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.

Related Concept Videos

Antimicrobial Effectiveness01:28

Antimicrobial Effectiveness

The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
744
Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence01:22

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
73
Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
5.8K