• Co-Trimoxazole
  
• Trimethoprim-Sulfamethoxazole

Alteration of intestinal microflora is a common side effect of antibiotic treatment (Nord 1993; Beaugerie 1996). These changes can affect the availability of vitamins B and K.

Altering the balance of probiotic organisms in the gastrointestinal tract may reduce resistance to infection and disease. Symptoms of deficiency include gas, abdominal distress, diarrhea, and yeast infections (Galland 1997).

Prophylactic administration of a combination of L. acidophilus and L. bulgaricus prevents ampicillin-induced diarrhea (Gotz et al. 1979). Other bacterial strains that may prevent or treat antibiotic-induced diarrhea include L. casei GG, Saccaromyces boulardii, and Bifidobacterium longum (either alone or combined with L. acidophilus) (Elmer et al. 1996). Administration of preparations containing 1 to 2 billion organisms are typically required (Murray and Pizzorno 1998). Positive results have been observed with S. boulardii at doses of 250 mg bid (Surawicz et al. 1989) or 1 g/day containing 3 x 10¹⁰ colony-forming units (the equivalent of 2 x 250 mg capsules bid) (McFarland et al. 1995).

Intestinal bacteria synthesize vitamin K and B vitamins such as biotin, B2, B12, and folic acid; they are a potentially rich source of these nutrients (Albert et al. 1980; Hill 1997). Although it is unusual to see measurable deficiencies, chronic antibiotic therapy could deplete these vitamins by altering and destroying the normal intestinal bacteria that synthesize them (Hill 1997).

Vitamin B2: Riboflavin deficiency usually occurs as a result of deficiencies in dietary protein and is associated with other B vitamin deficiencies (Covington 1999). Depleted levels of riboflavin affect carbohydrate and amino acid metabolism by interfering with enzyme systems involved in the production of ATP. Lack of an adequate supply of riboflavin disturbs several physiological and biochemical processes and results in retarded growth in infants and children (Covington 1999; Powers 1999). Symptoms include corneal vascularization, glossitis, cheilosis, seborrheic dermatitis, and impaired wound healing (Covington 1999).

Vitamin B12: Symptomatic vitamin B12 deficiency is rare because complications may appear only after the deficiency has existed for 10 to 15 years (Berger 1985; Carpentier et al. 1976). Low vitamin B12 levels could increase the risk of colon cancer, heart disease, brain dysfunction, birth defects, and irreversible neuropathy (Ames 2000; Covington 1999). Irritability, weakness, numbness, fatigue, glossitis, anorexia, headache, palpitations, and altered mental status, including personality and behavioral changes, are some of the signs and symptoms of vitamin B12 depletion (Covington 1999). Prolonged deficiency leads to pernicious or megaloblastic anemia that may be associated with leukopenia and thrombocytopenia.

Vitamin H: Although biotin deficiency is uncommon, nonspecific symptoms such as changes in skin color as well as the development of non-pruritic dermatitis, alopecia, and muscle pain may be indicative of depleted biotin levels (Covington 1999). Additionally, low levels of this nutrient may be associated with hypercholesterolemia, anemia, anorexia, depression, and insomnia.

Note: B vitamins are best if given as B-complex.

Vitamin B2: Doses of 5 to 25 mg/day are recommended for the treatment of riboflavin deficiency (Covington 1999). For replacement therapy, doses should be based upon the patient's individual needs, considering the clinical presentation, serum riboflavin levels, age, gender, dietary habits, and medication regimen.

Vitamin B12: Doses of 25 to 250 mcg/day of vitamin B12 have been used to correct nutritional deficiency (Covington 1999). Oral doses between 500 to 1000 mcg/day have been recommended for the treatment of pernicious anemia (Carmel 2000). Replacement therapy should be based on the patient's individual needs, considering the clinical presentation, serum B12 levels, age, gender, dietary habits, and medication regimen.

Vitamin H: Biotin deficiency is treated with doses between 1 mg and 10 mg to resolve symptoms and prevent recurrence (Mock et al. 1996). Replacement therapy should be based upon the patient's clinical presentation, serum biotin levels, age, gender, dietary habits, and medication regimen.

Trimethoprim acts as a folate antagonist by inhibiting dihydrofolate reductase; high-dose trimethoprim therapy decreases serum folate concentrations (Lambie and Johnson 1985; Naderer et al. 1997). Co-Trimoxazole does not appear to depress serum folate levels to the same extent as trimethoprim monotherapy (Bateson et al. 1976). However, there have been reports of co-trimoxazole affecting folate metabolism, usually following long-term or high-dose therapy (Taraszewski et al. 1989). Patients with compromised folate status prior to co-trimoxazole therapy may be at greater risk for developing a folate deficiency.

Low levels of folate have been linked to colon cancer, heart disease, cognitive deficits, and birth defects, specifically neural tube defects (Ames 2000; Covington 1999). Deficiency increases chromosome breakage and elevates serum homocysteine. Vitamin B9 deficiency may also lead to megaloblastic anemia.

The recommended dietary allowance (RDA) for adults is 300 to 600 mcg/day (Covington 1999). However, recommendations of doses of folic acid as high as 2000 mcg/day have been reported in the literature (Mayer et al. 1996). For replacement therapy, doses should be based upon the patient's individual needs, considering the clinical presentation, serum folate levels, age, gender, dietary habits, and medication regimen. Folate therapy has had a negative outcome on AIDS patients diagnosed with pneumocystis carinii pneumonia (Bygbjerg et al. 1988; Safrin et al. 1994). Therefore, folic acid supplementation may not be warranted in this population of patients.

Note: Folate may be administered concomitantly without interfering with the antibacterial action of trimethoprim (Hines Burnham et al. 2000).

Broad spectrum antibiotics reduce hepatic vitamin K2 (menaquinone) stores as well as gut microflora, which can deplete vitamin K by diminishing bacterial synthesis of this nutrient (Conly and Stein 1994; Stieger et al. 1992).

Interference with intestinal synthesis of vitamin K is usually not sufficient to cause a deficiency (Covington 1999). However, a reduction in prothrombin and other vitamin K-dependent factors may indicate a deficiency (Olson 1999). Severe deficiency may be associated with detectable plasma levels of descarboxyprothrombin (Vermeer and Schurgers 2000). Signs and symptoms of deficiency include coagulation disorders manifested by hypoprothrombinemia with internal and external hemorrhage (Covington 1999).

Generally, 45 to 80 mcg/day are recommended for daily intake to maintain overall health (Covington 1999). Individual requirements should be tailored to the patient's clinical presentation, serum levels, age, gender, dietary habits, and medication regimen.

This information is intended to serve as a concise reference for healthcare professionals to identify substances that may be depleted by many commonly prescribed medications. Depletion of these substances depends upon a number of factors including medical history, lifestyle, dietary habits, and duration of treatment with a particular medication. The signs and symptoms associated with deficiency may be nonspecific and could be indicative of clinical conditions other than deficiency. The material presented in these monographs should not in any event be construed as specific instructions for individual patients.

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