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Background A well-known clinical dilemma complicating the management of infections in people who inject drugs (PWID) is the restriction of outpatient parenteral antimicrobial therapy. As a result, PWID experience prolonged hospitalizations to complete parenteral antimicrobial courses inpatient. This strategy is also associated with increased rates of patient-directed discharge (PDD). Dalbavancin, a long-acting lipoglycopeptide, serves two unique roles in this population: step-down therapy to decrease inpatient length of stay once clinically stable and salvage therapy in the setting of imminent PDD. Methods This retrospective review of PWID from November 2019 through October 2021 identified patients in which on- or off-label dalbavancin could be considered. Day of hypothetical dalbavancin administration was determined when both ≥7 days of therapy and ≥48 hours of clinical stability (non-critical unit, afebrile, resolved leukocytosis, and source control or negative blood cultures) were completed. Included patients had ≥7 days of therapy remaining at time of hypothetical dalbavancin administration. A one-time dalbavancin dose was considered to provide up to 14 days of antimicrobial coverage. Patients were included in either the step-down cohort (completed entire parenteral antimicrobial course inpatient) or salvage therapy cohort (PDD prior to completing course). The number of potentially preventable inpatient days with dalbavancin and readmissions due to infection progression were assessed in each cohort, respectively. Results Nineteen patients were identified as potential dalbavancin candidates. In the step-down cohort (n=11) a one-time dalbavancin dose prevented a maximum of 146 inpatient days. In the salvage cohort (n=8), hypothetical dalbavancin administration at time of PDD could have prevented six readmissions due to infection progression, associated with 36 additional inpatient days. Conclusion Inpatient administration of dalbavancin may bridge treatment disparities experienced by PWID by reducing unnecessary inpatient days for parenteral antibiotic administration and by preventing hospital readmissions attributable to inadequate antimicrobial course. Disclosures All Authors: No reported disclosures.

Background The reliability of piperacillin-tazobactam (TZP) and cefepime (FEP) breakpoints for extended spectrum β-lactamase Enterobacterales (ESBL-E) isolates remains controversial. The Infectious Diseases Society of America recommends against the use of TZP and FEP for the treatment of bloodstream infections (BSIs) caused by ESBL-E, even when in-vitro susceptibility is demonstrated. The University of Pennsylvania Health System microbiology laboratory suppresses TZP susceptibilities on Escherichia coli and Klebsiella pneumoniae blood isolates nonsusceptible to ceftriaxone (CRO) or ceftazidime (CAZ) and specifies the presence of a multidrug resistant organism. However, FEP susceptibilities are reported. The objective of this study was to assess appropriate antimicrobial prescribing for the treatment of FEP-susceptible ESBL-E BSIs with our institution’s current susceptibility reporting practices. Methods This multicenter retrospective observational study included patients with blood cultures positive for E. coli, K. oxytoca, K. pneumoniae, and Proteus mirabilis nonsusceptible to CRO or CAZ but susceptible to FEP from August 1, 2018 through August 1, 2021. Patients with a concominant gram-negative infection or true beta-lactam allergy were excluded. Patients were assessed for appropriate therapy (demonstrated susceptibility to and administration of carbapenems fluoroquinolones, novel beta-lactam/beta-lactamase inhibitors, or sulfamethoxazole-trimethoprim) within 24 h following the availability of susceptibility results. Results During the study period 38 patients were included. Of the 38 patients, 52.6% (n=20) received appropriate therapy with an average time to appropriate therapy of 3.7 (SD 2.1) h. Among patients receiving inappropriate therapy (n=18), 50% (n=9) were changed to appropriate therapy >24 h after susceptibility results, with an average time to appropriate therapy of 46.5 (SD 44.4) h. The remaining 9 patients (23.7%) did not receive appropriate therapy beyond 24 h. Conclusion Reporting FEP susceptibility results on ESBL-E blood isolates may contribute to the prescribing of FEP for the treatment of ESBL-E BSIs and delay appropriate antimicrobial therapy. Given these findings, cefepime will now be suppressed on ESBL-E blood isolates. Disclosures All Authors: No reported disclosures.

