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Published on: January 22, 2021
Comparative in vitro effectiveness of ceftolozane/tazobactam against pediatric gram-negative drug-resistant isolates
Neena Kanwar1,2, Dithi Banerjee1,2, Christopher J Harrison3,4
1Children's Mercy, Department of Pathology and Laboratory Medicine, Kansas City, MO, USA.
Insights
Ceftolozane/tazobactam showed high in-vitro activity against pediatric Gram-negative Enterobacteriaceae resistant to common antibiotics. This combination therapy is a promising option for treating infections caused by these challenging pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Gram-negative Enterobacteriaceae pose a significant threat in pediatric healthcare settings.
- Limited effective treatment options exist for infections caused by these multidrug-resistant organisms.
Purpose of the Study:
- To evaluate the in-vitro activity of ceftolozane/tazobactam (C/T) against a collection of pediatric ESC-R/CR Gram-negative Enterobacteriaceae.
- To compare the efficacy of C/T with other antimicrobial agents.
Main Methods:
- A total of 299 pediatric isolates of ESC-R/CR Gram-negative Enterobacteriaceae were collected from three U.S. pediatric centers.
- Antimicrobial susceptibility testing was performed using microbroth dilution with custom Sensititre plates and interpreted using CLSI 2017 and EUCAST 2019 breakpoint criteria.
Main Results:
- Overall, 87.5% of the isolates were susceptible to C/T, with MIC50/90 values of 0.25/4 μg/ml.
- C/T demonstrated high susceptibility rates for E. coli (91%) and Klebsiella spp. (73.3%).
- Ceftolozane/tazobactam exhibited greater susceptibility compared to most tested agents, except for colistin (95.4%) and meropenem (97.4%).
Conclusions:
- Ceftolozane/tazobactam possesses potent in-vitro activity against a broad range of beta-lactam resistant pediatric Enterobacteriaceae.
- C/T represents a valuable therapeutic option for managing infections caused by these difficult-to-treat Gram-negative pathogens in children and adolescents.
Abstract:
Ceftolozane/tazobactam (C/T), a cephalosporin/beta-lactamase inhibitor combination, was evaluated in vitro vs. 10 comparators against 299 pediatric extended-spectrum-cephalosporin-resistant or carbapenem-resistant (ESC-R/CR) Gram-negative Enterobacteriaceae from three freestanding pediatric centers. Isolates were from urine or other sterile sites of children and adolescents through 21 years of age. Susceptibilities were assayed by microbroth dilution via custom Sensititre plates (Thermo Fisher Scientific). Susceptibility was determined using the Sensititre Vizion® system (Thermo Fisher Scientific). Susceptibility breakpoint criteria were those of the Clinical and Laboratory Standards Institute (CLSI) for 2017, except for colistin (EUCAST 2019). Overall, 87.5% isolates were C/T susceptible (MIC ≤2 μg/ml; MIC50/90, 0.25/4 μg/ml). Susceptibility to C/T was detected more frequently as compared to all other antimicrobials tested except for colistin (95.4%) and meropenem (97.4%). Percent susceptibility to C/T was high for E. coli (91%) and Klebsiella spp. (73.3%). C/T demonstrated good in-vitro activity and high potency against most beta-lactam resistant pediatric Enterobacteriaceae from three geographically diverse U.S. regions.
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