ß-glucan alleviates the immunosuppressive effects of oxytetracycline on the non-specific immune responses and resistance against Vibrio alginolyticus infection in Epinephelus fuscoguttatus × Epinephelus lanceolatus hybrids.

This study was conducted to examine the combinatory effects of ß-glucan and oxytetracycline (OTC) on hybrid giant tiger groupers (Epinephelus fuscoguttatus × Epinephelus lanceolatus). In vitro tests, OTC significantly reduced superoxide anion production and phagocytic activity in primary head kidney leukocytes. However, this suppressive effect was alleviated by co-treatment with ß-glucan. Subsequently, feeding trials were performed to investigate the potential immunomodulatory effects of dietary ß-glucan alone or in combination with OTC on groupers. A total of 210 healthy groupers (368.00 ± 51.03 g) were divided into six groups. Group 1 was the control group, group 2 (BG) received 5 g ß-glucan per kg feed weight, groups 3-5 received 5 g/kg ß-glucan in combination with 10, 30, or 50 mg OTC/kg fish weight/day (groups M1, M2, and M3, respectively), and group 6 (O) received 50 mg OTC/kg fish weight/day. Fish were sampled to determine the innate immunity parameters and residual OTC levels in the muscle tissue during a 28-day feeding regimen. Residual OTC levels were considerably higher in groups M3 and O compared with the other groups, and peaked on day 14. This was followed by a slight decrease on day 28, despite a continuous supply of OTC. Notably, fish fed with OTC alone had significantly decreased phagocytic rates and superoxide anion production observed in head kidney leukocytes, as well as poorer protection against Vibrio alginolyticus infection. These immunosuppressive effects were not observed in the fish fed with ß-glucan in combination with a lower dose of OTC (group M2). Thus, these data suggest that the combination of dietary ß-glucan and OTC exerts synergistic immunostimulating effects that protect groupers from bacterial infection.

Tear film concentrations of topically applied 0.5% oxytetracycline ointment in normal canine eyes.

OBJECTIVE: To determine the tear film levels of oxytetracycline in normal canine eyes after application of the ophthalmic ointment, Terramycin™ (0.5% oxytetracycline, polymyxin B sulfate), to guide appropriate treatment frequency. ANIMALS STUDIED: Ten research beagles. PROCEDURES: Ten research beagles with confirmed normal eyes were administered 0.02 mL of Terramycin™ ophthalmic ointment onto the dorsal bulbar conjunctival surface of the right eye. Tear samples were collected via dye-less Schirmer tear strips at 2, 4, 6, 8, and 12 hours post-administration. The sample for each timepoint was collected on a separate day, and concentrations of oxytetracycline were determined using high-performance liquid chromatography (HPLC). RESULTS: There was a semi-logarithmic decline in the median tear concentration of oxytetracycline. The median (2.5th and 97.5th percentiles) tear concentrations of oxytetracycline at 2, 4, 6, 8, and 12 hours were 43.5 µg/mL (11.1-302.2 µg/mL), 28.7 µg/mL (8.04-113.7 µg/mL), 16.1 µg/mL (4.96-37.7 µg/mL), 9.2 µg/mL (4.52-28.1 µg/mL), and 6.11 µg/mL (4.36-26.7 µg/mL), respectively. Mean (±SD) drug recovery via HPLC was 88% (±7.5%). CONCLUSIONS: Ophthalmic Terramycin™ achieves a substantially higher tear level than the MIC for common bacterial corneal pathogens up to 12 hours post-administration in normal eyes. Anti-collagenolytic tear levels were not achieved at the timepoints evaluated or with the manufacturer-prescribed dosing frequency. HPLC can be used to analyze tear concentrations of ophthalmic ointment formulations.

Plant extract supplementation as a strategy for substituting dietary antibiotics in broiler chickens exposed to low ambient temperature.

