antibiotic
Clinical TherapeuticsDecreased Overall and Inappropriate Antibiotic Prescribing in a Veterans Affairs Hospital Emergency Department following a Peer Comparison-Based Stewardship InterventionAntibiotic prescribing is very common in emergency departments (EDs). Optimal stewardship intervention strategies in EDs are not well defined. We conducted a prospective, observational cohort study in a Veterans Affairs ED in which clinician education and monthly e-mail-based peer comparisons were directed against all oral antibiotic prescribing for discharged patients. Oral antibiotic prescriptions were compared in baseline (June 2016...
Mechanisms of Action: Physiological EffectsComparison of Proteomic Responses as Global Approach to Antibiotic Mechanism of Action ElucidationNew antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of...
Clinical TherapeuticsRisk Factors Associated with Antibiotic Treatment Failure of Buruli UlcerCombination antibiotic therapy is highly effective in curing Buruli ulcer (BU) caused by Mycobacterium ulcerans. Treatment failures have been uncommonly reported with the recommended 56 days of antibiotics, and little is known about risk factors for treatment failure. We analyzed treatment failures among BU patients treated with ≥56 days of antibiotics from a...
Mechanisms of Action: Physiological EffectsIn Vitro and In Vivo Antibiotic Capacity of Two Host Defense PeptidesTwo nonamidated host defense peptides named Pin2[G] and FA1 were evaluated against three types of pathogenic bacteria: two (Staphylococcus aureus UPD13 and Pseudomonas aeruginosa UPD3) isolated from diabetic foot ulcer patients, and another (...
PharmacologyActivity of Antibiotics against Pseudomonas aeruginosa in an In Vitro Model of Biofilms in the Context of Cystic Fibrosis: Influence of the Culture MediumPseudomonas aeruginosa is a major cause of respiratory biofilm-related infections in patients with cystic fibrosis. We developed an in vitro pharmacodynamic model to study the activity of antipseudomonal antibiotics against PAO1 biofilms grown in artificial sputum medium with agar [ASM(+)] versus that against biofilms grown in Trypticase soy broth...
Editor's Pick Experimental TherapeuticsEvaluation of the Activity of a Combination of Three Bacteriophages Alone or in Association with Antibiotics on Staphylococcus aureus Embedded in Biofilm or Internalized in OsteoblastsStaphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm and to be internalized and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections, but data on its activity against the specific bacterial lifestyles...
Experimental TherapeuticsPharmacodynamics of ClpP-Activating Antibiotic Combinations against Gram-Positive PathogensIt is often difficult to cure endocarditis, osteomyelitis, and device-associated infections caused by Gram-positive pathogens, despite therapy with clinically appropriate antibiotics. This may be due to antibiotic tolerance or resistance development. Acyldepsipeptides (ADEPs) are a class of bactericidal compounds active against a variety of clinically important Gram-positive bacteria, including staphylococci, streptococci, and...
Experimental TherapeuticsMultiple-Ascending-Dose Phase 1 Clinical Study of the Safety, Tolerability, and Pharmacokinetics of CRS3123, a Narrow-Spectrum Agent with Minimal Disruption of Normal Gut MicrobiotaCRS3123 is a novel small molecule that potently inhibits methionyl-tRNA synthetase of Clostridioides difficile, inhibiting C. difficile toxin production and spore formation. CRS3123 has been evaluated in a multiple-ascending-dose placebo-controlled phase 1 trial.
Experimental TherapeuticsGC-072, a Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat PathogensBurkholderia pseudomallei, the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care; in the case of septicemia, left...
