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Background While immunosuppression poses a theoretical increase in the risk of COVID‐19, the nature of this relationship is yet to be ascertained. Aims To determine whether immunosuppressed patients are at higher risk of COVID‐19 to help inform the management of patients receiving immunosuppressant therapies during the pandemic. Methods We performed a random‐effects meta‐analysis of data from studies that reported on the prevalence of immunosuppression among patient cohorts with COVID‐19. Results Sixty full‐text publications were identified. In total, six individual studies were included in the final analysis, contributing a total of 10 049 patients with COVID‐19 disease. The prevalence of immunosuppressed patients among the study cohorts with COVID‐19 ranged from 0.126% to 1.357%. In the pooled cohort a total of 64/10 049 (0.637%) patients with COVID‐19 disease was immunosuppressed. Observed to expected ratios were used to compare the prevalence of immunosuppression in cohorts with confirmed COVID‐19 disease to the background prevalence of immunosuppression in the general community. The observed to expected ratio of immunosuppression among patients with COVID‐19 illness, relative to the general community, was 0.12 (95% confidence interval: 0.05–0.27). Conclusions Compared to the general population, immunosuppressed patients were not at significantly increased risk of COVID‐19 infection. This finding provides support for current expert consensus statements, which have recommended the continuation of immunosuppressant therapy in the absence of COVID‐19.

Summary Background Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. Aims To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI). Methods This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8‐week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52‐week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (, At Week 8 of OCTAVE Induction 1 and 2 and Week 52 of OCTAVE Sustain, proportions of patients achieving a clinical response with 5 or 10 mg twice daily (b.d.) tofacitinib were generally similar across body mass index (BMI) subgroups.Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other BMI subgroups (0.4%). Analyses were limited by small patient numbers in the BMI ≥30 subgroup.Conclusions: Efficacy and safety of tofacitinib were similar in patients with ulcerative colitis, regardless of baseline BMI.

ObjectiveTo assess the antibody response to disease-modifying antirheumatic drug (DMARD) therapy after the first and second dose of the ChAdOx1nCov-19 (AstraZeneca (AZ)) and BNT162b (Pfizer) vaccines in patients with immune-mediated inflammatory disease (IMID) compared with controls and if withholding therapy following the first vaccination dose has any effect on seroconversion and SARS-CoV-2 antibody (Ab) levels.MethodsA multicentre three-arm randomised controlled trial compared the immunogenicity of the Pfizer and AZ vaccines in adult patients on conventional synthetic (csDMARD), biologic (bDMARD) or targeted synthetic (tsDMARD) therapy for IMID (n=181) with a control group (n=59). Patients were randomised to continue or withhold DMARD therapy for 1–2 weeks post first dose vaccination only. Serum SARS-CoV-2 IgG detection (IgG ≥1.0 U/mL) and titres against the S1/S2 proteins were measured at baseline, 3–4 weeks post first vaccination and 4 weeks post second vaccination.ResultsAZ vaccination was given to 47.5%, 41.5% and 52.5% in the continue, withhold and control groups, respectively while Pfizer vaccination was given to 52.5%, 58.5% and 47.5% among the continue, withhold and control groups, respectively. Seroconversion rates following the first dose in the AZ and Pfizer groups were only 27.3% vs 79.2% (p=0.000) and 64.58% vs 100% (p=0.000), respectively in the IMID groups who continued therapy compared with the AZ and Pfizer controls, respectively. Withholding DMARD therapy following the first vaccination dose resulted in higher seroconversion to 67.7% and 84.1% in the AZ and Pfizer groups, respectively. Following the second AZ and Pfizer vaccinations when all DMARDs were continued, despite a slightly lower seroconversion rate (83.7% vs 100%, p=0.000 and 95.9% vs 100%, p=0.413), respectively, the mean SARS-CoV2 IgG Ab titres were not significantly different in the csDMARD and bDMARD groups compared with the controls regardless of hold while it was significantly lower in patients taking tsDMARD (12.88 vs 79.49 U/mL, p=0.000).ConclusionsFollowing the first vaccination dose, antibody responses were lower in IMID on DMARD therapy, however the final responses were excellent regardless of hold with the exception of the tsDMARD group where withholding therapy is recommended. At least 2 vaccinations are therefore recommended preferably with an messenger RNA vaccine.Trial registration numberANZCTR: 12621000661875.

