[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]
Activity of imipenem/relebactam against MDR Pseudomonas aeruginosa in Europe: SMART 2015–17
Sibylle H Lob, James A Karlowsky, Katherine Young, Mary R Motyl, Stephen Hawser, Nimmi D Kothari, Melinda E Gueny, Daniel F Sahm
Journal of Antimicrobial Chemotherapy, dkz191, https://doi.org/10.1093/jac/dkz191
Published: 13 May 2019
Relebactam is a diazabicyclooctane non-β-lactam inhibitor of Ambler class A and C β-lactamases that is in clinical development in combination with imipenem/cilastatin. The current study evaluated the in vitro activity of imipenem/relebactam against 5447 isolates of Pseudomonas aeruginosasubmitted to the SMART global surveillance programme in 2015–17 by 67 clinical laboratories in 22 European countries.
MICs were determined using the CLSI broth microdilution reference method (Eleventh Edition: M07, 2018). Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of imipenem. MICs were interpreted using EUCAST clinical breakpoints (version 8.1); imipenem breakpoints were applied to imipenem/relebactam.
Rates of susceptibility to imipenem and imipenem/relebactam (MIC ≤4 mg/L) were 69.4% and 92.4%, respectively, for all isolates of P. aeruginosa. Over one-third of all isolates (34.9%, 1902/5447) were MDR; lower respiratory tract isolates (38.3%, 1327/3461) were more frequently MDR than were intraabdominal (28.5%, 355/1245) or urinary tract (29.7%, 212/714) isolates. Of all MDR isolates, 78.2% were susceptible to imipenem/relebactam, a rate that was 50–77 percentage points higher than the rate of susceptibility to imipenem or any other β-lactam tested; rates of susceptibility to imipenem/relebactam were similar for MDR isolates from lower respiratory tract (77.8% susceptible), intraabdominal (80.3%) and urinary tract (76.4%) infections. Overall, relebactam restored imipenem susceptibility to 75.2% (1254/1668) of imipenem-non-susceptible isolates of P. aeruginosa and to 69.6% (947/1361) of imipenem-non-susceptible isolates with an MDR phenotype.
Relebactam restored in vitro susceptibility to imipenem for most imipenem-non-susceptible and MDR clinical isolates of P. aeruginosa from European patients.
Topic: phenotype – pseudomonas aeruginosa – imipenem – lactams – respiratory system – urinary tract – infection
Issue Section: ORIGINAL RESEARCH
Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Relebactam; Imipenem; European Region.