Recurrent Clostridium difficile-Associated Diarrhea and Colitis Treated with Sac

[Guest guest]

Hi All, I thought that you might find this interesting since this can happen

(as I know all to well) with strong or prolonged abx use.

Your Lyme Friend,

in VA

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From

Journal of the American Board of Family Practice

Recurrent Clostridium difficile-Associated Diarrhea and Colitis Treated with

Saccharomyces cerevisiae (Baker's Yeast) in Combination with Antibiotic

Therapy

A Case Report

J. Kovacs, MD, Ted Berk, MD, FACP, Carlisle Hospital, Carlisle, Penna.

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Abstract

Antibiotic-associated diarrhea is common in both inpatient and outpatient

settings, and 15% to 20% of the cases are caused by Clostridium difficile.[1]

Although antibiotic therapy with metronidazole or other agents is effective

for most patients with C difficile-associated diarrhea, approximately 10% to

20% of patients receiving treatment for C difficile infection will experience

a relapse following discontinuation of initial therapy,[2] and relapses are

often multiple. This clinical problem can be frequent and frustrating. [J Am

Board Fam Pract 13(2):138-140, 2000. © 2000 American Board of Family Practice]

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Introduction

C difficile-associated diarrhea is thought to occur when an alteration of the

normal bacterial flora of the intestinal tract permits proliferation of

toxigenic strains of C difficile. Various microorganisms have been used

therapeutically to repopulate the intestinal flora to enhance resistance

against C difficile. A randomized placebo-controlled trial has shown that the

yeast Saccharomyces boulardii is effective for the treatment of recurrent C

difficile disease.[3] This biotherapeutic agent, however, is not available as

a pharmaceutical preparation in the United States. We report herein a case of

C difficile-associated diarrhea with multiple relapses that responded to

treatment with antibiotics together with a commercial baker's yeast

(Fleischmann's Yeast), which contains the closely related species

Saccharomyces cerevisiae at a concentration of organisms at 1010/g.

continued...

Case Report

A 50-year-old woman came to the office complaining of a 1-week history of

diarrhea and weakness with crampy lower abdominal pain and 4 days of vomiting

and low-grade fever. One month earlier she had undergone a laparotomy with

hysterectomy and bilateral salpingo-oophorectomy for drainage of a large

pelvic abscess. She had received intravenous antibiotics during her

hospitalization and was sent home from the hospital with a prescription for

oral clindamycin, 300 mg four times a day, which she had taken for 20 days.

The patient was given a prescription for oral metronidazole for a presumptive

diagnosis of antibiotic-associated colitis, but she required hospitalization

the following day because of intractable vomiting and abdominal pain. A stool

sample was guaiac negative, but it was positive for C difficile by

enzyme-linked fluorescent immunoassay (ELFA) performed with the automated

VIDAS instrument and CDA Dual Reagent Strips (bioMe´ rieux Vitek, Inc.,

Hazelwood, Mo). Her white blood cell count was 7300/µL. A bowel obstruction

series was negative, and a computed tomographic scan of the abdomen and

pelvis showed no evidence of recurrent abscess. She continued to vomit when

given oral metronidazole, so she was given intravenous metronidazole and oral

vancomycin for 4 days. She was released from the hospital with instructions

to continue taking vancomycin, 125 mg four times a day, for 5 more days.

Several days after discharge she developed hives, and the vancomycin was

stopped. A few days later she developed recurrent diarrhea. Oral

metronidazole was started, but she developed nausea, vomiting, and abdominal

cramping. The metronidazole was stopped on the suspicion that these symptoms

might be side effects, and cholestyramine was prescribed. After a day or 2

she developed severe abdominal cramping, and the cholestyramine was stopped.

The vancomycin was restarted without recurrent hives, but she continued to

have nausea, vomiting, and diarrhea, and she was readmitted to the hospital.

She was given intravenous metronidazole for 6 days. Her C difficile toxin

assay was again positive, and a sigmoidoscopic examination showed

classic-appearing pseudomembranes. After she was sent home from the hospital,

she continued taking oral vancomycin for about 2 weeks.

One week after stopping the vancomycin she noted recurrence of nausea and the

following day developed diarrhea. The vancomycin was started again, but

because of the vomiting, she was admitted for the third time for colitis.

Treatment was started with intravenous metronidazole, and she responded

quickly. She was released from the hospital with a prescription for

vancomycin, 125 mg four times a day for 10 days, then twice a day for 7 days,

then every other day for 3 weeks, along with a lactobacilli preparation

(Lactinex) 1 g four times a day for 3 weeks.

Two weeks later the patient was readmitted a fourth time, just 2 days after

switching to the twice-a-day regimen, with vomiting and abdominal discomfort.

Although she had not yet developed diarrhea, she believed her symptoms were

the same as with previous relapses. Findings of a repeat sigmoidoscopy to 30

cm were normal. An infectious disease consultant recommended treatment with

Saccharomyces cerevisiae (Fleischmann's Yeast) 1/8 tsp, four times a day for

4 months, and vancomycin 125 mg four times a day for 30 days. With this

course of treatment there have been no further recurrences in more than 3

years.

continued...

