antibiotic
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...
Clinical TherapeuticsShock and Early Death in Hematologic Patients with Febrile NeutropeniaEmpirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data.
Mechanisms of Action: Physiological EffectsPyrrolomycins Are Potent Natural ProtonophoresThe escalating burden of antibiotic drug resistance necessitates research into novel classes of antibiotics and their mechanism of action. Pyrrolomycins are a family of potent natural product antibiotics with nanomolar activity against Gram-positive bacteria, yet with an elusive mechanism of action.
Mechanisms of ResistanceSpheroplast-Mediated Carbapenem Tolerance in Gram-Negative PathogensAntibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied and yet potentially widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen Vibrio cholerae can tolerate exposure to the typically bactericidal β-lactam antibiotics by assuming a...
Experimental TherapeuticsThiostrepton Hijacks Pyoverdine Receptors To Inhibit Growth of Pseudomonas aeruginosaPseudomonas aeruginosa is a biofilm-forming opportunistic pathogen and is intrinsically resistant to many antibiotics. In a high-throughput screen for molecules that modulate biofilm formation, we discovered that the thiopeptide antibiotic thiostrepton (TS), which is considered to be inactive against Gram-negative bacteria, stimulated...
Clinical TherapeuticsA First-in-Human Study To Assess the Safety and Pharmacokinetics of LYS228, a Novel Intravenous Monobactam Antibiotic in Healthy VolunteersInfections caused by antibiotic-resistant Gram-negative bacteria expressing extended-spectrum β-lactamases and carbapenemases are a growing global problem resulting in increased morbidity and mortality with limited treatment options. LYS228 is a novel intravenous monobactam antibiotic targeting penicillin binding protein 3 with potent activity against Enterobacteriaceae...
Clinical TherapeuticsMolecular Testing of Serial Blood Specimens from Patients with Early Lyme Disease during Treatment Reveals Changing Coinfection with Mixtures of Borrelia burgdorferi GenotypesBorrelia burgdorferi is the etiological agent of Lyme disease. In the current study, we used direct-detection PCR and electrospray ionization mass spectrometry to monitor and genotype B. burgdorferi isolates from serially collected whole-blood specimens from patients clinically diagnosed with early...
Chemistry; BiosynthesisStructure of Dirithromycin Bound to the Bacterial Ribosome Suggests New Ways for Rational Improvement of MacrolidesAlthough macrolides are known as excellent antibacterials, their medical use has been significantly limited due to the spread of bacterial drug resistance. Therefore, it is necessary to develop new potent macrolides to combat the emergence of drug-resistant pathogens.