LAUSR

Abstract Background Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBLE) are common pathogens in intensive care units (ICUs) causing infection at a range of body sites. While carbapenems are considered first-line agents, non-carbapenem beta-lactams such as piperacillin/tazobactam (TZP) and cefepime (FEP) are often used to treat non-severe ESBLE infections. Few studies have examined the molecular epidemiology and mechanisms of TZP and FEP resistance in non-bloodstream ESBLE isolates (e.g. urine, respiratory tract). Methods We screened Enterobacterales isolates collected between 2015-2019 for the ESBL gene blaCTX-M using multiplex PCR and performed nanopore sequencing positive isolates (n=164). FEP and TZP susceptibilities were determined by broth microdilution (BMD). We assessed the impact of genetic factors such as the location and genetic context of blaCTX-M, other beta-lactamase gene presence, and porin gene disruption on TZP and FEP MICs (Figure 1); univariable and multivariable logistic regression were used to test their association with FEP and TZP resistance. Results Most isolates belonged to Klebsiella pneumoniae (47%) or Escherichia coli(45%) and were highly clonally diverse. blaCTX-M-15 was the most common blaCTX-M allele (78%) followed by blaCTX-M-27 (15%). 47% of isolates demonstrated FEP resistance (MIC50/90 8/64 µg/mL), which was significantly associated with blaCTX-M allele, location, and copy number and narrow-spectrum β-lactamase co-carriage. Only 10% of isolates were resistant to TZP (MIC50/90 4/16 µg/mL), which did not appear to be modulated by presence of blaCTX-M. In multivariable analyses, FEP resistance was independently associated with blaCTX-M copies (OR 5.21, 95% CI 1.7-24.6, p=0.01) and association with truncated ISEcp1 (OR 12.9, 95% CI 3.1-65, p< 0.001); TZP resistance was associated with organism (OR 5.82 for K. pneumoniae versus E. coli, 95% CI 1.3-43.8, p=0.04), presence of blaOXA-1 (OR 5.2, 95% CI 1.3-35.9, p=0.04), and porin gene disruption (OR 6.5, 95% CI 1.3-32.3, p=0.02). Conclusion In summary, TZP resistance was uncommon and appeared to be independent of blaCTX-M carriage. TZP may be an appropriate treatment for nonbloodstream ESBLE infections in the ICU and should be evaluated further in clinical studies. Disclosures All Authors: No reported disclosures