Background Cascade reporting (CR) is a strategy of reporting antimicrobial susceptibility test results in which secondary agents are only reported if an organism is resistant to primary, narrow spectrum agents within a drug class. A multidisciplinary team developed CR algorithms for Gram-negative bacteria based on the local antibiogram and infectious diseases practice guidelines. Methods CR was implemented at a 399-bed tertiary care VAMC in March 2018. In a quasi-experimental study, antimicrobial use data across 8 inpatient units were extracted from the CDC’s NHSN AU module from April 2017 – March 2019 (12 months pre- and post-implementation of CR), reported as antimicrobial days of therapy (DOT) per 1000 days present (DP). T-tests and linear mixed models accounting for seasonal and random unit effects were used to compare antimicrobial use pre- and post-CR implementation. Figure 1A. Cascade reporting algorithm for antimicrobial susceptibility reporting for Enterobacteriaceae Figure 1B. Cascade reporting algorithm for antimicrobial susceptibility reporting for Pseudomonas aeruginosa Results Following CR implementation, mean monthly meropenem (p=0.005) and piperacillin/tazobactam (p=0.002) use decreased, while cefepime use increased (p< 0.001). The slope of ciprofloxacin use decreased by 2.16 DOTs/1,000 DP per month (SE=0.25, p< 0.001). The slope of cefpodoxime and moxifloxacin use decreased by 18% (p< 0.001), and 7% (p< 0.001), respectively. The slope of cephalexin use decreased by 0.55 DOTs/1,000 DP (SE=0.26, p< 0.001). The slope of ceftriaxone and cefepime use increased by 1.51 (SE=0.59, p=0.011) and 1.06 (SE=.32, p=0.002) DOTs/1000 DP per month, respectively. There were no significant changes in the slope of amoxicillin/clavulanate, levofloxacin, or meropenem consumption. Rates of Clostridioides difficile infection did not significantly change. Figure 2A. Average monthly use of oral antibiotics across all units in average days of therapy (DOTs) per 1000 days present. CR = Cascade reporting. *For Cefpodoxime and moxifloxacin medians were reported as data was not normally distributed. Figure 2B. Average monthly use of intravenous antibiotics across all units in average days of therapy (DOTs) per 1000 days present. CR = Cascade reporting. Table 1. Slope of Antimicrobial Utilization Pre and Post-Cascade Reporting Implementation. Conclusion After implementation of CR, the slope of ciprofloxacin use decreased and mean monthly meropenem use decreased. CR is a valuable tool that can be employed by ASPs to encourage optimal use of antibiotics. Disclosures All Authors: No reported disclosures

Background: Updated IDSA-SHEA guidelines recommend different diagnostic approaches to C. difficile depending on whether There are pre-agreed institutional criteria for patient stool submission. If stool submission criteria are in place, nucleic acid amplification testing (NAAT) alone may be used. If not, a multistep algorithm is suggested, incorporating various combinations of toxin enzyme immunoassay (EIA), glutamate dehydrogenase (GDH), and NAAT, with discordant results adjudicated by NAAT. At our institution, we developed a multistep algorithm leading with NAAT with reflex to EIA for toxin testing if NAAT is positive. This algorithm resulted in a significant proportion of patients with discordant results (NAAT positive and toxin EIA negative) that some experts have categorized as possible carriers or C. difficile colonized. In this study, we describe the impact of a multistep algorithm on hospital-onset, community-onset, and healthcare-facility–associated C. difficile infection (HO-CDI, CO-CDI, and HFA-CDI, respectively) rates and the management of possible carriers. Methods: The study setting was a 399-bed, tertiary-care VA Medical Center in Richmond, Virginia. A retrospective chart review was conducted. The multistep C. difficile testing algorithm was implemented June 4, 2019 (Fig. 1). C. difficile testing results and possible carriers were reviewed for the 5 months before and 4 months after implementation (January 2019 to September 2019). Results: In total, 587 NAATs were performed in the inpatient and outpatient setting (mean, 58.7 per month). Overall, 123 NAATs (21%) were positive: 59 in the preintervention period and 63 in the postintervention period. In the postintervention period, 23 positive NAATs (26%) had a positive toxin EIA. Based on LabID events, the mean rate of HO+CO+HCFA CDI cases per 10,000 bed days of care (BDOC) decreased significantly from 9.49 in the preintervention period to 1.15 in the postintervention period (P = .019) (Fig. 2). Also, 9 of the possible carriers (22%) were treated for CDI based on high clinical suspicion, and 6 of the possible carriers (14%) had a previous history of CDI. Of these, 5 (83%) were treated for CDI. In addition, 1 patient (2%) converted from possible carrier to positive toxin EIA within 14 days. The infectious diseases team was consulted for 11 possible carriers (27%). Conclusions: Implementation of a 2-step C difficile algorithm leading with NAAT was associated with a lower rate of HO+CO+HCFA CDI per 10,000 BDOC. A considerable proportion (22%) of possible carriers were treated for CDI but did not count as LabID events. Only 2% of the possible carriers in our study converted to a positive toxin EIA.Funding: NoneDisclosures: None

