title: Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Bacteria Isolated from Patients Hospitalized with Pneumonia in U.S. Medical Centers, 2011 to 2015.
abstract: Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms (n= 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. β-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates.Pseudomonas aeruginosaandKlebsiellaspp. were the most common Gram-negative bacteria isolated from PHP and VAP. Ceftazidime-avibactam was very active againstP. aeruginosa(n= 3,402; MIC50/MIC90, 2 and 4 μg/ml; 96.6% susceptible), including isolates nonsusceptible to meropenem (86.3% susceptible to ceftazidime-avibactam), piperacillin-tazobactam (85.6% susceptible), or ceftazidime (80.6% susceptible). Ceftazidime-avibactam was also highly active againstEnterobacteriaceae(MIC50/MIC90, 0.12 and 0.5 μg/ml; 99.9% susceptible), including carbapenem-resistantEnterobacteriaceae(CRE) (n= 189; MIC50/MIC90, 0.5 and 2 μg/ml; 98.0% susceptible) and multidrug-resistant (MDR) (n= 674; MIC50/MIC90, 0.25 and 1 μg/ml; 98.8% susceptible) and extensively drug-resistant (XDR) (n= 156; MIC50/MIC90, 0.5 and 2 μg/ml; 98.1% susceptible)Enterobacteriaceaeisolates, as well asKlebsiellaspecies isolates showing an extended-spectrum β-lactamase (ESBL) screening-positive phenotype (n= 433; MIC50/MIC90, 0.25 and 1 μg/ml; 99.5% susceptible). AmongEnterobacterspp. (24.8% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.4% of ceftazidime-nonsusceptible isolates, were susceptible to ceftazidime-avibactam. The most common β-lactamases detected amongKlebsiella pneumoniaeandE. coliisolates wereK. pneumoniaecarbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209Enterobacteriaceaeisolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 μg/ml and five isolates with ceftazidime-avibactam MIC values of 16 μg/ml and negative results for all β-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA helio-sader@jmilabs.com.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D000046:Academic Medical Centers; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D015870:Gene Expression; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007709:Klebsiella / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D014481:United States / Q000453:epidemiology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D002442:Ceftazidime; D001618:beta-Lactamases; D010878:Piperacillin
keywords: Klebsiella pneumoniae carbapenemase; NDM-1; Pseudomonas aeruginosa; ceftazidime-avibactam; pneumonia; ventilator-associated pneumonia