On May 1, 2020, after review of yet unpublished data from available clinical trials, the US Food and Drug Administration issued an emergency use authorization (EUA) to permit the use of remdesivir, a nucleotide analog that inhibits viral RNA-dependent RNA polymerase (RDRP), for treatment of adults and children hospitalized with severe coronavirus disease 2019 (COVID-19). EUA was granted after an interim analysis of 606 recoveries in the randomized, placebo-controlled National Institute of Allergy and Infectious Diseases Adaptive Covid-19 Treatment Trial (n51063 participants from 47 United States sites and 21 international sites). Remdesivir reduced the median time to recovery (11 versus 15 days; hazard ratio, 1.31; 95% confidence interval, 1.12 to 1.54; P,0.001) compared with placebo, and overall mortality among patients treated with remdesivir was 8.0% compared with 11.6% among those treated with placebo (P50.59). 1 Notably, patients with severe AKI and ESKD were excluded from this and all other remdesivir trials on the basis of eGFR cutoffs (either 50 or 30 ml/ min per 1.73 m 2 ) (Table 1). As a result, the EUA fact sheet for health care providers states the following. 1

Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well-described and serious adverse event associated with receipt of fluoroquinolones is tendinitis and tendon rupture. These tendon injuries can result in long-term sequelae, including chronic pain and mobility restrictions, and may warrant surgery. Due to the severity of these adverse events, a black box warning is included in the product labeling of all fluoroquinolones. In light of the mounting concerns surrounding fluoroquinolone-associated toxicities, the purpose of this clinical review is to provide a comprehensive summary of the risk of tendinopathy associated with levofloxacin, one of the most widely prescribed antibiotics in the United States, across in vitro, animal, and clinical studies, relative to other antibiotics. As part of this review, clinical presentation and onset, proposed mechanisms, patient-specific risk factors, and management of fluoroquinolone-induced tendon injury are summarized. Data were obtained from a comprehensive PubMed literature search and a review of U.S. Food and Drug Administration documents. Although tendinopathy is considered a fluoroquinolone class-wide toxicity, data from in vitro studies, animal studies, patient-level analyses, and large national and international surveillance reports suggest that levofloxacin, as well as its parent compound ofloxacin, possess higher propensities to cause tendon damage relative to other fluoroquinolones. Risk with ofloxacin and levofloxacin appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy. Other well-described patient risk factors for fluoroquinolone-associated tendinopathy include older age (older than 60 yrs), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation. Given widespread use of levofloxacin across patient care settings, knowledge of both patient- and drug-specific characteristics associated with increased risk of tendinitis and tendon rupture can promote safe use of levofloxacin and other fluoroquinolones.

bThis analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rates exceeded 25% regardless of geographic location or hospital characteristics. The findings suggest that fluoroquinolones should be reserved and third-generation cephalosporins be used with caution as empirical agents for hospitalized patients with UTIs due to E. coli. It is well established that Escherichia coli is the predominant cause of urinary tract infections (UTIs) (1, 2). In the hospital setting, fluoroquinolones or third-generation cephalosporins are commonly prescribed to provide empirical coverage against this pathogen among patients with UTIs. However, the effectiveness of these first-line agents has been compromised by the emergence of antibiotic resistance (3). The Infectious Diseases Society of America (IDSA) discourages empirical use of therapeutic agents for UTIs when resistance rates exceed 10 to 20% (1). While this is broadly recognized, few published contemporary surveillance studies among hospitalized patients have documented resistance rates for commonly used antibiotics for UTIs due to E. coli. This study was conducted to identify geographic locations and hospital characteristics associated with elevated resistance rates for fluoroquinolones and third-generation cephalosporins among hospitalized patients with UTIs due to E. coli.This retrospective observational study used hospital discharge data from approximately 160 U.S. health care facilities in the Premier research database (1 January 2009 to 31 March 2013) with accessible microbiology results. Patients from the database were included if they had positive urine culture results for E. coli and had received an antibiotic with activity against Gram-negative organisms on the index culture date or within the 3-day period thereafter. For patients with multiple UTIs during a hospitalization, subsequent UTI episodes within 30 days after the first episode were excluded.Nonsusceptibility was determined according to individual guidelines for susceptibility testing at each participating site. Fluoroquinolone resistance was defined as nonsusceptibility to levofloxacin, ciprofloxacin, or gatifloxacin. Third-generation-cephalosporin resistance, a surrogate marker of organisms that produce an extended-spectrum ␤-lactamase (ESBL), was classified as nonsusceptibility to ceftazidime, ceftriaxone, or cefotaxime. Fluoroquinolone and third-generation-cephalosporin resistance rates were stratified by U.S. geographic region (nine Centers for Disease Control and Prevention regions, namely, Mountain, Pacific, West North Central, West South Central, East North Central, East South Central, New England, Middle Atlantic, and South Atlantic) and hospital type (teaching versus nonteaching and urban versus rural).Descriptive statistics for patient demogra...

This meta-analysis identified a significant decrease in mortality associated with cefazolin therapy for MSSA bacteraemia compared with ASPs, though no differences in clinical failure were observed. Additionally, cefazolin appeared to be better tolerated. These results should be interpreted with caution given the uncontrolled and retrospective nature of the included studies.

There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug–drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens.

Purpose Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. Results 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. Conclusions Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.

Multidrug resistance(MDR) among Pseudomonas aeruginosa (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR‐PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR‐PSA (e.g., ceftolozane‐tazobactam, ceftazidime‐avibactam, imipenem‐relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR‐PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR‐PSA.

Although limited to small groups of healthy volunteers, these exploratory results support clinical study of extended treatment durations with tedizolid at 200 mg once daily.