Clostridium difficile: prevalence in horses and environment,and antimicrobial susceptibility

REASONS FOR PERFORMING STUDY: Clostridium difficile has been associated with acute colitis in mature horses. OBJECTIVES: To survey C. difficile colonisation of the alimentary tract with age, occurrence of diarrhoea and history of antibiotic therapy; and to study the occurrence and survival of C. difficile in the environment and antimicrobial susceptibility of isolated strains. METHODS: A total of 777 horses of different breeds, age and sex were studied. Further, 598 soil samples and 434 indoor surface samples were examined. Antimicrobial susceptibility of 52 strains was investigated by Etest for 10 antibiotics. RESULTS: In horses that developed acute colitis during antibiotic treatment, 18 of 43 (42%) were positive to C. difficile culture and 12 of these (28%) were positive in the cytotoxin B test. Furthermore, C. difficile was isolated from a small number of diarrhoeic mature horses (4 of 72 [6%]) with no history of antibiotic treatment, but not from 273 healthy mature horses examined or 65 horses with colic. An interesting new finding was that, in normal healthy foals age < 14 days, C. difficile was isolated from 1/3 of foals (16 of 56 [29%]). All older foals (170) except one were negative. Seven of 16 (44%) nondiarrhoeic foals treated with erythromycin or gentamicin in combination with rifampicin were also excretors of C. difficile. On studfarms, 14 of 132 (11%) outdoor soil samples were positive for C. difficile in culture, whereas only 2 of 220 (1%) soil samples from farms with mature horses were positive for C. difficile (P = < 0.001). By PCR, it was demonstrated that strains from the environment and healthy foals can serve as a potential reservoir of toxigenic C. difficile. The experimental study conducted here found that C. difficile survived in nature and indoors for at least 4 years in inoculated equine faeces. The susceptibility of 52 strains was investigated for 10 antibiotics and all were susceptible to metronidazole (MIC < or = 4 mg/l) and vancomycin (MIC < or = 2 mg/l). CONCLUSIONS: C. difficile is associated with acute colitis in mature horses, following antibiotic treatment. Furthermore, C. difficile was isolated from 1 in 3 normal healthy foals age < 14 days. POTENTIAL RELEVANCE: Strains from healthy foals and the environment can serve as a potential reservoir of toxigenic C. difficile.     

Effects of alternation of drug classes on the development of oxibendazole resistance in a herd of horses.

Anthelmintic schedules that alternate between drug classes are widely used in horses. However, the results of investigations in which ovine nematode parasites were used have established that alternation of drug classes does not delay the development of drug resistance. This field study was designed to assess the effect of alternation of drug classes on the development of oxibendazole (OBZ) resistance in benzimidazole (BZD)-resistant equine small strongyles. A privately owned herd of horses was used for this study. These animals grazed the same pasture and had been treated with the same anthelmintic schedule for several years. Prior studies had determined that the animals were parasitized with BZD-resistant small strongyles. The herd was divided into 2 groups of 20 and 21 horses. Group-1 horses were given OBZ 6 times a year and had a total of 25 treatments with the drug. Group-2 horses were given OBZ 3 times a year, in alternation with non-BZD drugs, and had a total of 16 treatments. Statistical analysis revealed no difference between groups for the change in pretreatment fecal egg count following treatments 1, 4, 7, 10, 13, and 16. Alternation of drug classes did not effect the development of drug resistance in this trial. The efficacy of OBZ decreased with repeated treatments with the drug. By treatment 13, the efficacy, as evaluated by the fecal egg count reduction test, had decreased to less than 70% in both groups.     

Common helminth infections of donkeys and their control in temperate regions

Roundworms and flatworms that affect donkeys can cause disease. All common helminth parasites that affect horses also infect donkeys, so animals that co‐graze can act as a source of infection for either species. Of the gastrointestinal nematodes, those belonging to the cyathostomin (small strongyle) group are the most problematic in UK donkeys. Most grazing animals are exposed to these parasites and some animals will be infected all of their lives. Control is threatened by anthelmintic resistance: resistance to all 3 available anthelmintic classes has now been recorded in UK donkeys. The lungworm, Dictyocaulus arnfieldi, is also problematical, particularly when donkeys co‐graze with horses. Mature horses are not permissive hosts to the full life cycle of this parasite, but develop clinical signs on infection. In contrast, donkeys are permissive hosts without displaying overt clinical signs and act as a source of infection to co‐grazing horses. Donkeys are also susceptible to the fluke, Fasciola hepatica. This flatworm can be transmitted, via snails and the environment, from ruminants. As with cyathostomins, anthelmintic resistance is increasing in fluke populations in the UK. A number of the anthelmintic products available for horses do not have a licence for use in donkeys, and this complicates the design of parasite control programmes. As no new equine anthelmintic classes appear to be near market, it is important that the efficacy of currently effective drugs is maintained. It is important that strategies are used that attempt to preserve anthelmintic efficacy. These strategies should be based on the concept that the proportion of worms in a population not exposed to anthelmintic at each treatment act as a source of ‘refugia’. The latter is an important factor in the rate at which resistance develops. Thus, it is imperative that parasite control programmes take into account the need to balance therapy to control helminth‐associated disease with the requirement to preserve anthelmintic effectiveness.     

Suspected adverse drug reactions in 2004

We received 62 reports of suspected adverse events (SARs) for the year 2004. Their number and repartition according to affected animals and active substances were comparable with the previous year. The distributors or manufacturers submitted most of the declarations, but the proportion submitted by practicing veterinarians is slowly growing. 72% of the declarations dealt with adverse reactions in small animals (cats and dogs), followed by cattle and horses. Antiparasitics, anti-inflammatory drugs and immunologicals were the most frequently mentioned therapeutic classes, which are listed here according to the international ATCvet classification. A report from abroad about a fatality following injection of an antibiotic preparation for cattle prompted Swissmedic to review the security of this medication also sold on the Swiss market. It was decided to modify the package insert to warn about the danger of inadvertent self-injection in humans, to reduce the risk of similar accidents in Switzerland. We hope that the pharmacovigilance system will enjoy an increasing awareness by the practicing veterinarians.     

The consequences of generic marketing on antibiotic consumption and the spread of microbial resistance: the need for new antibiotics

In both human and veterinary medicine, it has been shown that flooding the market with different generics and/or ‘me‐too’ branded drugs has increased overall antibiotic consumption correlating with the emergence and spread of bacterial resistance to antibiotics. Another possible undesirable consequence of the promotion of generics is the promotion of an economic incentive that encourages the use of old drug products with very poor oral bioavailability, marketed with historical dosage regimens and extensively excreted in the environment. What veterinary medicine rather needs is new innovative and ‘ecofriendly’ antibiotics to actually enforce a more prudent use of antibiotics. For a pharmaceutical company, generics are inexpensive to manufacture and on a short‐term basis, the generic market is very appealing. However, on a long‐term basis, this marketing orientation provides a disincentive to the development of new and innovative products that will be required to meet the therapeutic needs of the veterinary community while being consistent with public health concerns. Indeed, for veterinary medicine, the key issue surrounding antibiotics is public health. It is the opinion of the authors that veterinary antibiotics and/or veterinary drug formulations should be innovative in terms of selectivity (no or minimal impact on the commensal gut flora), biodegradable (with minimal environmental disruption), and more expensive, with a strictly regulated market rather than unselective, cheap, and freely available drugs.     

Oral administration of tepoxalin in the horse: a PK/PD study

Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasma concentrations of tepoxalin were undetectable, whereas in fasting animals they were close to the limit of quantification of the method. No differences between the fasting/fed groups in RWJ-20142 plasma concentrations were shown. Tepoxalin showed a strong and long-lasting ex vivo inhibitory activity against cyclooxygenase (COX)-1, mainly due to its main metabolite RWJ-20142. Tepoxalin and RWJ-20142 do not seem to possess either COX-2 or 5-lipoxygenase inhibitory activity in the horse. These features suggest that the drug is a selective COX-1 inhibitor in horses, with no significant anti-inflammatory activity. Thus, its long term use in equine practice could be of concern.     

