IMPORTANCE Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias.OBJECTIVE To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTSThis was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURESChange in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [−15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI,). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCEIn this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

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Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin’s biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.

The role of enterococci in infectious diseases has evolved from a gut and urinary commensal to a major pathogen of concern. Few options exist for resistant enterococci, and appropriate use of the available agents is crucial. Areas covered: Herein, the authors discuss antibiotics with clinically useful activity against Enterococcus faecalis and E. faecium. The article specifically discusses: antibiotics active against enterococci and their mechanism of resistance, pharmacokinetic and pharmacodynamic principles, in vitro combinations, and clinical studies which focus on urinary tract, intra-abdominal, central nervous system, and bloodstream infections due to enterococci. Expert opinion: Aminopenicillins are preferred over all other agents when enterococci are susceptible and patients can tolerate them. Daptomycin and linezolid have demonstrated clinical efficacy against vancomycin-resistant enterococci (VRE). Synergistic combinations are often warranted in complex infections of high inoculum and biofilms while monotherapies are generally appropriate for uncomplicated infections. Although active against resistant enterococci, the pharmacokinetics, efficacy and safety of tigecycline and quinupristin/dalfopristin can problematical for severe infections. For cystitis, amoxicillin, nitrofurantoin, or fosfomycin are ideal. Recently, approved agents such as tedizolid and oritavancin have good in vitro activity against VRE but clinical studies against other resistant enterococci are lacking.

IMPORTANCEAlthough prescribers face numerous patient-centered challenges during transitions of care (TOC) at hospital discharge, prolonged duration of antimicrobial therapy for common infections remains problematic, and resources are needed for antimicrobial stewardship throughout this period.OBJECTIVE To evaluate a pharmacist-driven intervention designed to improve selection and duration of oral antimicrobial therapy prescribed at hospital discharge for common infections. DESIGN, SETTING, AND PARTICIPANTSThis quality improvement study used a nonrandomized stepped-wedge design with 3 study phases from September 1, 2018, to August 31, 2019. Seventeen distinct medicine, surgery, and specialty units from a health system in Southeast Michigan participated, including 1 academic tertiary hospital and 4 community hospitals. Hospitalized adults who had urinary, respiratory, skin and/or soft tissue, and intra-abdominal infections and were prescribed antimicrobials at discharge were included in the analysis. Data were analyzed from

A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.

Background: Antimicrobial stewardship (AMS) is recommended in hospital, postacute, and outpatient settings. Transitions of care (TOC) are important in each of these settings; however, AMS efforts during TOC have been limited. Beginning in October 2018, we sequentially implemented a pharmacist-led multidisciplinary review of oral antimicrobial therapy prescribed at hospital discharge from general and specialty medicine wards across a health system. Pharmacists facilitated data input of discharge prescriptions following early identification and collaborative discussion of patients to be discharged on oral antimicrobials The purpose of this study was to evaluate the impact of AMS during TOC. Methods: This project was an IRB-approved stepped-wedge, quasi-experimental study in a 5-hospital health system that included hospitalized adults with skin, urinary, intra-abdominal, and respiratory tract infections who had been discharged from general and specialty wards with oral antimicrobials. Patients with complicated infections, neutropenia, or who were transferred from an outside hospital were excluded. The primary end point was optimization of antimicrobial therapy at time of hospital discharge, defined by correct selection, dose, and duration according to institutional guidance. Outcomes were compared before and after the intervention. Results: In total, 800 patients were included: 400 in the preintervention period and 400 in the postintervention period. Among this cohort, 252 (63%) received the intervention by a pharmacist per protocol during TOC. Patients had similar comorbid conditions before and after the intervention. Preintervention patients were more likely to be discharged from community hospitals. Before the intervention, 36% of discharge regimens were considered optimized, compared to 81.5% after the intervention (P < .001); this difference was largely driven by a reduction in patients receiving a duration of therapy beyond the clinical indication (44.5 vs 10%; P < .001). We observed similar clinical resolution, 30-day readmission, and adverse drug events (ADEs) between the pre- and postintervention periods. Postdischarge antimicrobial duration of therapy was reduced from 4 days (range, 3–5) to 3 days (range, 2–4) (P < .001) Severe ADEs occurred more frequently in the preintervention group (9 vs 3.3%; P = .001), which was driven by isolation of multidrug-resistant pathogens (7 vs 2.5%; P = .003) and Clostridioides difficile (1.8 vs 0.5%; P = .094). Patients who received optimal therapy at discharge were less likely to develop an ADE (aOR, 0.530; 95% CI, 0.363–0.773). Conclusions: Implementation of an AMS TOC protocol reduced antimicrobial days, optimized therapy selection, and reduced duration. This intervention was associated with improved safety without compromise of clinical effectiveness. To increase patient safety, AMS programs should target antimicrobial optimization during TOC.Funding: This work was completed under CDC contract number 200-2018-02928.Disclosures: None

Purpose of Review The looming threat of antimicrobial resistance requires robust stewardship and new developments in infectious diseases pharmacotherapy. This review discusses the pertinent spectrum and clinical data of lefamulin (Xenleta®), with a focus on potential real-world use. Recent Findings Lefamulin is a novel pleuromutilin antibiotic that obtained Food and Drug Administration labeling for community-acquired bacterial pneumonia (CABP) in 2019. Lefamulin is available in both intravenous and oral formulations, and it inhibits bacterial protein synthesis inhibition through interactive binding to unique sites of the peptidyl transferase center of the 50s bacterial ribosome subunit. Resistance, including cross-resistance with other antibiotics, is infrequent. Lefamulin demonstrates activity against most Gram-positive pathogens and other organisms commonly associated with CABP, i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae. Lefamulin may also be an option for serious public health threats like methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus faecium, and multi-drug-resistant organisms associated with sexually transmitted infections, e.g., Neisseria gonorrhoeae, Mycoplasma genitalium. Lefamulin lacks activity against Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacterales, most anaerobes, and E. faecalis. In Phase III trials, lefamulin monotherapy was non-inferior to moxifloxacin with or without linezolid for CABP. Summary Lefamulin is a well-tolerated agent with a unique mechanism, availability in both IV and PO formulations, and it has been rigorously studied for safety and efficacy for CABP.