C-reactive protein as a tool for monitoring response to treatment in dogs with acute hemorrhagic diarrhea syndrome

ObjectivesC-reactive protein (CRP) is an established marker for systemic inflammation in dogs that is especially elevated in dogs with sepsis. Some dogs with acute hemorrhagic diarrhea syndrome (AHDS) develop bacterial translocation and consequent sepsis during hospitalization. This study aimed to evaluate the course of CRP plasma concentrations during hospitalization and its correlation with clinical and other laboratory variables in dogs with AHDS.MethodsIn this prospective, observational study, CRP was evaluated on days 0, 1, 2, and 3 in 27 client-owned dogs who presented with AHDS. Clinical examination data, blood pressure, acute patient physiologic and laboratory evaluation (APPLE) full and APPLE fast scores, and canine hemorrhagic diarrhea severity (CHDS) index were measured on the same days to evaluate the severity of the disease.ResultsTwenty-five of the 27 dogs were discharged from hospital. Nineteen dogs received antimicrobial treatment due to sepsis or neutropenia. CRP values were mildly elevated on day 0 (median 27.3 mg/L; 1.0–125.8 mg/L) and markedly elevated on day 1 (median 88.9 mg/L; 1.4–192.7 mg/L). CRP concentrations decreased gradually over the following days. Moreover, CRP concentrations correlated moderately with albumin, leucocyte count, neutrophil count, and APPLE full and fast scores, but not with antimicrobial treatment.Conclusion and relevanceCRP concentrations were significantly elevated in patients with AHDS. In this study population, CRP did not help in detecting the requirement of antimicrobial treatment in dogs with AHDS. Nevertheless, as CRP can monitor the response to treatment, regular analysis can guide treatment

Utility of diagnostic tests in vomiting dogs presented to an internal medicine emergency service

IntroductionVomiting is a common sign in dogs presenting to emergency services. It can be self-limiting, a sign of a life-threatening extraintestinal, or intestinal disorder. Reasonable diagnostics should be performed to determine the underlying cause. This study aimed to assess the utility of diagnostic tests in vomiting dogs, and its correlation with patient history, and physical examination results. Additionally, parameters to differentiate uncomplicated vomiting from complicated vomiting were investigated.MethodsIn this prospective, observational, clinical study, data from 99 client-owned dogs with vomiting, presenting as first opinion cases, were evaluated. History, physical examination, duration of clinical signs, overall number of episodes of vomiting, appetite, and additional clinical signs were recorded. The standardized diagnostic evaluation of all patients included venous blood gas analysis, complete blood count, serum biochemistry profile, canine pancreatic lipase, abdominal radiographs, ultrasound, and urinalysis. Follow-up was performed 4–5 days later. Based on severity of disease and clinical course, dogs were categorized to “uncomplicated vomiting” (UN), or “complicated vomiting” (COM). The utility of each test for diagnosing the cause of vomiting was evaluated. Spearman correlation coefficient, Chi-squared-, unpaired t-, and Mann–Whitney U-test were used. Statistical significance was defined as p ≤ 0.05.ResultsOut of the 99 dogs, 34 had uncomplicated courses of disease (UN). In 60/99 cases, a diagnosis was obtained, and in 39/99 cases, the cause for vomiting remained unknown. Longer duration of clinical signs, and reduced appetite were associated with higher utility of abdominal ultrasound. A poor mentation was associated with a higher utility of blood examinations and abdominal radiographs. Dogs presenting with an impaired mentation or with additional clinical signs other than diarrhea, were more likely to be in the COM group.DiscussionBased on this investigation, general recommendations concerning the diagnostic approach for patients with vomiting could not be provided. For dogs who have exclusively vomiting as a clinical sign, and present in good mentation, further investigations might not be beneficial, and these dogs may recover with symptomatic treatment alone. Additional diagnostics could be indicated in dogs with additional clinical signs other than diarrhea

The Effect of Metronidazole versus a Synbiotic on Clinical Course and Core Intestinal Microbiota in Dogs with Acute Diarrhea