Background Disseminated gonococcal infection (DGI) is an uncommon manifestation of N. gonorrhoeae that is estimated to occur in 0.5-3% of cases, with a decreasing incidence that has been attributed to changes in circulating serotypes. At a Veterans Affairs Medical Center (VAMC), 3 cases were identified within 4 months in 2019. Methods A case series of patients with DGI between March and July 2019 was conducted at a 399-bed tertiary care VAMC that serves central Virginia. Clinical case data was abstracted from the medical record, and data regarding prior gonorrhea cases at the facility was obtained from the laboratory information system. Results In 2019, the rate of DGI was 4.9%, with 3 cases out of 61 reported. All occurred in immunocompetent, African-American males with a mean age of 59 years, and all had female sexual partners (Table 1). All presented with joint symptoms, 2 had skin manifestations, and none had genital symptoms. Two patients had positive synovial fluid cultures and the third had a positive blood culture. All isolates were beta-lactamase negative. Orogenital testing by nucleic acid amplification was only positive in 1 patient. No other sexually transmitted infections were identified. One patient underwent surgical washout of the involved shoulder joint, but the others were managed non-operatively. All received a single dose of azithromycin and a 14-day course of ceftriaxone with full symptom resolution. These were the first positive N. gonorrhoeae isolates from invasive specimens at this VAMC since at least 2016. Table 1. Clinical History and Laboratory Results at Presentation for Patients with Disseminated Gonococcal Infection Conclusion This cluster of DGI cases was unusual given the recent rarity at this VAMC, the age of the patients, and lack of overt risk factors. In Virginia, DGI is reported to the health department no differently than uncomplicated infections, so the actual rate of DGI regionally is unknown. One isolate was preserved and sent to the Centers for Disease Control and Prevention for deidentified whole genome sequencing. More refined reporting is necessary to improve understanding of local gonorrhea epidemiology, as well as coupling with additional methodologies such as serotyping or whole genome sequencing. Clinicians should be aware of the possibility of DGI, even in older patients without classic risk factors. Disclosures All Authors: No reported disclosures

A novel antimicrobial consumption metric designed to identify the proportion of carbapenem consumption (PoCC) among broad-spectrum antipseudomonal antimicrobials has been shown to vary significantly by US Census Bureau region. This retrospective surveillance study identified significant total PoCC variability (27%; P = .001) across 8 inpatient units from January 2017 through June 2018. This metric may be useful in identifying and comparing inpatient units that may be overusing antipseudomonal carbapenems.

Background Several classes of drugs, such as antibiotics, may interact with warfarin to cause an increase in wafarins anticoagulant activity and the clinical relevance of warfarin–antibiotic interactions in older adults is not clear. Objective The aim of this study was to determine the effect of oral antibiotics, such as amoxicillin, azithromycin, cephalexin, ciprofloxacin, levofloxacin, and moxifloxacin, on the international normalized ratio (INR) in patients ≥65 years on stable warfarin therapy. The secondary objective was to compare the effect of warfarin–antibiotic interactions on outcomes of overanticoagulation. Methods Data for this retrospective cohort study were collected through a medical record review of patients in an outpatient anticoagulation clinic of a Veterans Affairs medical center. Patients aged ≥65 years on stable warfarin therapy and with at least 1 prescription of an oral antibiotic of interest during the period from January 1, 2003 to March 1, 2011 were included. A mixed-effects repeated-measures ANOVA model was used to determine the effect of antibiotics on the mean change in patients' INR. The Fisher exact test was used to determine the association between the antibiotics and secondary outcomes of overanticoagulation, using cephalexin as the control. Statistical significance was defined as a P value

Background and Aims Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD. Methods We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition. Results Fifty-five studies were included in this review. Thirty-one focused on the impact of IBD on body composition with a total of 2279 patients with a mean age 38.4 years. Of these, 1071 [47%] were male. In total, 1470 [64.5%] patients had Crohn’s disease and 809 [35.5%] had ulcerative colitis. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. Twenty-four additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition in IBD are associated with poorer prognoses including higher rates of surgical intervention, post-operative complications and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response are seen in patients with myopaenia. Conclusions Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impacts of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.