A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea

Shmalberg, Justin; Montalbano, Christina; Morelli, Giada; Buckley, Gareth

doi:10.3389/fvets.2019.00163

Cited by 40 publications

(45 citation statements)

References 56 publications

(96 reference statements)

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“…We compared FMT to metronidazole in this study because, while acute uncomplicated diarrhea is often self-limiting, treatment with antibiotics is still initiated in 50% to 71% of patients in practice (2,3). Just recent data would suggest that there is limited clinical benefit of giving metronidazole over placebo as both treatments had similar outcomes in clinical signs (4,5), but both studies did not report effects on the microbiota and metabolome (4,5). Therefore, future studies should also include comparisons between FMT and placebo to evaluate whether FMT treatment has improved outcomes in the metabolome and microbiota.…”

Section: Discussionmentioning

confidence: 99%

“…Only very recent studies have examined whether administration of antimicrobials does lead to shorter duration of diarrhea, and the results remain unclear. While one study has shown metronidazole to shorten duration of acute diarrhea (mean duration 2.1 vs. 3.6 days for placebo), another study did not reveal statistical differences in the duration of diarrhea when dogs were treated either with a probiotic (mean duration 3.5 days) metronidazole (4.6 days), or placebo (4.8 days) (4,5).…”

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole

Chaitman¹,

Ziese²,

Pilla

et al. 2020

Front. Vet. Sci.

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The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole

Chaitman¹,

Ziese²,

Pilla

et al. 2020

Front. Vet. Sci.

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“…Acute diarrhea, including acute hemorrhagic diarrhea syndrome is frequently encountered in dogs and cats. This condition is commonly treated with metronidazole, but several recent publications suggest that the disease is typically self-limiting and that probiotic administration can result in as rapid a resolution of clinical signs as antimicrobial therapy (55,56). It has been argued that in the absence of sepsis, antimicrobial therapy is not justified for management of acute diarrhea in small animals (57).…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Prescribing Practices in Small Animal Emergency and Critical Care

et al. 2020

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Background: Antimicrobial use contributes to emergence of antimicrobial resistance. It was hypothesized that antimicrobial prescribing behavior varies between the emergency (ER) and critical care (CC) services in a veterinary teaching hospital. This study aimed to: (i) describe antimicrobial prescribing patterns in the ER and CC services; (ii) assess adherence to stewardship principles; (iii) evaluate the prevalence of multidrug resistant (MDR) bacterial isolates. Methods: Institution electronic medical records were queried for all antimicrobial prescriptions from the ER and CC services between 1/1/2017 and 12/31/2017. Prescriptions were manually reviewed, and the following data recorded: drug, dosage, duration, diagnosis, outcome, hospitalization duration, culture submission, and susceptibility results. Results: There were 5,091 ER visits, of which 3,125 were not transferred to another service. Of these emergency visits, 516 (16.5%) resulted in 613 antimicrobial drug prescriptions. The most commonly prescribed drugs for the ER were amoxicillin/clavulanate (n = 243, 39.6%), metronidazole (n = 146, 23.8%), and ampicillin/sulbactam (n = 55, 9.0%). The most common reasons for antimicrobial prescriptions were skin disease (n = 227, 37.0%), gastrointestinal disease (n = 173, 28.2%), and respiratory disease (n = 50, 8.2%). For ER patients 18 cultures were submitted, equivalent to a 3.5% submission rate. The CC service managed 311 case visits for 822 patient days. Of these, 133 case visits (42.7%) resulted in 340 prescriptions. The most commonly prescribed drugs for the CC service were ampicillin/sulbactam (n = 103, 30.3%), enrofloxacin (n = 75, 22.1%), and metronidazole (n = 59, 17.4%). The most common reasons for antimicrobial prescriptions were gastrointestinal disease (n = 106, 31.2%), respiratory disease (n = 71, 20.9%), and sepsis (n = 61, 17.9%). On the CC service, 46 patients had ≥1 culture submitted, equivalent to a 34.6% submission rate. Of patients prescribed antimicrobials, 13/38 (34%) with urinary tract disease, 2/28 (7%) with pneumonia, 1/11 (9%) with canine infectious respiratory disease complex and 2/8 (25%) with feline upper respiratory infection were compliant with published guidelines. Robbins et al. Antimicrobial Prescribing Emergency Critical Care Conclusions: Antimicrobial prescription was common in both ER and CC services and followed similar patterns. Adherence to published guidelines for urinary and respiratory infections was poor.

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“…Owners also maintained fecal scoring logs (Supplementary File S2) using the Bristol scoring system (Supplementary File S3), and a laminated copy of the Bristol fecal chart was provided to owners to aid in fecal scoring. This scoring system has not been validated in dogs, but it has been validated and utilized extensively in humans and it shares many similarities with other non‐validated scoring scales that have been used in studies of diarrheic dogs . Briefly, fecal scores could range from 1 to 7, with scores of ≤4 considered to be non‐diarrheic .…”

Section: Methodsmentioning

confidence: 99%

“…Beyond its antimicrobial activity, metronidazole possesses immunomodulatory and anti‐inflammatory properties that further add to its appeal for treating intestinal disorders . However, controlled studies of metronidazole treatment of acute diarrhea are limited, and it is unknown if metronidazole alters the clinical course of disease . The commonplace usage of antibiotics for treating a self‐limiting condition raises concerns regarding appropriate antimicrobial stewardship because this practice could promote bacterial resistance .…”

Section: Introductionmentioning

confidence: 99%

Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo‐controlled clinical trial

Langlois

Koenigshof

Mani

2019

Veterinary Internal Medicne

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Background: Metronidazole is commonly administered to dogs with acute diarrhea, but there is limited evidence to support this practice.Objective: To investigate the effects of metronidazole administration on dogs with acute nonspecific diarrhea.Animals: Thirty-one dogs, including 14 test population dogs and 17 controls.Methods: Randomized controlled clinical trial. Dogs with acute diarrhea in which causation was not determined by routine fecal diagnostic testing were randomly assigned to metronidazole treatment (10-15 mg/kg PO q12h for 7 days) or placebo.Fecal cultures and characterization of Clostridium perfringens isolates also were performed. Owners maintained medication and fecal scoring logs, and fecal diagnostic tests were repeated on day 7.Results: The mean ± SD time to resolution of diarrhea for test population dogs (2.1 ± 1.6 days) was less than that for controls (3.6 ± 2.1 days, P = .04). Potential relationships of C. perfringens with acute diarrhea pathogenesis were not investigated, but only 3 of 13 (23.1%) test population dogs had persistent C. perfringens carriage at day 7, which was less than the 11 of 14 (78.6%) controls with persistent growth (P = .007).Conclusions and Clinical Importance: Our results suggest that metronidazole treatment can shorten duration of diarrhea and decrease fecal culture detection of C. perfringens in some dogs with acute nonspecific diarrhea. Additional studies are needed to assess the benefits and risks of routine use of metronidazole for this purpose because most dogs achieve resolution of diarrhea within several days regardless of treatment.

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A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea

Cited by 40 publications

References 56 publications

Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole

Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole

Antimicrobial Prescribing Practices in Small Animal Emergency and Critical Care

Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo‐controlled clinical trial

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