The usefulness of antibiotics in dogs with acute diarrhea (AD) is controversial. It is also unclear what effect metronidazole has on potential enteropathogens such as Clostridium perfringens and Escherichia coli. Thus, the aim of this study was to evaluate the effect of metronidazole vs. a synbiotic on the clinical course and core intestinal bacteria of dogs with AD. Twenty-seven dogs with AD were enrolled in this prospective, randomized, blinded clinical trial and treated with either metronidazole (METg) or a synbiotic (SYNg; E. faecium DSM 10663; NCIMB 10415/4b170). The Canine Acute Diarrhea Severity (CADS) index was recorded daily for eleven days. Bacteria were quantified using qPCR. Data were analyzed using mixed models with repeated measures. A higher concentration of E. coli was observed in the METg group vs. the SYNg group on Day 6 (p < 0.0001) and Day 30 (p = 0.01). Metronidazole had no effect on C. perfringens. C. hiranonis was significantly lower in the METg group than in the SYNg group on Days 6 and 30 (p < 0.0001; p = 0.0015). No significant differences were observed in CADS index, fecal consistency, or defecation frequency between treatment groups (except for the CADS index on one single day). In conclusion, metronidazole negatively impacts the microbiome without affecting clinical outcomes. Thus, synbiotics might be a preferred treatment option for dogs with AD

Comparison of the Gut Microbiome between Atopic and Healthy Dogs—Preliminary Data

Human studies show that in addition to skin barrier and immune cell dysfunction, both the cutaneous and the gut microbiota can influence the pathogenesis of atopic diseases. There is currently no data on the gut-skin axis in allergic canines. Therefore, the aim of this study was to assess the bacterial diversity and composition of the gut microbiome in dogs with atopic dermatitis (AD). Stool samples from adult beagle dogs (n = 3) with spontaneous AD and a healthy control group (n = 4) were collected at Days 0 and 30. After the first sampling, allergic dogs were orally dosed on a daily basis with oclacitinib for 30 days, and then re-sampled. Sequencing of the V3–V4 region of the 16S rRNA gene was performed on the Illumina MiSeq platform and the data were analyzed using QIIME2. The atopic dogs had a significantly lower gut microbiota alpha-diversity than healthy dogs (p = 0.033). In healthy dogs, a higher abundance of the families Lachnospiraceae (p = 0.0006), Anaerovoracaceae (p = 0.006) and Oscillospiraceae (p = 0.021) and genera Lachnospira (p = 0.022), Ruminococcustorques group (p = 0.0001), Fusobacterium (p = 0.022) and Fecalibacterium (p = 0.045) was seen, when compared to allergic dogs. The abundance of Conchiformibius (p = 0.01), Catenibacterium spp. (p = 0.007), Ruminococcus gnavus group (p = 0.0574) and Megamonas (p = 0.0102) were higher in allergic dogs. The differences in alpha-diversity and on the compositional level remained the same after 1 month, adding to the robustness of the data. Additionally, we could also show that a 4-week treatment course with oclacitinib was not associated with changes in the gut microbiota diversity and composition in atopic dogs. This study suggests that alterations in the gut microbiota diversity and composition may be associated with canine AD. Large-scale studies preferably associated to a multi-omics approach and interventions targeting the gut microbiota are needed to confirm these results

Effect of amoxicillin‐clavulanic acid on clinical scores, intestinal microbiome, and amoxicillin‐resistant Escherichia coli in dogs with uncomplicated acute diarrhea

Background Despite limited evidence of efficacy, antibiotic treatment is still frequently prescribed in dogs with uncomplicated acute diarrhea (AD). Objective To assess whether amoxicillin‐clavulanic acid has a clinical benefit, an effect on the fecal microbiome, and the proportion of amoxicillin‐resistant Escherichia coli in dogs with AD. Animals Sixteen dogs with AD of <3 days duration. Methods Prospective, placebo‐controlled, double‐blinded study. Clinical scores were compared between client‐owned dogs randomly assigned to an antibiotic (AG) or a placebo (PG) group. The intestinal microbiome was analyzed using quantitative PCR assays. Amoxicillin‐resistant fecal E. coli were assessed semiquantitatively with microbiological methods. Results There was no difference in clinical recovery between treated dogs or controls (CADS index day 10: AG group median: 2 (range: 1‐3; CI [1.4; 2.6]); PG group median: 1.6 (range: 1‐3; CI [1.1; 2.4]); P > .99). All dogs gained normal clinical scores (CADS index ≤3) after 1 to 6 days (median 2 days) after presentation. There was no significant difference in the fecal dysbiosis index (during treatment: AG mean −2.6 (SD 3.0; CI [−5.1; 0.0]); PG mean −0.8 (SD 4.0; CI [−4.2; 2.5]; P > .99) or its bacterial taxa. The proportion of resistant fecal E. coli increased (to median: 100%; range: 35%‐100%) during treatment with amoxicillin‐clavulanic acid and was still increased (median: 10%; range 2%‐67%) 3 weeks after treatment, both of which were significantly higher proportions than in the placebo group for both time points (during treatment AG median 100% versus PG median 0.2% (P < .001); after treatment AG median 10% versus PG median 0.0% (P = .002)). Conclusions and Clinical Importance Our study suggests that treatment with amoxicillin‐clavulanic acid confers no clinical benefit to dogs with AD, but predisposes the development of amoxicillin‐resistant E. coli , which persist for as long as 3 weeks after treatment. These findings support international guideline recommendations that dogs with diarrhea should not be treated with antimicrobials unless there are signs of sepsis

The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease.

Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal microbiome of dogs with defined disease phenotypes

Prevalence of Clostridioides difficile in Canine Feces and Its Association with Intestinal Dysbiosis

The role of Clostridioides (C.) difficile as an enteropathogen in dogs is controversial. In humans, intestinal bile acid-dysmetabolism is associated with C. difficile prevalence. The relationship between fecal qPCR-based dysbiosis index (DI) and especially the abundance of bile acid-converting Clostridium hiranonis with the presence of C. difficile in dogs was explored across the following 4 cohorts: 358 fecal samples submitted for routine diagnostic work-up, 33 dogs with chronic enteropathy, 14 dogs with acute diarrhea, and 116 healthy dogs. Dogs that tested positive for C. difficile had significantly higher DI (median, 4.4 (range from 0.4 to 8.6)) and lower C. hiranonis (median, 0.1 (range from 0.0 to 7.5) logDNA/g) than dogs that tested negative for C. difficile (median DI, −1 (range from −7.2 to 8.9); median C. hiranonis abundance, 6.2 (range from 0.1 to 7.5) logDNA/g; p < 0.0001, respectively). In 33 dogs with CE and 14 dogs with acute diarrhea, the treatment response did not differ between C. difficile-positive and -negative dogs. In the group of clinically healthy dogs, 9/116 tested positive for C. difficile, and 6/9 of these had also an abnormal DI. In conclusion, C. difficile is strongly linked to intestinal dysbiosis and lower C. hiranonis levels in dogs, but its presence does not necessitate targeted treatment

Long-term effects of canine parvovirus infection in dogs

Background Canine parvovirus (CPV) is the most important viral cause of acute canine enteritis leading to severe damage of the intestinal barrier. It has been speculated that dogs might develop chronic disorders after surviving CPV infection. However, no studies regarding the longterm implications of CPV infection have been published to date. The aim of this study was to evaluate whether dogs that have survived CPV infection will have an increased risk for developing chronic gastroenteritis, atopic dermatitis, or cardiac disease. Methodology/Principal findings Dogs that had been treated at the Clinic of Small Animal Medicine, LMU Munich, for CPV infection for which a follow-up of at least 12 months was available, were included in the study. Owners completed a questionnaire on the presence of chronic gastrointestinal and cutaneous signs, cardiac disease, and other potential disorders. An identical questionnaire was sent to owners of matched control dogs during the same time period. Seventy-one questionnaires of dogs with CPV infection and 67 of control dogs were analyzed. Significantly more CPV-infected dogs (30/71) compared to control dogs (8/67) had developed chronic gastrointestinal signs later in their lives (P < 0.001). No significant differences were observed regarding skin diseases (P = 1), cardiac problems (P = 0.160), or any other diseases (P = 0.173) later in life. Conclusions: Results of this study suggest that dogs that survive CPV infection have a significantly higher risk (odds ratio = 5.33) for developing a chronic gastrointestinal disease. Further prospective studies to identify the trigger for the development of chronic diarrhoea and possible targeted treatment strategies are needed

Proposal for rational antibacterials use in the diagnosis and treatment of dogs with chronic diarrhoea

Chronic diarrhoea is a frequent complaint in canine practice and the diagnostic path is often characterised by numerous diagnostic tests and stepwise empirical treatments, often applied before gastrointestinal (GI) endoscopy/mucosal biopsies. These include dietary interventions (novel protein, hydrolysed protein diet), parasiticides and still, in many cases, antibacterials. Indiscriminate use of antibacterial drugs risks detrimental consequences for both the individual patient (antimicrobial resistance, long-term disruption of intestinal bacterial populations, potential worsening of GI signs) and general public. For that reason, in this Perspective essay we advocate use of antibacterials only after histopathologic evaluation of GI biopsies or, for those cases in which endoscopy is not possible, after other therapeutic trials, such as diet/pre-probiotics or anti-inflammatory drugs have proven unsuccessful. They should be reserved, after appropriate dietary trials, for those canine chronic diarrhoeic patients with signs of true primary infection (i.e. signs of systemic inflammatory response syndrome or evidence of adherent-invasive bacteria) that justify antibacterial use