udomonas-derivedcephalosporinase (PDC), and Klebsiella-pneumoniae carbapenemase (KPC).
Resistance
Clinical isolates may produce multiple beta lactamases, express varying levels of beta lactamases, haveamino acid sequence variations, or have other resistance mechanisms that have not yet been identified.
Culture and susceptibility information and local epidemiology should be considered in selecting ormodifying antibacterial therapy.
Mechanisms of beta lactam resistance in gram-negative organisms include the production of betalactamases,up-regulation of efflux pumps, and loss of outer membrane porins. Imipenem/relebactamretains activity in the presence of the tested efflux pumps. Imipenem/relebactam has shown activityagainst some isolates of P. aeruginosa and Enterobacteriaceae that produce relebactam-susceptiblebeta-lactamases concomitant with loss of entry porins. Imipenem/relebactam is not active against most
isolates containing metallo-beta-lactamases (MBLs), some oxacillinases with carbapenemase activity, aswell as certain alleles of GES.
Imipenem/relebactam demonstrated in vitro activity against some Enterobacteriaceae isolatesgenotypically characterized for some beta-lactamases and extended-spectrum beta-lactamases (ESBLs)of the following groups: KPC, TEM, SHV, CTX-M, CMY, DHA, and ACT/MIR. Many of theEnterobacteriaceae isolates that were not susceptible to imipenem-relebactam were genotypicallycharacterized and the genes encoding MBLs or certain oxacillinases were present.Imipenem/relebactam demonstrated in vitro activity against genotypically characterized P. aeruginosaisolates containing certain known resistance factors: some chromosomal PDC alleles with ESBLs, and
those with loss of outer membrane porin (OprD) that co-expressed up-regulated efflux pumps (MexAB,MexCD, MexJK, and MexXY). Genotypically characterized P. aeruginosa isolates that were notsusceptible to imipenem/relebactam encoded some MBL, KPC, PER, GES, VEB, and PDC alleles.
Methicillin-resistant staphylococci should be considered resistant to imipenem. Imipenem is inactive invitro against Enterococcus faecium, Stenotrophomonas maltophilia, and some isolates of Burkholderiacepacia.
No cross-resistance with other classes of antimicrobials has been identified. Some isolates resistant tocarbapenems (including imipenem) and to cephalosporins may be susceptible to RECARBRIO.
Interaction with Other Antimicrobials
In vitro studies have demonstrated no antagonism between imipenem/relebactam and amikacin,azithromycin, aztreonam, colistin, gentamicin, levofloxacin, linezolid, tigecycline, tobramycin, orvancomycin.
Activity against Imipenem-Nonsusceptible Bacteria in Animal Infection ModelsRelebactam restored activity of imipenem/cilastatin in animal models of infection (e.g., mouse disseminatedinfection, mouse thigh infection, and mouse pulmonary infection) caused by imipenem-nonsusceptibleKPC-producing Enterobacteriaceae and imipenem-nonsusceptible P. aeruginosa(imipenem-nonsusceptible due to production of chromosomal PDC and loss of OprD porin).
Antimicrobial Activity
RECARBRIO has been shown to be active against most isolates of the following bacteria, both in vitroand in clinical infections [see Indications and Usage (1.1) and (1.2)].
Complicated Urinary Tract Infections (cUTI)
Aerobic Bacteria
Gram-negative Bacteria
Klebsi |
