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Metronidazole Dosage For Ulcerative Colitis

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Predictors Of Response To Steroids

Metronidazole Antibiotics – Mechanism of Action, Indications, and Side Effects

Response to steroids is indicated by improvement in patients symptoms and improved laboratory parameters .

At day 3 of admission, response to steroids should be measured by assessing stool frequency and CRP levels .1). In the landmark study by Travis et al, which included patients with 51 episodes of severe UC, presence of more than 8 stools/d or 3-8 stools/d plus a CRP > 45 mg/L at day 3 predicted a colectomy rate of 85%. In another prospective study by Lindgren et al which included 97 episodes of severe UC, the following mathematical model was devised to predict colectomy: number of stoolsd + 0.14 × CRP 8 predicted a colectomy rate of 72%.

Algorithm for treatment decisions for patients with acute severe ulcerative colitis on intensive steroid therapy. AZA: Azathioprine.

Therefore regular assessment of response to steroids is of paramount importance in treating patients with acute severe UC. In a group of 80 patients who underwent emergency colectomy for severe UC between 1994 and 2000 in Oxford, patients with signicantly longer duration of preoperative medical therapy were more likely to have major post-operative complications.

The Role Of The Microbiome In Ibd

Gut flora comprises an enormously complex microenvironment, with the microbial genome outnumbering the human genome by at least an order of magnitude . The majority of gut microbiota has never been cultured, and the advancement in our understanding of its complex role has only begun to flourish with the development of newer culture-independent technologies. Adding to the complexity of this microenvironment is the uncertain role of other members of this microbial community including fungi and bacteriophages.

Indirect support for the role of gut flora in IBD pathogenesis is provided by fecal stream diversion improving disease activity in CD, with restoration of fecal stream inducing recurrence. This does not occur, however, when ileostomy effluent is filtered to remove bacteria prior to reintroduction . Ileal microflora undergoes significant expansion on restoration of contiguity with colonic remnant, however the microbial pattern in patients with CD varies significantly from that of patients without CD upon restoration of fecal flow, with significantly higher counts of E coli and bacteroides in patients with CD, as compared to higher counts of bifidobacteria and ruminococci amongst controls .

Before Taking This Medicine

You should not use this medicine if you are allergic to metronidazole, secnidazole, or tinidazole, or if:

  • you drank alcohol in the past 3 days

  • you consumed foods or medicines that contain propylene glycol in the past 3 days or

  • you took disulfiram within the past 14 days.

May harm an unborn baby. Do not use metronidazole to treat trichomoniasis during the first trimester of pregnancy. Tell your doctor if you become pregnant.

Not all uses of metronidazole are approved for treating children and teenagers. Metronidazole is not approved to treat vaginal infections in girls who have not begun having menstrual periods.

To make sure you can safely take this medicine, tell your doctor if you have ever had:

  • kidney disease

  • a heart rhythm disorder

  • a stomach or intestinal disease such as Crohn’s disease

  • a blood cell disorder such as anemia or low white blood cell counts

  • a fungal infection anywhere in your body or

  • a nerve disorder.

Metronidazole has caused cancer in animal studies. However, it is not known whether this would occur in humans. Ask your doctor about your risk.

You should not breastfeed within 24 hours after using metronidazole. If you use a breast pump during this time, throw out the milk and do not feed it to your baby.

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Metronidazole In Crohn’s Disease And Ulcerative Colitis

Last edited 06/2019

  • antibacterials, such as metronidazole and ciprofloxacin, may be prescribed in the treatment of fistulating Crohn’s Disease to treat accompanying abscesses or in perianal Crohn’s Disease or sepsis
  • antibiotics, including metronidazole, are indicated in
    • the treatment of symptoms attributable bacterial overgrowth
    • perineal disease
  • significant side-effects of metronidazole include peripheral neuropathy if used long term , a bad taste in the mouth and a disulfiram-like interaction with alcohol
  • antibiotics such as ciprofloxacin have also been used in the place of steroids to treat moderate relapses of ulcerative colitis

NICE suggest :

  • to maintain remission in people with ileocolonic Crohn’s disease who have had complete macroscopic resection within the last 3 months, consider azathioprine in combination with up to 3 months’ postoperative metronidazole

Reference:

  • Prescriber 15.
  • Prescribers’ Journal 37: 232-42

Active Fistulizing Perianal Cd

Metronidazole Dosage For Cats

Active fistulizing perianal CD is likely the most frequent indication for antibiotics in IBD management. Oral ciprofloxacin with or without metronidazole can be used as an adjunct to immunosuppressant therapy, usually anti-TNF. This is usually continued for 3 weeks with extension of the antibiotic course as required.

