<p>The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and occurrence of subsequent resistant infections in children with index infections due to extended-spectrum cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of index and subsequent isolates. Extended-spectrum cephalosporin-resistant E. coli and Klebsiella spp. isolated from normally sterile sites of patients aged &lt;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 (K. pneumoniae) type were identical to 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 index and first subsequent infection was 123 days (interquartile range 43, 225). 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 (71%) of 17 patients with E. coli 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.</p>