• Cinoxacin
  
• Ciprofloxacin
  
• Enoxacin
  
• Gatifloxacin
  
• Levofloxacin
  
• Lomefloxacin
  
• Moxifloxacin
  
• Nalidixic Acid
  
• Norfloxacin
  
• Ofloxacin
  
• Sparfloxacin
  
• Trovafloxacin
  

Alteration of intestinal microflora is a common side effect of antibiotic treatment (Beaugerie 1996; Nord 1993). Quinolone antibiotics selectively alter the ecology of the human intestine (Edlund and Nord 1999). These changes can affect 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 B9: 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.

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 B9: 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.

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.

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.

Albert MJ, Mathan VI, Baker SJ. Vitamin B12 synthesis by human small intestinal bacteria. Nature. 1980;283(5749):781-782.

Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci. 2000;889:87-106.

Beaugerie L. [Diarrhea caused by antibiotic therapy]. Rev Prat. 1996;46(2):171-176.

Berger W. Incidence of severe side effects during therapy with sulfonylureas and biguanides. Horm Metab Res Suppl. 1985;15:111-115.

Carmel R. Current concepts in cobalamin deficiency. Ann Rev Med. 2000;51:357-375.

Carpentier JL, Bury J, Luyckx A, Lefebvre P. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabetes Metab. 1976;2(4):187-190.

Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994;17(6):531-539.

Covington T, ed. Nonprescription Drug Therapy Guiding Patient Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.

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Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA. 1996;275(11):870-876.

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Gotz V, Romankiewicz JA, Moss J, Murray HW. Prophylaxis against ampicillin associated diarrhea with a lactobacillus preparation. Am J Hosp Pharm. 1979;36:754-757.

Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev. 1997;6(Suppl 1):S43-45.

Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol. 1996;27(3):517-527.

McFarland LV, Surawicz CM, Greenberg RN, et al. Prevention of Beta-lactam-associated diarrhea by Saccharomyces boulardi compared with placebo. Am J Gastroenterol. 1995;90(3):439-448.

Mock DM. Biotin. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7^th ed. Washington, DC: ILSI Press; 1996:231.

Murray, M, Pizzorno, J. Encyclopedia of Natural Medicine 2^nd ed. Rocklin: Prima Publishing; 1998:435.

Nord CE. The effect of antimicrobial agents on the ecology of the human intestinal microflora. Vet Microbiol. 1993;35(3-4):193-197.

Olson RE. Vitamin K. In: Shils, ME, Olson JA, Shike, M, eds. Modern Nutrition in health and disease. 9th ed. Media, PA: Williams & Wilkins; 1999:363-380.

Powers HJ. Current knowledge concerning optimum nutritional status of riboflavin, niacin and pyridoxine. Proc Nutr Soc. 1999;58(2):435-440.

Stieger R, Baumgartner K, Neff U. [Dangerous hypothrombinemic hemorrhage in antibiotic therapy]. Helv Chir Acta. 1992;58(6):775-778.

Surawicz CM, Elmer GW, Speelman P, et al. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospecive study. Gastroenterol. 1989;96(4):981-988.

Vermeer C, Schurgers LJ. A comprehensive review of vitamin K and vitamin K antagonists. Hematol Oncol Clin North Am. 2000;14(2):339-353.