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Objectives To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. Methods We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. Results All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4–3.3, P value = 0.79). Conclusions These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.

Background Despite multiple studies indicating a low prevalence of bacterial coinfection in coronavirus disease 2019 (COVID-19) patients, the majority of hospitalized COVID-19 patients receive one or more antibiotics. Patients with coinfection usually have multiple risk factors and poor clinical outcomes. Methods A retrospective case control study was conducted comparing clinical characteristics and antimicrobial use in hospitalized adult COVID-19 patients with bacterial co-infections vs. randomly selected patients without co-infections (matched on month of admission). The study was conducted at three hospitals within the Montefiore Medical Center, Bronx, NY between March 1, 2020 and October 31, 2020. A multivariable logistic regression model was developed to assess the relationship of each predictor variable with coinfection status. Secondary outcomes included hospital mortality, antibiotic days of therapy (DOT), and C. difficile infection. Results A total of 150 patients with coinfection and 150 patients without co-infection were included in the analysis. Table 1 summarized baseline characteristics and risk factors. The multivariable logistic regression model indicated that presence of a central line (OR=5.4, 95% CI: 2.7-11.1), prior antibiotic exposure within 30 days (OR=5.3, 95% CI: 2.8-10.0), prior ICU admission (OR=3.6, 95% CI: 1.7-7.6), steroid use (OR=2.7, 95% CI: 1.4-4.9), and any comorbid condition (OR=2.7, 95% CI: 1.4-5.2) were significantly associated with the development of coinfection (table 2). Mortality was higher in patients with coinfection (56% vs. 11%, p < 0.0001) (table 3). Average antibiotic DOT was 10.5 in coinfected patients compared to 4 in non-coinfected patients, (p < 0.0001). Forty-one percent of coinfected patients had a multidrug resistant organism isolated. C. difficile rate was higher in coinfected patients (4% vs. 0%, p=0.03). Conclusion As the healthcare community contends with a 3rd year of COVID-19 pandemic, understanding risk factors most predictive of bacterial coinfection can guide empiric antimicrobial therapy and targeted stewardship interventions. Ideally, co-infection risk scores are developed which may be useful for future inpatient surges. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support Kelsie Cowman, MPH, Merck: Grant/Research Support.

Background Dalbavancin is approved for the treatment of acute bacterial skin and soft structure infections (ABSSSI). There is less data on outcomes of off-label use of dalbavancin for orthopedic and other complex infections. In this case series, we aim to analyze clinical outcomes of deep-seated infections treated with IV dalbavancin instead of long-term IV antibiotics post-discharge. Methods We conducted a retrospective review of adult patients treated with off-label IV dalbavancin between January 2020 and February 2022 at an academic center in the Bronx, NY within a long-standing outpatient parenteral antibiotic therapy (OPAT) program. Outcomes of interest included 90-d infection recurrence, prothesis retention, mortality, adverse events, and characteristics of antibiotic regimens. Results Nineteen patients received dalbavancin for off-label indications. Dalbavancin was used primarily for hardware, bone and joint, and complicated soft tissue infections (table 1). The predominant pathogen was Staphylococcus aureus. Source control was achieved in 12 (63%) patients via debridement alone (5), debridement with prosthetic device retention (4), or debridement and complete hardware removal (3). The most common dosing regimen was two-doses (1000-mg, 500-mg) one week apart. Two (11%) patients (both with initial prosthesis retention) had infection recurrence within 90 days of dalbavancin and eventually required removal (table 2). One patient experienced recurrence after 90 days and required removal. The remaining patient with prothesis retention has not experienced infection recurrence to date. Concomitant antibiotics while on dalbavancin and suppressive antibiotics following therapy were common. No patient died within 90 days of therapy and no adverse drug effects were reported. Conclusion Dalbavancin use for hardware infections, osteomyelitis, complicated soft tissue infections, and spinal infections is associated with favorable cure rates, safety profile, and tolerability. Improved outcomes may be achieved with hardware removal. Dalbavancin off-label use within an OPAT program may facilitate early discharge or prevent admissions in eligible patients, although further study is needed. Disclosures All Authors: No reported disclosures.

