Meropenem/Vaborbactam, the First Carbapenem/ß-Lactamase Inhibitor Combination.

OBJECTIVE: To review the pharmacology, spectrum of activity, pharmacokinetics, pharmacodynamics, safety, efficacy, administration, and considerations for clinical use of meropenem/vaborbactam (M/V). DATA SOURCES: A literature search using PubMed and clinicaltrials.gov (June 2013 to December 2017) was conducted using the search terms meropenem, vaborbactam, RPX7009, biapenem, RPX2003, and carbavance. References from relevant articles and conference abstracts were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical, phase I studies, and phase III studies written in the English language were evaluated. DATA SYNTHESIS: M/V is a novel carbapenem/ß-lactamase inhibitor antimicrobial with in vitro activity against nearly 99% of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. M/V is approved for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis. In a phase III cUTI trial (TANGO I), 98.4% of patients treated with M/V experienced overall clinical success compared with 94% of patients treated with piperacillin/tazobactam (95% CI = 0.7 to 9.1). When compared with best available therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections in TANGO II, patients receiving M/V were more likely to achieve clinical cure at both the end of therapy (64.3% vs 33.3%, P = 0.04) as well as at the test of cure (57.1% vs 26.7%, P = 0.04). The most common adverse effects associated with M/V were headache, infusion-site reactions, and diarrhea. CONCLUSION: M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.

Moving Closer to Zero: Effect of "Just in Time" Dosing of Prophylactic Antibiotics on Surgical Site Infections.

Background: A local quality initiative to improve compliance with surgical antibiotic prophylaxis measures resulted in a high percentage of patients receiving antibiotics within minutes of surgical incision. Studies examining the association between timing of prophylaxis and the risk for surgical site infection (SSI) have produced heterogeneous results. Objective: To examine risk factors for SSI, including "just in time" dosing of antibiotic prophylaxis (dose administered within 5 minutes of incision). Methods: This was a retrospective matched case-control study. Case patients developed SSI in the 30 days following a clean or clean-contaminated surgical procedure. Control patients did not develop SSI following similar procedures and were matched to ensure comparable baseline risk. We assessed the rate of guideline-compliant antibiotic prophylaxis and calculated odds ratios (ORs) to determine the association of patient covariates with the risk for SSI. Results: Forty case patients and 104 controls were included in the study. The rate of appropriate prophylaxis was high in both groups (98% and 94% for case and control groups, respectively). Approximately 15% of case and control patients received antibiotic prophylaxis within 5 minutes of incision, thus, "just in time" dosing did not appear to increase the risk for SSI (OR, 0.814; 95% CI, 0.274-2.415). There was a nonsignificant association between receipt of vancomycin and SSI (OR, 2.844; 95% CI, 0.926-8.737). Conclusion: "Just in time" dosing of prophylactic antibiotics was not associated with increased risk for SSI. Further study is needed to clarify the impact of antibiotic choice on the risk for subsequent SSI.

Detection of Neisseria meningitidis from negative blood cultures and cerebrospinal fluid with the FilmArray blood culture identification panel.

The FilmArray blood culture identification (BCID) panel is a rapid molecular diagnostic test approved for use with positive blood culture material. We describe a fatal case of meningococcemia with central nervous system (CNS) involvement detected using the BCID test with culture-negative blood and cerebrospinal fluid.

Time to positivity of blood cultures supports antibiotic de-escalation at 48 hours.

BACKGROUND: Appropriate de-escalation of empirical antimicrobial therapy is a fundamental component of antimicrobial stewardship. Concern for the late detection of bloodstream pathogens may undermine early streamlining efforts and subject patients to protracted courses of nonessential therapy. OBJECTIVE: To quantify the prevalence of bacterial bloodstream infection (BSI) detection after more than 48 hours of culture incubation. We also assessed the impact of antimicrobial therapy delivered prior to blood sample collection. METHODS: We retrospectively evaluated time to blood culture positivity (TTP) in adult patients at an academic tertiary care hospital. Microbiology reports were reviewed to identify the TTP for the first positive blood culture bottle for each episode of BSI occurring from February 1, 2011, to July 31, 2011. Isolates were classified as true pathogens or contaminants. Blood culture results after 48 hours of incubation were compared with results after 120 hours of incubation. RESULTS: The median TTP of 416 monomicrobial BSIs and 210 contamination episodes was 13.7 and 24.4 hours, respectively (P < .001). The median TTPs in those who received and did not receive prior antibiotics were 17.0 and 12.8 hours, respectively (P < .001). By 48 hours, 98% of aerobic Gram-positive and Gram-negative BSIs were detected. Culture results at 48 hours were 97% sensitive and had a negative predictive value of 99.8%. CONCLUSION: Few true BSIs are detected after more than 48 hours of culture incubation. Clinicians may adjust empirical antibiotic coverage at this time with little risk for subsequent bacterial pathogen detection.

The journey of remdesivir: from Ebola to COVID-19.

Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.

Ridinilazole: a novel antimicrobial for Clostridium difficile infection.

Clostridium difficile (C. difficile) infection remains a global healthcare threat worldwide and the limited options available for its treatment are of particular concern. Ridinilazole is one potential future agent, as it demonstrates rapid bactericidal activity against C. difficile. Current studies show that ridinilazole has a lower propensity for collateral damage to the gut microbiome and appears to diminish the production of C. difficile toxins. Results from phase II studies demonstrate that patients receiving ridinilazole had a higher sustained clinical response compared with patients receiving vancomycin (66.7% vs. 42.4%; P=0.0004). Adverse reactions were similar between ridinilazole and vancomycin (40% vs. 56%, respectively), with most being gastrointestinal-related. Nausea (20%) and abdominal pain (12%) were the most commonly reported adverse reactions associated with ridinilazole. Phase II study results are promising and future availability of phase III trial results will help further delineate the role and value of ridinilazole.

Clinical and economic impact of antimicrobial stewardship interventions with the FilmArray blood culture identification panel.

The purpose of this study was to evaluate the impact of the FilmArray Blood Culture Identification (BCID) Panel on the management of patients with blood cultures growing gram positive cocci and Candida. We retrospectively compared clinical and economic outcomes between patients during the BCID testing period and a matched historical control group before BCID testing was introduced. A total of 84 BCID patients were matched to 252 historical controls. BCID identification of coagulase negative staphylococci contaminants resulted in shorter post-culture length of stay (P < 0.008) and saved roughly $30,000 per 100 patients tested. The BCID led to shorter duration of empirical vancomycin for patients with contaminated blood cultures (P = 0.005) and methicillin-susceptible Staphylococcus aureus bacteremia (P < 0.001). Patients with vancomycin-resistant enterococcal bacteremia received active therapy earlier than historical controls (P = 0.047). The BCID, coupled with antimicrobial stewardship intervention, was a cost effective tool to improve patient care.

Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review.

Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline's continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable.