haemophilus influenzae. It had no impact on the in vitro activity of ceftazidime and ceftaroline against staphylococci and streptococci. This study demonstrates that addition of avibactam enhances the activities of ceftazidime, ceftaroline and aztreonam against Enterobacteriaceae and P. aeruginosa but not against A. baumannii.
AstraZeneca Pharmaceuticals LP, Waltham, MA, USA. Electronic address: testa3r@msn.com.
Raymond
R
Testa
Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Biomédica (IRYCIS), Madrid, Spain.
Rafael
R
Cantón
Department of Medical Technologies, University of Siena, Siena, Italy.
Tommaso
T
Giani
Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Biomédica (IRYCIS), Madrid, Spain.
María-Isabel
MI
Morosini
AstraZeneca Pharmaceuticals LP, Waltham, MA, USA.
Wright W
WW
Nichols
German Centre for Infection Research (DZIF), Bonn-Cologne, Germany; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Harald
H
Seifert
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Danuta
D
Stefanik
Department of Medical Technologies, University of Siena, Siena, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Clinical Microbiology Unit, Florence Careggi University Hospital, Florence, Italy.
Gian Maria
GM
Rossolini
Medical and Molecular Microbiology Unit, University of Fribourg, Fribourg, Switzerland; INSERM Research Unit, Hospital Bicêtre, South-Paris University, Paris, France. Electronic address: patrice.nordmann@unifr.ch.
Patrice
P
Nordmann
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D005060:Europe; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006761:Hospitals; D006801:Humans; D008826:Microbial Sensitivity Tests; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; C543519:avibactam
Avibactam; Enterobacteriaceae; Pseudomonas aeruginosa; Staphylococcus; Streptococcus; Susceptibility