Background The 2022 IDSA Guidance on the Treatment of Antimicrobial-Resistant Gram-negative Infections recommends the use of a novel beta-lactam/beta-lactamase inhibitor, such as ceftolozane-tazobactam (C/T) or ceftazidime-avibactam (C/A), as first-line for treatment of resistant Pseudomonas aeruginosa infections. C/T is often preferred for these infections due to a narrower spectrum and lower cost. However, from December 2020 to January 2022, a global shortage of C/T resulted in widespread adoption of C/A as an alternative. While in vitro susceptibilities support the use of C/A for P. aeruginosa, real-world experience comparing clinical outcomes to C/T is limited. Methods This multicenter, retrospective analysis was conducted at an urban, academic healthcare system in the Bronx, NY. Between January 2018 and December 2020, admitted adult patients who received C/A or C/T to treat P. aeruginosa infections were included. Patients were excluded if in vitro resistance to either drug was demonstrated or if susceptibility was missing. The primary outcome was clinical success, defined as resolution of signs and symptoms of infection, by end of treatment. Secondary outcomes included 30-day mortality, resistance to study drug after therapy, modification of therapy, 14-day microbiological failure, 90-day infection recurrence, and length of stay. Results A total of 46 patients received C/A and 56 patients received C/T to treat P. aeruginosa infections. Most baseline characteristics were similar between the two arms, though more patients were critically ill in the C/A arm (Table 1). Clinical success was similar between C/A and C/T patients (72% vs. 63%, p=0.33). No significant differences between arms were identified for secondary outcomes (Table 2). Development of drug resistance within 90 days of treatment occurred more frequently in the C/A arm, approaching significance. On multivariate regression analysis, vasopressor use at the time of study drug initiation was the only variable associated with reduced clinical success. Conclusion C/A may be an effective alternative treatment for multidrug-resistant P. aeruginosa infections with close monitoring for development of resistance. Larger comparative studies are needed to confirm these findings. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support.

Background Montefiore Medical Center (MMC), Bronx, NY, established an ambulatory program to offer COVID-19 treatments (monoclonal antibodies [mAB] and oral antivirals) to patients with mild-moderate illness according to emergency use authorization criteria. Given multiple pandemic waves in the area, several patients have been reinfected and were treated twice. The objective of this analysis is to identify clinical characteristics and outcomes in patients with repeated COVID-19 infections and treatments. Methods Electronic health records were reviewed to identify patients between December 1, 2020 and April 28, 2022 who received COVID-19 treatment on more than one occasion at MMC. Data collected included demographics, risk factors for progression to severe illness, name and date of COVID-19 treatments received, vaccination status, and clinical outcomes of 30-day emergency department (ED) presentation or hospital admission following each treatment. Results Out of 3,042 total treated patients, 13 (0.4%) received multiple treatments with either mAB or oral antivirals for COVID-19 reinfection during the study period. Median age of reinfected patients requiring treatment was 50 years. Median days between first and second treatments was 298 days (range 91-468 days). The most common risk factor for progression to severe disease were cardiovascular disease (54%) and immunocompromised status (62%) (Table 1). Ten patients had received at least two doses of vaccine (77%) with Pfizer (54%) or Moderna (23%) vaccines prior to reinfection. No patients reported any adverse reactions to either treatment. Four patients presented to the ED or were hospitalized following treatment of reinfection, three of which were for COVID-related symptoms. Of these, two had two risk factors for progression and the third had been hospitalized previously for initial COVID-19 infection. Conclusion Though COVID-19 reinfection has been described, especially during Omicron surges, there were relatively few reinfected patients requiring treatment in our cohort. Patients with risk factors for disease progression may also be at increased risk for reinfection, especially the immunocompromised. Disclosures Kelsie Cowman, MPH, Merck: Grant/Research Support Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support.

