Purpose We present the case of a 56-year-old man with stage IV sarcoidosis on veno-venous extracorporeal membrane oxygenation (VV-ECMO) support for the management of respiratory failure receiving treatment with isavuconazole for invasive aspergillosis. Summary VV-ECMO is an increasingly utilized life support therapy for patients with cardiac and/or respiratory failure, but its impact on medication dosing is poorly understood. In our patient with invasive Aspergillus infection receiving VV-ECMO, because of difficulty achieving therapeutic serum concentrations of voriconazole, we administered isavuconazole 372 mg intravenously (IV) every 8 hours for 6 doses followed by 372 mg IV once daily. Isavuconazole has a favorable pharmacokinetic and safety profile compared to other azole antifungal agents, but its high protein binding and lipophilicity raise concerns about drug sequestration in the VV-ECMO circuit. To optimize the efficacy and safety of this treatment, the isavuconazole trough concentration was measured at days 5 and 17, at which time it was 1.7 and 0.7 μg/mL, respectively. The dose was subsequently increased to 744 mg IV once daily, and serum trough concentrations were measured 5 and 8 days after dose adjustment, corresponding to 3.7 and 2.9 μg/mL, respectively. To our knowledge, this is the third report to describe inadequate isavuconazole trough concentrations during VV-ECMO support when utilizing standard doses. Conclusion In the case described here, standard-dose isavuconazole (372 mg every 8 hours for 6 doses followed by 372 mg daily) did not achieve target trough concentrations in a patient receiving concomitant ECMO support.

Patient acceptance of long-acting injectable antiretroviral (LAI-ARV) HIV-1 regimens will determine uptake. Although previous literature reports high satisfaction, these data stem from clinical trials subject to selection bias. This cross-sectional survey from the HIV practices of an urban academic medical center assessed perceptions and preferences using Likert scales toward overall acceptability, proposed frequencies, injection-site reaction durations, and distribution venue. 59% of surveys were completed resulting 202 respondents. 60% were male, 72% black, and the median age was 49 (IQR 36-58). 93% reported a once daily tablet frequency, 69% reported single tablet regimens, and 59% reported missing zero doses in the prior 30 days. Patients self-categorized as likely (57%) or unlikely (43%) to accept LAI-ARV. Both decreasing frequencies between injections and durations of injection-site reactions resulted higher acceptability scores. 57% of respondents preferred receiving an injectable from their clinician’s office over other potential options. These data demonstrate positive LAI-ARV acceptance potential.

Background Two-drug antiretroviral (ARV) regimens to achieve and maintain HIV viral suppression may lead to decreases in associated drug interactions, adverse events, and pill burden. Dolutegravir-lamivudine (DTG-3TC) has been established as safe and effective in treatment naïve and experienced adults. Further research is warranted to assess insertion into real-world practice. Methods This descriptive retrospective cohort consisted of all patients at an academic medical center HIV practice with a confirmed order of DTG-3TC between April 2019 and March 2020. Patients who were not linked to care by the site’s practices were excluded. The primary endpoint was number of patients initiated on DTG-3TC to determine uptake. Secondary endpoints included demographics and viral outcomes. Descriptive measures of central tendencies and variability were used for analysis. Results DTG-3TC was initiated in 49 patients. Sixty-nine percent were male (34/49), 90% carried publicly funded insurance (44/49), median age at DTG-3TC initiation was 55 years (IQR 46-60), and mean years since HIV diagnosis was 14 (SD ±8). The largest racial/ethnic category represented was Black (45%, 22/49). Forty-seven patients with a mean CD4 of 753 cells/mm3 (±413) and viral load of 88.2 copies/mL (±525) were switched from alternative regimens, mostly containing an integrase inhibitor (41/47, 87%), and with the primary rationale of medication modernization (27/47, 58%) followed by avoidance of adverse drug reactions (15/47, 32%). From 42 assessed patients, 62% had previous ARV exposure length of over 10 years. No patients were found to have significant resistance mutations to the involved agents. After initiation, 6% (3/49) of patients reported side effects. Among switch patients with follow up lab values, median CD4 (n=20) and viral load (n=21) deltas were -10 cells/mm3 (-59-67) and 0 copies/mL (0-0) respectively. Overall median length of therapy through April 1, 2020 was 110 days (71-156). Conclusion Initial implementation of DTG-3TC was successful in a northeast academic HIV practice primarily among virally suppressed treatment switch patients with long exposures to ARV and time since diagnosis. No clinically relevant change in CD4 or Viral Loads were immediately seen. Disclosures David E. Koren, PharmD, BCPS, AAHIVP, Gilead Sciences (Advisor or Review Panel member)Janssen Pharmaceuticals (Advisor or Review Panel member)Thera Technologies (Advisor or Review Panel member)