Background Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use. Methods This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored ≥ 5 on the World Health Organization (WHO) ordinal scale for ≤ 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system. Results This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 – 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 – 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%); other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 – 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home. Conclusion Patients who received TCZ for severe COVID-19 experienced 20.9% mortality; mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ. Disclosures George L Anesi, MD, MSCE, AHRQ, NHLBI, UpToDate: Advisor/Consultant|AHRQ, NHLBI, UpToDate: Grant/Research Support Kathleen Degnan, MD, Gilead: Grant/Research Support.

Background Adverse drug events are associated with an increase in hospital stay and cost. Risks from these events are minimized by adjusting a medication’s dose or frequency, and changes in renal function may necessitate adjustments. Currently, there is no formal procedure for a prospective audit of renal function over the weekend at our institution. This pharmacist-driven initiative will evaluate if a prospective review identified by real-time clinical decision support alerts over the weekend will reduce the time from change in renal function to dose adjustment of select antimicrobials and/or anticoagulants. Methods This monitoring initiative is comprised of a pre- and post-cohort population. The pre-cohort population included patients admitted to Penn Presbyterian Medical Center (PPMC) from January to March of 2018 on select antimicrobials and/or anticoagulants, who were identified to have a change in renal function (serum creatinine change of 0.3 mg/dL or greater) over the weekend. The post-cohort population was identified with a clinical decision support system (ILÚM Health Solutions, Kenilworth, NJ) and included patients admitted to PPMC from January to March of 2019. A pharmacy resident reviewed alerts in the clinical decision support system over the weekend and contacted providers with dose adjustment recommendations. The Mann–Whitney U test was used to analyze the primary endpoint while descriptive statistics were used for the secondary endpoints Results Eighteen interventions were completed within the 3-month post-cohort intervention period, with a time to dose adjustment between the pre/post-cohort being reduced by 50 hours (P = 0.0001) resulting in a median time to change of 11 hours in the post-cohort. All pharmacy recommendations were accepted by the provider, and 94% of medication adjustments were antimicrobials. Conclusion The application of this prospective weekend initiative utilizing a clinical decision support system demonstrated a clinically and statistically significant reduction in the time to dose adjustments for antimicrobials and/or anticoagulants. Implementation of this initiative will further establish a role for pharmacist-led evaluations and could potentially be expanded to other clinical areas. Disclosures All authors: No reported disclosures.

Background Higher CHG skin levels may be needed to adequately control infection and transmission of pathogens in the ICU. We assessed whether measurement and feedback of patient CHG skin concentrations could improve CHG bathing quality and identified factors associated with higher CHG skin concentrations. Methods We conducted 6 one-day surveys from January 2018 to February 2019 in 7 academic hospital MICUs with established daily CHG bathing. Adults admitted >1 day were assessed for CHG skin levels with a semi-quantitative colorimetric assay using swabbed 25 cm2 areas of anterior neck, axilla, and inguinal skin. Prior to survey 4, results from the first 3 surveys (baseline) were reported to ICU leadership and front-line staff to retrain and reeducate on bathing technique. Feedback of results from prior surveys also occurred before surveys 5 and 6. For statistical analysis, mixed-effects models accounted for clustering of CHG measurements within patients and ICUs. We categorized CHG product type as “cloth” for no-rinse 2% CHG-impregnated cloth and “liquid” for 4% CHG liquid or foam. Results In total, 681 of 704 (97%) patients were enrolled. Three ICUs used CHG cloth, 3 ICUs used CHG liquid, and 1 ICU switched from liquid to cloth after the second survey. Median CHG skin concentrations were higher in both the baseline and feedback period for institutions using CHG cloth, as compared with liquid (table). Across all time points, axillary and inguinal regions had higher skin CHG concentrations than the neck (median 39.1, 78.1, 19.5 µg/mL, respectively, P < 0.001). After controlling for age, mechanical ventilation, presence of a central venous catheter, body site, and hours since last CHG bath, institutions that used CHG cloth had a 3-fold increase in adjusted CHG skin concentrations in the feedback period compared with the baseline period (P = 0.001, Figure). There was no significant change in CHG skin concentrations from baseline to feedback period for institutions that used liquid CHG. Conclusion CHG skin concentrations on MICU patients receiving daily CHG bathing varied by body site and CHG product type. The use of CHG cloth was associated with higher CHG skin levels, compared with CHG liquid. For ICUs using CHG cloth, feedback of CHG skin concentration results to ICU staff improved CHG bathing quality. Disclosures All Authors: No reported Disclosures.

