Antibiotic Prophylaxis Is Associated with Subsequent Resistant Infections in Children with an Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection

Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02656-16. doi: 10.1128/AAC.02656-16. Print 2017 May.

Abstract

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged <22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.

Keywords: antibiotic resistance; pediatric infectious disease.

MeSH terms

  • Adhesins, Escherichia coli / genetics
  • Anti-Bacterial Agents / therapeutic use*
  • Antibiotic Prophylaxis / adverse effects*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Proteins / genetics
  • Cephalosporin Resistance / genetics
  • Cephalosporins / therapeutic use
  • Child
  • Child, Preschool
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / prevention & control*
  • Female
  • Fimbriae Proteins / genetics
  • Humans
  • Infant
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / prevention & control*
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Microbial Sensitivity Tests
  • beta-Lactam Resistance / genetics
  • beta-Lactamases / genetics

Substances

  • Adhesins, Escherichia coli
  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Cephalosporins
  • fimH protein, E coli
  • Fimbriae Proteins
  • AmpC beta-lactamases
  • beta-Lactamases