Search Results (60)

Pasteurella multocida (PM), Glaesserella parasuis (GPS), and Actinobacillus pleuropneumoniae (APP) are among the species with the top five isolation rates on Chinese pig farms annually. To understand the antimicrobial susceptibility and genotypes of these three pathogens that are currently prevalent on pig farms, we investigated 151 bacterial strains (64 PM, 48 GPS, and 39 APP) isolated from 4190 samples from farms in 12 Chinese provinces between 2021 and 2023. The prevalent serotypes were PM type D (50.0%), GPS type 5/12 (47.92%), and APP type 7 (35.90%). A relatively high proportion of PM and APP were resistant to ampicillin (PM, 93.75%; APP, 71.79%), tilmicosin (PM, 64.06%; APP, 58.97%), tetracycline (PM, 43.75%; APP, 61.54%), and enrofloxacin (PM, 34.38%; APP, 10.26%). Ampicillin, tetracycline, and enrofloxacin exhibited low MIC₉₀ values against GPS (8 µg/mL), while sulfamethoxazole-trimethoprim had a high MIC₉₀ value (512 µg/mL). A total of 18 genes conferring resistance to various antimicrobial classes were identified, and tet(L), tet(M), tet(A), bla_TEM, sul2, aph(3′)-Ia, dfrA12, qnrS1, strA, sul3, and mef(B) exhibited a high frequency of identification (≥70%). The analysis of regular virulence factor genes showed that several genes, including fimB, fimA, fimD, fimF, and fepG, were found in all PM, GPS, and APP strains. However, certain genes exhibited species-specific preferences, even if they belonged to the same category. Full article

Commercial organic fertilizers (COFs), as an alternative to chemical fertilizers, have been widely promoted and applied to agricultural soils to improve soil fertility and develop green agriculture. However, the residues of veterinary antimicrobials in COFs could be transferred to agricultural soils and pose ecological risk that should not be ignored. This study quantified the occurrence of fifty-seven veterinary antimicrobials, covering five classes (i.e., twenty-three sulfonamides, nineteen quinolones, seven macrolides, six tetracyclines, and two lincosamides) in ninety-three COFs collected from five provinces in China. Twenty-two veterinary antimicrobials, including eleven quinolones, six sulfonamides, four macrolides, and one lincosamide, were detected in the COFs with total contents up to 3870 ng/g. The contents of individual antimicrobials ranged from 0.66 to 3310 ng/g, and their detection frequencies were between 2% and 49%. The composition and contents of antimicrobials in the COFs varied significantly, depending on their raw materials, production processes, and source regions. Seven antimicrobials, including ciprofloxacin, enrofloxacin, and tilmicosin, could pose low to medium potential ecological risk to soil organisms in the amended soils. The wide occurrence of antimicrobials in COFs and their potential ecological risk indicate the urgent need to establish regulatory limits of antimicrobial residues in COFs to control and prevent antimicrobial pollution in agricultural soils brought by their amendment. Full article

Bovine respiratory disease causes significant economic losses in cattle farming due to mortality, treatment costs, and reduced productivity. It involves viral and bacterial infections, with Pasteurella multocida and Mannheimia haemolytica key bacterial pathogens. These bacteria contribute to severe pneumonia and are often found together. Poland has one of the highest levels of antimicrobial use in food-producing animals among European Union countries. A total of 70 bacterial strains were analyzed, 48 P. multocida and 22 M. haemolytica, collected from affected calves’ respiratory tracts. The bacterial species were confirmed molecularly using PCR, which was also employed to detect antimicrobial resistance and virulence-associated genes. Antimicrobial susceptibility was determined using the broth microdilution method. Antimicrobial resistance varied between the two bacterial species studied. The highest resistance in P. multocida was to chlortetracycline 79.2% (38/48) and oxytetracycline 81.3% (39/48), while M. haemolytica showed 63.6% (14/22) resistance to penicillin and tilmicosin. The highest susceptibility was found for fluoroquinolones: P. multocida demonstrated 91.7% (44/48) susceptibility to enrofloxacin and 87.5% (42/48) to danofloxacin, while 77.3% (17/22) of M. haemolytica were susceptible to both tested fluoroquinolones. The tetH and tetR genes were observed only in P. multocida, at frequencies of 20.8% (10/48) and 16.7% (8/48), respectively. Both species carried the mphE and msrE genes, though at lower frequencies. All M. haemolytica contained the lkt, gs60, and gcp genes. All P. multocida carried the sodA gene, while the hgbB and ompH genes were present in 37.5% (18/48) and 20.8% (10/48) of strains, respectively. The highest resistance was observed against the most commonly used antibiotics in the European Union, although the resistance differed between the studied bacterial species and each strain exhibited the presence of at least one virulence gene. Full article

