1257. Re-Evaluation of Cefepime or Piperacillin-Tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales Urinary Tract Infections (REDUCE-UTI)

Abstract Background Carbapenems (CBP) are considered first-line for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). However, recent literature suggests that cefepime (FEP) and piperacillin-tazobactam (TZP) may produce similar outcomes vs. CBPs for the treatment of ESBL-E urinary tract infections (UTIs). The goal of this study was to determine if non-carbapenem (NCBP) therapy with FEP or TZP is as effective as CBPs for the treatment of ESBL-E UTIs. Methods This was a retrospective observational study of patients admitted to the hospital from January 1st, 2016 to June 30th, 2020 with a urine culture positive for ESBL-E. Patients were included if they received a study antibiotic (meropenem, ertapenem, TZP, or FEP). Patients were excluded if they had any of the following: absence of pyuria, prior receipt of study antibiotic, CBP-resistant organism isolated in urine culture, polymicrobial urine culture, end-stage renal disease, or concomitant gram-negative infection. The primary outcome was clinical cure defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days, and resistance within 30 days. Results A total of 133 patients were included based on definitive therapy received; 69 (52%) received CBP and 64 (48%) received NCBP therapy. Of the total patient population, 17 (13%) were admitted to the intensive care unit, 84 (63%) had a complicated UTI, and 64 (48%) had pyelonephritis. Baseline characteristics were similar between the two groups. There was no difference in clinical cure between the CBP and NCBP therapy groups (96% vs. 97%, p = 1.0). Additionally, no differences in secondary outcomes were observed. Subgroup analyses were performed in patients with specific pathogens, uncontrolled genitourinary source, complicated UTI, and pyelonephritis. These analyses did not reveal any differences in primary or secondary outcomes between the two groups. Conclusion FEP and TZP may be reasonable CBP-sparing alternatives for the treatment of ESBL-E UTIs as clinical and microbiological outcomes were similar with these NCBP agents vs. CBPs in this study population. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry)


. AUROCs
Conclusion. Discriminative ability of the risk prediction models showed varying performance. The model by Lodise et al. appears to be most useful when a low risk level is deemed acceptable for failure rate, while at a moderate to high risk of missing a CRE case (20% and 30% FNR), the methods by Seligman and Vazquez-Guillamet et al. are most desirable as they minimize the chance of over-treatment. Additional work to increase sample size and to evaluate the models inter-rater reliability is currently on going.
Disclosures. Background. Carbapenems (CBP) are considered first-line for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). However, recent literature suggests that cefepime (FEP) and piperacillin-tazobactam (TZP) may produce similar outcomes vs. CBPs for the treatment of ESBL-E urinary tract infections (UTIs). The goal of this study was to determine if non-carbapenem (NCBP) therapy with FEP or TZP is as effective as CBPs for the treatment of ESBL-E UTIs.
Methods. This was a retrospective observational study of patients admitted to the hospital from January 1st, 2016 to June 30th, 2020 with a urine culture positive for ESBL-E. Patients were included if they received a study antibiotic (meropenem, ertapenem, TZP, or FEP). Patients were excluded if they had any of the following: absence of pyuria, prior receipt of study antibiotic, CBP-resistant organism isolated in urine culture, polymicrobial urine culture, end-stage renal disease, or concomitant gram-negative infection. The primary outcome was clinical cure defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days, and resistance within 30 days.
Results. A total of 133 patients were included based on definitive therapy received; 69 (52%) received CBP and 64 (48%) received NCBP therapy. Of the total patient population, 17 (13%) were admitted to the intensive care unit, 84 (63%) had a complicated UTI, and 64 (48%) had pyelonephritis. Baseline characteristics were similar between the two groups. There was no difference in clinical cure between the CBP and NCBP therapy groups (96% vs. 97%, p = 1.0). Additionally, no differences in secondary outcomes were observed. Subgroup analyses were performed in patients with specific pathogens, uncontrolled genitourinary source, complicated UTI, and pyelonephritis. These analyses did not reveal any differences in primary or secondary outcomes between the two groups.
Conclusion. FEP and TZP may be reasonable CBP-sparing alternatives for the treatment of ESBL-E UTIs as clinical and microbiological outcomes were similar with these NCBP agents vs. CBPs in this study population.
Disclosures. Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry) Background. Antibiotic resistance in nontyphoidal Salmonella can limit treatment options for patients requiring antibiotic therapy. We assessed the contribution of international travel to resistance among nontyphoidal Salmonella infections.

