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Infectious Diseases > MEDICAL TOPICS
Bacterial Overgrowth Syndrome
Article Last Updated: Oct 18, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
Richard E Frye is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and International Neuropsychological Society
Coauthor(s):
M Akram Tamer, MD, Program Director, Professor, Department of Pediatrics, University of Miami;
Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Editors: Mark Raymond Wallace, MD, Chief, Clinical Professor, Department of Internal Medicine, Division of Infectious Disease, Naval Medical Center at San Diego; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veteran's Administration Medical Center; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Author and Editor Disclosure
Synonyms and related keywords:
bacterial overgrowth syndrome, BOS, acquired monosaccharide intolerance of infancy, blind-loop syndrome, blind loop syndrome, contaminated small bowel syndrome, small intestinal stasis syndrome, stagnant loop syndrome, fat malabsorption, protein malabsorption, carbohydrate malabsorption, vitamin malabsorption, malabsorption, neonatal chronic diarrhea, neonatal diarrhea
Background
Symbiotic colonic bacteria assist digestion. The upper GI tract was once believed to be sterile, but normal colonization of the duodenum, jejunum, and ileum is now appreciated. Bacterial overgrowth syndrome (BOS) occurs when the normally low bacterial colonization in the upper GI tract significantly increases.
BOS was first appreciated in patients with iatrogenic intestinal blind loops. Disorders associated with low gastric acidity, reduced peristaltic activity, and mucosal damage or atrophy were later recognized. Indeed, cases in infants and elderly individuals presenting with wasting or failure to thrive and prolonged nonspecific diarrhea are not uncommon. A particular bacterial pathogen has never been implicated; instead, abnormally large numbers of normal or pathological florae appear to cause BOS. Treatment is aimed at reducing the damage caused by malabsorption and restoring nutritional health and normal gut florae. Prompt recognition and treatment can prevent the development of severe malnutrition.
Pathophysiology
Fat, protein, carbohydrate, and vitamin malabsorption result from poor enterocyte function and bacterial transformation of nutrients into nonabsorbable and toxic metabolites. Toxic metabolites damage the intestinal mucosa. Malabsorption and enterocyte dysfunction further degrade the health of the gut by reducing local and systemic nutrition delivery.
Frequency
United States
Approximately 20-43% of chronic diarrhea in patients with diabetes is associated with BOS. In many cases, gastric and upper intestinal tract surgery result in BOS; however, preservation of the normal anatomy and antroduodenal vagal innervation appears to be protective. BOS causes 50% of neonatal chronic diarrhea. The prevalence of BOS as the cause of wasting in elderly individuals is not known but is suspected to be significant.
Mortality/Morbidity
- Neonates, young infants, and elderly individuals, especially those who are malnourished, are particularly at risk.
- Poor nutritional status at presentation puts an individual at risk for prolonged treatment.
- Patients with underlying medical conditions are at risk for relapse if the underlying medical condition is not corrected.
Age
- Neonates, young infants, and elderly individuals are particularly at risk for developing BOS. Mucosal injury resulting from a minor viral or bacterial gastroenteritis can induce BOS in these individuals if a proper postinfectious dietary regimen is not followed.
- Elderly individuals may experience diarrhea and malabsorption for many years without a diagnosis of BOS.
- Elderly individuals with diabetes mellitus and autonomic dysfunction may be predisposed to BOS.
History
- GI symptoms may occur from one to several hours following food ingestion. They include the following:
- Mild abdominal distention and discomfort
- Bloating
- Meteorism
- Flatulence
- Patients with the following medical conditions are at increased risk for BOS:
- History of upper intestinal tract surgery
- Gastrojejunal anastomosis
- Vagotomy, but not selective parietal cell vagotomy
- Antral resection
- Pancreatic exocrine insufficiency
- Decreased peristalsis due to the following may result in BOS:
- Diabetic autonomic neuropathy
- Scleroderma
- Pseudoobstruction
- Amyloidosis
- Hypothyroidism
- Blind pouches resulting from the following may result in BOS:
- Side-to-side or end-to-side anastomoses
- Intra-abdominal reservoirs
- Duodenal or jejunal diverticula
- Segmental dilatation of the ileum
- Blind loop syndrome
- Biliopancreatic diversion
- Chagasic megacolon
- Abnormal bowel communication may cause BOS, due to the following:
- Gastrocolic fistulae
- Jejunal-colic fistulae
- Partial obstructions caused by the following may result in BOS:
- Strictures
- Adhesions
- Abdominal masses
- Leiomyosarcoma
- Reduced gastric acid secretion from the following may result in BOS:
Causes
- Under normal conditions, gram-positive bacteria and fungi colonize the duodenum and jejunum in quantities less than 1 X 105 organisms per milliliter of fluid. Aerobic and anaerobic bacteria colonize the ileum in quantities less than 1 X 108 organisms per milliliter of fluid. This is in sharp contrast to the 1 X 1011 organisms per milliliter of fluid that colonize the colon. Studies of duodenal aspirates have not identified any particular bacteria as a cause of BOS; however, 1 X 105 organisms per milliliter of aspirate fluid is diagnostic for BOS. Usually, abnormally large numbers of anaerobic bacteria and normal florae grow from cultured fluid of patients with BOS.
