Gamithromycin

BACKGROUND: Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits. RESULTS: Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86...

Data collected from the German national resistance monitoring program GE RM -Vet showed slowly increasing prevalence of macrolide resistance among bovine respiratory disease (BRD)-associated Pasteurellacae from cattle over the last decade. The focus of this study was to analyze the genetic basis of antimicrobial resistance (AMR) and the prevalence of multidrug-resistance (MDR)-mediating integrative and conjugative elements (ICEs) in 13 German BRD-associated Mannheimia haemolytica isolates collected between 2009 and 2020 via whole-genome sequencing...

UNLABELLED: The fattening of calves is often associated with high antimicrobial use and the selection of antimicrobial resistance (AMR). The objective of this observational longitudinal study was to describe the AMR and strain dynamics, using whole-genome sequencing (WGS), of fecal Escherichia coli in a cohort of 22 calves. All calves received antimicrobial group treatments on Day (D) 1 (oxytetracycline, intramuscularly) and on D4 through D12 (doxycycline, in-feed). Additionally, eight calves received individual parenteral treatments between D7 and D59, including florfenicol, amoxicillin, marbofloxacin, and gamithromycin...

This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)...

Rhodococcus equi is responsible for foal pneumonia worldwide, with a significant economic impact on the production and breeding of horses. In Chile, the first case was reported in 2000, and since then, its incidence has been increasing. Distinctive characteristics of R. equi as an intracellular pathogen in macrophages, emergence of virulence plasmids encoding surface lipoprotein antigens, and appearance of antibiotic resistance against macrolides and rifampicin have significantly complicated the treatment of R...

The present network meta-analysis was performed to compare the effects of antibiotics used in treating footrot in some ruminants and to rank these antibiotics based on their efficacy. Data of 14 eligible studies consisting of 5622 affected animals was included in the analysis. A Bayesian method and Markov Chain Monte Carlo (MCMC) simulations were utilized to analyze data. The estimated results were reported in the form of odds ratios (ORs) with 95% credible intervals (CrI). The Surface Under the Cumulative Ranking Curve (SUCRA) was used to rank antibiotics...

To date, antimicrobial susceptibility has not been reported for Australian Mycoplasma bovis isolates. This study determined minimal inhibitory concentrations (MICs) for 12 different antimicrobials against Australian M. bovis isolates and used whole genome sequencing to screen those showing high macrolide MICs for point mutations in target genes. Most lung tissue/swab samples from bovine respiratory disease cases (61/76, 80.3%) tested positive for M. bovis. A set of 50 representative isolates (50/61, 82.0%) that showed adequate growth, was used for MIC testing...

The purpose of this report is to provide information about the different presentations of cardiac and extra-cardiac histophilosis and, to assess the antimicrobial (ATM) susceptibility of Histophilus somni isolated from these cardiac lesions to different ATM agents commonly used for treating bovine bacterial respiratory pathogens. Eight feedlot calves, which died after suffering from food rejection, apathy, hyperthermia, cough and nasal mucous discharge, and lack of response to ATM therapy, were studied. Cardiac lesions observed at necropsy included valvular/mural endocarditis, myocardial infarction, and necrotizing myocarditis, miliar non-suppurative myocarditis, myocardic necrotic sequestrum, and/or pericarditis...

Mastitis is a significant disease in dairy ruminants, causing economic losses to the livestock industry and severe risks to public health. Antibiotic therapy is one of the most crucial practices to treat mastitis, although the susceptibility of caprine mastitis pathogens to current antibiotics has not been tested under standard or modified incubation conditions. This work evaluated the in vitro activity of tildipirosin, gamithromycin, oxytetracycline, and danofloxacin against caprine mastitis pathogens incubated following standard conditions of Clinical and Laboratory Standards Institute (CLSI) and deviation method by 25% supplementation with goat serum...

Gamithromycin is a long-acting azalide antibiotic that has been developed recently for the treatment of swine respiratory diseases. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff, and optimum dosing regimen of gamithromycin were evaluated in piglets against Streptococcus suis in China, including a subset with capsular serotype 2. Short post-antibiotic effects (PAEs) (0.5-2.6 h) and PA-SMEs (2.4-7.7 h) were observed for gamithromycin against S. suis . The serum matrix dramatically facilitated the intracellular uptake of gamithromycin by S...

Traditionally, in vivo metabolism and total residue studies in veterinary drug research were conducted using radiolabeled drug where information on metabolite profiles and marker residue to total residue ratio is obtained. The Veterinary International Conference on Harmonisation (VICH) guideline GL46 indicates that the metabolism and residue kinetics in food-producing animals may be documented by an alternative approach, one other than the traditional radiolabeled study. High-resolution mass spectrometry (HRMS) has been widely used in human pharmaceutical R&D from metabolite profiling and identification in early drug discovery to first-in-human (FIH) studies in development...