Bacterial killing is important for recovering from infection. Pasteurella multocida is a key bacterial pathogen causing swine respiratory disease and is associated with substantial mortality. Antimicrobial therapy remains an important therapeutic intervention for treating infected animals. Pradofloxacin (fluoroquinolone) is the most recently approved antimicrobial agent for treating pigs with swine respiratory disease. We compared in vitro killing of swine P. multocida strains by pradofloxacin in comparison to ceftiofur, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin, and tulathromycin over a range of bacterial densities and four clinically relevant drug concentrations. Pradofloxacin killed 92–96.9% of cells across 10⁶–10⁸ cfu/mL densities at the mutant prevention drug concentration following 2–24 h of drug exposure, 96.9–98.9% of cells across 10⁶–10⁹ cfu/mL at the maximum serum drug concentration following 30 min of drug exposure, increasing to 99.9–100% kill following 12–24 h of drug exposure. At the maximum tissue drug concentration and against bacterial densities of 10⁶–10⁹ cfu/mL, pradofloxacin killed 91.3–99.8% of cells following 2 h of drug exposure, which increased to 99.9–100% kill following 12–24 h of drug exposure. Pradofloxacin was rapidly bactericidal across a range of bacterial densities and at clinically relevant drug concentrations. Pradofloxacin will be an important antibiotic for treating pigs with swine respiratory disease and where clinically indicated. Full article

Glaesserella parasuis is the etiological agent of Glässer’s disease, which causes high morbidity and mortality in pigs worldwide. Macrolide resistance poses an urgent threat to their treatment, as macrolides are widely used for preventing and treating G. parasuis infections. Here, we determined the susceptibilities to five macrolides and characterized the genetic markers of macrolide resistance. The antimicrobial susceptibility of 117 G. parasuis isolates to erythromycin, tulathromycin, gamithromycin, tylosin, and tilmicosin was evaluated using broth microdilution method. Erythromycin-resistant isolates were sequenced using whole-genome sequencing. Further analysis of these sequences revealed the genetic basis of macrolide resistance in G. parasuis. Our results show that most G. parasuis isolates remained susceptible to the macrolide drugs. For commonly used agents (e.g., tylosin and tilmicosin), elevated minimum inhibitory concentrations (MICs) were observed, whereas for the newer macrolides (e.g., tulathromycin and gamithromycin), the MICs remained almost unchanged. The macrolide resistance gene erm(T) and the A2059G mutation in 23S rRNA were detected in the current study. To the best of our knowledge, integrative and conjugative element (ICE)-borne erm(T) in G. parasuis is reported for the first time in this study. Taken together, these results provide insights into the susceptibility of G. parasuis to macrolides. The presence of erm(T) on ICEs may facilitate its transfer, reducing the effectiveness of macrolide treatment. Full article

The impact of antibiotic therapy on the spread of antibiotic resistance genes (ARGs) and its relationship to gut microbiota remains unclear. This study investigated changes in ARGs, mobile genetic elements (MGEs), and gut microbial composition following tilmicosin administration in pigs. Thirty pigs were randomly divided into control (CK), low-concentration (0.2 g/kg; L), and high-concentration (0.4 g/kg; H) groups. Tilmicosin concentration in manure peaked on day 16 of dosing and dropped below detectable levels by day 13 of the withdrawal period. While tilmicosin did not significantly affect the total abundance of macrolide resistance genes (MRGs) (p > 0.05), it significantly increased the abundance of the multidrug resistance gene tolC in the H group compared with the L and CK groups during the withdrawal period (p < 0.05). This increase was associated with a coincidental rise in the abundance of MGEs (e.g., int1 and int2) and the growth of potential tolC-hosting bacteria such as Paenalcaligenes and Proteiniclasticum. Redundancy analysis showed gut microbial composition as the primary driver of MRG abundance, with MGEs, tilmicosin concentration, and manure physicochemical properties playing secondary roles. These findings suggest that high-dose tilmicosin may alter the gut microbiota and promote ARG spread via MGE-mediated transfer. Full article