Recommended Reading: How To Diagnose Gastric Ulcer

Evidence For Antibiotics In Perianal Cd

Antibiotics have long been used in clinical practice for active perianal CD however the evidence remains relatively limited. Three randomized placebo controlled trial have been performed, two of which assessed antibiotics in combination with biological therapy . One small RCT comparing metronidazole, ciprofloxacin and placebo was too underpowered to detect any statistically significant effect . Ciprofloxacin as an adjunct to infliximab had a higher response than infliximab alone , and was also found to be significantly better as adjunct to adalimumab .

A large open label trial assessed response of perianal disease to ciprofloxacin or metronidazole in addition to azathioprine at 8 weeks, prior to expected azathioprine efficacy. Half of patients had a significant improvement in perianal disease scores .

Topical metronidazole ointment was assessed in an RCT and while both groups had the same mean reduction in perianal CD activity index scores, more patients applying metronidazole ointment had at least 5 point reduction in the score , significantly reduced perianal discharge and a trend to less perianal pain .

Pooled analysis of ciprofloxacin in perianal CD demonstrates efficacy in reducing fistula drainage but not for fistula healing . These results suggest that antibiotics should be used as adjunctive therapy for perianal CD, but not as sole therapy .

How Should I Use Metronidazole

Take metronidazole exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Metronidazole oral is taken by mouth. The injection is given as an infusion into a vein. A healthcare provider will give you the injection if you are unable to take the medicine by mouth.

Shake the oral suspension . Measure a dose with the supplied measuring device .

Swallow the extended-release tablet whole and do not crush, chew, or break it.

If you are treating a vaginal infection, your sexual partner may also need to take metronidazole so you don’t become reinfected.

Metronidazole is usually given for up to 10 days in a row. You may need to repeat this dosage several weeks later.

Keep using this medicine even if your symptoms quickly improve. Skipping doses could make your infection resistant to medication. This medicine will not treat a viral infection .

Metronidazole will not treat a vaginal yeast infection. You may even develop a new vaginal yeast infection, which may need to be treated with antifungal medication. Tell your doctor if you have symptoms such as itching or discharge during or after treatment with this medicine.

Do not share this medicine with another person, even if they have the same symptoms you have.

This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using this medicine.

Store at room temperature away from moisture and heat.

Also Check: How To Get Remission In Ulcerative Colitis

Flagyl Dosage For Bacterial Infections

Flagyl treats a wide range of infections caused by anaerobic bacteria, which is bacteria that can live without oxygen. Gastrointestinal infections including Helicobacter pylori and Clostridium difficile infections, skin infections including acne and rosacea, some respiratory infections, endocarditis , septicemia , dental and oral infections, abdominal infections, bone infections, joint infections, brain and spinal cord infections, and gynecological infections are commonly caused by anaerobic bacteria.

Metronidazole is also used to heal intestinal abscesses caused by Crohns disease or ulcerative colitis. Many infections will be treated with a combination of metronidazole and another antibiotic, such as amoxicillin. A severe infection may be initially treated with a large intravenous injection of metronidazole, the active ingredient in Flagyl, followed by daily dosing with Flagyl.

  • Standard adult dosage: 7.5 mg/kg taken every six hours for seven to 10 days

  • Maximum adult dosage: No more than 4 grams per day

Asc And Chronic Refractory Colitis

Metronidazole | mechanism of action and side effects

Given the inconsistent data and the high-risk nature of ASC, antibiotics are not currently routinely recommended in UC. However it is reasonable to consider an oral antibiotic cocktail of amoxicillin, metronidazole, doxycycline and vancomycin if standard therapies have failed. In ASC this is usually considered if refractory to IV steroids, however salvage therapy or colectomy should never be delayed while trialing this approach.