Background Monoclonal antibodies (mAb) prevent COVID-19 progression when administered early. We compared mAb treatment outcomes among vaccinated and unvaccinated patients during Delta wave and assessed the feasibility of implementing stricter eligibility criteria in the event of mAb scarcity. Methods We conducted a retrospective observational study of casirivimab/imdevimab recipients with mild-to-moderate COVID-19 infection in an emergency department or outpatient infusion center (July 1–August 20, 2021). Primary outcome was all-cause hospital admission within 30 days post-treatment between vaccinated vs. unvaccinated patients during Delta surge in the Bronx, NY. Results A total of 250 patients received casirivimab/imdevimab (162 unvaccinated vs. 88 vaccinated). The median age was 39 years for unvaccinated patients, and 52 years for vaccinated patients (p Conclusions All-cause 30-day admission was not statistically different between vaccinated and unvaccinated patients. When federal allocation of therapies is limited, programs must prioritize patients at highest risk of hospitalization and death regardless of vaccination status.

Our objectives were to evaluate the role of procalcitonin in identifying bacterial co-infections in hospitalized COVID-19 patients and quantify antibiotic prescribing during the 2020 pandemic surge. Hospitalized COVID-19 patients with both a procalcitonin test and blood or respiratory culture sent on admission were included in this retrospective study. Confirmed co-infection was determined by an infectious diseases specialist. In total, 819 patients were included; 335 (41%) had an elevated procalcitonin (0.5 ng/mL) and of these, 42 (13%) had an initial bacterial co-infection. Positive predictive value of elevated procalcitonin for co-infection was 13% while the negative predictive value was 94%. Ninety-six percent of patients with an elevated procalcitonin received antibiotics (median 6 days of therapy), compared to 82% with low procalcitonin (median 4 days of therapy) (adjusted OR:3.3, P0.001). We observed elevated initial procalcitonin in many COVID patients without concurrent bacterial co-infections which potentially contributed to antibiotic over-prescribing.

Background Monoclonal antibodies were given emergency use authorization (EUA) by the Food and Drug Administration for the treatment of high-risk, outpatient COVID-19 infection. In New York City (NYC), the emergence and rapid growth of the B.1.526 variant of concern (VOC) possessing the E484K mutation was first noted in February 2021. In-vitro studies subsequently confirmed attenuated monoclonal antibody neutralization against VOCs. At our institution, bamlanivimab (BAM) alone or with etesevimab (B/E) and casirivimab/imdevimab (C/I) were utilized at different phases of the pandemic. The objective of this study was to assess their comparative efficacies in a highly variant prevalent setting. Methods This retrospective analysis was conducted at an urban hospital in the Bronx, NY and evaluated adult monoclonal antibody recipients from any of our infusion sites. Patients initially received BAM but given the high prevalence of variants, treatment was transitioned to first B/E and then C/I exclusively. We compared BAM versus combination therapy as well as B/E versus C/I individually. The primary outcome was all-cause hospital admission within 30 days post infusion. Results From February 1 to March 7, 2021, 358 patients received BAM and from March 17 to May 9, 2021, 86 and 179 patients received B/E and C/I, respectively. Compared to any combination infusion, patients who received BAM were significantly older, more likely to possess ≥ 2 qualifying EUA criteria, and less likely to be vaccinated for COVID-19 prior to infusion (Table 1). Following B/E and C/I, 4.5% of patients were admitted versus 10.1% for BAM, p=0.011. There were no significant differences in admission between B/E and C/I recipients, p=0.485. After excluding fully vaccinated patients (n=14) and adjusting for age and ≥ 2 EUA criteria, combination therapy remained associated with decreased odds of hospitalization compared to BAM (odds ratio, 0.48; 95% confidence interval, 0.24-0.94). Conclusion Combination therapy may be associated with fewer hospital admissions following infusion, although there were no statistically significant differences between the individual combination infusions. We suggest similar studies be conducted by other sites to understand the clinical impact of local SARS-CoV-2 variants on antibody efficacy. Disclosures Yi Guo, PharmD, BCIDP, Merck (Research Grant or Support) Kelsie Cowman, MPH, Merck (Research Grant or Support) Priya Nori, MD, Merck (Grant/Research Support) Priya Nori, MD, Nothing to disclose

