β-Lactam/β-Lactamase Inhibitor Combinations Non-Susceptible ESBL-Producing Enterobacteriaceae Bloodstream Infections: An Underestimated Clinical Entity.

BACKGROUND

To describe the clinical and molecular characteristics of β-lactam/β-lactamase inhibitor combinations (BLBLIs) non-susceptible ESBL-producing Enterobacteriaceae (BnESBL-E) bloodstream infections (BSIs).

METHODS

A cohort study was performed with ESBL-E-BSI cases from 2017 to 2019 in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. Whole-genome sequencing and antibiotic susceptibility testing were performed.

RESULTS

Among the 187 patients with ESBL-E-BSI, 39.57% (74/187) had BnESBL-E-BSI. Nosocomial infections constituted 63.51% of BnESBL-E-BSIs, and 39.19% of cases originated from intra-abdominal sources. Risk factors for BnESBL-E-BSI included BLBLIs exposure within the preceding 3 months, ICU admission within the last 3 months, and the duration of hospital stay prior to BSI. Notably, a urinary source of bacteremia emerged as a protective factor against BnESBL-E-BSI(OR, 0.177; 95% CI, 0.049-0.647; p=0.009). BnESBL-E-BSIs were associated with a higher 28-day mortality compared to BLBLIs-susceptible cases (31.08%vs.16.81%; p=0.031). Multivariate analysis identified the Pitt bacteremia score, CRP level, and hospitalization within the preceding 3 months as risk factors for BnESBL-E-BSI-related mortality, while receipt of carbapenems within 72 hours of symptom onset improved survival(OR, 0.128; 95% CI, 0.018-0.912; p = 0.04). BnESBL-E isolates demonstrated no clonal transmission and remained highly susceptible to amikacin, carbapenems and tigecycline. Coexistence of multiple ESBL types was frequently observed, occurring in 40.6% of BnESBL-Ec and 72.7% of BnESBL-Kp isolates.

CONCLUSION

Given the high prevalence and mortality of BnESBL-E-BSI, carbapenems may be preferable treatment option for non-urinary ESBL-E-BSIs. BnESBL-E represents an underestimated clinical threat, warranting timely identification of risk factors and the consideration of appropriate empirical therapy.