Remission of Histiocytic Ulcerative Colitis in Boxer Dogs Correlates with Eradication of Invasive Intramucosal Escherichia coli

Background: Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology.
Hypothesis: Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission.
Animals: Seven Boxer dogs with HUC.
Methods: Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli .
Results: Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7±3.06 mg/kg q24 h, for 9.5±3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17–62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed.
Conclusions and Clinical Relevance: The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli .     

Treatment response and long term follow up in nineteen dogs diagnosed with chronic enteropathy in Australia

Chronic enteropathy (CE) in dogs is common worldwide, but little data is available from Australia. The aim of this study was to describe treatment response and long‐term outcome in a cohort of dogs with CE. Dogs were prospectively enrolled at Murdoch University and the University of Melbourne. After diagnostic investigation to rule out diseases other than CE, dogs underwent sequential therapeutic trials until achieving a clinical response (diet then antibiotics, and finally immunosuppressants). Success was defined as 75% reduction of clinical severity for a minimum of five weeks. A total of 21 dogs were enrolled, and 19 completed the study. One dog was euthanised for lack of response to treatment and one excluded for lack of owner compliance. Most dogs responded to diet (n = 10), followed by antibiotics (n = 7) and immunosuppressants (n = 2). Long‐term remission (median 21.1 months, [3.0‐44.7]) was achieved in eight out of ten dietary responders without additional treatment. In contrast, only two dogs with antibiotic response remained in long‐term remission, of which one needed on‐going antibiotic treatment. Longer term remission was achieved in the two dogs treated with immunosuppressants with on‐going low dose therapy. This study concludes that most dogs referred for CE in Australia respond to dietary treatment (even after previous dietary interventions), and remission is long‐term compared to dogs treated with an antibiotic. Furthermore, the need for long‐term antibiotics in some dogs to maintain response may lead to antibiotic resistance. This study supports adequate dietary trials for CE in dogs, and a need for alternative second‐line treatments.     

Fecal polymerase chain reaction with 16S ribosomal RNA primers can detect the presence of gastrointestinal Helicobacter in dogs

Questions about pathogenesis and therapy for Helicobacter infections in dogs could be answered with a simple, noninvasive, sensitive, and specific diagnostic test. We hypothesized that a fecal polymerase chain reaction (PCR) assay would detect Helicobacter and could be useful for assessing therapeutic responses. Paired gastric biopsies and fecal samples were obtained from 39 random source dogs (group 1). Gastric biopsies from each of these dogs had histologic evidence of gastric spiral bacteria, and paired gastric tissue and fecal samples produced a 375-base pair (bp) product when amplified by PCR with Helicobacter-specific primers. Specificity of the PCR product was confirmed by detection of expected 60-, 119-, and 196-bp products following Hinfl digestion. Direct sequencing of amplicons from paired PCR products from gastric biopsy and fecal samples from 8 group I dogs showed that gastric products had the highest homologies with known gastric Helicobacter species, whereas fecal products had the highest homologies with intestinal species. Healthy mixed-breed dogs (group II; n = 8) with histologically confirmed spiral bacteria infection were treated with a 21-day course of metronidazole, amoxicillin, and famotidine. Fecal samples were collected from group II dogs twice before and within 3 days of completion of treatment. The PCR results correctly identified 15/16 pretreatment samples as positive: 1 pretreatment sample was negative. PCR results identified 8/8 posttreatment samples as Helicobacter negative. Fecal PCR is a useful test for detecting Helicobacter infection in dogs. This assay may be useful as a screening test for infection and could be used to address questions relevant to pathogenesis and therapy.     

Histiocytic ulcerative colitis in a French bulldog

A 9-month-old French bulldog was referred for signs of chronic large bowel diarrhea. The dog had an increased frequency of defecation, tenesmus and hematochezia. Flexible colonoscopy showed hyperemia, irregularities and ulcerations with multifocal hemorrhages in the mucosa from the descending colon to the proximal rectum. Multiple colonic biopsies were characterized by infiltrations of PAS positive histiocytes in the lamina propria. A diagnosis of histiocytic ulcerative colitis (HUC) was made, and the animal showed only minimal improvement, although it was treated with nutritional and medical therapies. This is the second case of HUC in French bulldog, a breed which has ancestral relations to Boxer dogs.     

