Antimicrobial agents and chemotherapy.
Publisher:
American Society for Microbiology
Frequency: Monthly
Country: United States
Language: English
Author(s):
American Society for Microbiology.
Start Year:1972 -
Identifiers
| ISSN: | 0066-4804 (Print) 1098-6596 (Electronic) 0066-4804 (Linking) |
| NLM ID: | 0315061 |
| (DNLM): | A55830000(s) |
| (OCoLC): | 01778594 |
| Coden: | AMACCQ |
| LCCN: | 72621133 |
| Classification: | W1 AN874 |
Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B. Botulism is a rare, life-threatening paralytic disease caused by Clostridium botulinum neurotoxin (BoNT). Available treatments, including an equine antitoxin and human immune globulin, are given postexposure and challenging to produce and administer. NTM-1632 is an equimolar mixture of 3 human IgG monoclonal antibodies, B1, B2, and B3, targeting BoNT serotype B (BoNT/B). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1632. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy vol...
Horsing around: Escherichia coli ST1250 of equine origin harbouring epidemic IncHI1/ST9 plasmid with bla CTX-M-1 and an operon for short-chain fructooligosaccharides metabolism. The relatedness of the equine-associated ST1250 and its single- and double-locus variants (ST1250-SLV/DLV), obtained from horses in Europe, was studied by comparative genome analysis. A total of 54 isolates of ST1250 and ST1250-SLV/DLV from healthy and hospitalized horses across Europe [Czech Republic (n=23), the Netherlands (n=18), Germany (n=9), Denmark (n=3) and France (n=1)] from 2008-2017 were subjected to whole-genome sequencing. An additional 25 draft genome assemblies of ST1250 and ST1250-SLV/DLV were obtained from the public databases. The isolates were compared for genomic feature...
Emergence of Resistance to Macrolides and Rifampin in Clinical Isolates of Rhodococcus equi from Foals in Central Kentucky, 1995 to 2017. The objective of this study was to determine the prevalence of strains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if the bacterium was cultured and tested for susceptibility to erythromycin or rifampin. susceptibility testing to erythromycin was available for 2,169 isolates of , while s...
Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1. Trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front-line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active a...
Colostrum hexasaccharide, a novel Staphylococcus aureus quorum-sensing inhibitor. The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in Staphylococcus aureus. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase hig...
The equine antimicrobial peptide eCATH1 is effective against the facultative intracellular pathogen Rhodococcus equi in mice. Rhodococcus equi, the causal agent of rhodococcosis, is a major pathogen of foals and is also responsible for severe infections in immunocompromised humans. Of great concern, strains resistant to currently used antibiotics have emerged. As the number of drugs that are efficient in vivo is limited because of the intracellular localization of the bacterium inside macrophages, new active but cell-permeant drugs will be needed in the near future. In the present study, we evaluated, by in vitro and ex vivo experiments, the ability of the alpha-helical equine antimicrobial peptide eCATH1 to kill int...
In vitro potential of equine DEFA1 and eCATH1 as alternative antimicrobial drugs in rhodococcosis treatment. Rhodococcus equi, the causal agent of rhodococcosis, is a severe pathogen of foals but also of immunodeficient humans, causing bronchopneumonia. The pathogen is often found together with Klebsiella pneumoniae or Streptococcus zooepidemicus in foals. Of great concern is the fact that some R. equi strains are already resistant to commonly used antibiotics. In the present study, we evaluated the in vitro potential of two equine antimicrobial peptides (AMPs), eCATH1 and DEFA1, as new drugs against R. equi and its associated pathogens. The peptides led to growth inhibition and death of R. equi and ...
Imidocarb dipropionate clears persistent Babesia caballi infection with elimination of transmission potential. Antimicrobial treatment of persistent infection to eliminate transmission risk represents a specific challenge requiring compelling evidence of complete pathogen clearance. The limited repertoire of antimicrobial agents targeted at protozoal parasites magnifies this challenge. Using Babesia caballi as both a model and a specific apicomplexan pathogen for which evidence of the elimination of transmission risk is required for international animal movement, we tested whether a high-dose regimen of imidocarb dipropionate cleared infection from persistently infected asymptomatic horses and/or elimi...
Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug valacyclovir in healthy adult horses. The purpose of this study was twofold. The first aim was to evaluate the oral bioavailability and pharmacokinetics (PKs) of acyclovir in horses after intravenous (i.v.) administration and after oral administration of acyclovir and its prodrug, valacyclovir. Second, we aimed to combine these PK data with pharmacodynamic (PD) information, i.e., 50% effective concentrations (EC(50) values) from in vitro studies, to design an optimal dosage schedule. Three treatments were administered to healthy adult horses: 10 mg of acyclovir/kg of body weight delivered as an i.v. infusion over 1 h, 20 mg of acy...
