195. Intravenous to Oral Antibiotics Versus Intravenous Antibiotics: A Step-Up or a Step-Down for Extended Spectrum Beta-Lactamase Producing Urinary Tract Infections?

Abstract Background The treatment of extended-spectrum beta-lactamase (ESBL)-producing urinary tract infections (UTI) may include either intravenous (IV) or oral (PO) antibiotics, according to the Infectious Diseases Society of America guidelines for resistant gram negative infections. The purpose of this study is to evaluate if PO step-down antibiotics, the switch group, compared to continued IV therapy in these UTIs affects clinical outcomes. Methods This multicenter retrospective cohort study was conducted in hospitalized patients with an ESBL-producing UTI between July 2016 and March 2020. The control group received a complete antibiotic course with a carbapenem. The switch group was transitioned to an oral agent within five days from initiation of a carbapenem. The primary endpoint was a composite all-cause clinical failure, which was defined as readmission or hospital mortality within 30 days of hospital discharge or a change in antibiotic during hospital admission. The secondary endpoints included individual components of the primary outcome, readmission indication, inpatient length of stay, direct antibiotic costs, and adverse events. Results The study included 153 patients: 95 and 58 patients in the control and switch groups, respectively. Demographics between the two groups were similar (Table 1). The mean ± SD duration of therapy was 8.7 ± 3.1 and 7.1 ± 3.3 days, respectively. Four oral agents were used for step-down therapy (Figure 1). The primary outcome occurred in 28% in both groups (27 vs 16 patients, p=0.91). The individual components of the primary outcome and readmission indication were also similar: readmission (93% vs 94%, p=0.95), readmission due to a recurrent UTI (33% vs 25%, p=0.73), hospital mortality (7% vs 6%, p=1.0), and change in antibiotic (0% vs 2%, p=0.38). The median (IQR) length of stay and direct antibiotic cost in the control and switch groups were 8 (6) vs 5 (2) days (p< 0.01) and &278 (&244) vs &180 (&104) (p< 0.01), respectively. Adverse events were similar in both groups except for diarrhea (15% vs 2%, p=0.01). Table 1. Baseline Demographics. SD: standard deviation, ICU: intensive care unit, qSOFA: quick Sequential Organ Failure Assessment, ESBL: extended spectrum beta-lactamase, UTI: urinary tract infection Figure 1. Oral Antibiotics. QD: once daily, BID: twice daily, Q2D: every 2 days, Q3D: every 3 days, DS tab: double strength tablet Conclusion There was no difference in clinical failure, readmission rate, mortality rate, or change in antibiotic between the control and switch groups; however, the switch group was associated with reduced hospital length of stay and direct antibiotic cost. Disclosures All Authors: No reported disclosures

Probability of progression to cUTI Table. Sensitivity analyses of the probability of uUTI progressing to cUTI in patients with non-susceptible versus susceptible isolates (matched population)