The present study was conducted to investigate the effects of two plant extracts as alternatives to dietary antibiotics in broiler chickens exposed to low ambient temperature. A total of 300 one-day-old male broiler chickens were randomly assigned to four dietary treatments (5 replicate pens; 15 broiler chickens each) which consisted of starter (d 0 to 10), and grower (d 10 to 28) diets. Dietary treatments included a basal diet (negative control, NC) and three similar diets that were either supplemented with 200 mg/kg of Prosopis farcta extract (PFE), Rhus coriaria L. extract (RCE) or an antibiotic premix containing oxytetracycline (positive control, PC). In order to simulate low ambient temperature, room temperature was maintained at 32°C during the first 3 d of the trial and afterwards, the temperature was gradually reduced by approximately 1.5°C each day to 14°C on d 21. PFE and PC treatments exerted a significant effect on body weight gain at d 28. Diet PFE was effective in reducing mortality when compared with diet NC (p < 0.05). Furthermore, diet PFE caused increases in ileal  digestibility of gross energy, dry matter and organic matter when compared with diet NC (p < 0.05). Diets PFE and PC decreased coliforms, total aerobic bacteria and total anaerobic bacteria loads in the caeca when compared with diet NC (p < 0.05). Moreover, the addition of PFE to the diet improved villous height in all small intestinal segments as well as villous height:crypt depth ratio in the duodenum when compared with diet NC (p < 0.05). The results indicated that PFE is not only a valid alternative to oxytetracycline under cold stress conditions, with no antibiotic resistance, but also has the potential to increase the resistance of broiler chickens against ascites syndrome. Moreover, the addition of RCE at the concentration of 200 mg/kg to the diet was not sufficient to improve the performance of broiler chickens (similar to diet PC) but maybe more effective at higher concentrations.

Effect of zinc oxide nanoparticles on broilers' performance and health status.

The current study investigated the effects of zinc oxide nanoparticles (ZONPs) and oxytetracycline (OTC) supplementation on broilers' behavior, performance, carcass quality, biochemical parameters, and intestinal microbial populations and birds' response to Newcastle disease (ND) vaccine. A total of 336 seven-day-old IR broiler chicks were randomly allotted to six dietary treatments containing 0, 10, 20, 30 and 40 ppm ZONPs or 50 ppm OTC. Each diet was fed to 7 replicates (8 birds/pen). The results clarified that 10 ppm ZONPs significantly improved the body weight gain and feed conversion in comparison to the control. No changes in behavior were recorded. The 10 ppm and 30 ppm ZONPs and OTC significantly reduced the gizzard weight in comparison to the control. While, 10 ppm ZONPs significantly increased the spleen weight, and all ZONPs doses increased bursa weight in comparison to the control and OTC groups. 20 ppm ZONPs increased the eviscerated yield and edible yield in comparison to the control and OTC groups. 40 ppm ZONPs increased pH, reduced meat color and overall acceptability in comparison to the control. In addition, results revealed that the 20 ppm ZONPs increased Calcium (Ca), High density low cholesterol (HDL-C), reduced urea (UA) and triglyceride (TG). Also, 40 ppm ZONPs and OTC increased creatinine (Cr) and reduced ND-HI titer in comparison to the control. For microbial population, OTC group was significantly lower than ZONPs groups in the total anaerobic, aerobic and lactobacilli count. In conclusion, the dietary inclusion of ZONPs can be applied as antibiotic growth promoter substitutions in broilers' diet. However, further investigations are still needed.

Evaluation of new generation macrolides for the treatment and metaphylaxis of contagious bovine pleuropneumonia (CBPP) in cattle experimentally infected with Mycoplasma mycoides subspecies mycoides.

