Evaluation of Ceftazidime Use in the Neonatal Intensive Care Unit and Association With Cephalosporin-Resistant Gram-Negative Bacteria

Ann Pharmacother. 2022 Dec;56(12):1325-1332. doi: 10.1177/10600280221088270. Epub 2022 Apr 29.

Abstract

Background: Cefotaxime shortage in 2015 led to increased ceftazidime use in the neonatal intensive care unit (NICU).

Objective: The purpose was to explore whether ceftazidime increases risk for development of resistant gram-negative organisms.

Methods: Retrospective evaluation of NICU patients with cultures positive for Escherichia coli, Pseudomonas aeruginosa, Klebsiella species, or Stenotrophomonas maltophilia between January1, 2015 and August 31, 2020. Isolates were excluded if obtained from same patient and source within 90 days or if patient ≤7 days of life or admitted from a referring hospital. Data collection included demographics and clinical parameters, and culture/susceptibility data. The primary objective was comparison of pathogens and clinical parameters in those with and without third-generation cephalosporin resistance. The secondary objectives included a comparison between those with and without ceftazidime exposure and identification of factors associated with resistance. Comparisons were made using χ2, Fisher exact tests, or Wilcoxon tests. A logistic regression was used to identify risk factors for resistance.

Results: Overall, 349 isolates, representing 215 patients, were included. The most common source was endotracheal (n = 192, 55.0%) and pathogens were E coli (31.8%) and P aeruginosa (29.2%). Overall, 12.3% (n = 43) were resistant and these were obtained after longer parenteral nutrition (PN), central line access, and antibiotic days versus susceptible isolates. Higher resistance was noted after ceftazidime exposure versus no exposure, 19.1% versus 6.6%. Each day of ceftazidime was associated with 13% greater odds of P aeruginosa resistance (adjusted odds ratio: 1.13 [95% confidence interval: 1.03-1.23]).

Conclusion and relevance: Ceftazidime duration was associated with increased risk for P aeruginosa resistance. Additional studies are needed to confirm these findings.

Keywords: antibiotic resistance; ceftazidime; neonate.

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Cefotaxime
  • Ceftazidime* / pharmacology
  • Ceftazidime* / therapeutic use
  • Cephalosporins* / adverse effects
  • Escherichia coli
  • Gram-Negative Bacteria
  • Humans
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Microbial Sensitivity Tests
  • Monobactams
  • Retrospective Studies

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Monobactams
  • Ceftazidime
  • Cefotaxime