Conclusion.
Patients with uUTI and AB-resistant isolates were significantly more likely to progress to cUTI than those with susceptible isolates. This finding highlights the need for greater understanding of antimicrobial resistance and has implications for the clinical management of uUTI.
Disclosures. Jason Shafrin, PhD, Precision Medicine Group (Employee, Former employee of Precision Medicine Group, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. ( Background. The treatment of extended-spectrum beta-lactamase (ESBL)-producing urinary tract infections (UTI) may include either intravenous (IV) or oral (PO) antibiotics, according to the Infectious Diseases Society of America guidelines for resistant gram negative infections. The purpose of this study is to evaluate if PO step-down antibiotics, the switch group, compared to continued IV therapy in these UTIs affects clinical outcomes.
Methods. This multicenter retrospective cohort study was conducted in hospitalized patients with an ESBL-producing UTI between July 2016 and March 2020. The control group received a complete antibiotic course with a carbapenem. The switch group was transitioned to an oral agent within five days from initiation of a carbapenem. The primary endpoint was a composite all-cause clinical failure, which was defined as readmission or hospital mortality within 30 days of hospital discharge or a change in antibiotic during hospital admission. The secondary endpoints included individual components of the primary outcome, readmission indication, inpatient length of stay, direct antibiotic costs, and adverse events.
Results. The study included 153 patients: 95 and 58 patients in the control and switch groups, respectively. Demographics between the two groups were similar ( Table  1). The mean ± SD duration of therapy was 8.7 ± 3.1 and 7.1 ± 3.3 days, respectively. Four oral agents were used for step-down therapy (Figure 1). The primary outcome occurred in 28% in both groups (27 vs 16 patients, p=0.91). The individual components of the primary outcome and readmission indication were also similar: readmission (93% vs 94%, p=0.95), readmission due to a recurrent UTI (33% vs 25%, p=0.73), hospital mortality (7% vs 6%, p=1.0), and change in antibiotic (0% vs 2%, p=0.38). The median (IQR) length of stay and direct antibiotic cost in the control and switch groups were 8 (6) vs 5 (2) days (p< 0.01) and $278 ($244) vs $180 ($104) (p< 0.01), respectively. Adverse events were similar in both groups except for diarrhea (15% vs 2%, p=0.01). Table 1. Baseline Demographics. SD: standard deviation, ICU: intensive care unit, qSOFA: quick Sequential Organ Failure Assessment, ESBL: extended spectrum beta-lactamase, UTI: urinary tract infection Figure 1. Oral Antibiotics. QD: once daily, BID: twice daily, Q2D: every 2 days, Q3D: every 3 days, DS tab: double strength tablet Conclusion. There was no difference in clinical failure, readmission rate, mortality rate, or change in antibiotic between the control and switch groups; however, the switch group was associated with reduced hospital length of stay and direct antibiotic cost.
Disclosures. All Authors: No reported disclosures Methods. This was a prospective, cross-sectional survey of US females aged ≥ 18 years with a self-reported uUTI in the 60 days prior to participation. Participants were included if they received oral antibiotic treatment and participated in surveys fielded by Dynata, Lucid/Federated, or Kantar Profiles. See Table 1 for inclusion/exclusion criteria. Study objectives were to describe activity impairment (using the Activity Impairment Assessment [AIA]) and HRQoL (assessed with Short Form 36 version 2, Physical Component Score [PCS], Mental Component Score [MCS], and health utility index [SF-6D]) associated with uUTI. After screening, participants completed an online questionnaire on their most recent uUTI. Outcomes were reported with descriptive statistics, chi-squared tests, and t-tests. Analysis of HRQoL used 1:1 propensity score matching to compare to a matched US population from the 2020 National Health and Wellness Survey.

Table 1. Inclusion and exclusion criteria
Results. In total, 375 participants completed the questionnaire. Common impaired activities were: sexual intercourse (66.9%), sleep (60.8%), exercise (52.3%), housework (51.5%), and social activities (46.9%; Table 2). Overall mean AIA score was 11.1/20 (higher score = more impairment). Most participants (58.7%) had a PCS that was the same or better than the matched population, while for MCS, most participants (52.8%) had scores well below the matched population average. Overall PCS, MCS, and SF-6D composite scores were 46.5, 40.0, and 0.63, respectively; these outcomes were significantly worse compared to the matched population, most notably MCS (Table 3). Stratification by number of antibiotics used revealed statistically significant differences in the effect of uUTI on exercise, PCS, SF-6D (based on use of 1 or ≥ 3 therapies), and on sleep (based on use of 2 or ≥ 3 therapies; Table 4).  Table 3. Matched analysis of SF-36v2-measured HRQoL outcomes Table 4. Outcomes stratified by number of oral antibiotics used to treat last uUTI Conclusion. uUTIs are significantly associated with adverse patient outcomes for daily activities and HRQoL, compounded by suboptimal treatment evident by the use of multiple antibiotics. MCS was notably affected, which is important as this is not often studied in uUTI.