BACKGROUND: Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subspecies mycoides (Mmm) is an important disease of cattle that causes serious economic losses. With the known effectiveness of new generation macrolides, tulathromycin and gamithromycin were assessed in comparison with oxytetracycline as a positive control and saline as a negative control for effectiveness in inhibiting lung lesion development, promoting resolution, preventing spread and bacteriological clearance in susceptible local cattle breeds in two separate studies in Kenya and Zambia. Animals were monitored for clinical signs, sero-conversion as well as detailed post-mortem examination for CBPP lesions. RESULTS: Using the Hudson and Turner score for lesion type and size, tulathromycin protected 90%, gamithromycin 80%, and oxytetracycline 88% of treated animals in Kenya. In Zambia, all animals (100%) treated with macrolides were free of lung lesions, while oxytetracycline protected 77.5%. Using the mean adapted Hudson and Turner score, which includes clinical signs, post-mortem findings and serology, tulathromycin protected 82%, gamithromycin 56% and oxytetracycline 80% of the animals in Kenya whereas in Zambia, tulathromycin protected 98%, gamithromycin 94% and oxytetracycline 80%. The saline-treated groups had 93 and 92% lesions in Kenya and Zambia respectively, with Mmm recovered from 5/14 in Kenya and 10/13 animals in Zambia. Whereas the groups treated with macrolides were free from lesions in Zambia, in Kenya 5/15 tulathromycin-treated animals and 6/15 gamithromycin-treated animals showed lesions. Oxytetracycline-treated animals showed similarities with 3/14 and 4/15 showing lesions in Zambia and Kenya respectively and Mmm recovery from one animal in Kenya and six in Zambia. In both studies, lesion scores of saline-treated groups were significantly higher than those of the antibiotic treated groups (p < 0.001). In sentinel animals, CBPP lesions were detected and Mmm recovered from one and two animals mixed with the saline-treated groups in Kenya and Zambia respectively. CONCLUSIONS: This study demonstrated that tulathromycin, a mycoplasmacidal, can achieve metaphylactic protection of up to 80%, while non-recovery of Mmm from sentinels suggests macrolides effectiveness in preventing spread of Mmm. It is recommended that further studies are conducted to evaluate strategies comparing vaccination alone or combining vaccination and antibiotics to control or eradicate CBPP.

Risk factors for antimicrobial use in veal calves and the association with mortality.

The intensive use of antimicrobials in the veal industry is heavily criticized, but drivers for antimicrobial usage (AMU) are still poorly understood. The industry fears that a drastic reduction in AMU would increase mortality, creating an unacceptable welfare issue. The objectives of the present study were to identify risk factors for AMU and to explore the relationship between AMU and mortality. A retrospective cohort study was performed on the antimicrobial registration data from the largest Belgian veterinary veal practice. The data set contained 295 production cycles from 78 farms, representing 146,014 calves and 8 veal companies (also called integrations). The average AMU was 32.3 defined daily dose animal per year (standard deviation: 11.04), of which 76.2% was administered orally and 23.8% parentally. The AMU remained stable between 2014 and 2016 with only a slight, but significant increase in total AMU between 2015 (31.0 defined daily dose animal per year, standard deviation: 10.5) and 2016 (35.1, 10.8). Use of almost all antimicrobial classes decreased over 2014 to 2016; however, use of long-acting macrolides, doxycycline, and aminosides increased significantly. Analysis identified breed (higher use in beef calves compared with dairy and crossbreeds), month of arrival (lower use when arrived in April or May compared with winter months), and veal company as risk factors. The veal company not only significantly affected total AMU, but also affected the majority of the antimicrobial classes. Additionally, breed differences were present for oxytetracycline, colistin, and classic macrolides, and a month effect was present for doxycycline only. These data illustrate that this veterinary practice realized a reduction of 46% in total AMU and of 96% in critically important antibiotics (fluoroquinolones, cephalosporins of the third and fourth generation) compared with the Belgian benchmark from 2007 to 2009. Replacement of critically important drugs by an increased use of long-acting macrolides is worrisome. Mortality risk was very low compared with benchmarks referenced internationally and did not increase with decreasing AMU. Use of trimethoprim-sulfonamides was a risk factor, whereas use of oxytetracycline was a protective factor for mortality. The absence of a relationship with mortality at the current levels of AMU suggests that a further rational reduction is possible. Attention should be paid to consider different AMU benchmarks for different breeds and to include the veal company as a target for antibiotic awareness campaigns.

Comparative analysis of two microbiological tests in the detection of oxytetracycline residue in chicken using ELISA as gold standard.

The validity of two microbiological methods: Tube (Premi® Test) and Plate (Three Plate Test) Test for the detection of oxytetracycline (OTC) in poultry was done using Enzyme Linked Immunosorbent Assay (ELISA) immunoassay as gold standard. OTC was administered to two groups of birds: intramuscular drug administration (group A) and oral drug administration (group B). Liver and muscle tissue samples from birds in both groups were tested for the presence of OTCwith the Four Plate Test (FPT), Premi® Test and ELISA. For muscle tissues, FPT had a sensitivity of 71.4% and 60%, while Premi® Test had a sensitivity of 57% and 20% for intramuscular and orally treated birds, respectively. For the liver tissues, FPT had 87.5% and 83.5% while Premi® Test had 37.5% and 16.6% sensitivity for intramuscular and orally treated birds, respectively. The two tests had 100% specificity for OTC in tissues of birds from both treatment groups. There is a strong correlation (r = 0.93) between the inhibition zones of FPT and ELISA concentrations in OTC detection. FPT, therefore, has a higher sensitivity for OTC than Premi® Test.

