Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) in Species.

Manogepix (MGX) targets the conserved fungal Gwt1 enzyme required for acylation of inositol early in the glycosylphosphatidylinositol biosynthesis pathway. The prodrug fosmanogepix is currently in clinical development for the treatment of invasive fungal infections. We determined that the median frequencies of spontaneous mutations conferring reduced susceptibility to MGX in , , and ranged from 3 × 10 to <1.

Comparison of the in vitro antibacterial activity of Ramizol, fidaxomicin, vancomycin, and metronidazole against 100 clinical isolates of Clostridium difficile by broth microdilution.

Antibiotic drug development remains a major challenge with few candidates in clinical development. Ramizol, a first-in-class styrylbenzene antibiotic, is under development for the treatment of Clostridium difficile associated disease. Here, we investigate the in vitro antibacterial activity of Ramizol in comparison to fidaxomicin, vancomycin and metronidazole against 100 clinical isolates of C.

In vitro potency and fungicidal activity of CD101, a novel echinocandin, against recent clinical isolates of Candida spp.

Candida infections vary in severity and manifestation. Common infections include invasive bloodstream infections among hospitalized/immunocompromised patients and vulvovaginal candidiasis among women. Echinocandins and azoles are commonly utilized to treat Candida infections, although echinocandin use has been restricted to indications amenable to once-daily IV administration.

Evaluation of the bactericidal activity of Telavancin against Staphylococcus aureus using revised testing guidelines.

The in vitro broth microdilution testing method for telavancin, a lipoglycopeptide active against S. aureus, was revised in 2014 to include polysorbate-80 in the test media. This study evaluates the bactericidal activity of telavancin against S.

Comparative in vitro activity of oritavancin and other agents against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a threat to the public health due to their prevalence and associated mortality and morbidity. Several agents have been recently approved to treat MRSA skin infections including lipoglycopeptides (dalbavancin, oritavancin, and telavancin), ceftaroline, and tedizolid. This study compared the MIC, minimum bactericidal concentration (MBC), and time-kill of these agents alongside daptomycin, linezolid, and vancomycin against MRSA (n=15); meropenem, cefazolin, and nafcillin were also included against methicillin-susceptible S.

In vitro susceptibility testing of eravacycline is unaffected by medium age and nonstandard assay parameters.

Eravacycline is a fluorocycline antibiotic in phase 3 clinical development for complicated intra-abdominal and urinary tract infections. To support its clinical development, a study was conducted to evaluate the effects of various susceptibility test parameters on the MIC values for aerobic bacteria. The results showed that eravacycline appears to be largely unaffected by medium age, medium additives, and other nonstandard assay conditions.

Five-year longitudinal assessment (2008 to 2012) of E-101 solution activity against clinical target and antimicrobial-resistant pathogens.

This study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens.

Tricyclic GyrB/ParE (TriBE) inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes.

In vitro activity and microbiological efficacy of tedizolid (TR-700) against Gram-positive clinical isolates from a phase 2 study of oral tedizolid phosphate (TR-701) in patients with complicated skin and skin structure infections.

Tedizolid (TR-700, formerly torezolid) is the active moiety of the prodrug tedizolid phosphate (TR-701), a next-generation oxazolidinone, with high potency against Gram-positive species, including methicillin-resistant Staphylococcus aureus (MRSA). A recently completed randomized, double-blind phase 2 trial evaluated 200, 300, or 400 mg of oral tedizolid phosphate once daily for 5 to 7 days in patients with complicated skin and skin structure infections. This report examines the in vitro activity of tedizolid and Zyvox (linezolid) against Gram-positive pathogens isolated at baseline and describes the microbiological and clinical efficacy of tedizolid.

Multidrug resistance among Acinetobacter spp. in the USA and activity profile of key agents: results from CAPITAL Surveillance 2010.

Multidrug resistance among Acinetobacter spp. leaves few effective antibiotic options for treatment. To monitor antibiotic resistance in Acinetobacter spp.

Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) 2009 surveillance study.