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Flagyl Dosage For Amoeba Infections

Flagyl is approved for amoeba infections of the intestines and liver . Because metronidazole kills amoebas only in their growing stage, other drugs are required to kill the amoebas at other stages in their life cycle.

  • Standard adult dosage: 750 mg taken every eight hours for 5 to 10 days for intestinal amebiasis or 500750 mg taken every eight hours for 5 to 10 days for amebic liver abscess

What Interacts With Flagyl

As with all medicines, Flagyl may cause possible drug interactions that will limit taking other types of prescription drugs. People taking Flagyl should not drink alcohol or take disulfiram during treatment. Metronidazole has been reported as causing psychotic reactions in people taking disulfiram.

Metronidazole can increase the toxicity of some drugs, such as busulfan and lithium, so therapies may have to be adjusted. The blood-thinning properties of warfarin and similar anticoagulant drugs are increased by metronidazole, so the dosages will need to be modified.

Some drugs, such as cimetidine , interfere with the bodys ability to eliminate metronidazole, leading to an increase in the plasma concentrations of metronidazole. As a result, the likelihood and severity of temporary side effects, such as nausea, diarrhea, constipation, and a metallic taste in the mouth, can increase. These interactions also increase the likelihood of severe adverse effects such as peripheral neuropathy , encephalopathy, or meningitis.

Dosages will also need to be adjusted when metronidazole is taken with prescription drugs, such as phenytoin , that speed up the bodys elimination of metronidazole.

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Antibiotics In Inflammatory Bowel Diseases: Do We Know What Were Doing

Oren Ledder1,2

The Hebrew University of Jerusalem , , Israel

Correspondence to:

Abstract: Despite the revolution in inflammatory bowel disease treatment over the past two decades with the advent of biological therapies, there remains a substantial proportion of patients with inadequate or unsustained response to existent therapies. The overwhelming focus of IBD therapeutics has been targeting mucosal immunity, however with the developing evidence base pointing to the role of gut microbes in the inflammatory process, renewed focus should be placed on the impact of manipulating the microbiome in IBD management. This review provides an overview of the evidence implicating bacteria in the pathogenesis of gut inflammation in IBD and provides an overview of the evidence of antibiotics in IBD treatment. We also suggest a potential role of antibiotics in clinical practice based on available evidence and clinical experience.

Keywords: Inflammatory bowel disease antibiotics

Submitted Oct 11, 2018. Accepted for publication Nov 26, 2018.

doi: 10.21037/tp.2018.11.02

Investigations Required At Admission

Metronidazole For Uti Treatment

In addition to monitoring patients clinical feature and vital signs, all patients should have their full blood counts, liver and kidney function tests, electrolytes including serum magnesium and inflammatory markers . At least 3 stool samples for Clostridium difficile toxin should be obtained to rule out superimposed pseudo-membranous colitis. A plain abdominal X-ray should be done to exclude megacolon. Plain radiograph can also provide information about the extent of disease and can also predict response to treatment. The distal distribution of fecal residue can provide a rough estimate of disease extent as it correlates with the proximal extent of disease. The predictors of poor response to treatment on a plain abdominal radiograph are presence of mucosal islands which are small, circular opacities that represent residual mucosa isolated by surrounding ulceration, or presence of more than two gas-filled loops of small bowel. Flexible unprepared sigmoidoscopy with minimal air insufflation should be performed to confirm the diagnosis and exclude superimposed infection, especially cytomegalovirus colitis. Endoscopic markers of severe disease activity include hemorrhagic mucosa with deep ulceration, mucosal detachment on the edge of these ulcerations, and well like ulcerations.

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Switching Between Infliximab And Cyclosporin

In cases of non-response to infliximab or cyclosporin, switching to either therapy is associated with significant morbidity and mortality and is not recommended. In the largest study of 86 patients on this aspect, 65 patients were administered infliximab after cyclosporin and 21 patients had cyclosporin after infliximab. Thirty three percent patients underwent colectomy within 3 mo and 1/3rd of the patients had adverse effects in form of infections.

Flagyl Dosage For Pets

Metronidazole is not approved for use in animals, but a veterinarian may prescribe this drug to a pet to treat bacterial or protozoal infections such as giardiasis, trichomoniasis, or balantidiasis, or inflammatory bowel disease. Dose amounts will depend on the animals weight. Doses will be given orally one to three times a day for three to ten days depending on the medical condition being treated.

