Abstract
Background
Drug resistance in Gram-negative bacteria is of particular concern in children. Relebactam, a novel diazabicyclooctane inhibitor, coupled with imipenem has broad-spectrum activity against β-lactamase producing organisms. Here, we compare the in vitro activity of imipenem-relebactam to 10 standard comparator drugs against resistant Gram-negative isolates from two US pediatric hospitals.
Methods
We tested 100 isolates (50 per site) from pediatric clinical specimens tested during 2015–2017. All isolates were extended-spectrum cephalosporin-resistant (ESC-R); more than half were multidrug resistant (67%). Selected ESC-R isolates included Escherichia coli (90), Klebsiella pneumoniae (8), Klebsiella oxytoca (1), and Enterobacter cloacae (1) that were resistant or intermediate to ≥1 cephalosporins and/or aztreonam. A 0.5 McFarland suspension was prepared from colonies grown on blood agar plates (Thermo Scientific) at 35 ± 1°C for 18–24 hours. A final inoculum of 5 × 105 CFU/mL was prepared in Mueller–Hinton broth. Sensititre plates (Thermo Fisher Scientific) containing graded concentrations of imipenem/relebactam and 10 comparator drugs were inoculated and incubated at 35 ± 1°C for 18–24 hours. The minimum inhibitory concentration (MIC) was determined using the Sensititre Vizion system (Thermo Fisher Scientific) and endpoints were interpreted using CLSI (2019) breakpoint criteria, with the exception of colistin (EUCAST 2019).
Results
Selected ESC-R isolates had high rates of resistance to cephalosporins (64%–97%), aztreonam (80%), and levofloxacin (61%). All isolates were susceptible to imipenem/relebactam, imipenem and meropenem (MIC, ≤1 μg/mL for all). The imipenem/relebactam MIC50 (0.06 μg/mL) and MIC90 (0.12 μg/mL) values for ESC-R isolates were within one dilution of MICs of imipenem alone (0.12 μg/mL and 0.25 μg/mL). Among the comparators, colistin, amikacin, and piperacillin/tazobactam demonstrated comparable activities with 100%, 99%, and 94% susceptibilities, respectively.
Conclusion
Meropenem, imipenem alone and in combination with relebactam exhibited 100% susceptibilities against ESC-R Enterobacteriaceae isolated from pediatric specimens, demonstrating the high potency of carbapenems.
Disclosures
All authors: No reported disclosures.
Genomic Investigation Reveals Contaminated Detergent as the Source of an Extended-Spectrum-β-Lactamase-Producing Klebsiella michiganensis Outbreak in a Neonatal Unit