Effects of hypertonic dextrose and paraffin solution as non-antibiotic treatments of clinical endometritis on reproductive performance of high producing dairy cows.

The objective of this study was to compare the reproductive performance of cows affected by clinical endometritis (CE) following treatment with an intrauterine infusion of 50% dextrose solutions (DEX) and liquid paraffin (LP) as alternative therapies with routine treatments including PGF2α injection and intrauterine infusion of oxytetracycline (OTC). Moreover, the reproductive indices of cows treated with endometritis were compared with those of healthy ones. At postpartum reproductive tract examination (28-35 DIM) in one Iranian dairy farm, cows with CE without any selection were assigned to four groups: (a) OTC, a common treatment in Iran, was administered (5 g) to 396 cows, (b) PGF2 α (PG) was injected to 496 cows, (c) dextrose solution (DEX): intrauterine infusion of 50% dextrose solution (200 ml) was done in 427 cows, and (d) liquid paraffin (LP) was administered (100 ml) to 423 cows via intrauterine route. We further assigned 2,233 clinically healthy cows to the control group. The incidence of endometritis was 41.6% in this study. Based on the results of reproductive indices including median days to first AI, days open (DO), first service conception rate, conception rate in 2nd and 3rd services, conception rate in all three services, pregnancy rate < 100 days and pregnancy rate < 200 days, except for median days to first AI in other reproductive indexes, reproductive performance was significantly lower in LP group compared with the healthy cows and other treatment groups (p < 0.05). Except for the first service conception rate and proportion of cows pregnant before 100 days in milk (DIM), there existed no significant difference between the DEX group and the control as far as reproductive performance is concerned (p ≥ 0.05). The first service conception rate was recognizably lower in DEX group compared with OTC and PG (p < 0.05). In conclusion, the use of a non-antibiotic special solution of dextrose 50% is a good alternative to antibiotic agents concerning the treatment of CE in dairy cows.

Impact of parenteral antimicrobial administration on the structure and diversity of the fecal microbiota of growing pigs.

While antimicrobials are cost-effective tools for prevention and treatment of infectious disease, the impact of their use on potentially beneficent mucosal microbial communities of growing pigs has not been widely explored. The objective of this study was to characterize the impact of parenteral antibiotics administration on the composition and diversity of the resident fecal microbiota in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Oxytetracycline (OTC), Procaine Penicillin G (PPG) and Tulathromycin (TUL) at label dose and route. Individual fecal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. Genomic DNA was extracted, and the V1-V3 hypervariable region of 16S rRNA gene was amplified and sequenced using Illumina Miseq-based sequencing. Across all groups, the most abundant phyla were Firmicutes, Bacteroidetes, and Proteobacteria. Linear discriminant analysis and stacked area graphs, showed a pronounced, antimicrobial-dependent shift in the composition of fecal microbiota over time from day 0. By day 14, the fecal microbial compositions of the groups receiving CHC and TUL had returned to a distribution that closely resembled that observed on day 0, but differences were still evident. In contrast, animals that received PPG, OTC and CCFA, showed a tendency towards a balanced homeostatic microbiota structure on day 7, but appeared to deviate away from the day 0 composition by day 14. Based on our results, the observed changes in fecal microbiota showed antimicrobial-specific variation in both duration and extent. Understanding the impact of these important antimicrobial-induced changes will be a critical step in optimizing the use of antimicrobials in health management programs in the swine industry.

Isosteric Substitution of 4 H-1,2,4-Triazole by 1 H-1,2,3-Triazole in Isophthalic Derivative Enabled Hydrogel Formation for Controlled Drug Delivery.