Subclinical leptospirosis may impair athletic performance in racing horses

The infection by Leptospira in horses, in both its acute disease and subclinical forms, is very common, particularly in endemic regions. Therefore, the objective of this study was to evaluate the effects of subclinical leptospirosis in the athletic performance of racing thoroughbred horses. Athletic performance of 119 racing Thoroughbred horses from Rio de Janeiro, Brazil, was calculated by assigning a point value for the results in racing (performance index (PI)), and serology for leptospirosis was conducted. A total of 85 (71.4?%) horses showed reactive titers (??100), and of which 52 had high titers (34 with 400 and 18 with ??800). Although those animals had high titers against Leptospira, no clinical signs associated with leptospirosis were observed. Seventeen (89.5?%) out of the 19 horses with substandard performance were seroreactive with high titers, in contrast with 35?% of seroreactivity in horses with good athletic performance (P?<?0.0001). Additionally, seroreactivity to leptospirosis was more often observed in horses with substandard athletic performance in contrast to those with good performance (P?<?0.0001, odds ratio 15.8). The Average PI of this group increased to 133?% after treatment (P?<?0.0001). Leptospirosis may impair performance in racing horses, and antibiotic therapy may improve the performance of affected animals.     

Chloramphenicol 3. Clinical pharmacology of systemic use in the horse

The use of chloramphenicol in the horse is now prohibited as horses are classified as food-producing animals. However, chloramphenicol has until recently been widely available for oral, intramuscular or intravenous administration. A critical appraisal of the published literature on the use of chloramphenicol in the horse clearly demonstrates that there are sound pharmacokinetic and microbiological reasons for concluding that chloramphenicol is not an appropriate antibiotic for systemic use. The short half-life of chloramphenicol in the horse, together with the broad range of minimum inhibitory concentrations of target pathogens, preclude the use of practical dosage regimens. It can be concluded that the withdrawal of chloramphenicol will have no adverse effects on chemotherapy in the horse.     

Effect of probenecid on disposition kinetics of ampicillin in horses.

The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present 25 hours after it was administered. The disposition kinetics of ampicillin were altered by the presence of probenecid and as a result the antibiotic had a slower body clearance (ClB; 109.4 +/- 6.71 ml/kg hours compared with 208.9 +/- 26.2 ml/kg hours) a longer elimination half-life (t1/2 beta 1.198 hours compared with 0.701 hours) and consequently a larger area under the plasma concentration versus time curve (AUC 92.3 +/- 5.09 mg/ml hours compared with 35.95 +/- 3.45 mg/ml hours) when compared with animals to which ampicillin was administered alone. The ampicillin concentrations observed suggest that the dosing interval for horses may be increased from between six and eight hours to 12 hours when probenecid is administered in conjunction with the ampicillin.     

Treatment of respiratory infections in horses with ceftiofur sodium.

Ceftiofur sodium was evaluated as a therapy for respiratory infections in horses. This cephalosporin antimicrobial was administered intramuscularly every 24 h and at a dose of 2.2 mg/kg (1.0 mg/lb) of body weight. The efficacy of ceftiofur sodium was compared with that of a positive control drug, ampicillin sodium (recommended dose of 6.6 mg/kg [3 mg/lb], given every 12 h). Both treatments were continued for 48 h after clinical symptoms were no longer evident (maximum of 10 days). Fifty-five (55) horses with naturally acquired respiratory infections were included in the study; 28 were treated with ceftiofur and 27 with ampicillin. Clinical improvement was recorded for 92.9% of the patients treated with ceftiofur and 92.6% of the animals receiving ampicillin. Both therapies reduced body temperatures to an afebrile level after 2 days of treatment. Complete recovery/cure was noted for 78.6% of the ceftiofur patients and 59.3% of the horses treated with ampicillin. Supporting variables (depression/malaise, respiration/dyspnoea, nasal discharge) were assessed and these also substantiated the effectiveness of the treatments. Both antibiotics were well tolerated. Neither pain nor swelling were noted at the ceftiofur injection site(s). None of the animals developed diarrhoea. Data from this study indicated that ceftiofur sodium is an effective and safe treatment for respiratory infections in horses.     

