The macrolytic lactone F28249-alpha was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ED95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (<less than or equal to 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.

Streptococcal species isolated from dairy cows with clinical mastitis were obtained from mastitis research workers in Florida, Louisiana, New York, Vermont, Washington, and West Virginia. Seventy-one streptococcal isolates were tested, including 39 strains of Streptococcus agalactiae, 21 strains of S dysgalactiae, and 11 strains of S uberis. The minimal inhibitory concentration of erythromycin, lincomycin, oxytetracycline, penicillin, spectinomycin, streptomycin, and tetracycline was determined for each isolate. Differences were not detected among strains with respect to geographic origin. None of the strains was resistant to penicillin. Lincomycin was the next most effective antimicrobial, with only 2 resistant strains of each streptococcal species. There were no differences among the streptococcal species with respect to resistance to either penicillin or lincomycin. Streptococcus uberis was more likely to be resistant to erythromycin than were S agalactiae and S dysgalactiae (P < 0.02). Streptococcus agalactiae and S uberis had similar distributions for resistance to oxytetracycline, tetracycline, spectinomycin, and streptomycin. Strains of S dysgalactiae were more likely to have intermediate resistance to oxytetracycline and streptomycin than were strains of S agalactiae and S uberis, which were highly resistant to oxytetracycline and streptomycin (P < 0.001). Differences were not detected among the streptococcal species with respect to resistance to spectinomycin. Resistance to multiple antimicrobials was observed in all streptococcal species tested. Although S dysgalactiae appeared to have a greater percentage of strains (73%) that were resistant to multiple antimicrobials than did S agalactiae (31%) or S uberis (45%), differences were not statistically significant.

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four ratio (T4 ratio) to increase from 50% to 75%. After recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered IV, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded. Within 1 minute of gentamicin administration, the mean +/= SD T1 response decreased from 49 +/- 5% to 33 +/- 8% of baseline and the T4 ratio decreased from 28 +/- 19% to 14 +/- 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 +/- 6% of baseline and a T4 ratio of 13 +/- 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 +/- 7% of baseline and the T4 ratio had increased to 21 +/- 13%. The time for recovery significantly (P less than 0.03) increased from 9.9 +/- 3.4 minutes during the control study to 18.1 +/- 10.7 minutes during the gentamicin study. In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium.

Gentamicin sulfate, equivalent to 4 mg of gentamicin base/kg of body weight, was administered IV to 6 Thoroughbred foals on day 1 (12 to 24 hours of age) and at 5, 10, 15, and 30 days after birth. On day 40 after parturition, gentamicin was given to the mares at a dosage similar to that used in foals. Decay of serum gentamicin concentrations was best described by a 2-compartment model. Among foals, the overall elimination rate constant at 30 days of age was significantly (P less than 0.05) greater than at days 1, 10, and 15. There was, however, no difference in the overall elimination rate constant between foals and mares. The volume of distribution (Vd), determined on the basis of total area under the disposition curve, did not change between day 1 and day 30. Mean values of Vd of foals were between 1.5 and 2.5 times higher than the mean Vd of the mares; however, only values from the foals at days 5 and 10 were significantly greater. Both age and interindividual differences were reflected in the total body clearance (ClB) of gentamicin. Total body clearance of gentamicin of foals on day 1 was less than that of foals on days 5, 10, and 30. Additionally, ClB of gentamicin on day 15 was less than that on day 30. There was no significant difference between ClB of foals and mares except for the day-30 group, which had a higher clearance rate than did the adults. Protein binding of gentamicin was less than 30% in all groups, and there were no apparent age-related differences.

Streptococcal species isolated from dairy cows with clinical mastitis were obtained from mastitis research workers in Florida, Louisiana, New York, Vermont, Washington, and West Virginia. Seventy-one streptococcal isolates were tested, including 39 strains of Streptococcus agalactiae, 21 strains of S dysgalactiae, and 11 strains of S uberis. The minimal inhibitory concentration of erythromycin, lincomycin, oxytetracycline, penicillin, spectinomycin, streptomycin, and tetracycline was determined for each isolate. Differences were not detected among strains with respect to geographic origin. None of the strains was resistant to penicillin. Lincomycin was the next most effective antimicrobial, with only 2 resistant strains of each streptococcal species. There were no differences among the streptococcal species with respect to resistance to either penicillin or lincomycin. Streptococcus uberis was more likely to be resistant to erythromycin than were S agalactiae and S dysgalactiae (P < 0.02). Streptococcus agalactiae and S uberis had similar distributions for resistance to oxytetracycline, tetracycline, spectinomycin, and streptomycin. Strains of S dysgalactiae were more likely to have intermediate resistance to oxytetracycline and streptomycin than were strains of S agalactiae and S uberis, which were highly resistant to oxytetracycline and streptomycin (P < 0.001). Differences were not detected among the streptococcal species with respect to resistance to spectinomycin. Resistance to multiple antimicrobials was observed in all streptococcal species tested. Although S dysgalactiae appeared to have a greater percentage of strains (73%) that were resistant to multiple antimicrobials than did S agalactiae (31%) or S uberis (45%), differences were not statistically significant.