In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-( 4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1 H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upon sonication, leading to the formation of stable supramolecular viscoelastic hydrogels with a critical gelation concentration of 6 g/L. Hydrogels made of click-TIA as well as hybrid hydrogels made of the mixture click-TIA + 5-TIA (molar ratio 1:0.2) were used to compare different properties of the materials (i.e., rheological properties, thermal properties, mechanical stability, morphology). In terms of toxicity, neither click-TIA nor 5-TIA showed cytotoxic effects on cellular viability of HeLa cells up to 2.3 × 10-3 g/L when compared to untreated cells incubated with DMSO. Furthermore, the hydrogels were used for the encapsulation and in vitro controlled release of oxytetracycline that followed first-order kinetics. For the hydrogel made of click-TIA, a maximum drug release of ∼60% was reached after ∼8 h within a pH range between 6.5 and 10. However, the release rate was reduced to approximately half of its value at pH values between 1.2 and 5.0, whereas the use of hybrid hydrogels made of click-TIA + 5-TIA allowed to reduce the original rate at pH ≤ 6.5.

Control of Citrus Huanglongbing via Trunk Injection of Plant Defense Activators and Antibiotics.

Citrus huanglongbing (HLB) or greening is a devastating disease of citrus worldwide and no effective control measure is currently available. Plant defense activators environmentally friendly compounds capable of inducing resistance against many plant pathogens. Earlier studies showed that foliar spray of plant defense inducers could slow down HLB disease progress. In this study, eight plant defense activators and three antibiotics were evaluated in three field trials for their effect to control HLB by trunk injection of young and mature sweet orange trees. Results showed that four trunk injections of several activators, including salicylic acid, oxalic acid, acibenzolar-S-methyl, and potassium phosphate, provided significant control of HLB by suppressing 'Candidatus Liberibacter asiaticus' titer and disease progress. Trunk injection of penicillin, streptomycin, and oxytetracycline hydrochloride resulted in excellent control of HLB. In general, antibiotics were more effective in reduction of 'Ca. L. asiaticus' titer and HLB symptom expressions than plant defense activators. These treatments also resulted in increased yield and better fruit quality. Injection of both salicylic acid and acibenzolar-S-methyl led to significant induction of pathogenesis-related (PR) genes PR-1 and PR-2 genes. Meanwhile, injection of either potassium phosphate or oxalic acid resulted in significant induction of PR-2 or PR-15 gene expression, respectively. These results suggested that HLB diseased trees remained inducible for systemic acquired resistance under field conditions. In summary, this study presents information regarding controlling HLB via trunk injection of plant defense activators and antibiotics, which helps citrus growers in decision making regarding developing an effective HLB management program.

Pharmacokinetic-pharmacodynamic integration and modelling of oxytetracycline for the calf pathogens Mannheimia haemolytica and Pasteurella multocida.

A calf tissue cage model was used to study the pharmacokinetics (PK) and pharmacodynamics (PD) of oxytetracycline in serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids. After intramuscular administration, the PK was characterized by a long mean residence time of 28.3 hr. Based on minimum inhibitory concentrations (MICs) for six isolates each of Mannheimia haemolytica and Pasteurella multocida, measured in serum, integration of in vivo PK and in vitro PD data established area under serum concentration-time curve (AUC0-∞ )/MIC ratios of 30.0 and 24.3 hr for M. haemolytica and P. multocida, respectively. Corresponding AUC0-∞ /MIC ratios based on MICs in broth were 656 and 745 hr, respectively. PK-PD modelling of in vitro bacterial time-kill curves for oxytetracycline in serum established mean AUC0-24 hr /MIC ratios for 3log10 decrease in bacterial count of 27.5 hr (M. haemolytica) and 60.9 hr (P. multocida). Monte Carlo simulations predicted target attainment rate (TAR) dosages. Based on the potency of oxytetracycline in serum, the predicted 50% TAR single doses required to achieve a bacteriostatic action covering 48-hr periods were 197 mg/kg (M. haemolytica) and 314 mg/kg (P. multocida), respectively, against susceptible populations. Dosages based on the potency of oxytetracycline in broth were 25- and 27-fold lower (7.8 and 11.5 mg/kg) for M. haemolytica and P. multocida, respectively.

