Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations.

The antibiotic polymyxin B sulfate is a cationic polypeptide with a unique cyclical configuration and distinct cationic characteristics. In this investigation, polymyxin B was evaluated to determine its ability to prevent synthesis of lactic acid and tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide-stimulated strain RAW 2647 macrophage-like cell populations. In this context, gradient concentrations of polymyxin B were formulated in the presence of fixed concentrations of lipopolysaccharide fractions from Escherichia coli (B4:0111), E. coli (J5), Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella minnesota, and S. typhimurium (Re). Quantitation of TNF-alpha was established by the application of a tissue culture-based biological assay system, using the WEHI 164 clone 13 indicator cell line. Investigations also included evaluation of the ability of gradient concentrations of lipopolysaccharide fractions from E. coli (B4:0111), E. coli (J5), K. pneumoniae, P. aeruginosa, S. minnesota, and S. typhimurium (Re) to form a complex with polymyxin B. This was established through application of high-performance thin-layer chromatography techniques. On the basis of the known molecular characteristics of lipopolysaccharide, its lipid A-core subfractions, and polymyxin B, these results imply that cytoprotective properties of polymyxin B are attributable to direct interaction and subsequent complex formation. More specifically, the mechanism by which polymyxin B exerts affinity for lipopolysaccharide fractions is proposed to occur through attractive ionic interactions established between the cationic diaminobutyric acid residues of polymyxin B and the mono- or diphosphate group(s) of the lipid A-core moiety. It is highly probable that this molecular phenomenon is accompanied by hydrophobic interactions established between the terminal methyloctanoyl or methylheptanoyl groups of polymyxin B and the saturated carbon chains of the lipid A-core subfraction of lipopolysaccharide fractions.

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.

Sixteen 7-week-old Holstein male calves were inoculated with sporulated oocysts of Eimeria zuernii. Four calves (controls) were euthanatized and necropsied at 14 and 20 days after inoculation (DAI). Two calves were treated with 20 mg of dexamethasone (IM) on 13, 14, and 15 DAI and euthanatized and necropsied 17 DAI and 2 calves were given similar treatments and necropsied 20 DAI. The 8 other calves were euthanatized and necropsied 20 DAI. Two were started on the anticoccidial drug decoquinate in feed 13 DAI; 2 others were given decoquinated on the same schedule plus dexamethasone on 13, 14, and 15 DAI. Two calves were given the antibiotic narasin in feed beginning 13 DAI and 2 calves were given parasin on the same schedule plus dexamethasone on 13, 14, and 15 DAI. All calves, except 2 controls necropsied 14 DAI and 4 calves given decoquinate, discharged moderate-to-large numbers of oocysts in feces and had moderate-to-severe changes in fecal consistency. Histologic examintions revealed large numbers of endogenous stages in tissues of calves treated or not treated with dexamethasone. Few endogenous stages were observed in tissues from calves that were given decoquinate or decoquinate plus dexamethasone. Calves given narasin or narasin plus dexamethasone had moderate-to-large numbers of endogenous stages in the tissues.

Resistance of gram-negative bacteria to gentamicin has become an increasingly common problem among clinical isolates from human beings. Susceptibility of isolates from horses to gentamicin and amikacin was evaluated for the period from July, 1983 to June, 1985. All isolates of Escherichia coli, and species of Enterobacter, Klebsiella, Proteus, and Pseudomonas examined were susceptible to amikacin, except 2 of the 46 Pseudomonas isolates. In contrast, 13 to 50% of isolates were resistant to gentamicin. Escherichia coli, and Klebsiella, Proteus, and Enterobacter species isolates were highly significantly more susceptible to amikacin (P less than 0.01) than to gentamicin. Pseudomonas spp (P = 0.13) were not significantly different in susceptibility to the 2 drugs. There was significant variation among genera in their susceptibility to gentamicin (P = 0.002), primarily because of the frequency of resistance in isolates of Klebsiella spp and Proteus spp, compared with the other 3 organisms (E coli, Enterobacter spp, and Pseudomonas spp). There was no significant difference of susceptibility to amikacin among the genera studied (P = 0.06).

The effect that topical administration of cyclosporine would have on the number and type of microorganisms isolated from the corneal surface of dogs with keratoconjunctivitis sicca was studied. Schirmer tear tests were performed on and corneal swab specimens were collected from 61 eyes of 31 dogs with keratoconjunctivitis sicca prior to and after 3, 6, and 12 months of treatment with cyclosporine. In eyes that responded to cyclosporine treatment (Schirmer tear test value increased by greater than or equal to 5 mm/min, compared with pretreatment value), the percentage of eyes from which bacteria were isolated after 3, 6, and 12 months of treatment was significantly (P < 0.001) less than the percentage from which bacteria were isolated prior to treatment. However, among eyes that did not respond to treatment, we did not detect a significant change over time in prevalence of bacteria or type of bacteria isolated. The percentage of eyes from which fungi were isolated decreased during treatment; however, the small number of eyes in which fungal culture results were initially positive precluded demonstration of a significant change. For all eyes, we did not detect any significant differences over time in the frequency with which specific bacterial genera were isolated, with the exception of beta-hemolytic Streptococcus spp. Opportunistic corneal infections were not detected even though none of the dogs received antibiotics. An increase in production of tears, which contain anti-infection proteins, was believed to be the primary factor responsible for the decrease in the percentage of eyes from which microorganisms could be isolated.