Treatment of aseptic dogs with hemorrhagic gastroenteritis with amoxicillin/clavulanic acid: a prospective blinded study

Background: Antibiotics generally are recommended to treat hemorrhagic gastroenteritis (HGE). Inappropriate use of antibiotics may promote risk of antimicrobial resistance and unnecessary adverse drug reactions. The necessity of antimicrobial therapy in dogs with HGE has not been demonstrated. Objective: The purpose of this prospective, placebo‐controlled, blinded study was to evaluate whether treatment with amoxicillin/clavulanic acid improves the clinical course and outcome of HGE in dogs that show no signs of sepsis. Animals: The study included 60 dogs diagnosed with HGE between 2007 and 2009 at the Clinic of Small Animal Medicine, LMU University of Munich, Germany. The inclusion criterion was the presence of acute hemorrhagic diarrhea (<3 days). Dogs pretreated with antibiotics, with signs of sepsis, or diagnosed with any disease known to cause bloody diarrhea were excluded from the study. Methods: Patients were randomly divided into treatment (amoxicillin/clavulanic acid for 7 days) and placebo groups. To evaluate treatment efficacy, severity of clinical signs (based on a newly developed HGE index), duration of hospitalization, and mortality rate were compared between the 2 groups. Results: Fifty‐three of 60 dogs completed the study. No significant difference between treatment groups concerning mortality rate, dropout rate, duration of hospitalization, or severity of clinical signs, either on any individual day or over the course of disease, was observed. Conclusions and Clinical Importance: In some dogs with HGE that show no signs of sepsis, antibiotics may not change the case outcome or time to recovery.     

Hematogenous septic arthritis in the dog: results of five patients treated nonsurgically with antibiotics

This retrospective study evaluates the effectiveness of nonsurgical treatment using antibiotics to treat hematogenous septic arthritis in five dogs. Giant-breed dogs were over-represented, with all dogs <1 year of age. Synovial fluid cultures were positive in all cases, with common bacterial species isolated that included Streptococcus B-haemolytic spp., Pasteurella multocida, and Staphylococcus intermedius. Dogs treated with appropriate duration and selection of antibiotics had clinical resolution with no residual deficits. This report and a previous clinical report demonstrate that hematogenous septic arthritis can be successfully treated nonsurgically with antibiotic therapy.     

Histiocytic ulcerative colitis in three non-boxer dogs

Histiocytic ulcerative colitis (HUC) is described in three non-boxer dogs. Clinical signs were typical of large-bowel diarrhea and included soft stool, hematochezia, tenesmus, and an increased frequency of defecation. Diagnosis in each case was made by light microscopic evaluation of endoscopically obtained colonic biopsy specimens. Treatment regimes varied, but included immunosuppressive agents, anti-inflammatory drugs, antimicrobials, and dietary modification. Clinical response was substantial in two patients, while the third patient was euthanized due to treatment failure. The authors' observations indicate that HUC may be encountered in non-boxer dogs.     

Antimicrobial susceptibility of canine Clostridium perfringens strains from Switzerland

Fifty Clostridium perfringens strains were isolated from individual dogs with acute diarrhoea that were not given antibiotics. Toxin types and minimal inhibitory concentrations of 15 antibiotics were determined for each of them. All strains harboured the alpha-toxin gene, 12 of them had both the alpha- and entero-toxin gene and 5 had both the alpha- and beta2-toxin gene. Eighteen percent of the isolates showed resistance to tetracycline and 54 % showed decreased susceptibility to metronidazole which is one of the most frequently used antibiotics in the treatment of canine diarrhoea. Apart from that, all isolates were susceptible to the remaining antibiotics tested. These findings lead to the conclusion that despite a general susceptibility to antibiotics in C. perfringens, resistance is developing in isolates from dogs. Therefore, careful identification of the pathogenic agent and antibiotic susceptibility testing should be performed prior to therapy in order to minimise further selection of antibiotic resistance.     

