Limited antiretrovirals are currently available for the management of multidrug-resistant (MDR) HIV-1 infection. Ibalizumab, a recombinant humanized monoclonal antibody, represents the first novel agent for HIV-1 management in over a decade and is the first monoclonal antibody for the treatment of MDR HIV-1 infection in combination with other forms of antiretroviral therapy in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Ibalizumab demonstrates a novel mechanism of action as a CD4-directed postattachment inhibitor and has a favorable pharmacokinetic profile that allows for a dosing interval of every 14 days after an initial loading dose. Clinical studies have demonstrated reasonably substantial antiretroviral activity with ibalizumab among a complex patient population with advanced HIV-1 infection who are receiving an optimized background regimen, where limited therapeutic options exist. Ibalizumab was well tolerated in clinical trials, and the most common adverse effects included diarrhea, nausea, dizziness, fatigue, pyrexia, and rash. Resistance to ibalizumab has also been observed via reduced expression or loss of the potential N-linked glycosylation sites in the V5 loop of the envelope glycoprotein 120. The mechanism of action, pharmacokinetic parameters, efficacy, and safety of ibalizumab present an advance in the management of MDR HIV-1 infection. Future studies and postmarketing experience will further determine longer-term clinical efficacy, safety, and resistance data for ibalizumab.

Cefiderocol is a novel siderophore cephalosporin that forms a complex with extracellular free ferric iron, which leads to transportation across the outer cell membrane to exert its bactericidal activity through cell wall synthesis inhibition. This pharmacological property has rendered cefiderocol active against several clinically relevant MDR Gram-negative bacteria as evidenced by several in vitro and in vivo studies. Cefiderocol was first approved by the US FDA on 14 November 2019 for the treatment of complicated urinary tract infections. On 28 September 2020, cefiderocol was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The FDA-approved indications are based on clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In APEKS-cUTI, cefiderocol demonstrated non-inferiority to imipenem/cilastatin for the treatment of complicated urinary tract infection caused by MDR Gram-negative bacteria. In APEKS-NP, cefiderocol demonstrated non-inferiority to meropenem for treatment of nosocomial pneumonia. However, in CREDIBLE-CR, higher all-cause mortality was observed with cefiderocol compared with best available therapy for the treatment of severe infections caused by Gram-negative bacteria, primarily in the subset of patients with Acinetobacter spp. infections. Several case reports/series have demonstrated clinical success with cefiderocol for a variety of severe infections. The purpose of this article is to review available data on the mechanism of action, in vitro and in vivo data, pharmacokinetics, pharmacodynamics, susceptibility testing, efficacy and safety of cefiderocol to address its role in therapy.

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Background Infectious diseases (ID) consultation has been associated with improved outcomes for Staphylococcus aureus bacteremia (SAB) largely by providing guidance to follow widely accepted standards. However, ID consultation may be delayed due to numerous factors. ID pharmacists may be able to facilitate timely and optimal management of SAB in collaboration with ID providers and microbiology. The primary outcome of this study was to evaluate the impact of a pharmacist-driven collaborative initiative for SAB. Methods This was a single-center, quasi-experimental study of patients with SAB before (8/1/16–7/31/17) and after (8/1/18-7/31/19) implementation of pharmacist-driven collaborative initiative for SAB management. After direct notification of SAB and penicillin-binding protein assay results from microbiology personnel, the ID pharmacist promptly contacted the primary team to facilitate ID consultation and identified opportunities to optimize treatment or diagnosis prior to consult. Recommendations were also collaboratively discussed with the ID consult service. Included patients were ≥18 years old with SAB. Excluded patients were < 18 years old, under palliative care or expired prior to S. aureus speciation, refused care against medical advice, pregnant, incarcerated, or had polymicrobial bacteremia. Results Ninety and 111 patients were included in the pre- and post-intervention cohort, respectively. Demographic data were similar between cohorts. Most SAB cases were community-acquired (72% vs 81%, p=0.137), complicated (83% vs 71%, p=0.059), and methicillin-susceptible (57% vs 65%, p=0.236). The most common sources were catheter (23%) and skin and soft tissue (30%) in pre- and post-intervention cohorts, respectively. Table 1 displays compliance with evidence-based SAB measures and clinical outcomes. Compliance with the SAB bundle was significantly higher in the post-intervention cohort (91% vs 50%, p< 0.001). Table 1. Compliance with Evidence-Based Staphylococcus aureus Bacteremia Management Bundle Elements and Clinical Outcomes Conclusion Increased compliance with evidence-based SAB recommendations decreased SAB duration, time to targeted antibiotics, and infection-related hospital length of stay after implementation of a pharmacist-driven collaborative initiative for SAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member)