OBJECTIVEAn improved understanding of carbapenem-resistant Klebsiella pneumoniae (CRKP) in long-term acute care hospitals (LTACHs) is needed. The objective of this study was to assess risk factors for colonization or infection with CRKP in LTACH residents.METHODSA case-control study was performed at a university-affiliated LTACH from 2008 to 2013. Cases were defined as all patients with clinical cultures positive for CRKP and controls were those with clinical cultures positive for carbapenem-susceptible K. pneumoniae (CSKP). A multivariate model was developed to identify risk factors for CRKP infection or colonization.RESULTSA total of 222 patients were identified with K. pneumoniae clinical cultures during the study period; 99 (45%) were case patients and 123 (55%) were control patients. Our multivariate analysis identified factors associated with a significant risk for CRKP colonization or infection: solid organ or stem cell transplantation (OR, 5.05; 95% CI, 1.23–20.8; P=.03), mechanical ventilation (OR, 2.56; 95% CI, 1.24–5.28; P=.01), fecal incontinence (OR, 5.78; 95% CI, 1.52–22.0; P=.01), and exposure in the prior 30 days to meropenem (OR, 3.55; 95% CI, 1.04–12.1; P=.04), vancomycin (OR, 2.94; 95% CI, 1.18–7.32; P=.02), and metronidazole (OR, 4.22; 95% CI, 1.28–14.0; P=.02).CONCLUSIONSRates of colonization and infection with CRKP were high in the LTACH setting, with nearly half of K. pneumoniae cultures demonstrating carbapenem resistance. Further studies are needed on interventions to limit the emergence of CRKP in LTACHs, including targeted surveillance screening of high-risk patients and effective antibiotic stewardship measures.Infect. Control Hosp. Epidemiol. 2015;37(1):55–60

Background Despite advances in rapid organism identification, clinicians must make empiric antibiotic decisions prior to knowing the causative organism. Though many risk factors and patient characteristics have been studied and incorporated into predictive clinical decision support tools for empiric antibiotic prescription, little evidence exists on the relative importance of these factors in clinician judgment. The purpose of this study was to establish how providers evaluate patient and clinical risk factors when making empiric antimicrobial decisions. Methods An anonymous survey tool was distributed in February 2019 to medical providers who routinely prescribe antibiotics in 4 acute care hospitals throughout the University of Pennsylvania Health System. Providers were asked to rank the importance of 12 clinical factors using a 5-point scale from not important at all (1) to extremely important (5) in 3 unique clinical scenarios: uncomplicated cystitis, septic shock of unknown etiology, and uncomplicated pneumonia. Results Response rate was 30% (217/732). The importance of each factor varied among different clinical scenarios except for prior antibiotic exposure, local resistance patterns, drug-drug interactions, and treatment guidelines. However, the absolute difference varied by the factor and clinical scenario. Presence of indwelling catheter(s) had the largest absolute variation (median difference of 2 between septic shock and pneumonia, P < 0.001), and it was one of the top 5 most important factors for septic shock, but the least important factor for pneumonia. Conclusion The importance of clinicians place on clinical factors varies in different clinical scenarios. A better understanding of clinical decision-making in empiric antibiotic prescribing has the potential to guide stewardship efforts and clinical decision support. Disclosures All authors: No reported disclosures.