Background The rate of bacterial co-infection in inpatients with COVID-19 is unknown, however, patients who are hospitalized with COVID-19 often receive antibiotics for community-acquired bacterial pneumonia (CABP). Reducing unnecessary antibiotic usage in this population is important to prevent adverse effects and slow the development of antimicrobial resistance. Methods We performed a retrospective chart review on patients admitted to our health system between March and May 2020 with confirmed COVID-19 by nasopharyngeal PCR. We reviewed patients with positive cultures from urine, blood, sputum, and sterile sites. Positive cultures were reviewed to determine if they represented a true infection versus a contaminant or colonization. Patients with true infections were categorized as having a co-infection (CI) if the positive culture was collected within 48 hours of initial positive SARS-CoV-2 PCR test. Additional data was collected on patient demographics, types of infections, organisms grown, and antibiotic usage. Results 902 patients were admitted with positive SARS-CoV-2 tests during the study period. Of these, 47 patients (5.2%) had a bacterial CI. Some patients had more than one CI, with 53 total CIs identified. The median age of patients with CI was 66 years old (39 – 90). Tables 1 and 2 describe patient characteristics and infections. A subgroup analysis on types of bacteria was done on the 20 patients with a respiratory CI, who accounted for 2.2% of all COVID-positive patients admitted during the study period. In these infections, Staphylococcus aureus, Streptococcus species, and Haemophilus influenzae were the most common organisms, accounting for 60%, 15%, and 10% infections, respectively. Table 1. Patient Characteristics Table 2. Co-infections Conclusion The overall rate of CIs in patients admitted with COVID-19 was low. Some of these CIs may represent an “incidentally positive” COVID-19 test if a patient presented with one infection and had asymptomatic carriage of SARS-CoV-2 when community prevalence was high. Further analysis is needed to evaluate specific risk factors for co-infection. Disclosures Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Astellas (Consultant, Speaker’s Bureau)Merck (Consultant, Grant/Research Support, Speaker’s Bureau)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant) Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Astellas (Individual(s) Involved: Self): Speakers' bureau; Merck (Individual(s) Involved: Self): Consultant, Grant/Research Support; Nabriva: Consultant; Qpex (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant

Background The incidence of organisms with extended-spectrum beta-lactamases (ESBLs) is increasing. The data for using cefepime in ESBL-producing Enterobacterales infections is conflicting. More favorable outcomes are likely if minimum inhibitory concentrations (MICs) < 2 mcg/mL. The aim of this study is to compare the efficacy of cefepime versus carbapenems for ESBL-producing, non-bloodstream Enterobacterales infections. Methods This study was a single-center retrospective cohort study of patients who received cefepime or a carbapenem for at least 72 hours for the definitive treatment of an ESBL-producing Enterobacterales non-bloodstream infection between Jan. 1, 2011 and Sept. 30, 2021. ESBL production was identified if the isolate either had a positive confirmatory ESBL test from VITEK 2 (bioMérieux) or phenotypic resistance to ceftriaxone. Isolates had to have a MIC < 2 mcg/mL to cefepime or be susceptible to carbapenems. Isolates with a cefepime MIC 4-8 mcg/mL were not included due to likely higher rates of treatment failure. The primary endpoint was clinical failure, defined as persistence of symptoms requiring escalation of therapy or death. Descriptive statistics were used to compare groups. A univariate analysis and odds ratio was calculated for clinical outcomes. Results One hundred patients were included. Twenty-two patients received cefepime and 78 received a carbapenem. Table 1 describes patient characteristics and clinical outcomes. Most patients had a urinary tract infection (UTI) (94%). More patients receiving cefepime were admitted to the intensive care unit (40.9% versus 15.4%). Treatment with cefepime displayed higher rates of clinical failure when compared to treatment with carbapenems (13.6% versus 6.4%). Cohen’s d-test for clinical failure was 0.46, indicating a medium effect. Conclusion Based on our analysis, cefepime may have higher rates of clinical failure when compared to carbapenem treatment for ESBL-producing Enterobacterales. Most of our patients were treated for UTIs and the sample size for both arms were limited, particularly for the cefepime arm. Further research is needed to confirm the role of cefepime as a carbapenem-sparing option in the treatment of these drug-resistant infections. Disclosures Madeline King, PharmD, Shionogi: Honoraria|Tetraphase: speakers' bureau.