Previous work indicated that adult Ancylostoma caninum can be removed from experimentally infected dogs, using a formulation of milbemycin oxime at dosage of 0.5 mg/kg of body weight. To determine the efficacy of this treatment in dogs naturally infected with adult hookworms, 24 mixed-breed dogs with patent hookworm infections were purchased from an out-of-state vendor, and 6 male and 6 female dogs were assigned to either a control group or a group that would be treated. Dogs were treated 10 days after their arrival and were euthanatized 1 week after treatment. Beginning 3 days before treatment, fecal samples were collected daily from all dogs, and the number of Ancylostoma eggs per gram of dry weight of feces was determined from each sample. By 1 week after treatment, the mean number of eggs being passed by the treated dogs had dropped from 12,700 to 10 eggs/g of dried feces; there was no apparent change in fecal egg counts for dogs of the control group. At necropsy, the mean number of adult A caninum in dogs of the treated and control groups was 1.3 and 56, respectively; in these naturally infected dogs, efficacy of treatment was calculated to be 97.8%. The mean number of adult Trichuris vulpis recovered in dogs of the control and treated groups at necropsy was 24 and 0, respectively, which yielded treatment efficacy of 100%. Although Uncinaria stenocephala and Toxocara canis appeared also to be removed by use of this dosage, too few dogs were in the study to calculate meaningful efficacies. The milbemycin oxime formulation appeared to have no effect on the cestodes (Taenia pisiformis and Dipylidium caninum) and spirurids (Physaloptera rara) that were present in some dogs.

The effect Of bovine mammary secretion during the nonlactating period and of antibiotic preparations on bovine polymorphonuclear neutrophil (PMN) phagocytic function and morphology were evaluated in a series of in vitro multifactorial experiments. Benzathine cloxacillin (CL), benzathine cephapirin (CE), sodium novobiocin (NO), and a combination of dihydrostreptomycin with procaine penicillin G (DP) were prepared in the presence and absence of a peanut oil aluminum monostearate vehicle. The PMN were isolated from bovine blood, and the effect of each antibiotic preparation on PMN function and morphology was evaluated in a buffer, fat, skim, and a combination of fat with skim from bovine mammary secretion during the nonlactating period. The fat and skim were diluted with buffer to approximate their concentration in mammary secretion. Phagocytic functions of PMN were monitored by fluorescent microscopy, which made it possible to estimate both ingestion and intracellular killing of bacteria by PMN. Changes in PMN morphology were monitored by transmission electron microscopy. The ability of PMN to ingest and kill Staphylococcus aureus ATCC 25923 was significantly decreased by fat, skim, CL, CE, NO, and DP. Effects of some antibiotics on ingestion and killing of bacteria by PMN were influenced by the addition of vehicle and by interactions with mammary secretion. Neutrophil morphology was altered by fat, skim, CL, CE, NO, and DP. The detrimental effects of CL, CE, NO, and DP on PMN morphology were influenced (some significantly) by the presence of vehicle and interactions with mammary secretion. There were significant correlations among secretion- and antibiotic-induced changes in PMN ingestion of bacteria, PMN killing of bacteria, and PMN morphology.

The effects of 2 antibiotic preparations administered intramammarily on phagocyte recruitment, function, an morphology were evaluated at the beginning of the nonlactating period. Twelve cows with no clinical or micro biologic evidence of mastitis were assigned to 1 of 2 treatment groups. At the end of lactation, 1 of the antibiotic preparations was infused in a fore- and hind quarter of each cow; the remaining quarters were untreated controls. One group was given benzathine cephapirin; the second group was given sodium novobiocin. Secretion samples were collected from 1 treated and 1 control quarter at 16 hours, and from the remaining 2 quarters at 64 hours after treatment. Total and differential somatic cell counts were determined, and morphology of mammary polymorphonuclear neutrophils (PMN) and macrophages was observed by transmission electron microscopy. In vitro ingestion and killing of Staphylococcus aureus by mammary PMN and macrophages were assessed by fluorescent microscopy, using acridine orange stain. Cells resident in a fixed volume of secretion were incubated with a known concentration of S aureus. Total cell and PMN concentrations were higher in treated than in control quarters. Neutrophils were the predominant cell type in both treated and control quarters over the sampling period. As measured in this study, in vitro ingestion and killing of S aureus by individual PMN from treated quarters was reduced. Antibiotic treatment also increased the proportion of morphologically abnormal phagocytes. There were significant correlations among PMN ingestion, killing, and morphology. However, increased PMN concentrations tended to compensate for the reduced phagocytic function of individual cells. Therefore, efficacy of antibiotic treatment of nonlactating cows may depend, at least in part, on increased PMN concentration, which may tend to compensate for reduced phagocytic function. Compared with PMN, macrophages appeared to have only a minor role in phagocytosis of bacteria.