Background CHG bathing is used to suppress patients’ microbial skin colonization, in order to prevent infections and transmission of multidrug-resistant organisms. Prior work has suggested that microbial growth is inhibited when CHG skin concentrations exceed threshold levels. Methods We conducted 6 single-day surveys from January 2018 to February 2019 in 7 academic hospital MICUs with established CHG patient bathing. Adult patients were eligible to have skin swabbed from adjacent 25 cm2 areas on the neck, axilla, and inguinal region for culture and CHG concentration determination. CHG skin concentrations were measured by a semi-quantitative colorimetric assay. Selective media were used to isolate targeted microorganisms (Table 1). Species were confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry; antibiotic susceptibility was determined by MicroScan (Beckman Coulter). We modeled the relationship between CHG skin concentrations (log2-transformed) and microorganism recovery (yes/no as primary outcome) using multilevel models controlling for clustering of body sites within patients and within ICUs, assessing slope and threshold effects. Results We enrolled 736/759 (97%) patients and sampled 2176 skin sites. Gram-positive bacteria were detected most frequently (Table 1). The adjusted odds of identifying gram-positive organisms decreased linearly as CHG skin levels increased (Figure 1a), without evidence of a threshold effect. We also found significant negative linear slopes without evidence of threshold effects for other pathogens tested (Table 2; Figure 1), with the exception of gram-negative bacteria and vancomycin-resistant enterococci. When modeling quantitative culture results (colony-forming units) for gram-positive organisms as a continuous outcome variable, a similar relationship was found. Conclusion Higher concentrations of CHG were associated with less frequent recovery of gram-positive bacteria and Candida species on the skin of MICU patients who were bathed routinely with CHG. For microbial inhibition, we did not identify a threshold concentration of CHG on the skin; rather, increasing CHG skin concentrations led to additional gains in inhibition. For infection prevention, aiming for high CHG skin levels may be beneficial. Disclosures All authors: No reported disclosures.

Summary Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a rare disease that is often fatal despite treatment. Haemophagocytic syndrome is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of lymphocytes or histiocytes with uncontrolled haemophagocytosis and cytokine overproduction. The syndrome is characterised by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinaemia. Haemophagocytic syndrome can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections. Infections associated with haemophagocytic syndrome are most frequently caused by viruses, particularly Epstein-Barr virus (EBV). We present a case of EBV-associated haemophagocytic syndrome in a young adult with no known immunosuppression. We briefly review haemophagocytic syndrome and then discuss its associated infections, particularly EBV and other herpes viruses, HIV, influenza, parvovirus, and hepatitis viruses, as well as bacterial, fungal, and parasitic organisms.

Hepatitis B (HBV) reverse seroconversion is rare in HIV disease but can be fatal. We present a case series of 6 patients with reverse seroconversion and review 18 additional cases described in the literature. Elevated transaminases were seen in 13/21 (62%). Reverse seroconversion occurred more frequently in the setting of HIV virologic failure. Only 3 patients demonstrated reverse seroconversion in the setting of lamivudine or tenofovir withdrawal. 2/24 (8%) patients died from their HBV flare.

Background A new generation of diagnostic tests, the interferon-γ release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their use in HIV-infected persons. Methods A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB [TSPOT] and QuantiFERON-TB Gold in Tube [QFT-3G]) compared to the tuberculin skin test (TST). Results 336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/μl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, [κ = 0.16, 95% CI (-0.06, 0.39)], TST and QFT-3G [κ = 0.23, 95% CI (-0.05, 0.51)], QFT-3G and TSPOT [κ = 0.06, 95% CI (-0.1, 0.2)]. An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 ≤ 200 cells/μl were significantly more likely to have an indeterminate result [OR = 3.6, 95% CI (1.9, 6.8)]. Conclusion We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts ≤ 200 cells/μl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.

Background There is limited data on the effect of HIV status and CD4 counts on performance of Interferon-g Release assays (IGRAs) for diagnosis of latent tuberculosis infection (LTBI). Methods A cross sectional study was conducted to assess the prevalence of and risk factors for a positive diagnostic test for LTBI, using tuberculin skin test (TST) and IGRAs among HIV-discordant couples in Zambia. Results A total of 596 subjects (298 couples) were enrolled. Median CD4 count among HIV positive persons was 388 cells/μl, (range 51-1330). HIV negative persons were more likely than their HIV positive partner, to have a positive diagnostic test for LTBI with TST (203 vs 128), QFT (171 vs 109) and TSPOT (156 vs. 109). On multivariate analysis, HIV negative status was an independent predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46) and TSPOT (OR = 1.79, 95% CI 1.16-2.77). Among HIV positive subjects a CD4 count ≥ 388 cells/μl was associated with a positive TST (OR = 1.76 95% CI 1.10-2.82) and QFT (OR = 1.71 95% CI 1.06-2.77) but not TSPOT (OR = 1.20 95% CI 0.74-1.94). Conclusions Persons with HIV had significantly fewer positive diagnostic tests for LTBI with TST, QFT and TSPOT. Persons with a CD4 count < 388 cells/μl were less likely to have a positive TST or QFT, but not less likely to have a positive TSPOT. TSPOT may perform better than TST or QFT in HIV positive individuals.