The in vitro antimicrobial activities of aditoprim (AP), a new dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (MIC) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia. All B bronchiseptica strains were resistant to AP and TMP. The MIC50 values of AP and TMP for P multocida were 0.25 and 0.06 microgram/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 microgram/ml, respectively. The MIC50, values of SDM and SDM for B bronchiseptica were 4 and 1 microgram/ml, respectively; for P multocida, 16 and 8 microgram/ml, respectively; and for A pleuropneumoniae, 16 and 8 microgram/ml, respectively. The investigated combinations of the DHFR inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the MIC90 values of the combinations were less than or equal to 0.06 microgram/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The MIC of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the DHFR inhibitors in the combinations. For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type-9 strains to AP and TMP as well as to SDM and SMX (at least a fourfold difference in MIC between the 2 types of strains). The MIC of the combinations were similar for the 2 types of strains.

Plasma elimination rates of sulfamethazine (100 mg/kg of body weight, IV), trimethoprim (20 mg/kg, IV), and antipyrine (35 mg/kg, IV) were studied in adult female dwarf goats (n = 5) before and after implantation with trenbolone acetate (5 mg/kg). Pretreatment with trenbolone caused a significant decrease in the elimination rate of the drugs tested: for sulfamethazine, 5 times; for antipyrine, 3 times; and for trimethoprim, 2 times. After treatment with testosterone (1 mg/kg, SC, twice weekly for 2.5 weeks), female goats (n = 5) had a similar decrease in the elimination rate of sulfamethazine. Other induced effects included a change in social behavior, a lower voice, and the development of a typical billy goat-like odor. Plasma creatinine concentrations after androgen administration were significantly higher than those before androgen administration; changes were not observed in plasma urea values. Because of the differences observed, we believe that more attention should be paid to the effects of androgenic agents on drug kinetic properties, with particular reference to studies on clinical efficacy, side effects, and drug residues in food products.

Vaginal aerobic bacterial flora was studied in 5 healthy bitches before, during, and after a 10-day period of treatment with ampicillin and an equally long period of treatment with trimethoprim-sulfamethoxazole. Blood variables and antimicrobial drug susceptibility also were studied. Bacteria were isolated from all bitches before the first treatment period. Bitches from which only a sparse number of bacteria were isolated had flora that varied from day to day. In most instances when bitches were given an antibiotic to which their vaginal bacterial flora was susceptible, these bacteria were eradicated after only 1 day of treatment. This was true for pasteurellae, streptococci, and, in all but one case, Escherichia coli. Staphylococcus intermedius was more difficult to eradicate, and, although susceptible in vitro, it was unaffected by antibiotic treatment in 1 bitch and it took 7 days to eradicate in another. Eradication of aerobic bacteria in the vagina was total only in the bitch that had sparse flora from the beginning. Bacteria colonized within 0 (in 4/5 bitches) to 4 days after termination of treatment with ampicillin and within 0 (in 4/5 bitches) to 3 days for trimethoprim-sulfamethoxazole. Mycoplasmas emerged during and after both treatment periods, and E coli became apparent during treatment with trimethoprim-sulfamethoxazole. Because mycoplasmas may be genital pathogens in bitches and E coli is a common uropathogen, their appearance should be an argument against widespread use of antibiotics in healthy breeding bitches. Two bitches developed a vaginal discharge during treatment or shortly after. Blood variables did not change during the study, nor did antimicrobial drug resistance of the isolated bacteria.

The article presents a rapid and simple analytical procedure for determination of four sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine and sulfamethoxazole), trimethoprim, tylosin and amoxicillin in animal medicated feed.

Integrons are mobile DNA elements that allow for acquisition and dissemination of antibiotic-resistance genes among pig farm-derived bacteria. Limited information is available on integrons of Staphylococcus aureus from pig farms. The aim of this study was to characterise and investigate the prevalence of class 1 and 2 integrons in multi-drug resistant (MDR) S. aureus isolates from pig farms. A total of 724 swabs were collected from 12 pig farms in Chongqing, China, and examined by conventional microbial and molecular methods. In total, 68 isolates were S. aureus, 57 of which were methicillin resistant (MRSA). All 68 isolates were MDR strains and carried integrons, of which 88.2% (60/68) harboured both class 1 and 2. In addition, 85.3% (58/68) of the class 2 integron-positive isolates carried the β-lactam resistance gene (blaTEM₋₁), and 66.7% (40/60) of the class 1 integron–positive isolates carried the aadA1c, aadA1 or dfrA1 gene for respective streptomycin and spectinomycin or trimethoprim resistance. Class 1 and 2 integrons are common among the pig farm-derived S. aureus isolates. On account of their significance for public health, the prevalence of the integrons and their associated resistance genes in pig farm-derived S. aureus isolates should be paid special attention.

