Importance of Reviewing Antibiotic Courses by 48 Hours: Risk Factors for Third-Generation Cephalosporin Resistance Among AmpC Harboring Organisms in Urine and Respiratory Cultures.

Background: Citrobacter, Enterobacter, Morganella, and Serratia (AmpC organisms) species can exhibit third-generation cephalosporin (TGC) resistance after TGC exposure. We aimed to assess if institutional TGC utilization correlated with institutional AmpC organism susceptibility and if prior TGC exposure ≤48 hours were associated with TGC resistance in the first culture of a future infection episode caused by an AmpC organism.

Methods: A 5-year retrospective cohort study was performed, including AmpC organisms isolated from pediatric urinary and respiratory tract cultures at an institution with TGC courses reviewed by the antimicrobial stewardship program at 48 hours. Correlations were assessed by Pearson's correlation. Multivariable logistic regression identified factors independently associated with TGC resistance in a subcohort of infection episodes.

Results: Among 654 cultures, AmpC organism TGC susceptibility increased from 74% in 2013 to 89.3% in 2017, and this correlated with a 26.1% decrease in TGC utilization (R = -0.906; P = 0.034). Among 275 AmpC organism infections, 21.1% were resistant. Resistance occurred in 13.6%, 17.4%, and 56.5% of infections with no exposure, ≤48 hours, and >48 hours of TGC exposure in the past 30 days, respectively. TGC exposure ≤48 hours was not associated with resistance (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.32-4.94; P = 0.74), whereas, TGC exposure >48 hours was (OR, 8.7; 95% CI, 3.67-20.6; P  < 0.001). Infections in 2017 were less likely to be resistant (OR, 0.25; 95% CI, 0.08-0.8; P = 0.019).

Conclusions: Decreased TGC utilization, likely related to antimicrobial stewardship, correlated with increased AmpC organism susceptibility. Limiting TGC exposure to ≤48 hours when possible may reduce AmpC organism resistance in future infections.