Background: SARS-CoV-2 has drastically affected healthcare globally and causes COVID-19, a disease that is associated with substantial morbidity and mortality. We aim to describe rates and pathogens involved in co-infection or subsequent infections and their impact on clinical outcomes among hospitalized patients with COVID-19. Methods: Incidence of and pathogens associated with co-infections, or subsequent infections, were analyzed in a multicenter observational cohort. Clinical outcomes were compared between patients with a bacterial respiratory co-infection (BRC) and those without. A multivariable Cox regression analysis was performed evaluating survival. Results: A total of 289 patients were included, 48 (16.6%) had any co-infection and 25 (8.7%) had a BRC. No significant differences in comorbidities were observed between patients with co-infection and those without. Compared to those without, patients with a BRC had significantly higher white blood cell counts, lactate dehydrogenase, C-reactive protein, procalcitonin and interleukin-6 levels. ICU admission (84.0 vs 31.8%), mechanical ventilation (72.0 vs 23.9%) and in-hospital mortality (45.0 vs 9.8%) were more common in patients with BRC compared to those without a co-infection. In Cox proportional hazards regression, following adjustment for age, ICU admission, mechanical ventilation, corticosteroid administration, and pre-existing comorbidities, patients with BRC had an increased risk for in-hospital mortality (adjusted HR, 3.37; 95% CI, 1.39 to 8.16; P = 0.007). Subsequent infections were uncommon, with 21 infections occurring in 16 (5.5%) patients. Conclusions: Co-infections are uncommon among hospitalized patients with COVID-19, however, when BRC occurs it is associated with worse clinical outcomes including higher mortality.

Increased antibiotic utilization and resistance have previously been demonstrated in the initial wave and surges of the COVID-19 pandemic but there are few evaluations of long-term impact. We sought to assess the utilization of antibiotics and incidence of resistant pathogens prior to and during the first two years of the COVID-19 pandemic. Patients age ≥ 18 years admitted between March 2019 – February 2022 were eligible for inclusion. The study timeframe was divided into three phases: pre-pandemic (PRE, March 2019-February 2020), pandemic year 1 (PAN1, March 2020-February 2021), and pandemic year 2 (PAN2, March 2021-February 2022). Antimicrobial utilization (administration) data was summarized as days of therapy per 1,000 patient days (DOT/1000PD). Antibiotic resistance data was summarized as incidence per 100 hospital admissions. Interrupted time-series analysis with linear regression was performed to assess trends in antibiotic utilization and resistance between study time periods. Significant increases in ceftriaxone (+20.4 DOT/1000PD, P=0.002), azithromycin (+13.3, P=0.002), and anti-pseudomonal β-lactams (APBL; +17.4, P=0.001) utilization were observed between PRE and PAN1 (Figure 1). Subsequently, these increases were followed by significant decreases in utilization from PAN1 to PAN2. Non-significant increases in the incidence of third-generation cephalosporin resistant bacteria (Figure 2A; +0.71, P=0.171) and carbapenem-resistant bacteria (Figure 2C; +0.34, P=0.068) were observed between PRE and PAN1 (Figure 2). Increased use of key inpatient antibiotics and gram-negative resistance were observed in the first year of the COVID-19 pandemic. Utilization and resistance in PAN2 was similar to that of PRE levels and may represent encouraging signs for the long-term impact on antibiotic resistance. Matthew P. Crotty, PharmD, BCIDP, Paratek Pharmaceuticals Inc.: Grant/Research Support

Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein–Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines. IMPORTANCE: Guidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a strategic plan to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.