Mycoplasma ovipneumoniae (M. ovipneumoniae) is a respiratory pathogen associated with mild to moderate respiratory disease in domestic lambs and severe pneumonia outbreaks in wild ruminants such as bighorn sheep. However, whether M. ovipneumoniae by itself causes clinical respiratory disease in domestic sheep in the absence of secondary bacterial pathogens is still unclear. The goal of our study was to better understand the role of M. ovipneumoniae as a respiratory pathogen in domestic sheep and to explore potential antibiotic treatment approaches...

In the context of a development program to obtain the market authorization of injectable gamithromycin 15% w/v solution (Zactran®, Boehringer Ingelheim) for use in sheep against footrot, the pharmacokinetic profile of gamithromycin was established and the safety and efficacy of the treatment were confirmed in a multicenter field study in Europe. The basic pharmacokinetic parameters established in healthy young Merino sheep administered gamithromycin at 6 mg/kg body weight based on the analysis of plasma samples which were collected in intervals up to 12 days after subcutaneous injection were: area under the curve until last quantifiable concentration, 8...

Antimicrobial drug (AMD) use for bovine respiratory disease (BRD) continues to be concerning for development of antimicrobial resistance (AMR) in respiratory and enteric bacteria of cattle. This study aimed to provide data regarding AMR in respiratory isolates, and identify relationships between respiratory and enteric AMD susceptibility, in weaned dairy heifers. A cross-sectional study was performed between June of 2019 and February 2020, on 6 calf rearing facilities in California. Deep nasopharyngeal and rectal swabs were collected from 341 weaned heifers and submitted for selective bacterial culture and AMR testing...

Mycoplasma bovis causes many health and welfare problems in cattle. Due to the absence of clear insights regarding transmission dynamics and the lack of a registered vaccine in Europe, control of an outbreak depends mainly on antimicrobial therapy. Unfortunately, antimicrobial susceptibility testing (AST) is usually not performed, because it is time-consuming and no standard protocol or clinical breakpoints are available. Fast identification of genetic markers associated with acquired resistance may at least partly resolve former issues...

Bovine respiratory disease (BRD) causes high morbidity and mortality in beef cattle worldwide. Antimicrobial resistance (AMR) monitoring of BRD pathogens is critical to promote appropriate antimicrobial stewardship in veterinary medicine for optimal treatment and control. Here, the susceptibility of Mannheimia haemolytica and Pasteurella multicoda isolates obtained from BRD clinical cases (deep lung swabs at post-mortem) among feedlots in four Australian states (2014-2019) was determined for 19 antimicrobial agents...

A high throughput method was developed and validated for the quantitation of gamithromycin residues in eggs, milk and animal tissues (leg muscle, kidney, liver and fat) of different species and genera. This was undertaken using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The samples were extracted with acetonitrile and purified using an Oasis MCX solid phase extraction cartridge. Subsequently, a C18 column was used for chromatographic separation using acetonitrile and 0...

Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia, a chronic respiratory disease, causing significant economic losses. Results from the 2015-2016 MycoPath pan-European antimicrobial susceptibility monitoring survey of M. hyopneumoniae are presented. In total, 147 M. hyopneumoniae porcine isolates from Belgium, France, Germany, Great Britain, Hungary, Italy, and Spain were tested. One isolate per farm was retained from pigs that had not been recently treated with antimicrobial agents...

Mycoplasma bovis is an important pathogen causing mostly pneumonia in calves and mastitis in dairy cattle. In the absence of an effective vaccine, antimicrobial therapy remains the main control measure. Antimicrobial use in veal calves is substantially higher than in conventional herds, but whether veal calves also harbor more resistant M. bovis strains is currently unknown. Therefore, we compared antimicrobial susceptibility test results of M. bovis isolates from different cattle sectors and genomic clusters...

We investigate the antimicrobial activity of combined colistin and gamithromycin against nine Pasteurella multocida strains by testing in vitro susceptibility. Two high-colistin minimal inhibitory concentration (MIC) isolates (D18 and T5) and one low-colistin MIC isolate (WJ11) were used in time-kill tests and therapeutic effect experiments using a neutropenic murine pneumonia model over 24 h. Pharmacokinetics (PK) in plasma was calculated along with pharmacodynamics (PD) to determine the PK/PD index. Synergy between colistin and gamithromycin was observed using high-colistin MIC isolates, equating to a 128- or 256-fold and 4- or 8-fold reduction in colistin and gamithromycin concentration, respectively...