Purpose: To determine the antibacterial susceptibility profile of bacterial pathogens from ocular infections against relevant aminoglycoside, β-lactam, cephalosporin, chloramphenicol, fluoroquinolone, glycopeptide, lincosamide, and macrolide antibacterial agents.

Design: Laboratory investigation.

Methods: Isolates from patients with bacterial eye infections were collected prospectively by 34 institutions across the United States and were submitted to a central laboratory for inclusion in the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) study.

In vitro time-kill experiments with besifloxacin, moxifloxacin and gatifloxacin in the absence and presence of benzalkonium chloride.

Objectives: To compare the bactericidal activity of besifloxacin, moxifloxacin and gatifloxacin and determine the contribution of the preservative benzalkonium chloride (BAK) to bactericidal activity.

Methods: Time-kill experiments were performed against four species (n=12) with besifloxacin, moxifloxacin and gatifloxacin, in the presence or absence of BAK, at t=0, 5, 15, 30, 45, 60, 120 and 360 min, according to standard CLSI methods.

Results: In the presence of BAK, bactericidal activity was observed within 5 min, regardless of the fluoroquinolone tested.

Bactericidal activity of besifloxacin against staphylococci, Streptococcus pneumoniae and Haemophilus influenzae.

Objectives: Besifloxacin is a novel fluoroquinolone that was recently approved for topical treatment of bacterial conjunctivitis. The compound was shown to be active in vitro against a broad spectrum of bacteria, including isolates resistant to other antibacterials. Here, the bactericidal activity of besifloxacin was evaluated against the most common bacterial conjunctivitis pathogens.

Comparative in vitro activity profile of oritavancin against recent gram-positive clinical isolates.

Oritavancin activity was tested against 15,764 gram-positive isolates collected from 246 hospital centers in 25 countries between 2005 and 2008. Organisms were Staphylococcus aureus (n = 9,075), coagulase-negative staphylococci (n = 1,664), Enterococcus faecalis (n = 1,738), Enterococcus faecium (n = 819), Streptococcus pyogenes (n = 959), Streptococcus agalactiae (n = 415), group C, G, and F streptococci (n = 84), and Streptococcus pneumoniae (n = 1,010). Among the evaluated staphylococci, 56.

In vitro activity of doripenem, a carbapenem for the treatment of challenging infections caused by gram-negative bacteria, against recent clinical isolates from the United States.

Doripenem, a 1beta-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis.

In vitro activity of tigecycline against gram-positive and gram-negative pathogens as evaluated by broth microdilution and Etest.

The current surveillance establishes the activity profile of tigecycline against recent clinical U.S. isolates of target pathogens.

In vitro activity profile of ceftobiprole, an anti-MRSA cephalosporin, against recent gram-positive and gram-negative isolates of European origin.

Objectives: To determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA), for use as a contemporary baseline to help detect any changes in its activity profile throughout the course of clinical development and use.

Methods: MICs were determined by broth microdilution testing for ceftobiprole and comparators against 6680 isolates [1201 S. aureus, 460 coagulase-negative staphylococci (CoNS), 526 Streptococcus pneumoniae, 1213 Escherichia coli, 854 Klebsiella pneumoniae, 443 Proteus mirabilis, 406 Enterobacter cloacae, 387 Citrobacter spp.

Prevalence of multidrug-resistant, methicillin-resistant Staphylococcus aureus in the United States: findings of the stratified analysis of the 2004 to 2005 LEADER Surveillance Programs.

Surveillance data for methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistance (MDR) among MRSA were analyzed by patient location and age. MRSA rates were 55.7% among inpatients (53.

Structure and DNA-binding properties of the cytolysin regulator CylR2 from Enterococcus faecalis.

Enterococcus faecalis is one of the major causes for hospital-acquired antibiotic-resistant infections. It produces an exotoxin, called cytolysin, which is lethal for a wide range of Gram-positive bacteria and is toxic to higher organisms. Recently, the regulation of the cytolysin operon was connected to autoinduction by a quorum-sensing mechanism involving the CylR1/CylR2 two-component regulatory system.