Preliminary investigation of the use of dietary supplementation with probiotic Bacillus subtilis strain QST713 shows that it attenuates antimicrobial-induced dysbiosis in weaned piglets.

Growth performance of pigs has been associated with healthy gut microbiota. To improve production, pigs are usually treated with antimicrobials. Nonetheless, while antimicrobials harm the gut-indigenous microbiota, probiotic supplementation seems to help keep it healthy. Here, using antimicrobials, we artificially induced dysbiosis in pigs and evaluated a possible preventive effect of probiotic supplementation. Three 6-week-old piglets were given a basal feed, and 3 more the feed supplemented with 2.0 × 106  CFU of Bacillus subtilis QST713/g of feed. After 14 days, antimicrobial enrofloxacin (5 mg/kg B.W.) was injected intramuscularly to all pigs on days 14-16. Feces were collected on days 14, 17, 19, 21, and 23. Total bacteria count was unaffected by enrofloxacin or QST713. However, Lactobacillus spp. and, in particular, Escherichia coli were affected by enrofloxacin, the latter not being observed in the feces on days 17 and 19. Interestingly, a reciprocal increase in E. coli was observed in control pigs on days 21 and 23, although in QST713-supplemented piglets, this increase was attenuated. While the gut microbiota composition did not return to initial levels in antimicrobial-administered piglets, it did in QST713-supplemented piglets. QST713 supplementation was likely crucial to keep the microbiota of piglets healthy.

Effects of prophylactic antibiotic-treatment on post-surgical recovery following intraperitoneal bio-logger implantation in rainbow trout.

Bio-logging devices can provide unique insights on the life of freely moving animals. However, implanting these devices often requires invasive surgery that causes stress and physiological side-effects. While certain medications in connection to surgeries have therapeutic capacity, others may have aversive effects. Here, we hypothesized that the commonly prescribed prophylactic treatment with enrofloxacin would increase the physiological recovery rate and reduce the presence of systemic inflammation following the intraperitoneal implantation of a heart rate bio-logger in rainbow trout (Oncorhynchus mykiss). To assess post-surgical recovery, heart rate was recorded for 21 days in trout with or without enrofloxacin treatment. Contrary to our hypothesis, treated trout exhibited a prolonged recovery time and elevated resting heart rates during the first week of post-surgical recovery compared to untreated trout. In addition, an upregulated mRNA expression of TNFα in treated trout indicate a possible inflammatory response 21 days post-surgery. Interestingly, the experience level of the surgeon was observed to have a long-lasting impact on heart rate. In conclusion, our study showed no favorable effects of enrofloxacin treatment. Our findings highlight the importance of adequate post-surgical recovery times and surgical training with regards to improving the welfare of experimental animals and reliability of research outcomes.

EVALUATION OF LOCALIZED INFLAMMATORY REACTIONS SECONDARY TO INTRAMUSCULAR INJECTIONS OF ENROFLOXACIN IN STRIPED BASS (MORONE SAXATILIS).

Enrofloxacin is a fluoroquinolone widely used in animals including fish. Intramuscular (IM) injection of enrofloxacin is a feasible and efficacious option for drug delivery. In many species IM injection has been associated with injection site reactions and increases in serum muscle enzymes. Injection site reactions have not been well characterized in fish. Three groups of striped bass (Morone saxatilis) received an IM injection of enrofloxacin 2.27% in the right epaxial musculature 24, 48, or 96 hr prior to evaluation. Mean dose was 7.69 mg/ kg (6.14-9.69 mg/kg). The 24- and 48-hr groups received an injection of equal-volume 0.9% saline in the left epaxial musculature. A corresponding noninjected tissue sample was designated in the left epaxial musculature from each fish of the 96-hr group. Fish were euthanized and injection sites and noninjection control sites were evaluated grossly and histologically. Grades 1-4 were assigned to samples, with grade 1 corresponding to normal tissue and grades 2, 3, and 4 corresponding to mild, moderate, and severe inflammation and/or necrosis respectively. Externally, all control and injection sites appeared visually unremarkable. On cut surface, epaxial muscle of the enrofloxacin-injected tissue appeared moderately to severely hemorrhagic compared to saline and noninjected tissue, which was normal or mildly hemorrhagic. Histologically, eight of eight noninjected tissues were grade 1. For saline-injected tissues, 14 of 16 tissues were grade 2 and 2 samples were grade 3 when 24- and 48-hr groups were combined. For enrofloxacin-injected tissues, 8 of the 8 24-hr samples were grade 3 and 16 of the 16 48- and 96-hr samples were grade 4. These data show that IM injection of enrofloxacin 2.27% is associated with severe hemorrhage, necrosis, and inflammation in striped bass, and may negatively affect animal welfare.

Administration of enrofloxacin during late pregnancy failed to induce lesions in the resulting newborn foals.