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Antibiotics And Ibd: The Evidence

IBD is a diverse condition with response to treatment dependent on multiple interrelated variables. To assess antibiotics in IBD as a whole, or even overall in CD or UC independently, is overly simplistic and will not reflect the true effect in specific circumstances. Hence we have attempted to review the role of antibiotics in more specific scenarios.

Evidence relating to efficacy of therapeutic interventions generally depends on a number of large, high quality randomized controlled trials . Due to the relatively low number of high quality studies in antibiotics, and the high variability in antibiotics trialed, treatment course and outcome measures, drawing firm conclusions remains difficult.

Further complicating attempts at analysis of existent data is the potential diverse conclusions drawn from individual studies. For example, in the seminal Australian antibiotic RCT of anti-MAP combination therapy including over 200 patients followed for 3 years , the primary endpoint of prolonged relapse-free course out to 3 years was not met, however the antibiotic group had a higher 16-week remission rate , and a clear trend to lower 12 months and 24 months relapse rate . However, considering that the antibiotic course was specifically tailored to target MAP, concerns were raised regarding possible underdosing of antibiotics, lack of pre-treatment testing for MAP, and levels of antibiotic resistance, further casting a doubt on the applicability of the evidence .

Evidence For Antibiotics In Ulcerative Colitis

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Induction of remission in active ulcerative colitis

A number or RCT and uncontrolled studies have been reported on antibiotics for induction of remission in chronically active and acute severe colitis . Multiple different antibiotic combinations were trialed with very different outcomes reported, ranging from dramatic induction of complete remission, through to no response.

Two meta-analyses demonstrate overall higher remission rates with antibiotics compared to placebo . Considering the diverse range of antibiotics trialed, different methods of administration and course length, and the vastly divergent responses, interpretation of the data is limited, and recommendations for clinical practice is difficult to formulate. Indeed it is unclear whether it is appropriate to pool studies with a diverse assortment of antibiotics.

Interestingly, upon independent analysis of the trials a striking contrast is revealed. Those trials in which antibiotics were administered orally seemed to have a greater response than those in which they were administered intravenously. It may be that the effect of the antibiotics is by way of a local luminal effect, possibly effecting beneficial change on the microbiome, or as has been suggested, by direct effect on a particular pathogen .

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Gut Microbiota And Ibd

The adult gut ecosystem contains trillions of organisms from over 1000 species, with the most abundant species being from the Firmicutes and Bacteroidetes phyla. Changes in gut bacterial population occur over time, and depend on age, diet, hygiene, climate, geography and ethnicity. Nowadays over 25 diseases or syndromes have been linked to an altered intestinal microbiome. There is abundant data confirming the importance of gut microbiota in the inflammatory process that exists in IBD. For example, genetically engineered mice deficient in the cytokines IL-2 and IL-10 or rats containing the HLA-B27 transgene are protected from colitis in the germ-free state, but develop IBD upon reconstitution of normal gut flora, thus implying that colitis depends on the presence of gut bacteria.

There is also ongoing debate whether mucosa attached bacteria play a more important role than luminal bacteria in the propagation of IBD. Mucosal surfaces of IBD patients were found to be densely colonized with Bacteroides fragilis.

When To Get Treatment

An increase in inflammation causes a flare, and the nature of inflammation means that you should treat it as quickly as you can. Inflammation grows exponentially, because inflammation itself causes an increase in inflammation. The longer you leave it untreated, the worse it will get. In addition, untreated inflammation not only leads to the symptoms associated with ulcerative colitis, it can also increase your risk of developing complications such as colorectal cancer down the line. Pay attention to your symptoms, and visit your physician if you notice that they change or increase even a small amount.

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Antibiotic Treatment For Cd

The greatest number of clinical studies concerning antibiotic treatment for IBD has been conducted on patients with CD. Antibiotics can be used to treat primary active disease including: luminal disease and fistulizing disease, and they may be used for secondary septic complications such as abscesses, post operative infections or even for the maintenance of remission. Different antibiotics have been evaluated in clinical trials, most often ciprofloxacin, metronidazole , rifaximin, clarithromycin and anti-tuberculous regimens.

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