ella aerogenes
Enterobacter cloacae
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Complicated Intra-abdominal Infections (cIAI)
Aerobic Bacteria
Gram-negative Bacteria
Citrobacter freundii
Klebsiella aerogenes
Enterobacter cloacae
Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
Pseudomonas aeruginosa
Anaerobic Bacteria
Gram-negative Bacteria
Bacteroides caccae
Bacteroides fragilis
Bacteroides ovatus
Bacteroides stercoris
Bacteroides thetaiotaomicron
Bacteroides uniformis
Bacteroides vulgatus
Fusobacterium nucleatum
Parabacteroides distasonis
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent ofthe following bacteria exhibit an in vitro (MIC) less than or equal to the susceptible breakpoint forRECARBRIO against isolates of similar genus or organism group. However, the efficacy of RECARBRIOin treating clinical infections due to these bacteria has not been established in adequate andwell-controlled clinical trials.
Aerobic Bacteria
Gram-positive Bacteria
Enterococcus faecalis
Methicillin-susceptible Staphylococcus aureus
Streptococcus anginosus
Streptococcus constellatus
Gram-negative Bacteria
Citrobacter koseri
Enterobacter asburiae
Anaerobic Bacteria
Gram-positive Bacteria
Eggerthella lenta
Parvimonas micra
Peptoniphilus harei
Peptostreptococcus anaerobius
Gram-negative Bacteria
Fusobacterium necrophorum
Fusobacterium varium
Parabacteroides goldsteinii
Parabacteroides merdae
Prevotella bivia
Veillonella parvula
Susceptibility Test Methods
For specific information regarding susceptibility testing methods, interpretive criteria, and associated testmethods and quality control standards recognized by FDA for RECARBRIO, please see:https://www.fda.gov/STIC.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Carcinogenicity studies with imipenem/cilastatin or relebactam have not been conducted.
Mutagenesis
Genotoxicity studies were performed in a variety of bacterial and mammalian tests in vivo and in vitro.
None of these tests showed any evidence of genetic damage.
The tests conducted with imipenem, cilastatin, or imipenem/cilastatin included: V79 mammalian cellmutagenesis assay (imipenem, cilastatin), Ames test (imipenem, cilastatin), unscheduled DNA synthesisassay (imipenem/cilastatin), and in vivo mouse cytogenetics test (imipenem/cilastatin).
The tests conducted with relebactam included: Ames test, in vitro chromosomal aberration in ChineseHamsters Ovary (CHO) cells, and in vivo rat micronucleus test.
Impairment of Fertility
No adverse effects on fertility, reproductive performance, fetal viability, growth or postnatal developmentwere observed in male and female rats given imipenem/cilastatin at intravenous doses up to80 mg/kg/day and at a subcutaneous dose of 320 mg/kg/day. In rats, a dose of 320 mg/kg wasapproximately double the MRHD based on body surface area. Slight decreases in live fetal body weightwere restricted to the highest dosage level.
In fertility studies, relebactam was administered in intravenous doses of 50, 150, and 450 mg/kg/day tomale rats beginning 15 days before mating, through mating, and for an additional 3 weeks and to femalerats beginning 15 days before mating |