Background: Variation in providers' education and training may contribute to potential antibiotic overprescribing in outpatient settings. Providers in rural settings may not be exposed to or have similar resources readily available as those in urban settings, or be affiliated with academic medical centers. Thus, we sought to evaluate providers' knowledge and perceptions towards antibiotic stewardship (AS) and antibiotic prescribing in rural primary care clinics. Methods:A cross-sectional, multicenter, electronic survey assessing providers' knowledge and perceptions towards AS and antibiotic prescribing was distributed to family medicine and internal medicine clinic providers in rural New York and Pennsylvania.Results: Seventy responses were included resulting in a survey response rate of 33.5% (70/209) with 42.9%, 30%, and 27.1% of responses from physicians, advanced practice providers, and resident physicians, respectively. The most common barrier to improving antibiotic prescribing was patient demands (54.3%). Providers felt more pressured to prescribe antibiotics based on appointment visits of ≤20 minutes compared with >20 minutes (46.4% vs 7.1%, P = .006), as well as those that encountered ≥50 patients in a week compared with <50 patients (55% vs 16.7%, P = .001). All providers strongly agreed or agreed that antibiotics are overprescribed and inappropriate antibiotic use can lead to resistance. However, only 42.9% of providers selected correctly that 90% to 98% of rhinosinusitis are viral and only 5.7% recommended supportive care without antibiotics. Ten percent of providers never heard of AS, yet most providers (84.3%) were interested in receiving more AS education. Importantly, most providers (57.1%, 40/70) indicated that pharmacists were useful resources to assist in appropriate antibiotic prescribing. Conclusions: Variability exists among providers' knowledge and perceptions towardsAS and antibiotic prescribing in rural primary care clinics, yet most providers are interested in additional AS education. Pharmacists are well-positioned to educate providers and implement initiatives related to AS and appropriate antibiotic prescribing.

BackgroundRural outpatient clinics serve the healthcare needs of many individuals, especially for acute sick visits and infectious processes. A better understanding of providers’ knowledge and attitudes toward antibiotic stewardship in the outpatient rural setting is needed to facilitate more effective education regarding appropriate antibiotic prescribing.MethodsA cross-sectional, multi-center, 28-item survey assessing providers’ knowledge and attitudes toward antibiotic prescribing and antibiotic stewardship in the rural setting was distributed to providers from Guthrie and United Health Services primary care clinics in rural New York and Pennsylvania.ResultsSixty-five providers participated (31% response rate) with 43%, 29%, and 28% of responses from physicians, resident physicians, and advanced practice providers, respectively. More than half of respondents practiced for ≤5 years since terminal training. The most significant barrier to improving antibiotic prescribing was patient demands (55%) followed by uncertain diagnosis of bacterial infection (22%) and short appointment visit times (11%). Providers that spent ≤20 minutes per visit were more likely to feel pressured to prescribe antibiotics for upper respiratory tract infections (URI) to ensure patient satisfaction than those who spent >20 minutes (41% vs. 7%, P = 0.024). Additionally, providers who saw >50 patients per week were more likely to feel pressured to prescribe antibiotics for URIs than those who saw ≤50 patients (50% vs. 18%, P = 0.009). Only 42% of providers selected the correct answer that 90–98% of URIs are viral. The majority of providers strongly agreed that antibiotics are overused (71%) and inappropriate antibiotic use can lead to resistance (82%). Thirty-eight percent of providers never heard the term antibiotic stewardship or heard the term but were unsure about the definition. However, more than 75% of providers strongly agreed or agreed that they were interested in receiving more education regarding antibiotic stewardship.ConclusionVariability exists among providers’ knowledge and attitudes toward antibiotic stewardship and antibiotic prescribing in rural outpatient settings. Increased educational efforts are warranted to increase consistency of these concepts and practices.Disclosures All authors: No reported disclosures.