title: Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007-09.
abstract: BACKGROUND
  Antibiotic resistance is problematic in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii, and is often associated with serious infections. Carbapenems are often one of the few remaining therapeutic options, so it is important to monitor carbapenem activity against these pathogens and to identify resistance mechanisms.
  
  
  METHODS
  Carbapenem susceptibilities were determined for 14 359 Enterobacteriaceae, 3614 P. aeruginosa and 994 A. baumannii from the USA (2007-09). Klebsiella pneumoniae with doripenem MICs ≥2 mg/L (n = 88), and P. aeruginosa (n = 452), A. baumannii (n = 349) and other enterics (n = 13) with doripenem MICs ≥4 mg/L were screened for carbapenem resistance mechanisms.
  
  
  RESULTS
  Doripenem/meropenem and imipenem susceptibilities for Enterobacteriaceae were >99% and 89%, respectively. Doripenem susceptibility (2007-09) for P. aeruginosa was 87.4%-84.1%; comparable to meropenem and higher than imipenem. For A. baumannii, doripenem susceptibility (2007-09) was 63%-58.2%; lower than imipenem and meropenem. Resistant K. pneumoniae had KPC and lacked porins OmpK35/OmpK36. In 2009, 3.4% of all K. pneumoniae possessed KPC. Five other enterics and one P. aeruginosa possessed KPC. Resistance mechanisms in P. aeruginosa were loss of porin OprD (90%), efflux (55%) and elevated AmpC activity (25%). Acquired carbapenemases OXA-23/-24 were present in 48% of resistant A. baumannii. VIM metallo-β-lactamases were present in three P. aeruginosa and one A. baumannii isolates.
  
  
  CONCLUSIONS
  Doripenem and meropenem were more active than imipenem against Enterobacteriaceae and P. aeruginosa from the USA. Carbapenem resistance mechanisms included serine carbapenemases, elevated AmpC activity, efflux and porin deficiencies occurring mostly in P. aeruginosa. Metallo-β-lactamases were found in <0.1% of isolates.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 1000 US Route 202, Raritan, NJ 08869, USA. tdavies1@its.jnj.com
authors.forename: Todd A
authors.initials: TA
authors.lastname: Davies
authors.forename: Anne
authors.initials: A
authors.lastname: Marie Queenan
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morrow
authors.forename: Wenchi
authors.initials: W
authors.lastname: Shang
authors.forename: Karen
authors.initials: K
authors.lastname: Amsler
authors.forename: Wenping
authors.initials: W
authors.lastname: He
authors.forename: A Simon
authors.initials: AS
authors.lastname: Lynch
authors.forename: Chris
authors.initials: C
authors.lastname: Pillar
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology*; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D005838:Genotype; D015378:Imipenem / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D008137:Longitudinal Studies; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000172:deficiency / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D013845:Thienamycins / Q000494:pharmacology; D014481:United States; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D018272:Porins; D013845:Thienamycins; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem; D000077726:Doripenem; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C547585:beta-lactamase KPC-2, Klebsiella pneumoniae; C063912:carbapenemase; D000077731:Meropenem