Evaluation of the ability of colistin,amoxicillin (components of Potencil®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Escherichia coli is one of the major pathogens in humans and animals causing localized and systemic infections, which often lead to acute inflammation, watery diarrhea, and hemorrhagic colitis. Bacterial lipopolysaccharide (LPS) and Shiga exotoxins (Stx) are mostly responsible for such clinical signs. Therefore, highly effective treatment of E. coli infections should include both eradication of bacteria and neutralization of their toxins. Here, for the first time, we compared the in vitro ability of common antibiotics to decrease LPS‐ and Stx‐mediated cytotoxicity: colistin, amoxicillin (used separately or combined), enrofloxacin, and its metabolite ciprofloxacin. Three experimental scenarios were realized as follows: (a) the direct effect of antibiotics on endotoxin, (b) the effect of antibiotic treatment on LPS‐mediated cytotoxicity in an experiment mimicking “natural infection,” (c) the effect of antibiotics to decrease Stx2e‐mediated cytotoxicity. Two cell lines, A549 and Vero cells, were used to perform cytotoxic assays with the methyl tetrazolium (MTT) and lactate dehydrogenase leakage (LDH) methods, respectively. Colistin and amoxicillin, especially used in combination, were able to attenuate LPS toxic effect, which was reflected by increase in A549 cell viability. In comparison with other antibiotics, the combination of colistin and amoxicillin exhibited the highest boster or additive effect in protecting cells against LPS‐ and Stx2e‐induced toxicity. In summary, in comparison with fluoroquinolones, the combination of colistin and amoxicillin at concentrations similar to those achieved in plasma of treated animals exhibited the highest ability to attenuate LPS‐ and Stx2e‐mediated cytotoxicity.     

Influence of antibiotic therapy on serum levels of reactive oxygen species in ovariectomized bitches

This study was conducted on 60 ovariectomized bitches. The objectives were to measure the mean reactive oxygen species (ROS) concentrations before, during and after surgery, and to investigate the effect of the administration of five different antibiotic treatments: amoxicillin, benzylpenicillin/dihydrostreptomycin, sulfametazine/sulfamerazine/sulfathiazole, enrofloxacin, lincomycin/spectinomycin. The first value recorded represented the mean ROS concentration in anestral bitches and constitutes a reference level with which to compare the subsequent measurements. After premedication, induction of anesthesia and during maintenance and surgery, ROS serum concentrations showed constant values until the end of surgery. After surgery and during antibiotic administration, an increase in ROS concentration occurred, which differed among the five groups in relation to the antibiotics employed. The lowest increases occurred in the groups treated with the combination of lincomycin/spectinomycin, and with amoxicillin; whereas the highest increases were detected in the group treated with enrofloxacin. The three other antibiotics showed an intermediate level of influence on oxidative status.     

Antibiotic susceptibility of bacteria isolated from infections in cats and dogs throughout Europe (2002–2009)

A monitoring program of the pre-treatment susceptibility of clinical isolates of bacteria from diseased dogs and cats was active between the years 2002 and 2009. Susceptibility of each isolated strain to a panel of nine antibiotics (amoxicillin/clavulanic acid, ampicillin, penicillin, clindamycin, doxycycline, enrofloxacin, marbofloxacin, trimethoprim and trimethoprim/sulfamethoxazole) was assessed. The Minimum Inhibitory Concentration (MIC) of marbofloxacin was also determined by a standardized microdilution technique following CLSI recommendations. In total, 1857 bacterial strains were collected throughout Europe from cases of otitis, respiratory, urinary and dermatological infections. Although bacterial susceptibility varied for each of the antibiotics within the panel, patterns of susceptibility were similar to those described in the literature for comparable time periods and geographical areas. With a clinical resistance varying from 0 to 14.48% against the isolated strains, marbofloxacin susceptibility was very high and remains an effective antibiotic for the treatment of otitis, urinary, respiratory and dermatological infections in companion animals.     

Efficacy of tulathromycin or enrofloxacin for initial treatment of naturally occurring bovine respiratory disease in feeder calves

After undergoing arrival processing at one of two commercial feedlots, feeder calves with clinical signs of bovine respiratory disease (BRD) were randomly assigned to receive either tulathromycin (2.4 mg/kg SC) or enrofloxacin (12.5 mg/kg SC). Additional therapy for calves that did not respond to initial treatment followed a prescribed course. Initial treatment with tulathromycin resulted in significantly higher (P = .009 and P = .031 at sites 1 and 2, respectively) therapeutic success (87.9% and 80%, respectively) than did initial treatment with enrofloxacin (70.2% and 62.5%, respectively). Animals treated with tulathromycin also had fewer subsequent treatments and higher weight gains compared with those treated with enrofloxacin.     