Mycoplasma hyopneumoniae, an important cause of enzootic pneumonia in pigs in many countries, has recently been shown to exhibit reduced susceptibility to several antimicrobial classes. In the present study, a total of 185 pig lung tissue samples were collected from abattoirs in Australia, from which 21 isolates of M. hyopneumoniae were obtained. The antimicrobial resistance profile of the isolates was determined for 12 antimicrobials using minimum inhibitory concentration (MIC) testing, and a subset (n = 14) underwent whole-genome sequence analysis. MIC testing revealed uniformly low values for enrofloxacin (≤1 μg/mL), florfenicol (≤8 μg/mL), lincomycin (≤4 μg/mL), spectinomycin (≤4 μg/mL), tetracycline (≤0.5 μg/mL), tiamulin (≤2 μg/mL), tildipirosin (≤4 μg/mL), tilmicosin (≤16 μg/mL) tulathromycin (≤2 μg/mL), and tylosin (≤2 μg/mL). Higher MICs were observed for erythromycin (MIC range: 16–32 μg/mL), gamithromycin, and tilmicosin (MIC range of both: 32–64 μg/mL). Whole-genome sequencing of the isolates and additional screening using mismatch amplification mutation assay PCR did not identify any known genetic resistance markers within 23S rRNA (macrolides), DNA gyrase A, and topoisomerase IV genes (fluoroquinolones). The WGS data also indicated that the Australian M. hyopneumoniae isolates exhibited limited genetic diversity and formed a distinct monophylectic clade when compared to isolates from other countries. These findings indicate that Australian M. hyopneumoniae likely remains susceptible to the major antimicrobials used to treat enzootic pneumonia in pigs and have evolved in isolation from strains identified in other pig-producing countries. Full article

Tilmicosin, an antibiotic widely used in animal husbandry to prevent and treat bacterial infections, raises concerns due to its residual accumulation, which impacts both animal health and food safety. In this study, we conducted a comprehensive analysis of tilmicosin clearance patterns in different tissues, assessed physiological impacts through blood biochemistry, and investigated changes in gut microbial composition with 16S rRNA sequencing of the tilmicosin-treated Silkie chickens. Initially, we observed rapid peaks in tilmicosin residues in all tissues within 1 day after treatment, but complete metabolism took longer, extending beyond 9 days. Moreover, tilmicosin treatment significantly decreased serum levels of total bile acid, blood urea nitrogen, and uric acid, while increasing the levels of direct bilirubin, total bilirubin, and glutathione peroxidase at day 3, followed by a decrease from day 5 onwards. The effects of tilmicosin use on microbial composition and diversity lasted for an extended period, with the relative abundance of Proteobacteria remaining significantly different between the control and tilmicosin-treated groups at 120 days. Additionally, correlation analysis revealed a strong positive correlation between Mucispirillum_schaedleri and tilmicosin residue in all tissues, while Parabbacteroide_distasonis, Faecalibacterium_prausnitzii, and others exhibited negative correlations with tilmicosin residue. Overall, our study indicates a significant correlation between intestinal microbes and antibiotic residues, providing a theoretical basis for guiding the withdrawal period after antibiotic use. Full article

Pradofloxacin is a dual targeting, bactericidal fluoroquinolone recently approved for treating bacteria causing swine respiratory disease. Currently, an abundance of in vitro data does not exist for pradofloxacin. We determined the minimum inhibitory concentration (MIC) and mutant prevention concentrations (MPC) of pradofloxacin compared to ceftiofur, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin and tulathromycin against swine isolates of Actinobacillus pleuropneumoniae and Pasteurella multocida. Overall, pradofloxacin had the lowest MIC and MPC values as compared to the other agents tested. For example, pradofloxacin MIC values for 50%, 90% and 100% of A. pleuropneumoniae strains were ≤0.016 µg/mL, ≤0.016 µg/mL and ≤0.016 µg/mL and for P. multocida were ≤0.016 µg/mL, ≤0.016 µg/mL and 0.031 µg/mL, respectively. The MPC values for 50%, 90% and 100% of A. pleuropneumoniae strains were 0.031 µg/mL, 0.063 µg/mL and 0.125 µg/mL and for P. multocida were ≤0.016 µg/mL, 0.031 µg/mL and 0.0.063 µg/mL, respectively. By MPC testing, all strains were at or below the susceptibility breakpoint. Based on MPC testing, pradofloxacin appears to have a low likelihood for resistance selection. This study represents the most comprehensive in vitro comparison of the above noted drugs and the first report for pradofloxacin and tildipirosin. Full article