Background Secondary oral vancomycin prophylaxis (OVP) has been utilized in adults with a history of Clostridioides difficile infection (CDI) while receiving systemic antibiotics to prevent CDI recurrence. However, this practice is poorly described in pediatric patients. Rates of CDI recurrence in pediatric patients range from 10-40% and is associated with morbidity and mortality. This study assessed the efficacy and safety of secondary OVP in pediatric patients with subsequent antibiotic exposure. Methods This retrospective study evaluated pediatric patients ≤18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter during the time period of 2013-2019. Patients who received OVP 10 mg/kg (up to 125 mg per dose) every 12 hours during concomitant antibiotics were compared to those who did not. The primary outcome was CDI recurrence within 8 weeks following antibiotic exposure. Secondary outcomes included time to recurrence, severity of recurrence, and isolation of vancomycin-resistant enterococci (VRE) from any site. Risk factors for CDI recurrence were assessed using logistic regression. Results A total of 153 patients were screened for inclusion, of which 32 and 47 patients were assigned to the OVP and no OVP group, respectively. Median age was 8.6 years and the most common comorbidities were malignancy (47%) and immunosuppression (46%). Median time since last CDI to study inclusion was 64.5 days in the OVP group and 90 days in the no OVP group, P=0.320. Compared to the no OVP group, OVP patients had longer hospital stays (5 vs 14 days, P=0.001) and more concomitant antibiotic exposure (8 vs 12.5 days, P=0.001). Median duration of OVP was 12 days. CDI recurrence occurred in 12 patients and was significantly lower in the OVP vs no OVP group (3.1% vs 23.4%; odds ratio, 0.106; 95% confidence interval, 0.013-0.864; P=0.022). VRE was not isolated in any patients. After adjustment in a multivariate analysis, only secondary OVP remained as a protective factor against recurrence (odds ratio, 0.082; 95% confidence interval, 0.009-0.748; P=0.027). Conclusion Secondary OVP effectively reduces the risk of recurrent CDI in pediatric patients with a history of CDI while receiving systemic antibiotics. Future prospective studies should validate these findings. Disclosures Cristian Merchan, PharMD, BCCCP, abbive (Speaker’s Bureau)

Background Cefpodoxime (CPD) and cefuroxime (CFX) are both oral cephalosporins indicated for urinary tract infection (UTI) treatment. CPD may have unfavorable pharmacokinetics (PK) given the lesser degree of renal excretion and urine concentration vs. CFX and risk of collateral damage. The objective of this study was to compare the efficacy and safety of these two agents for UTI treatment. Methods We conducted a retrospective evaluation among adult patients who received CPD or oral CFX for ≥48 hours for UTI treatment between January 2013 and July 2018. The primary outcome was the rate of subsequent UTI within 90 days following therapy. Safety outcomes included the rate of Clostridium difficile infection (CDI) and development of isolates resistant to third-generation cephalosporins (TGC) within 90 days. We also examined missed opportunities for antibiotic de-escalation in culture-positive patients. Results Of 747 patients assessed for study inclusion, 295 patients met eligibility criteria (CPD n = 165, CFX n = 130). Median age was 72 years (IQR 55–84) and 71% were female. More patients in the CPD vs. CFX group had pyelonephritis (29% vs. 11%, P = 0.0005) and were treated in the emergency department (42% vs. 16%, P = 0.0005). Escherichia coli was most commonly isolated (n = 139), followed by Klebsiella spp. The rate of subsequent UTI for CPD vs. CFX was 18% vs. 16%, P = 0.647 at median of 25 vs. 32 days, P = 0.399. CDI rate was 1% vs. 2%, P = 0.324 and resistance to TGC was detected in 4% vs. 1%, P = 0.068 for CPD vs. CFX, respectively. Missed opportunities to de-escalate antibiotics based on cultures were found in one-third of patients. After adjusting for multiple factors in multivariate analysis, genitourinary abnormality (Odds Ratio [OR] 2.2, 95% CI 1.10–4.29, P = 0.026) and prior history of UTI within 180 days (OR 2.2, 95% CI 1.08–4.398, P = 0.03), but not the choice of oral cephalosporin, were the only independent predictors of subsequent UTI. Conclusion Despite less favorable urinary PK of CPD compared with CFX, in this patient cohort, no differences in efficacy or safety between the two agents for UTI treatment were found. These findings warrant further exploration. Stewardship strategies for de-escalation from higher generation cephalosporins to narrow-spectrum antibiotics based on susceptibilities should be implemented. Disclosures All authors: No reported disclosures.