Effect of triple therapy on eradication of canine gastric helicobacters and gastric disease

Nine helicobacter-positive pet dogs with upper gastrointestinal signs were studied to evaluate the effect of a triple therapy, normally applied to humans for the eradication of gastric helicobacters, on clinical signs and gastric histology, as well as the recurrence of helicobacters after eradication in an extended follow-up in four dogs. Endoscopy was performed at entry to the study and repeated after eradication therapies and additional treatments. If the triple therapy (amoxycillin, metronidazole and bismuth subcitrate) failed, tetracycline and omeprazole were prescribed. Additional therapies were instituted if clinical signs persisted after eradication therapies. Helicobacter status was verified from gastric biopsy specimens by the urease test and histological examination, and in a few dogs also by brush cytology. Triple therapy eradicated gastric helicobacters in 7/9 dogs; gastric helicobacters were also eradicated in one dog treated with tetracycline and omeprazole. Eradication of helicobacters resulted in significant improvement, but not total resolution, of clinical signs. Subsequent additional therapies resulted in further alleviation of clinical signs. Neither triple therapy nor additional therapies had a significant effect on gastric histological changes. Gastric helicobacters recurred in 4/4 dogs within three years of the eradication treatment. Because canine gastric helicobacters alone were not definitively shown to induce clinical signs, routine eradication therapy seems not to be warranted at present.     

Estimation of the clinical and economic consequences of non-compliance with antimicrobial treatment of canine skin infections

The goal of this study was to estimate the health and economic consequences of non-compliance with oral antimicrobial treatment in dogs with superficial pyoderma, wounds or abscesses in the US. A mathematical model (Markov model) which simulated treatment with long-term injectable cefovecin versus oral amoxicillin/clavulanic acid was developed and accounted for the effect of non-compliance on clinical outcomes and mean total treatment costs per patient. Efficacy parameters considered in the model were derived from clinical studies. Treatment failure due to oral antimicrobial treatment non-compliance was approximated from published data at 13.6%. US cost data for 2009 were derived from public sources. When non-compliance was considered as a cause of treatment failure with oral medication, the long-term injectable antibiotic was more effective than oral comparator (162 versus 158 days without clinical signs). Mean total treatment costs were lower with cefovecin (USD 376.74) versus amoxicillin/clavulanic acid (USD 382.34) in dogs of 25 kg; and cefovecin remained cost-saving up to a body weight of 31 kg. In large dogs, cefovecin was more costly; however, total therapy costs were less than 6% greater than with amoxicillin/clavulanic acid. Accordingly the higher drug and administration costs of the long-term injectable antibiotic were totally or substantially offset when non-compliance was considered as reason for treatment failure with oral medication. The model also allowed for the estimation of the impact of various non-compliance scenarios.     

Efficacy and long-term outcome of gastritis therapy in cheetahs (Acinonyx jubatus).

A prospective clinical trial evaluating efficacy and long-term outcome of treatments for lymphoplasmacytic gastritis in cheetahs (Acinonyx jubatus) was conducted. The study evaluated efficacy of 11 different antibiotic and antiinflammatory treatment protocols in 32 cheetahs (19 male, 13 female) for reducing gastric inflammation and Helicobacter colonization and monitored the course of disease through histologic grading of gastric biopsies. All cheetahs were biopsied up to I wk before treatment and then rebiopsied within 1 mo after treatment. Most animals were reassigned to a second treatment regimen within 6 mo. Each animal received from one to three treatments during the study period. After the trial, gastric biopsies were obtained from each cheetah annually until death or transfer from the facility to assess disease progression. The trial and follow-up period spanned 10 yr. At onset of the trial, all 32 cheetahs had some degree of gastritis, and 26 cheetahs (81%) were colonized with Helicobacter. Inflammatory lesions worsened regardless of treatment or the presence of Helicobacter. No treatment had a significant effect on inflammatory changes except the lansoprazole/clarithromycin/amoxicillin treatment group, which produced a short-term decrease in inflammation when compared to controls. Prednisone had no effect on gastric inflammation. Overall, 65% of colonized cheetahs were initially cleared of histologic evidence of Helicobacter by treatment, with short-term eradication occurring in 100% of the animals treated with omeprazole/clarithromycin/amoxicillin or tetracycline/metronidazole/Pepto-Bismol for 28 days. Long-term follow-up of treated animals in this study clearly demonstrated that these treatments had little effect on life-long progression of gastritis or on Helicobacter burden in individual cheetahs, although some treatments provided short-term reduction in gastritis and Helicobacter. These results provide evidence that Helicobacter alone is not the cause of gastritis in cheetahs and do not support the use of antibacterial treatments in cheetahs unless significant clinical signs (e.g., frequent vomiting/regurgitation, weight loss) are apparent.     

Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases

The currently recommended treatment for metronidazole toxicosis is drug discontinuation and supportive therapy. Reported recovery times are 1-2 weeks. The records of 21 dogs with metronidazole toxicosis were retrospectively analyzed to determine whether diazepam improved recovery. The dosage and duration of metronidazole therapy and the response and recovery times of 13 dogs treated with diazepam were compared to those of 8 dogs receiving only supportive care. Response time was defined as the time to resolution of the debilitating clinical signs. Recovery time was the time to resolution of all residual clinical signs. The average dosage and duration of metronidazole administration for the diazepam-treated and untreated groups were 60.3 mg/kg/d for 44.9 days and 65.1 mg/kg/d for 37.25 days. The protocol for diazepam administration consisted of an initial i.v. bolus and then diazepam PO q8h for 3 days. The average dosage of both the i.v. and PO diazepam was 0.43 mg/kg. The average response time for the diazepam-treated dogs was 13.4 hours compared to 4.25 days for the untreated group. Recovery time also was markedly shorter for the diazepam-treated dogs (38.8 hours) compared to the untreated group (11 days). Results of this study showed that dogs with metronidazole toxicosis recover faster when treated with diazepam. Although the mechanism of metronidazole toxicosis or how diazepam exerts its favorable effect is not known, it is likely related to modulation of the gamma-aminobutyric acid (GABA) receptor within the cerebellar and vestibular systems.     

Cutaneous actinomycosis and nocardiosis in dogs: 48 cases (1980-1990).

Medical records of 48 dogs with cutaneous actinomycosis or nocardiosis were reviewed. Male, large-breed dogs kept outdoors were overrepresented. The mean age at admission was 3.6 years. Cutaneous swelling (68%), abscesses (65%), draining tracts (48%), fever (36%), and signs of pain (13%) were the most common clinical findings. The cervicofacial area was affected in 48% of the dogs. Abdominal and thoracic wall involvement was less common. Leukocytosis, neutrophilia with left shift, monocytosis, and hyperglobulinemia were common. The diagnosis was confirmed by cytologic examination, bacteriologic culture, or histologic examination. Gram-positive filamentous bacteria were seen in 69% of the fine needle aspirates and in 50% of the biopsy specimens. Actinomyces spp were isolated from cutaneous lesions in 27 (60%) dogs. Nocardia asteroides was isolated from 1 dog. Treatment consisted of surgical debridement, drainage, and administration of antibiotics in 29 dogs (group A) and antibiotics alone in 13 dogs (group B). The infection redeveloped in 10 (42%) group-A dogs and 6 (60%) group-B dogs. Of the 10 group-A dogs with recurrent infection, 6 had resolution after a second surgery and 4 were euthanatized. Of the 6 group-B dogs, 1 had resolution after surgery, 4 were euthanatized or died because of persistent disease, and 1 had an unresolved infection. The combination of surgery and antibiotic treatment appeared to be superior to antibiotic treatment alone in resolving cutaneous Actinomyces and Nocardia infections.     

Susceptibility to vancomycin and other antibiotics of 165 Enterococcus strains isolated from dogs in Italy

The prevalence of antibiotic resistance, with special attention to vancomycin, in 165 Enterococcus strains isolated from dogs subjected or not to previous antibiotics treatment(s) was determined. For each strain, the minimum inhibitory concentration (MIC) to 9 antibiotics was assessed. All strains were sensible to vancomycin. High frequencies of resistance to erythromycin, tetracycline, rifampicin, and enrofloxacin were detected. E. faecium strains isolated from dogs subjected to antibiotic treatment were more resistant to tetracycline with respect to control dogs. Although enterococci from dog show a high degree of antibiotic resistance, they are sensitive to vancomycin. Therefore, the risk of transmission of vancomycin-resistant enterococcal strains from dogs to man is close to zero.     

Successful management of histiocytic ulcerative colitis with enrofloxacin in two Boxer dogs

Two Boxer dogs with histologically confirmed histiocytic ulcerative colitis were treated with enrofloxacin, one as sole therapy and one in conjunction with prednisolone, after failure of standard therapy. Clinical remission occurred rapidly in both dogs after commencement of enrofloxacin and in one case where repeat colonoscopy was performed the endoscopic appearance of the mucosa was normal within 2 weeks. Histological examination of the colonic mucosa in this dog after 7 months showed resolution of the cellular infiltration characteristic of histiocytic ulcerative colitis. Histological improvement following therapy in Boxer dogs with histiocytic ulcerative colitis has not been reported previously.