- The following are 5 protective factors that stabilize the number and type of bacteria that colonize the upper GI tract. Abnormalities in these mechanisms put a patient at risk for bacterial overgrowth.
- Two coordinated motor phenomena produce the continuous propulsive peristaltic action of the upper GI tract. Both the migrating motor complex and the migrating action potential complex clear the upper intestine of unwanted bacteria and undigested substances. Desynchronization of these complexes results in diarrhea and weight loss in animal models. Anatomical defects can reduce peristaltic efficacy; for example, blind pouches result in a stagnate portion of the intestine. Patients with Billroth II anastomoses without steatorrhea predominately have streptococci in the blind loop. Other patients with steatorrhea predominately have various gram-negative organisms in the blind loop.
- Gastric acid reduces the proximal small intestine bacteria populations, particularly anaerobic bacteria.
- The bowel mucosa integrity and mucin layer protect the gut from bacteria.
- Immunoglobulin secretion and immune cells (eg, macrophages and lymphocytes) protect the gut from bacteria. The true pathogenic cause of BOS in patients with hypogammaglobulinemia is not known because this disorder is associated with achlorhydria.
- Normal intestinal florae (eg, Lactobacillus) protect the gut from bacterial overgrowth by maintaining a low pH; however, normal florae can facilitate an abnormal intraluminal environment. Abnormal communications produce pathways that allow enteric bacteria to pass between the proximal and distal bowel. The cause of idiopathic BOS in infants and elderly individuals may be different because antibiotics that eliminate anaerobic bacteria are effective in elderly patients but not infants.
- Malabsorption of bile acids, fats, carbohydrates, proteins, and vitamins causes many of the symptoms of diarrhea and weight loss associated with BOS.
- Anaerobes and Bacteroides fragilis actively deconjugate bile acids, thereby preventing proper bile acid function and enterohepatic circulation.
- Fatty acid absorption is reduced because deconjugated bile acids cannot help micelle form.
- Deconjugated bile acids directly inhibit carbohydrate transporters. These unabsorbed sugars ferment into organic acids because of the intestinal florae, which reduces the intraluminal pH and produces osmotic diarrhea. The unconjugated bile acids also damage intestinal enterocytes and induce water secretion by the colonic mucosa.
- Loss of bile acids in the stool reduces the bile acid pool.
Afferent Loop Syndrome
Amebiasis
Carcinoid Tumor, Intestinal
Celiac Sprue
Crohn Disease
Cryptosporidiosis
Cyclospora
Cytomegalovirus
Diverticulosis, Small Intestinal
Giardiasis
Inflammatory Bowel Disease
Intestinal Fistulas
Intestinal Motility Disorders
Intestinal Pseudo-obstruction: Surgical Perspective
Irritable Bowel Syndrome
Isosporiasis
Lactose Intolerance
Malabsorption
Microsporidiosis
Pancreatitis, Chronic
Sprue, Tropical
Ulcerative Colitis
VIPomas
Whipple Disease
Other Problems to be Considered
Acquired immunodeficiency syndrome
Intestinal pseudo-obstruction
Lab Studies
- Stool analysis can help detect abnormal stool components. The pH may be acidic, and reducing substance may be present in the stool.
- D-lactic acidosis syndrome can develop from carbohydrate fermentation.
- Lactic acid levels may need to be measured and, if elevated, monitored.
- D-lactic acid levels, measured in the blood or urine, can help differentiate BOS from other metabolic causes.
- Short-chain fatty acid levels may be elevated in the duodenal fluid but not the stool.
- Abnormal duodenal short-chain fatty acid levels average approximately 1 µmol/mL, with acetic acid, propionic acid, and n-butyric acid representing 61%, 16%, and 8% of the total, respectively.
- The average short-chain fatty acid level in a healthy patient is 0.27 µmol/mL, with acetic acid representing 84% of the total.
- Keto-bile acid concentration in duodenal fluid is increased and correlates with the type of bacterial overgrowth. The molar percent of keto-bile acids in normal duodenal fluid is very close to 0, while gram-negative aerobic and anaerobic overgrowth is associated with levels of 32 µmol/mL and 11 µmol/mL, respectively.