Discussion

C difficile is a spore-forming obligate anaerobic bacillus and is a component

of normal fecal flora in about 5% of healthy adults. It can be found in the

stool of 10% or more of hospitalized adults without diarrhea who have

received antibiotics or chemotherapeutic agents. In C difficile diarrhea,

colitis both with and without pseudomembranes is due to toxin-mediated

mucosal inflammation. The most commonly implicated antibiotics are ampicillin

and other penicillin derivatives, cephalosporins, and clindamycin. The

typical clinical manifestations of C difficile diarrhea are crampy abdominal

pain, profuse diarrhea, low-grade fever, and leukocytosis. The onset can be

as soon as after a few days of antibiotic therapy, or it might be delayed for

up to 8 weeks after its discontinuation. Fever can be as high as 40°C, and

leukocytosis can reach 50,000/µL.[2] The colitis is usually most severe in

the distal colon and rectum, but it can occur throughout the colon. Colitis

localized to the cecum might cause little or no diarrhea, but it can cause

fever, marked right lower quadrant abdominal pain and tenderness, marked

leukocytosis, and decreased intestinal motility.[4]

Endoscopy with biopsy of suspect lesions is the most rapid way to establish

the diagnosis of C difficile colitis. The characteristic lesions are raised,

yellowish nodules or plaque-like pseudomembranes, often with skip areas of

normal mucosa. Typical pseudomembranes are often absent, however. Tissue

culture tests for toxin B are the reference standard and can detect the

specific cytopathic effects of toxin B in more than 90% of patients with

pseudomembranous colitis. A negative test, however, does not rule out C

difficile as the cause of diarrhea. It is also not uncommon for patients to

continue to have positive tests for toxin B or the organism after otherwise

successful therapy. Enzyme immunoassay tests for toxin A or B are the most

widely used tests to diagnose C difficile infection. They are more specific

than they are sensitive, with sensitivities ranging from 70% to 95%. The

sensitivity can be improved by sending a second stool sample the next day,

rather than the same day.[1] Stool cultures for C difficile can yield

false-positive results in patients with simple antibiotic-induced diarrhea

who have coincidental colonization with C difficile. The finding of fecal

neutrophils raises the suspicion of C difficile-associated diarrhea.

Treatment of C difficile-associated diarrhea includes supportive therapy with

replacement of fluids and electrolytes. The patient should stop taking

antibiotics, if possible. Treatment with antiperistaltic or opiate

antidiarrheal agents should be avoided. Metronidazole, preferably given

orally, is the drug of choice for treating C difficile-associated diarrhea.

The usual dose of oral metronidazole is 250 mg four times a day for 10 days.

Vancomycin was prescribed for the patient reported above because she was

unable to tolerate oral metronidazole. Vancomycin is to be discouraged,

however, so as not to promote the spread of vancomycin-resistant enterococci

and staphylococci.[5] Vancomycin is also much more expensive and proved no

more effective than metronidazole in a prospective randomized trial comparing

the two agents.[6]

Relapses or recurrences, defined as the return of symptoms, signs, and

positive diagnostic tests a few weeks to months after discontinuing

successful treatment of C difficile diarrhea, are common, and occur in 15% to

35% of patients.[1] As in this case, relapses usually respond well to

treatment, but multiple recurrences are common, and up to 20 have been

reported in a single patient.

Metronidazole and vancomycin do not reliably kill the spore forms of C

difficile; in fact, they might encourage the formation of spores. The

persistence of both the spores and the antibiotic-induced reduction of the

colonic bacterial flora presumably account for the propensity for relapse.

There is no specific regimen that has been clearly proved to prevent

recurrences. Longer courses of metronidazole or vancomycin therapy have been

tried, sometimes with every-other-day administration or gradual tapering.

Lactobacillus preparations or yogurt with live cultures are sometimes tried.

Two small open trials involving a total of 9 patients have suggested that

Lactobacillus casei GG might be effective for the treatment of recurrent C

difficile colitis.[7,8]

The decision to use yeast to treat C difficile-associated diarrhea in our

patient was based on a promising randomized, double-blind, controlled study

using live yeast (Saccharomyces boulardii)to treat C difficile-related

diarrhea.[3] In that study, the addition of S boulardii to standard

antibiotic treatment in 60 patients with recurrent C difficile disease

reduced the subsequent relapse rate by about 50% when compared with placebo

plus antibiotics. In 64 patients with C difficile disease initially, there

was no significant difference in benefit with the addition of S boulardii,

although because so few patients with initial disease failed, there was only

a 10% power of detecting a significant difference. Patients who were

immunocompromised as a result of AIDS or cancer chemotherapy were excluded

from the study. The two adverse reactions noted with S boulardii were

increased thirst and constipation. Because S boulardii is not readily

available in the United States, some physicians have tried S cerevisiae

(baker's yeast, found in Fleishmann's Yeast) with anecdotal success.[9] The

principal author of the S boulardii study, however, responded to this report

with the assertion that S cerevisiae is a completely different species and

cited controlled experiments in mice where S boulardii showed a significant

protective effect against C difficile whereas S cerevisiae did not.[10]

continued...

Conclusion

A case of well-documented C difficile diarrhea with four recurrences is

described in which a novel and unproved variation of a yeast-based therapy

given with a more prolonged course of oral vancomycin was followed by no

further recurrences. Whereas no conclusions can be made about the efficacy of

S cerevisiae for preventing recurrences of C difficile diarrhea, this case

left a strong impression. Further study of this inexpensive and readily

available treatment should be considered.

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Address reprint requests to J. Kovacs, MD, Yellow Breeches Family

Practice, 1358 Lutztown Road, Boiling Springs, PA 17007.