Toxic effects of oxytetracycline and copper, separately or combined, on soil microbial biomasses.

The production of commercial livestock and poultry often involves using with antibiotics and feed additives, such as oxytetracycline (OTC) and copper (Cu). These are often excreted into the soil by animal feces; hence, combined pollutants may contaminate the soil. To evaluate single and combined toxic effects of OTC and Cu on the soil ecology, changes in quantities of bacteria, fungi, and actinomycetes in the soil were studied over a 28-d incubation period by a plate count method, microbes numbers counted on days 7, 14, 21, and 28. Abundances of ammonia monooxygenase (amoA) gene expression by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in soil samples also were tested by real-time polymerase chain reactions (RT-PCRs) on day 21. The results revealed that the numbers of bacteria, fungi and actinomycetes and amoA genes copies of AOA and AOB were reduced seriously by exposure to Cu (1.60 mmol/kg). Similarly, the combined pollution treatments (mole ratios of OTC: Cu was 1:2, 1:8, and 1:32) also had inhibitory effect on bacteria, fungi, and actinomycetes numbers and amoA gene copies of AOA and AOB; the inhibitory rate was on obvious growth trend with the increasing mole ratios. Effects from single OTC pollution were found on bacteria (days 7 and 14), fungi (days 7, 14, 21, and 28), and AOA-amoA gene copies (day 21), with promotion at a low concentration (0.05 mmol/kg) and suppression at higher concentrations (0.2 and 0.8 mmol/kg). Also, numbers of bacteria, fungi, and actinomycetes decreased with longer culture times. Combining OTC and Cu led to a higher inhibition of soil microbes than when either chemical was used alone. However, there was no significant relationship between single and combined toxic chemicals because of their complicated interactions, either antagonistic or synergistic. The results also indicated the sensitivity of bacteria, fungi, actinomycetes on toxic chemicals existed difference and that the AOA were more tolerant than the AOB to these chemicals.

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs.

This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis-induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested.IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment.

Disposition of a long-acting oxytetracycline formulation in Thai swamp buffaloes (Bubalus bubalis).

The present study aimed to characterize the pharmacokinetic profile of oxytetracycline long-acting formulation (OTC-LA) in Thai swamp buffaloes, Bubalus bubalis, following single intramuscular administration at two dosages of 20 and 30 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 504 h. The plasma concentrations of OTC were measured by high-performance liquid chromatography (HPLC). The concentrations of OTC in the plasma were determined up to 264 h and 432 h after i.m. administration at doses of 20 and 30 mg/kg b.w., respectively. The Cmax values of OTC were 12.11 ± 1.87 µg/mL and 12.27 ± 1.92 µg/mL at doses of 20 and 30 mg/kg, respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were 52.00 ± 14.26 h and 66.80 ± 10.91 h at doses of 20 and 30 mg/kg b.w, respectively. Based on the pharmacokinetic data and PK-PD index (T > MIC), i.m. administration of OTC at a dose of 30 mg/kg b.w once per week might be appropriate for the treatment of susceptible bacterial infection in Thai swamp buffaloes.

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs.

The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs and correlation between oral fluid and plasma were evaluated after a single intramuscular (i.m.) dose of 20 mg/kg body weight of long-acting formulation. The OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after drug administration. The maximum concentrations (Cmax ) of drug with values of 4021 ± 836 ng/ml in oral fluid and 4447 ± 735 ng/ml in plasma were reached (Tmax ) at 2 and 1 hr after drug administration respectively. The area under concentration-time curve (AUC), mean residence time (MRT) and the elimination half-life (t1/2ß ) were, respectively, 75613 ng × hr/ml, 62.8 hr and 117 hr in oral fluid and 115314 ng × hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC concentrations were remained higher in plasma for 48 hr. After this time, OTC reached greater level in oral fluid. The strong correlation (r = .92) between oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were within the therapeutic levels for most sensitive micro-organism in pigs (above MIC values) for 48 hr after drug administration, both in the plasma and in oral fluid.

Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27.