Antimicrobial resistance is recognized worldwide as one of the greatest threats to human and animal health and the environment. To evaluate the resistance rate of Gallibacterium anatis biovar haemolytica, which contributes to bacteremia, oophoritis, ovarian follicle degeneration, salpingitis, decreased egg production, and increased mortality in hens, strains isolated from the reproductive tracts of layers were analyzed. The oviducts were taken from three hens from each of 10 flocks manifesting clinical signs related to laying. Twenty-two isolates of G. anatis biovar haemolytica collected from the three parts of the reproductive system were identified using MALDI-TOF and molecular methods. The biovar’s resistance to 19 antimicrobial substances was assessed using the disk diffusion (n = 8) and broth microdilution (n = 11) methods. The presence of virulence (gtxA, gyrB, and flfA) and antibiotic resistance (bla_ROB, aphA, tetB, and tetH) genes was examined using PCR. All the isolates were resistant to four or more classes of antibiotics and were considered multidrug-resistant. All such isolates were resistant to tilmicosin, tylosin, and enrofloxacin, 88.2% were to tetracycline, and 82.4% to vancomycin. The gtxA, gyrB, tetB, and tetH genes were demonstrated. Considering the present prevalence of multidrug resistance among G. anatis biovar haemolytica isolates from laying hen reproductive tracts, surveillance in reproductive flocks is warranted. Full article

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates (p < 0.01), and feed conversion ratios (p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment (p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets (p < 0.05), while antibiotic treatment reduced beneficial bacteria (p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets. Full article

The emergence of inactivation enzyme-encoding genes tet(X), bla_EBR, and estT challenges the effectiveness of tetracyclines, β-lactams, and macrolides. This study aims to explore the concurrence and polymorphism of their variants in Empedobacter sp. strains from food-producing animals and surrounding environments. A total of eight tet(X) variants, seven bla_EBR variants, and seven estT variants were detected in tet(X)-positive Empedobacter sp. strains (6.7%) from chickens, sewage, and soil, including 31 Empedobacter stercoris and 6 novel species of Taxon 1. All of them were resistant to tigecycline, tetracycline, colistin, and ciprofloxacin, and 16.2% were resistant to meropenem, florfenicol, and cefotaxime. The MIC₉₀ of tylosin, tilmicosin, and tildipirosin was 128 mg/L, 16 mg/L, and 8 mg/L, respectively. Cloning expression confirmed that tet(X6) and the novel variants tet(X23), tet(X24), tet(X25), tet(X26), and tet(X26.2) conferred high-level tigecycline resistance, while all of the others exhibited relatively low-level activities or were inactivated. The bacterial relationship was diverse, but the genetic environments of tet(X) and bla_EBR were more conserved than estT. An ISCR2-mediated tet(X6) transposition structure, homologous to those of Acinetobacter sp., Proteus sp., and Providencia sp., was also identified in Taxon 1. Therefore, the tet(X)-positive Empedobacter sp. strains may be ignored and pose a serious threat to food safety and public health. Full article