Introduction: In the present study, some of the commercial fish farms located in the Black Sea region of Turkey, were screened for bacteria between 2012 and 2014.Material and Methods: The bacterial agents isolated from fish were identified by classical biochemical tests and the rapid diagnostic tests (API 20 E and API 20 Strep). All strains were further identified by sequencing of the 16S rRNA genes. The strains were also investigated for resistance to different antimicrobials by the disc diffusion method. Antibiotic resistance genes, including tetracycline (B), β-lactam (ampC, blaTEM, blaPSE), florfenicol (floR), erythromycine (ereA, ereB), sulphonamide (sulI, sulII), and trimethoprim (dhfr1) genes, were determined by the PCR method.Results:Vibrio anguillarum, Vibrio fluvialis, Photobacterium damselae subsp. piscicida, Pseudomonas luteola, Lactococcus garvieae, Streptococcus iniae, Aeromonas hydrophila, and Yersinia ruckeri were isolated from marine and freshwater cultured fish. According to the results of disc diffusion, all isolates were sensitive to florfenicol, trimethoprim+sulfamethoxazole, oxitetracycline, and enrofloxacin, and resistant to lincomycin, penicillin G, and amoxicillin. Also, sulI, sulII, and floR resistance genes were detected in the bacteria.Conclusion: The results of the study open up the opportunity to perform further investigations which could determine the possible role of ARGs in fish pathogens.

Some pharmacokinetic aspects of sulphadoxine alone and sulphadoxine-trimethoprim (TMP) combination were studied in goats following single intravenous (i.v) and intramuscular (i.m) administration of 15 mg kg–1 b.wt. After i.v injection the serum sulphadoxine concentration time course was best described by two compartment-open model with distribution half-lives (t0.5(.)) 2.48 and 2.31 h., elimination (t0.5(3)) half-lives 23.10 and 24.75 h., total body clearance (ClB) 0.076 and 0.073 L kg-1 h.-1 and steady state volume of distribution (Vdss) 368.54 and 411.73 ml kg-1 for sulphadoxine alone and sulphadoxine-trimethoprim combination, respectively. After i.m administration the mean peak serum concentrations (Cmax) 25.69 and 33.31 ug ml–1 were achieved after maximum time (tmax) of 3.09 and 2.79 h. for sulphadoxine alone and sulphadoxinetrimethoprim combination, respectively. The absorption half-lives (t0.5(ab)) were 0.58 and 0.42 h., respectively. It is concluded that a combination of sulphadoxine and TMP can provide a synergistic level for both antimicrobials and thus be a useful combination in the treatment of various goat diseases.

Healthy gilts and market-ready hogs were administered a single intramuscular (IM) injection of Borgal, a commercial formulation of trimethoprim-sulfadoxine (TMP-SDX), once or twice daily. The objectives were to determine if a newly-developed high-performance liquid chromatographic (HPLC) method would be suitable for measuring the residual concentrations of TMP in the plasma of these live animals, and to determine if the administration of this veterinary drug would leave measurable residues in their plasma and tissues at slaughter. Plasma and tissue concentrations of SDX and TMP from these animals were determined over a period of 14 d using thin-layer chromatography/densitometry (TLCD), and the newly-developed HPLC method, respectively. The lowest detectable limit (LDL) for SDX in plasma and tissue was 20 ppb by TLCD. The HPLC method had a LDL of 5 ppb for TMP in plasma and tissue. Both methods were then used to provide baseline data on the absorption and depletion of TMP and SDX from these healthy animals. It was observed that both TMP and SDX were readily absorbed into the blood and tissues, but TMP was eliminated much faster than SDX. No TMP residues were detected in the plasma of any of the gilts at and beyond 21 h after drug administration. Also, no TMP residues were detected in the plasma of any of the market-ready hogs 24 h after drug administration at either the label dose or twice the label dose. Sulfadoxine residues at concentrations above the maximum residue limit (MRL) of 100 ppb were, however, detected in the plasma, muscle, kidney, liver, and injection sites of hogs slaughtered 1 and 3 d after a single IM administration at the label dose. Although SDX residues were still detectable in the lungs, kidney, liver and plasma of some hogs 10 d after administration of the label dose and twice the label dose, these were below the MRL. Postmortem examination revealed necrosis and inflammation at the injection sites, but no visible deposits of the injected drug.