Antibiotic Resistant Nontyphoidal
Methods. We describe characteristics of nontyphoidal Salmonella infections in the Foodborne Diseases Active Surveillance Network during 2018 that were also reported to PulseNet and the National Antimicrobial Resistance Monitoring System. We defined genetic resistance to first-line antibiotics as the presence of genes or mutations known to confer decreased susceptibility or resistance to ciprofloxacin, azithromycin, or ceftriaxone. We used multivariable logistic regression to assess the association between resistance to first-line antibiotics and international travel in the 7 days before symptom onset overall and by United Nations statistical region, and we estimated the contribution of travel to resistance using population attributable fractions.
Results. Among 3,238 nontyphoidal Salmonella infections, 356 (11%) were in patients who traveled internationally in the 7 days before symptom onset. Of these, 109/356 (31%) had isolates with genetic resistance to first-line antibiotics, compared with 308/2882 (11%) non-travelers. Resistance was more likely following travel, after adjusting for age and sex (OR 3.7, 95% CI 2.9-4.8). Nine genes or mutations conferred resistance to first-line antibiotics among travel-associated isolates. The risk of resistance varied by region and was highest after travel to Asia (OR 7.5, 95% CI 4.7-12.0). Overall, 17.1% (95% CI 12.2%-21.7%) of genetic resistance to first-line antibiotics was attributable to international travel.
Conclusion. For patients with nontyphoidal Salmonella infections, international travel is associated with approximately three-fold increased risk that first-line agents could be ineffective. The estimated 17% of resistance to first-line antibiotics attributable to travel is encoded by relatively few genes and mutations. Investigation of the major sources of resistant strains could help target prevention efforts. Travel region should be considered when treating empirically; treatment should be adjusted based on results from antibiotic susceptibility testing.
Disclosures. All Authors: No reported disclosures

Session: P-72. Resistance Mechanisms
Background. Ceftriaxone-susceptible (CRO-S) and piperacillin-tazobactam-non susceptible (TZP-NS) Enterobacterales isolates have become a frequently isolated phenotype emerging in practice. The genotypic profile is still not clearly elucidated, although prior genotypic sequencing data of these isolates with this phenotypic profile suggests that they are not extended-spectrum beta-lactamase (ESBL) producers. Due to the unfamiliarity with this phenotype and the potential for overuse of broad-spectrum antibiotics, we investigated the clinical outcomes of CRO-S/TZP-NS isolates with carbapenem versus non-carbapenem beta-lactam (NCBL) therapy.
Methods. This was a retrospective chart review of patients with a diagnosed infection caused by a CRO-S/TZP-NS Enterobacterales isolate admitted to any of the three NYU hospitals: Long Island, Tisch, or Brooklyn campuses, treated with a betalactam (BL) antibiotic from October 2015 to October 2020. The primary outcome was treatment failure defined as an escalation of antibiotics due to clinical worsening, 30-day all-cause mortality, or relapse of infection with the same genus and species. Patients who received ≥ 72 consecutive hours of BL antibiotics were considered to be on definitive therapy.
Results. A total of 111 patients were included in this study, 9 in the carbapenem group and 102 in the NCBL group. There was no statistically significant difference in the clinical failure rate between the two groups (0% vs 10.8% respectively, P=0.56). A univariate analysis assessed the association of clinical failure with TZP, CRO, cefpodoxime, cefepime, and 1 st -3 rd generation cephalosporins grouped. There were no statistically significant increases in 30-day treatment failure in any of the individual categories.
Conclusion. There were no statistically significant differences in 30-day failure with the use of carbapenem vs NCBL antibiotics. No individual BLs or classes were associated with an increased risk of clinical failure. This study suggests that there is a role for NCBL antibiotics for Enterobacterales isolates with this phenotypic presentation and supports prior data that they are less likely to be ESBL producers. Prospective studies are warranted to confirm these findings.
Disclosures. All Authors: No reported disclosures