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Background: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity., Methods: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain., Results: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis., Conclusions: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis., (© 2024. The Author(s).)

Mycoplasma gallisepticum (MG) is a contagious avian pathogen that causes financial losses to the poultry industry. Isolation of the pathogen is difficult and time-consuming, and therefore, far from a routine method. Serological testing methods to detect antibodies resistant to MG are widely used in routine diagnosis. Tylosin is a class of macrolide antibiotics tremendously administered in veterinary medicine for the treatment of mycoplasmosis and prophylaxis. This study aimed to detect MG by immunoassay testing, culture, and polymerase chain reaction (PCR) in commercial poultry farms and to investigate the tylosin susceptibility of the isolates. To verify the presence of antibodies resistant to MG, 750 blood samples were randomly collected from 38 broiler farms from 2019 to 2022 in Mazandaran and Golestan provinces, Iran, and rapid slide agglutination (RSA) assay was performed. Positive results were analyzed by the enzyme-linked immunosorbent assay (ELISA) for further investigation. Here, 920 swab samples were collected from 38 non-vaccinated commercial farms for culture, and PCR tests were performed for the isolated strains. The activities of tylosin were tested in vitro against these isolates using the broth microdilution method. The lowest antibiotic concentration that resulted in a color change was considered the minimum inhibitory concentration (MIC) value. Twenty-four (63.1%) farms were positive in the RSA test, and 21 (55.2%) farms were positive in the ELISA test. Nine (23.68%) of the farms grew on culture media, and 8 (21.05%) were detected as Gallisepticum species by PCR. The geometric mean of MIC for tylosin was 5.75 µg/ml, MIC50 was 4 µg/ml, and MIC90 was 8 µg/ml. The results indicated that commercial farms were infected with MG. Considering the ability of MG to spread and the probable use of the RSA test as a rapid and cheap method, it can be argued that ELISA and RSA serological tests can be used to find MG in poultry flocks, and the positive result should be confirmed by standard microbiological tests or PCR. It was also found that the isolated parts of MG changed their sensitivity to tylosin, indicating the need for routine testing to optimize treatment dose and efficiency., Competing Interests: The authors declare that they have no conflict of interest.

Antimicrobial products are approved for the control of liver abscesses with varying amounts of data. When compared to negative controls, tylosin has the most data to support a reduction in total (risk ratio 0.34) and severe A+ (risk ratio 0.31) liver abscesses. Due to the reduction in the use of antimicrobials, vaccination to control liver abscess prevalence is intriguing. However, available vaccines do not appear to be effective in controlling the prevalence of liver abscesses, especially when the disease prevalence is high., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The current study was designed to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolated from bovine milk, along with its response to antibiotics, and ultimately reverse its mechanism of resistance by modulation with non-antibiotics. The synergistic combination of antibiotics with NSAIDs were tested in-vivo by giving MRSA challenge to rabbits. The current study reported an overall 23.79% prevalence of MRSA. The BLAST alignment of current study sequences revealed 99% similarity with mecA gene of MRSA from NCBI database. The current study isolates were more similar to each other and also with reference sequences as compared to other mecA gene sequences from Turkey, India, and Russia. Antibiogram of MRSA isolates showed a highly resistant response to cefoxitin, amoxicillin, and gentamicin. Amoxicillin, gentamicin, tylosin, vancomycin, and ciprofloxacin elicited a significant response (p < 0.05) in combination with non-antibiotics against tested MRSA isolates. The highest zone of inhibition (ZOI) increase was noted for vancomycin in combination with flunixin meglumine (145.45%) and meloxicam (139.36%); gentamicin with flunixin meglumine (85.71%) and ciprofloxacin with ivermectin (71.13%). Synergistic behavior was observed in the combination of gentamicin with ketoprofen; sulfamethoxazole and oxytetracycline with meloxicam. Hematological analysis showed significant differences (p < 0.05) among lymphocyte count and bilirubin. On histopathological examination of skin tissue, hyperplasia of epithelium, sloughed off epidermis, hyperkeratosis, infiltration of inflammatory cells, and hemorrhages were observed. The highest cure rate was observed in case of gentamicin in combination with ketoprofen as compared to other treatment groups. The current study concluded antibiotics in combination with non-antibiotics as potential therapeutic agents for resistance modulation against MRSA. This study will help to devise treatment and control strategies against bovine mastitis. Although the prospect of using NSAIDs to manage infections caused by MRSA appears to be a promising direction, further studies should be conducted to test these medications using suitable in-vivo models in controlled clinical trials to justify their repurposing as a treatment for MRSA infections., Competing Interests: Declaration of competing interest All authors have declared no conflict of interest in the submission/publication of this data., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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. Mycoplasma agalactiae, Escherichia coli, Staphylococcus aureus, Streptococcus spp., and coagulase-negative Staphylococci (CNS) were isolated from dairy goats with mastitis in Spain. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution technique. The lowest MIC 90 under standard conditions was obtained with danofloxacin for mastitis-causing pathogens. An exception was M. agalactiae, where danofloxacin and oxytetracycline obtained low values. However, after adding serum, gamithromycin showed the lowest MIC 50 for S. aureus, Streptococcus spp., and CNS. The lowest MIC 50 was obtained with all the antibiotics tested (< 0.125 µg/ml) against M. agalactiae. Supplementing with serum resulted in a significant variation in tildipirosin and gamithromycin MIC values for CNS, S. aureus, M. agalagtiae, and E. coli. In brief, the MIC for antibiotics used against mastitis should be determined under conditions closely resembling intramammary infections to obtain representative susceptibility patterns against mastitis pathogens. Caprine mastitis pathogens were broadly susceptible to danofloxacin under standard conditions. The potency of macrolides against caprine mastitis pathogens increases when serum is present in culture media., (© 2022. The Author(s).)