- Urine 4-hydroxyphenylacetic acid levels may be elevated.
- Enteric bacteria that possess L-amino acid decarboxylase produce 4-hydroxyphenylacetic acid from dietary tyrosine.
- Increased excretion has been demonstrated in adults with BOS.
- Creatinine levels higher than 120 mg/g are present in children with small bowel disease or BOS, including children with chronic Giardia lamblia gastroenteritis.
- Children with severe pancreatic dysfunction secondary to cystic fibrosis also have significantly high levels of this metabolite.
- A 2% false-positive rate and no false-negative results are found when this test is used to screen healthy control subjects and hospitalized children.
Imaging Studies
- Small bowel follow through evaluates structure and mobility. Strictures, malrotation, diverticulosis, fistula, and pseudo-obstruction can be found with this technique.
Procedures
- Breath tests use byproducts of bacterial metabolism to identify malabsorbed substances. Several studies suggest that 3 breath tests are of adequate specificity, but these studies are not in full agreement regarding the exact sensitivity. Studies that compare these tests with duodenal bacterial counts suggest that the xylose breath test has the highest specificity. The breath tests used are as follows:
- Hydrogen breath test
- Bacteria ferment malabsorbed carbohydrates. Fermentation releases hydrogen gas that is absorbed and excreted by the lungs. Under normal conditions, fermenting bacteria reside in the colon. With BOS, the exhaled hydrogen concentration rises early, corresponding to small intestinal bacteria fermentation of carbohydrates. Under such conditions, a later rise in exhaled hydrogen also may be detected during large bowel fermentation. Antibiotic administration invalidates this test.
- For diagnosis, use 1-2 g/kg of glucose, not to exceed 25-50 g. A rise in exhaled hydrogen to 20 parts per million is diagnostic.
- The specificity and sensitivity of this test are 80% and 20-75%, respectively.
- Bile acid breath test
- Give glycocholate tagged with carbon 14 with a light meal, and collect breath samples at 2, 4, and 6 hours. An abnormal rise in radioactive carbon dioxide indicates bacterial deconjugation of glycocholate.
- The specificity and sensitivity of this test are 60-76% and 33-70%, respectively.
- Xylose breath test
- Gram-negative bacteria metabolize xylose, resulting in the release of radioactive carbon dioxide.
- Administer 1 g of D-xylose tagged with carbon 14, as a liquid, after an overnight fast.
- Measure radioactive breath carbon dioxide at 30, 60, 90, and 120 minutes. An abnormally high carbon dioxide concentration is usually detected within 30-60 minutes.
- The specificity and sensitivity of this test are 89% and 30-90%, respectively.
Histologic Findings
Descending duodenal biopsies performed on a group of elderly individuals with BOS demonstrate that mean villus height, mean crypt depth, and total mucosal thickness may be reduced. These indexes are not significantly different from controls following 6 months of treatment. A significant drop in the number of intraepithelial lymphocytes is also seen over this observation period. Mucosal atrophy can result in an 80% reduction of intestinal surface area in infants. Once the offending agent is removed, repair of the small bowel progresses slowly. After 2 months, the villi surface area is 63% normal but the microvillous surface area is only 38% normal.
Medical Care
- General care includes antibiotic therapy aimed at rebalancing enteric florae.
- Patients with nonidiopathic BOS appear to respond well to tetracycline. Bacterial sensitivities from duodenal intubations in these patients suggest using amoxicillin-clavulanate. Amoxicillin-clavulanate appears to be 75% effective in patients with diabetes.
- Clindamycin and metronidazole are useful for elderly patients with idiopathic BOS.
- As outlined below, gentamicin, but not metronidazole, significantly improves intractable diarrhea in children younger than 1 year.
- Cholestyramine reduces diarrhea in infants and neonates with intractable diarrhea. Infants with 10-25 days of severe persistent diarrhea for which a cause could not be found despite an extensive infectious and immunologic workup were treated with cholestyramine and gentamicin or metronidazole. Cholestyramine and gentamicin significantly reduced stool weight within 4-5 days of therapy but had mild detrimental effects on fat and nitrogen absorption.
- Certain potential underlying abnormalities are amenable to treatment:
- Infectious diarrheas
- Malnutrition
- Malabsorption
- Hypothyroidism
- Inflammatory bowel disease
- Immunodeficiency
- Certain potential underlining diseases are not amenable to treatment, but prevention of their progression may be therapeutic:
- Diabetic autonomic neuropathy
- Scleroderma
- Pseudoobstruction
- Amyloidosis
- Achlorhydria
- Vagotomy
Surgical Care
- Repair postoperative strictures and blind loops; for example, a Billroth type II may need conversion to a Billroth type I. However, strictures, fistulae, and diverticula may require surgical correction.