Novel plasmid-borne gene qacJ mediates resistance to quaternary ammonium compounds in equine Staphylococcus aureus, Staphylococcus simulans, and Staphylococcus intermedius. We identified a novel plasmid-borne gene (designated qacJ) encoding resistance to quaternary ammonium compounds (QACs) in three staphylococcal species associated with chronic infections in four horses. qacJ was located on a 2,650-bp plasmid (designated pNVH01), a new member of the pC194 family of rolling-circle replication plasmids. The 107-amino-acid protein, QacJ, showed similarities to known proteins of the small multidrug resistance family: Smr/QacC (72.5%), QacG (82.6%), and QacH (73.4%). The benzalkonium chloride MIC for a qacJ-containing recombinant was higher than those for otherwise i...
In vitro susceptibilities of Rhodococcus equi and other common equine pathogens to azithromycin, clarithromycin, and 20 other antimicrobials. The objective of this study was to determine in vitro activities of azithromycin (AZM), clarithromycin (CLR), and 20 other antimicrobial agents against Rhodococcus equi and other common equine bacterial pathogens. A total of 201 bacterial isolates from various equine clinical samples were examined. CLR was more active than AZM against R. equi, with MICs at which 90% of the isolates were inhibited of 0.12 and 1.0 micro g/ml, respectively. Other antimicrobial agents highly active against at least 90% of R. equi isolates in vitro included rifampin, gentamicin, and imipenem. Both AZM and CLR showe...
Presence of vancomycin-resistant enterococci in farm and pet animals. Enterococcus faecium strains with vanA-mediated glycopeptide resistance were isolated by enrichment culture from the intestines and feces of several animal species, mainly horses and dogs (8% positive), chickens (7% positive), and pigs (6% positive). Other vanA-positive enterococcal strains were identified as E. durans in gallinaceous birds, E. faecalis in a horse, and E. gallinarum in a pheasant. Samples from pigeons, cage birds, and ruminants were negative. It was concluded that vancomycin resistance is widespread among isolates from farm and pet animals.
Relative activities of acyclovir and BW759 against Aujeszky’s disease and equine rhinopneumonitis viruses. Compound BW759 (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) was shown to be about 230 times more active than acyclovir (9-[2-hydroxyethoxymethyl]guanine) (ACV) against Equid herpesvirus type 1 infection in Syrian hamsters and was more effective against Aujeszky's disease in mice. The therapeutic superiority of BW759 over ACV was greater than expected from quantitative inhibitory results in tissue culture with these viruses. When administered to hamsters at dose rates sufficient to prevent any Equid herpesvirus type 1-induced mortality (100 mg of ACV per kg per day; 3 mg of BW759 per kg...
Isolation of antibiotic-resistant Salmonella krefeld from clinical veterinary materials. Six isolations of Salmonella krefeld were made from clinical veterinary specimens. These isolates were multiply resistant to several antimicrobial agents commonly used to treat salmonellosis.
In vitro susceptibility of Haemophilus equigenitalis, the causative organism of contagious equine metritis 1977, to antimicrobial agents. The in vitro susceptibility of recent clinical isolates of Haemophilus equigenitalis to various antimicrobial agents was determined by the disk diffusion test and the World Health Organization-International Collaborative Study agar dilution procedure. Ampicillin and tetracycline were the most active drugs. All strains were susceptible to beta-lactam antibiotics, chloramphenicol, trimethoprim-sulfamethoxazole, nalidixic acid, nitrofurantoin (Furadantin), and bacitracin. All but two strains were resistant to streptomycin, whereas all strains were susceptible to the other aminocyclitol antibodies...
Stability of cephalosporins in horse serum. The antibiotic activity of cephalothin, cephaloridine, cephalexin, cephaloglycin, cefazolin, and cefamandole was determined after storage for up to 30 days in horse serum at -10 and 4 degrees C. Cephalothin, cefamandole, cefazolin, and cephalexin were stable for at least 30 days at -10 degrees C, whereas cephaloridine lost 29% of its initial activity and cephaloglycin lost more than 50%. Cefamandole, cefazolin, and cephalexin could only be stored for 3 days at 4 degrees C without significant loss in activity, whereas cephalothin, cephaloridine, and cephaloglycin could be stored for only 1 day....