BACKGROUND: A recent study demonstrated that enrofloxacin and ciprofloxacin cross the equine placenta without causing gross cartilage or tendon lesions in the 9-month fetus; however, long-term effects of in utero fluoroquinolone exposure remain unknown. OBJECTIVES: To assess effects of fetal exposure to enrofloxacin on the resulting foal's cartilage and tendon strength. STUDY DESIGN AND METHODS: Healthy mares at 280 days' gestation were allocated into four groups: untreated (n = 5), therapeutic treatment (7.5 mg/kg enrofloxacin, PO × 14 days, n = 6), supratherapeutic treatment (15 mg/kg, PO × 14 days, n = 6) and no mare treatment with treatment of the foals post-partum (n = 2). Mares were allowed to carry pregnancy to term, and foals were maintained on pasture for 5 weeks. After that foals were euthanized, and their articular cartilage and extensor and flexor tendons were examined macroscopically and histologically for lesions. Tendon strength was tested by loading until failure. RESULTS: Administration of enrofloxacin at recommended doses in late gestation did not result in cartilaginous lesions or clinical lameness in any foal by 5 weeks old. Tensile strength was greater in hind tendons than front tendons, but no difference was found between foals born from treated and control mares. Expectedly, osteochondral changes were present both in foals born from enrofloxacin-treated mares and in negative control foals with no apparent association with fluoroquinolone treatment during pregnancy. MAIN LIMITATIONS: Only one time point in gestation was evaluated, and mares treated in the study were healthy at time of treatment. Additionally, it is possible that the assessments performed herein were not sensitive enough to detect subtle or functional changes in the articular cartilage. Further studies are needed to determine if enrofloxacin administration during late pregnancy potentiates osteochondral alterations in the first year of life. CONCLUSIONS: While this study did not assess other stages of gestation or long-term foal outcomes, short-term administration of enrofloxacin to late gestation mares did not result in macroscopic or microscopic lesions in the resulting foals by 5 weeks of age.

Randomized, controlled, crossover trial of prevention of antibiotic-induced gastrointestinal signs using a synbiotic mixture in healthy research dogs.

BACKGROUND: Synbiotics decrease antibiotic-associated gastrointestinal signs (AAGS) in cats, but data supporting synbiotic use to ameliorate AAGS in dogs are lacking. OBJECTIVES: To determine if administration of synbiotics mitigates AAGS in dogs. ANIMALS: Twenty-two healthy research dogs. METHODS: Randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study with an 8-week washout period. Each period included a 1-week baseline and 3-week treatment phase. Dogs received enrofloxacin (10 mg/kg PO q24h) and metronidazole (12.5 mg/kg PO q12h), followed 1 hour later by a bacterial/yeast synbiotic combination or placebo. Food intake, vomiting, and fecal score were compared using repeated-measures crossover analyses, with P < .05 considered significant. RESULTS: Hyporexia, vomiting, and diarrhea occurred in 41% (95% confidence interval [CI], 21-64), 77% (95% CI, 55-92), and 100% (95% CI, 85-100) of dogs, respectively, during the first treatment period. Derangements in food intake were smaller in both periods for dogs receiving synbiotics (F-value, 5.1; P = .04) with treatment-by-period interactions (F-value, 6.0; P = .02). Days of vomiting differed over time (F-value, 4.7; P = .006). Fecal scores increased over time (F-value, 33.5; P < .001), were lower during period 2 (F-value, 14.5; P = .001), and had treatment-by-period effects (F-value, 4.8; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Enrofloxacin/metronidazole administration is associated with a high frequency of AAGS. Synbiotic administration decreases food intake derangements. The presence of milder AAGS in period 2 suggests that clinical effects of synbiotics persist >9 weeks after discontinuation, mitigating AAGS in dogs being treated with antibiotics followed by placebo.

Influence of long-term oral application of quinolones on the ECG curve in dogs.

The aim of the study was to analyse the influence of enrofloxacin and pradofloxacin administered orally for 14 days on the ECG in dogs. The ECG was performed before and after a 14 day period of quinolone administration. There was an increase in the QTc and the TpTe interval in the group treated with quinolones. QTc was prolonged by 24 ms (p=0.001). The TpTe interval was shortened, on average, by 6.55 ms (p=0.048). In the group treated with enrofloxacin, QTc was prolonged by 16.27 ms (p=0.006) and the TpTe interval was shortened by 9.64 ms (p=0.050), the TpTe/QT index was reduced by 0.034 (p=0.050) on average. In dogs treated with pradofloxacin, QTc was prolonged by 21.55 ms (p=0.012) on average. The results suggest that a prolonged administration of quinolones can increase the risk of arrhythmias. Furthermore, different generations of these drugs increase this risk to various degrees. The study proved that second generation quinolones, such as enrofloxacin, significantly change the phase of depolarization and repolarization of the ventricles, at the same time increasing the risk of ventricular arrythmia. Pradofloxacin does not change the TpTe and TpTe/QT values, so it is safer in use.