Current status of food animal antidotes.

The availability of antidotes in veterinary medicine has been an issue for more than a decade. Antidotes are available for food animals through extralabel use, regulatory discretion, and compounding. There is little economic incentive for pharmaceutical companies to pursue approval of antidotes and other drug products that have a small market. In addition, human food safety concerns must be addressed when approving antidotes for use in food animals. This article provides a brief history of antidote availability, current mechanisms for procuring food animal antidotes, and availability of specific antidotes for use in food animals.     

A non-lethal method for assessment of efficacy of antiparasitics against parasites in horses such as Anoplocephala perfoliata and Gasterophilus intestinalis

Sourcing of horses naturally infected with parasites such as Anoplocephala perfoliata and Gasterophilus intestinalis for antiparasitic efficacy slaughter studies is often difficult, expensive, and usually excessive numbers of animals must be slaughtered before significant data can be obtained. To overcome this problem a "Modified Critical Treatment Method" was developed. This method does not require the horses to be sacrificed, but relies on the collection and processing of all faecal material containing expelled parasites from test animals. Efficacy is assessed by comparing, in the same horses, the numbers of parasites expelled with the test compound with the total numbers removed with test and reference endectocides. This, for the most part, means that farms that were previously unavailable, e.g. studs, can now be used for the collection of efficacy data.     

Relationship of biosecuriy practices with the use of antibiotics for the treatment of infectious disease on U.S. equine operations

This study is the first report estimating, on a national basis, the use of various biosecurity practices, singly and in combination, on U.S. equine operations. Use of biosecurity practices is described for operations by risk level, based on reported exposure of resident horses to outside horses during the previous 12 months. In addition, the association between use of various biosecurity practices and use of antibiotics to treat infectious disease in both adult equids and foals is reported. The comparison of these study findings with previously reported data in the literature is limited by the fact that few estimates of biosecurity practice use on equine operations have been reported and none has been published on a national basis beyond those in the National Animal Health Monitoring System (NAHMS) equine reports. A total of 78.5% of operations had some risk of exposure of resident horses to outside horses between summer 2004 and the time of the interview in summer 2005. For the majority of biosecurity practices, there was a significant (p<0.05) difference between different exposure risk levels in the percentage of operations using the practice. A higher percentage of high- and medium-risk operations implemented a combination of 4 or more biosecurity practices compared to low-risk operations. There was less use of antibiotics to treat infectious disease in adult horses on operations that required those who visit the operation to use separate equipment, change clothes/overalls, disinfect boots and equipment, or park vehicles away from animals than on those that did not. None of the other biosecurity practices were associated with use of antibiotics in adult horses and none of the biosecurity practices included in this study was associated with use of antibiotics in foals. For adults the use of antibiotics for infectious disease increased with decreasing herd size; this trend was reversed for antibiotic use in foals. The effect of exposure risk level was different for adults and foals. For adults, antibiotic use was lower for operations at higher risk; for foals, antibiotic use was higher for operations at higher risk.     

Bacterial isolates and antimicrobial susceptibilities in equine bacterial ulcerative keratitis (1993--2004)