Consultations
- Patients refractory to standard medical or surgical treatment or those who have severe symptoms should be referred to a gastroenterologist/infectious disease specialist.
The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.
Drug Category: Antibiotics
Therapy should be directed against B fragilis.
| Drug Name | Amoxicillin-clavulanic acid (Augmentin) |
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| Description | First-line antibiotic for BOS due to anatomic abnormalities and diabetes and for elderly patients with idiopathic BOS. Provides good gram-negative, gram-positive, and anaerobic coverage. Reduces number of bacteria in small bowel lumen. |
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| Adult Dose | 875 mg PO bid |
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| Pediatric Dose | 40 mg/kg/d PO divided bid |
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| Contraindications | Documented hypersensitivity to same or other beta-lactam drugs |
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| Interactions | Probenecid increases serum levels; decreases efficacy of oral contraceptives; increases effect of anticoagulants |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | Give for a minimum of 10 d to eliminate organism and prevent sequelae (endocarditis, rheumatic fever); following treatment, perform cultures to confirm eradication of streptococci |
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| Drug Name | Clindamycin (Cleocin) |
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| Description | Works well in elderly patients with idiopathic BOS, especially if bile malabsorption coexists. Good anaerobic and gram-positive coverage, except enterococci. |
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| Adult Dose | 300 mg PO q8h
600-2700 mg/d IV divided tid |
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| Pediatric Dose | 30 mg/kg/d PO divided qid
40 mg/kg/d IV divided tid/qid |
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| Contraindications | Documented hypersensitivity; hepatic dysfunction; pseudomembranous colitis; other diarrhea |
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| Interactions | Enhances action of nondepolarizing muscle relaxants |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
|
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| Precautions | Dose reduction with severe liver dysfunction; GI distress; pseudomembranous colitis; elevates LFT results; rash; Stevens-Johnson syndrome; granulocytopenia and thrombocytopenia |
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| Drug Name | Gentamicin (Garamycin, Gentacidin) |
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| Description | Useful in neonates and infants with idiopathic BOS. Aminoglycoside that provides excellent aerobic gram-negative coverage in bowel when administered PO.
Not well absorbed PO. Studies have not established serum levels with enteral administration and compromise of intestinal lumen. |
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| Adult Dose | PO dose not established |
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| Pediatric Dose | 50 mg/kg/d PO divided 4-6 times/d; not to exceed 360 mg/d |
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| Contraindications | Documented hypersensitivity (extremely rare) |
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| Interactions | Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly) |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
|
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| Precautions | Parenteral administration is associated with increased risk for ototoxicity and nephrotoxicity; minimal oral absorption |
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| Drug Name | Metronidazole (Flagyl) |
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| Description | First-line antibiotic for elderly patients with idiopathic BOS. Provides good anaerobic coverage. |
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| Adult Dose | 500 mg PO bid/tid |
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| Pediatric Dose | 30 mg/kg/d PO divided qid |
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| Contraindications | Documented hypersensitivity; severe renal or liver failure; category D in first trimester of pregnancy |
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| Interactions | Effects decreased by phenytoin and phenobarbital; alcohol induces disulfiramlike reaction; increases PT with warfarin; increases lithium serum levels and toxicity; serum level increased by cimetidine |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | GI distress; discontinue if seizures or neuropathy develops |
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| Drug Name | Tetracycline (Nor-tet, Panmycin) |
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| Description | Effective for patients with BOS. Provides anaerobic coverage. |
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| Adult Dose | 500 mg PO qid |
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| Pediatric Dose | <8 years: Not recommended
>8 years: Not established |
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| Contraindications | Documented hypersensitivity; children; severe renal and liver dysfunction |
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| Interactions | May interfere with efficacy of penicillins; increased PT in patients taking warfarin; antacids, calcium, iron, bicarbonate, and sucralfate decrease absorption |
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| Pregnancy | D - Unsafe in pregnancy
|
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| Precautions | GI distress; photosensitivity; increased BUN, hepatotoxicity |
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Prognosis
- If BOS is the result of an underlying medical problem that cannot be controlled, relapse will occur, with symptom-free periods.
Medical/Legal Pitfalls
- Because reoccurrence of BOS after several asymptomatic months is common, close follow-up is preferable for several months after treatment.
- Neonates must be hospitalized until a standard formula is well tolerated; for example, a neonate may require a lactose-free formula upon discharge, but the physician must ensure that the neonate has tolerated the formula for several days before discharging the patient. Rapid decompensation can occur if nutrient malabsorption reoccurs.
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Bacterial Overgrowth Syndrome excerpt Article Last Updated: Oct 18, 2006
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