The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model to explore the systemic molecular effect of feed supplementation with sub therapeutic levels of oxytetracycline (OTC) by analysis of serum proteome changes. Results showed that OTC promoted growth, coinciding with a significant down regulation of different serum proteins related to inflammation, oxidation and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non-hibernators is unclear, down regulation of HP-27 could be consistent with increased appetite, which is possibly linked to the anti-inflammatory action of OTC. Given that pigs are good models for human medicine due to their genetic and physiologic resemblance, the present results might also be used for rational intervention in human diseases in which inflammation plays an important role such as obesity, type 2 diabetes and cardiovascular diseases.

Comparison of the effects of dietary single and multi-probiotics on growth, non-specific immune responses and disease resistance in starry flounder, Platichthys stellatus.

An 8-week feeding trial was conducted to evaluate the effects of dietary probiotics on growth performance and non-specific immune responses in starry flounder, Platichthys stellatus. Fish averaging 46.5 ± 0.65 g (mean ± SD) were fed one of the six experimental diets; one control (Cont), and five other diets were prepared by supplementing single-probiotics 1 (Bacillus subtilis; SP1, 2 × 109 CFU kg-1 diet), single-probiotics 2 (Bacillus licheniformis; SP2, 2 × 109 CFU kg-1 diet), multi-probiotics 1 (Bacillus subtilis + Bacillus licheniformis; MP1, 2 × 109 CFU kg-1 diet), multi-probiotics 2 (commercial probiotics; Bacillus subtills + Bacillus licheniformis + Paenibacillus polymyxa + Aspergillus oryzae + Saccharomyces cerevisiae; MP2, 2 × 109 CFU kg-1 diet) and oxytetracycline (OTC) at 5 g OTC kg-1 diet. At the end of 8 weeks feeding trial, weight gain (WG) and specific growth rate (SGR) of fish fed SP1, MP1 and MP2 diets were significantly higher than those of fish fed control diet (P < 0.05). Superoxide dismutase (SOD) activity of fish fed MP2 diet was significantly higher than those of fish fed OTC diet (P < 0.05). Nitro blue tetrazolium (NBT) activity and lysozyme activity of fish fed SP1, MP1 and MP2 diets were significantly higher than those of fish fed OTC diet (P < 0.05). However, there was no significant difference among fish fed SP1, SP2, MP1 and MP2 diets. During the Edwardsiella tarda challenge test, the first mortality occurred on day 2. After the 14 days challenge test, cumulative survival rate of fish fed MP1 and MP2 diets were significantly higher than those of fish fed control diet (P < 0.05). However, there was no significant difference among fish fed SP1, SP2, MP1, MP2 and OTC diets in survival rate at the termination of the challenge test. Although there was little advantage in immunological parameters with fish fed MP diets, single and multi-probiotics were equally effective statistically. These results demonstrated that single or multi-probiotics had equal beneficial effect as an antibiotic replacer in terms of growth performance, non-specific immune responses and disease resistance in starry flounder.

Evaluation of the Spatiotemporal Dynamics of Oxytetracycline and Its Control Effect Against Citrus Huanglongbing via Trunk Injection.

Citrus huanglongbing (HLB) or greening is a devastating bacterial disease that has destroyed millions of trees and is associated with phloem-residing 'Candidatus Liberibacter asiaticus' (Las) in Florida. In this study, we evaluated the spatiotemporal dynamics of oxytetracycline in planta and its control effect against HLB via trunk injection. Las-infected 'Hamlin' sweet orange trees on 'Swingle' citrumelo rootstock at the early stage of decline were treated with oxytetracycline hydrochloride (OTC) using trunk injection with varying number of injection ports. Spatiotemporal distribution of OTC and dynamics of Las populations were monitored by high-performance liquid chromatography method and qPCR assay, respectively. Uniform distribution of OTC throughout tree canopies and root system was achieved 2 days postinjection. High levels of OTC (>850 µg/kg) were maintained in leaf and root for at least 1 month and moderate OTC (>500 µg/kg) persisted for more than 9 months. Reduction of Las populations in root system and leaves of OTC-treated trees were over 95% and 99% (i.e., 1.76 and 2.19 log reduction) between 2 and 28 days postinjection. Conditions of trees receiving OTC treatment were improved, fruit yield was increased, and juice acidity was lowered than water-injected control even though their differences were not statistically significant during the test period. Our study demonstrated that trunk injection of OTC could be used as an effective measure for integrated management of citrus HLB.