A study was designed to determine the effect of Pasteurella haemolytica infection on the rate and extent of penetration of sulfadiazine and trimethoprim into tissue chambers implanted SC in cattle. Thermoplastic tissue chambers were implanted SC in 6 calves. At 35 days after implantation, sulfadiazine (25 mg/kg of body weight) and trimethoprim (5 mg/kg) were administered IV to 5 of the calves. Chamber fluid and blood samples were collected from each animal at various time intervals for 24 hours after administration. Ten days later, all chambers were inoculated with P haemolytica serotype 1. At 36 hours after inoculation, a second pharmacokinetic study was conducted, using sulfadiazine and trimethoprim. Drug doses and sampling schedules were identical to those used prior to inoculation. A histologic study of infected chamber tissue was conducted, using the calf not included in the pharmacokinetic studies. Disposition curves of antimicrobials in serum and chamber fluid were well described by 2-compartment and 1-compartment pharmacokinetic models, respectively. Inoculation of P haemolytica into tissue chambers was accompanied by marked changes in the composition of chamber fluid. Increased total protein and albumin concentrations, decreased pH, and disruption of chamber tissue vasculature were associated with a significant increase in the penetration of sulfadiazine and trimethoprim into infected tissue chambers, compared with that in noninfected chambers. This increased penetration was accompanied by increases in the apparent volume of distribution for sulfadiazine and trimethoprim.

Sulfadiazine (SDZ)/trimethoprim (TMP; 30 mg of SDZ/TMP/kg of body weight) was given IV to the same 6 male calves at 1, 7, and 42 days of age and to 2 additional calves at 7 days of age. Serum concentrations of SDZ and TMP were best represented by a 2-compartment open model, but in 42-day-old calves, CSF concentrations of both drugs were best represented by a 1-compartment open model with first-order input. Between 1 and 42 days of age, the elimination half-life (t1/2(beta)) of SDZ decreased from 5.7 to 3.6 hours, and total body clearance (CLtot) increased from 1.43 to 1.88 ml/min/kg; the area under the curve (AUCo leads to x) decreased from 291.5 to 225.4 mg/L.h. The distribution coefficient (Vd(area)/kg of body weight) decreased with age, changing from 0.72 to 0.59 L/kg, between 1 and 42 days of age. Therapeutic concentrations of SDZ in serum (greater than 2 micrograms/ml) were maintained for 24 hours in 1-day-old calves and for about 15 hours in 7- and 42-day-old calves. The elimination rate of TMP increased about 9-fold; t1/2(beta) was 8.4, 2.1, and 0.9 hours, respectively, at 1, 7, and 42 days of age. Other values also reflected an increase in TMP elimination rate with age: CLtot increased from 2.8 to 12 to 28.9 ml/min/kg, k13 increased from 0.336 to 0.654 to 1.664/h and AUC(0 to infinity) decreased from 32.8 to 7.9 to 3.1 mg/L/h, respectively. Therapeutic concentrations (greater than 0.1 microgram/ml) were maintained for 15 hours, 8 hours, and about 6 hours in 1-, 7-, and 42-day-old calves, respectively. Penetration of SDZ and TMP into the CSF in 42-day-old calves was substantial; ratios of AUC(CSF)/AUCserum were 0.60 and 0.69, respectively. Therapeutic concentrations of drugs in CSF were maintained if serum concentrations were above therapeutic concentrations; elimination rates of both drugs from the CSF equaled those of serum. Sulfadiazine was excreted mainly unchanged; the percentage of dose excreted unchanged in 24 hours increased from 22.1 to 47.8 to 50.8% in 1-, 7-, and 42-day-old calves, respectively, paralleling the increase in CLtot. Trimethoprim was extensively biotransformed; the percentage of dose excreted unchanged in the urine in 24 hours decreased from 12.8 to 8.7 to 3.5%. Sulfadiazine and TMP were concentrated in the urine, and therapeutic concentrations of both drugs in urine were maintained for greater than 24 hours in calves of all ages.