REASONS FOR PERFORMING STUDY: Bacterial ulcerative keratitis is a common and often vision-threatening problem in horses. Emerging bacterial resistance to commonly used topical antibiotics has been demonstrated. Previous antibiotic use may alter the antimicrobial susceptibility of bacterial isolates. OBJECTIVES: To document aerobic bacterial isolates and associated bacterial susceptibilities from horses with ulcerative keratitis treated at the University of Tennessee between January 1993 and May 2004 and determine whether prior antibiotic therapy affected antimicrobial susceptibility of the isolates. METHODS: Medical records from horses with ulcerative keratitis and positive aerobic bacterial cultures and antimicrobial susceptibility were evaluated. Clinical history regarding antibiotic therapy prior to culture was documented. RESULTS: Fifty-one aerobic bacterial isolates from 43 horses were identified. Streptococcus equi subspecies zooepidemicus was the most commonly isolated organism, accounting for 33.3% of all isolates, followed by Pseudomonas aeruginosa (11.8%), Staphylococcus spp. (11.8%) and Gram-negative nonfermenting rods (7.8 %). No resistance was noted amongst S. equi ssp. zooepidemicus to cephalothin, chloramphenicol or ciprofloxacin. Only 64 % of S. equi ssp. zooepidemicus isolates were sensitive to bacitracin. No resistance was noted among P. aeruginosa to gentamicin, tobramycin or ciprofloxacin. Antibiotic therapy with neomycin-polymixin B-bacitracin prior to presentation and culture was documented in 11/17 horses in which S. equi ssp. zooepidemicus was isolated and in 4/6 horses in which P. aeruginosa was isolated. Three horses received topical corticosteroids prior to culture, of which 2 had polymicrobial infections. CONCLUSIONS: S. equi ssp. zooepidemicus and P. aeruginosa were the most frequently isolated bacterial organisms in equine ulcerative keratitis. No significant trends in aminoglycoside or fluoroquinolone resistance were noted among these organisms. However, the resistance of S. equi ssp. zooepidemicus to bacitracin with common use of this antibiotic suggests that previous antibiotic therapy probably affects antimicrobial resistance. POTENTIAL RELEVANCE: Therapy prior to culture may play an important role in antimicrobial susceptibility of corneal bacterial isolates. Corticosteroid use may increase the risk of polymicrobial infections of corneal ulcers, leading to a worse prognosis. Although significant fluoroquinolone resistance has not been documented in the veterinary literature, these antimicrobials should be reserved for known infected corneal ulcers and not used for prophylaxis. Empirical antibiotic therapy should not only be guided by clinical signs, but also take into consideration previous antimicrobial and corticosteroid therapy.     

Carbon dioxide laser as a surgical instrument for sarcoid therapy--a retrospective study on 60 cases.

The objective of this retrospective clinical study was to evaluate the carbon dioxide laser in the treatment of single and multiple sarcoids in 60 animals (44 horses, 13 donkeys, 2 mules, and 1 pony). Only animals that had been operated on 6 mo or more ago were included. Recurrence, new manifestation rate, and cosmetic outcome were determined. Recurrence was observed in 23 (38%) individuals. Animals with new sarcoid manifestation with or without recurrence of a sarcoid were observed in 35 cases (58%). Cases of scar tissue formation and, rarely, leukotrichia were observed. Animals presented with multiple sarcoids were more predisposed to recurrence. Donkeys showed a significantly lower recurrence rate than horses.     

Caprine serum fraction immunomodulator as supplemental treatment of lower respiratory disease in the horse

Suppurative lower airway disease is a common debilitating disease in performance horses and, while rarely fatal, is often recalcitrant to conventional therapy. A variety of treatments have been used to combat this condition and we conducted two types of studies to determine if caprine serum fraction--immunomodulator (CSFI), a nonspecific immunomodulator, improved recovery from lower respiratory disease. Two dose response studies were performed to ascertain the efficacy of CSFI. Horses were maintained daily on conventional antibiotic therapy. Respiratory tract exudate, nasal discharge, dyspnoea, chest auscultation and cough frequency were monitored weekly. One hundred percent of the horses treated with 2 i.m. injections of either 60 or 120 mg CSFI one week apart showed significant improvement with each weekly evaluation and were fully recovered by week 3. Horses treated with 15 or 30 mg CSFI did not differ significantly from the control group. Only 10% of the control horses responded to conventional antibiotic therapy. An expanded field trial utilising 80 horses diagnosed with lower respiratory disease and housed at 4 equine clinics was conducted. Thirty-five percent of the 40 control horses, treated solely by conventional antibiotic therapies, recovered while 75% of the horses treated with a supplemental administration of 60 mg CSFI as described above recovered. The combined data from these studies showed that CSFI was able to promote an overall recovery from lower respiratory disease of 86%.