Salmonella spp. pose a global threat as a leading cause of foodborne illnesses, particularly prevalent in the European Union (EU), where it remains the second cause of foodborne outbreaks. The emergence of antimicrobial resistance (AMR) in Salmonella spp. has become a critical concern, complicating treatment strategies and escalating the risk of severe infections. The study focuses on large and small ruminants, identifying a prevalence of Salmonella spp. in slaughterhouses and revealing varied AMR rates across antimicrobial families throughout a meta-analysis. Also, comparison with AMR in human medicine was carried out by a systematic review. The results of the present meta-analysis displayed a prevalence of Salmonella spp. in large and small ruminants at slaughterhouses of 8.01% (8.31%, cattle; 7.04%, goats; 6.12%, sheep). According to the AMR of Salmonella spp., 20, 14, and 13 out of 62 antimicrobials studied were classified as low (<5%), high (>5% but <10%), and very high (>10%), respectively. Salmonella spp. did not display AMR against aztreonam, mezlocillin, ertapenem, meropenem, cefoxitin, ceftazidime, levofloxacin, tilmicosin, linezolid, fosfomycin, furazolidone, quinupristin, trimethoprim and spectinomycin. In contrast, a prevalence of 100% of AMR has been described against ofloxacin, lincomycin, and cloxacillin. In the context of the main antibiotics used in the treatment of human salmonellosis, azithromycin was shown to have the highest resistance among Salmonella spp. isolates from humans. Regarding cephalosporins, which are also used for the treatment of salmonellosis in humans, the prevalence of Salmonella spp. resistance to this class of antibiotics was similar in both human and animal samples. Concerning quinolones, despite a heightened resistance profile in Salmonella spp. isolates from ruminant samples, there appears to be no discernible compromise to the efficacy of salmonellosis treatment in humans since lower prevalences of AMR in Salmonella spp. isolated from human specimens were observed. Although the resistance of Salmonella spp. indicates some degree of concern, most antibiotics are not used in veterinary medicine. Thus, the contribution of cattle, sheep and goats to the rise of antibiotic resistance of Salmonella spp. and its potential impact on public health appears to be relatively insignificant, due to their low prevalence in carcasses and organs. Nevertheless, the observed low prevalence of Salmonella spp. in ruminants at slaughterhouse and the correspondingly low AMR rates of Salmonella spp. to key antibiotics employed in human medicine do not indicate that ruminant livestock poses a substantial public health risk concerning the transmission of AMR. Thus, the results observed in both the meta-analysis and systematic review suggests that AMR is not solely attributed to veterinary antibiotic use but is also influenced by factors such as animal health management (i.e., biosecurity measures, prophylactic schemes) and human medicine. Full article

Pradofloxacin is the newest of the veterinary fluoroquinolones to be approved for use in animals—initially companion animals and most recently food animals. It has a broad spectrum of in vitro activity, working actively against Gram-positive/negative, atypical and some anaerobic microorganisms. It simultaneously targets DNA gyrase (topoisomerase type II) and topoisomerase type IV, suggesting a lower propensity to select for antimicrobial resistance. The purpose of this study was to determine the rate and extent of bacterial killing by pradofloxacin against bovine strains of Mannheimia haemolytica and Pasteurella multocida, in comparison with several other agents (ceftiofur, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin and tulathromycin) using four clinically relevant drug concentrations: minimum inhibitory and mutant prevention drug concentration, maximum serum and maximum tissue drug concentrations. At the maximum serum and tissue drug concentrations, pradofloxacin killed 99.99% of M. haemolytica cells following 5 min of drug exposure (versus growth to 76% kill rate for the other agents) and 94.1–98.6% of P. multocida following 60–120 min of drug exposure (versus growth to 98.6% kill rate for the other agents). Statistically significant differences in kill rates were seen between the various drugs tested depending on drug concentration and time of sampling after drug exposure. Full article

Pradofloxacin—a dual-targeting fluoroquinolone—is the most recent approved for use in food animals. Minimum inhibitory and mutant prevention concentration values were determined for pradofloxacin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin, and tulathromycin. For M. haemolytica strains, MIC_50/90/100 values were ≤0.016/≤0.016/≤0.016 and MPC_50/90/100 values were 0.031/0.063/0.063; for P. multocida strains, the MIC_50/90/100 values ≤0.016/≤0.016/0.031 and MPC_50/90/100 ≤ 0.016/0.031/0.063 for pradofloxacin. The pradofloxacin C_max/MIC₉₀ and C_max/MPC₉₀ values for M. haemolytica and P. multocida strains, respectively, were 212.5 and 53.9 and 212.5 and 109.7. Similarly, AUC₂₄/MIC₉₀ and AUC₂₄/MPC₉₀ for M. haemolytica were 825 and 209.5, and for P. multocida, they were 825 and 425.8. Pradofloxacin would exceed the mutant selection window for >12–16 h. Pradofloxacin appears to have a low likelihood for resistance selection against key bovine respiratory disease bacterial pathogens based on low MIC and MPC values. Full article