An international prospective cohort study to validate two prediction rules for infections caused by 3rd-generation cephalosporin-resistant Enterobacterales

Deelen JWT, Rottier WC, Giron Ortega JA, Rodriguez-Baño J, Harbarth S, Tacconelli E, Jacobsson G, Zahar JR, van Werkhoven CH, Bonten MJM; ESBL-PREDICT Study Team.

Clin Infect Dis. 2020 Jul 8:ciaa950. doi: 10.1093/cid/ciaa950., 12/2020.

Introduction: The possibility of bloodstream  infections caused by 3rd-generation cephalosporin-resistant  Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric  inappropriate treatment (IAT) and unnecessary carbapenem use (UCU).  Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally  validate two previously derived prediction rules for community-onset  (CO) and hospital-onset (HO) suspected bloodstream infections.

Methods: In  33 hospitals in 13 countries we prospectively enrolled 200 patients per  hospital in whom blood cultures were obtained and intravenous  antibiotics with coverage for Enterobacterales were empirically started.  Cases were defined as 3GC-R-BSI or 3GC-R Gram-negative infection  (3GC-R-GNI) (analysis 2), all other outcomes served as comparator. Model  discrimination and calibration were assessed. Impact on carbapenem use  was assessed at several cut-off points.

Results: 4,650  CO infection episodes were included and the prevalence of 3GC-R-BSI was  2.1% (n=97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398  of 4553 non-3GC-R-BSI patients (8.7%). Model calibration was good and  the AUC was 0.79 (95% CI: 0.75 - 0.83) for 3GC-R-BSI. The prediction  rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable  at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal.  IAT and UCU in all 3GC-R-GNI (analysis 2) improved at similar  percentages.1,683 HO infection episodes were included and the prevalence  of 3GC-R-BSI was 4.9% (n=83). Here model calibration was insufficient.

Conclusion: A  prediction rule for community-onset 3GC-R infection was validated in an  international cohort and could improve empirical antibiotic use.  Validation of the hospital-onset rule yielded suboptimal performance.