Background: The causes of respiratory disease in British gamebirds were investigated during 2016-2019 following concerns about poorer responses to antibiotic treatment. Emphasis was placed on Mycoplasma gallisepticum, but other possible bacterial and viral causes were included, along with gross and histopathological examination., Methods: Clinical respiratory disease outbreaks were investigated., Results: Mycoplasma gallisepticum was detected by PCR in 65 of 69 outbreaks in pheasants and partridges and isolated from 56 of these. Partial mgc2 gene sequences from 28 M. gallisepticum isolates were compared, and 26 proved identical, suggesting the prevalence of a dominant sequence type. Minimum inhibitory concentration values for tiamulin, tylosin, tylvalosin, doxycycline and tetracycline were significantly higher than the reference strain but could not be correlated with treatment failures. Other bacterial species were isolated from sinuses but were not consistently correlated with disease. RT-PCRs detected coronaviruses in 18% of 49 outbreaks and avian metapneumovirus in 8%. Histopathological lesions were typical of M. gallisepticum sinusitis and significantly associated with M. gallisepticum PCR outbreak positivity., Conclusion: Mycoplasma gallisepticum remains an important cause of respiratory disease in gamebirds. Synergism with other pathogens may have played a role in some outbreaks. Specific reasons for variable responses to antibacterial treatment were not identified., (© 2022 Crown copyright. Veterinary Record © 2022 British Veterinary Association. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

This study aimed to compare the effects of different levels of cashew nutshell liquid (CNSL) and castor oil (CNSL-castor oil) with growth-promoting antibiotics associated with anticoccidials in broiler chickens challenged with coccidiosis. In this work, 2520 one-day-old male broiler chicks (Cobb) were randomly assigned to 84 pens, containing 30 birds each. The experimental design was completely randomized, with seven treatments: enramycin (8 ppm), virginiamycin (16.5 ppm), and tylosin (55 ppm); different doses of CNSL-castor oil (0.5, 0.75, and 1.00 kg/t); and a control diet (without additives). All treatments received semduramicin + nicarbazin (500 g/t; Aviax® Plus) from 0 to 28 d and monensin sodium (100 ppm; Elanco) from 29 to 35 days of age, when the feed was without antibiotics. The challenge was introduced at 14 days of age by inoculating broiler chickens with sporulated Eimeria tenella, Eimeria acervulina, and Eimeria maxima oocysts via oral gavage. In addition to performance parameters, intestinal contents were collected at 28 and 42 days of age for microbiota analysis by sequencing the 16s rRNA in V3 and V4 regions using the Illumina MiSeq platform. Taxonomy was assigned using the SILVA database (v. 138) with QIIME2 software (v. 2020.11). After one week of challenge, the broilers that received tylosin had a higher body weight gain (BWG) than those in the control group (p < 0.05), while the other treatments presented intermediate values. At 28 d, the BWG was lower for the control, CNSL-Castor oil 0.5 kg/t, enramycin, and virginiamycin treatments than that in the tylosin treatment. The inclusion of CNSL-Castor oil at concentrations of 0.75 and 1 kg/t acted as an intermediate treatment (p < 0.05). For alpha diversity, using the Shannon index, it was possible to observe the effect of age, with substantial diversity at 42 d. The Firmicutes phylum had the highest abundance, with values between 84.33% and 95.16% at 42 d. Tylosin showed better performance indices than other treatments. CNSL-castor oil treatments with concentrations of 0.75 and 1 kg/t showed similar results to those of enramycin and virginiamycin. Furthermore, CNSL-castor oil acted as a modulator of intestinal microbiota, reducing the abundance of pathogenic bacteria., Competing Interests: The authors have declared that no competing interests exist.

Background: Antibiotic-responsive enteropathy (ARE) is diagnosed by excluding other causes of diarrhea and when there is a short-term response to administration of antibiotics., Objectives: To characterize the gut microbiota and clinical trend of dogs with suspected ARE and to evaluate the variation in microbiota before (T0), after 30 days (T30) of tylosin treatment, and 30 days after discontinuation of treatment (T60). A further objective was to evaluate whether changes in gut microbiota are related to relapses of diarrhea when the therapy is tapered., Animals: Study sample (group A) was composed of 15 dogs with chronic diarrhea, group B was composed of 15 healthy dogs. Group A was given tylosin for 30 days., Methods: A multicentric prospective study. Clinical Indexes, fecal score, and samples for microbiota analysis were collected at T0, T30, and T60 in group A and T0 and T30 in group B. The gut microbiota was analyzed via 16S ribosomal RNA gene. Qiime2 version 2020.2 was used to perform bioinformatic analyses, and Alpha- and Beta-diversity were computed., Results: Diarrhea recurred after T30 in 9 of 14 dogs, which were classified as affected by ARE. At T0, a difference was noted in the beta-diversity between groups (Bray Curtis metric P = .006). A T0-T30 difference in alpha-diversity was noted in group A (Shannon index P = .001, Faith PD P = .007)., Conclusions and Clinical Importance: Although tylosin influences the microbiota of dogs with ARE, we failed to find any specific characteristic in the microbiota of dogs with ARE., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)