Doxycycline and Penicillin G Procaine for Inhalational Anthrax (Post-Exposure)

Doxycycline and penicillin G procaine are antibiotics used to treat bacterial infections in many different parts of the body. Antibiotics do not work for viral infections (for example, the common cold). Doxycycline and penicillin G procaine have been approved for all forms of anthrax. (inhalational, gastrointestinal, and cutaneous). On November 2, 2001, FDA published a Federal Register notice (66 FR 55679) clarifying that these drugs are approved for inhalational anthrax (post-exposure). Use of doxycycline in children under 8 years presents special concerns because of possible tooth discoloration. Long-term use of intravenous doxycycline or penicillin G procaine presents safety concerns, and patients should be switched, when appropriate, to oral antibiotics to complete a 60 day course of therapy for inhalational anthrax (post-exposure). For more information, see Doxycycline Use by Pregnant and Lactating Women.

List of Published Literature Relied on in Issuing the Federal Register Notice on Doxycycline and Penicillin G Procaine Administration for Inhalational Anthrax (Post-Exposure)

1. Aach, R., and J. Kissane, eds., "A seventeen-year-old girl with fatty liver of pregnancy following tetracycline therapy," Stenographic Report of a Clinicopathologic Conference, American Journal of Medicine, 43:274-283, 1967.

2. Abramova, F. A., et al., "Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979," Proceedings of the National Academy of Sciences of the United States of America, 90:2293-2294, 1993.

3. Abramowicz, M. et al., "Levels of penicillin in serum of newborn infants," American Journal of Diseases in Children, 111:267-272, 1966.

4. Akova, M. et al., "Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin," Antimicrobial Agents & Chemotherapy, 37:1831-1834, 1993.

5. American Academy of Pediatrics, Committee on Infectious Diseases, "Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis," Pediatrics, 106:362-366, 2000.

6. Andriole, V. T. et al., "Penicillin G Procaine," in Current Infectious Disease Drugs, 1st ed., Philadelphia: Current Medicine, 1996, pp. 96-97.

7. Ariza, J. et al., "Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin: randomized, double-blind study," Annals of Internal Medicine, 117:25-30, 1992.

8. Bhagavan, B. S. et al., "Long-term use of tetracycline," Journal of the American Medical Association, 247:2780, 1982.

9. Bolme, P. et al., "Malnutrition and pharmacokinetics of penicillin in Ethiopian children," Pharmacology and Toxicology, 76:259-262, 1995.

10. Boston Collaborative Drug Surveillance Program, "Tetracycline and drug-attributed rises in blood urea nitrogen: A report from the Boston Collaborative drug surveillance program," Journal of the American Medical Association, 220:377-379, 1972.

11. Brachman, P. S., "Inhalation anthrax," Annals of the New York Academy of Sciences, 353:83-93, 1980.

12. Brachman, P. S. et al., "An epidemic of inhalation anthrax: the first in the twentieth century; II. Epidemiology," American Journal of Hygiene, 72:6-23, 2001.

13. Brown, S. T., "Therapy for nonvenereal treponematoses: review of the efficacy of penicillin and consideration of alternatives," Reviews of Infectious Diseases, 7 Suppl 2:S318-S326, 1985.

14. Cabellos, C. et al., "Current usefulness of procaine penicillin in the treatment of pneumococcal pneumonia," European Journal of Clinical Microbiology and Infectious Diseases, 17:265-268, 1998.

15. Campistron, G. et al., "Pharmacokinetics and bioavailability of doxycycline in humans," Arzneimittel-Forschung (Aulendorf), 36:1705-1707, 1986.

16. Carson, J. L. et al., "Acute liver disease associated with erythromycins, sulfonamides, and tetracyclines," Annals of Internal Medicine, 119: 576-583, 1993.

17. Ceccarelli, G. et al., "Pharmacokinetic study of doxycycline in children," Chemotherapy, 16:1-10, 1971.

18. Cisneros, J. M. et al., "Multicenter prospective study of treatment of Brucella melitensis Brucellosis with doxycycline for 6 weeks plus streptomycin for 2 weeks," Antimicrobial Agents & Chemotherapy, 34:881-883, 1990.

19. Colvin, B., M. Rogers, and C. Layton, "Benzylpenicillin-induced leucopenia: Complication of treatment of bacterial endocarditis," British Heart Journal, 36:216-219, 1974.

20. Corbett, G. M., D. J. Perry, and T. R. D. Shaw. "Penicillin induced leukopenia," New England Journal of Medicine, 307:1642-1643, 1982.

21. Crowe, G. et al., "Acceptability and compliance with daily injections of procaine penicillin in the outpatient treatment of syphilis-treponemal infection," Sexually Transmitted Diseases, 24:127-130, 1997.

22. Council on Drugs, "Evaluation of a new antibacterial agent: Doxycycline monohydrate and doxycycline hyclate (Vibramycin)," Journal of the American Medical Association, 209:549-550, 1969.

23. Dattwyler, R. J. et al., "Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease," New England Journal of Medicine, 337:289-294, 1997.

24. Del Rosso, J. Q., "Systemic therapy for rosacea: focus on oral antibiotic therapy and safety," Cutis, 66 Suppl 4:7-13, 2000.

25. Dittert, L. W. et al., "Pharmacokinetic interpretation of penicillin levels in serum and urine after intravenous administration," Antimicrobial Agents and Chemotherapy, 9:42-48, 1969.

26. Dixon, T. C. et al., "Anthrax," New England Journal of Medicine, 341:815-826, 1999.

27. Doganay, M., and N. Aydin, "Antimicrobial susceptibility of Bacillus anthracis," Scandinavian Journal of Infectious Diseases, 23:333-335, 1991.

28. Dunlop, E. M., S. S. Al Egaily, and E. T. Houang. "Penicillin levels in blood and CSF achieved by treatment of syphilis," Journal of the American Medical Association, 241:2538-2540, 1979.

29. Durack, David D., and Paul D. Hoeprich, "Infective Endocarditis," in Infectious Diseases: A Modern Treatise of Infectious Processes, ed. Paul D. Hoeprich and M. Colin Jordan, 4th ed., Philadelphia: J.B. Lippincott Company, 1989. pp. 1237-1253.

30. Ellingson, H. V., P. J. Kadull, and H. L. Howe C. Bookwalter, "Cutaneous anthrax: Report of twenty-five cases," Journal of the American Medical Association, 131:1105-1108, 1946.

31. Fanning, W. L., D. W. Gump, and R. A. Sofferman, "Side effects of minocycline: a double-blind study," Antimicrobial Agents and Chemotherapy, 11:712-717, 1977.

32. Fernandez-Obregon, A. C., "Azithromycin for the treatment of acne," International Journal of Dermatology, 39:45-50, 2000.

33. Friedlander, A. M. et al., "Postexposure prophylaxis against experimental inhalation anthrax," Journal of Infectious Diseases, 167:1239-1243, 1993.

34. Galpin, J. E. et al., ""Pseudoanaphylactic" reactions from inadvertent infusion of procaine penicillin G," Annals of Internal Medicine, 81:358-359, 1974.

35. Garraffo, R. et al., "Effects of rifampicin on the pharmacodynamics of doxycycline," Pathologie Biologie (Paris), 35:746-749, 1987.

36. Gaston, M. H. et al., "Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial," New England Journal of Medicine, 314:1593-1599, 1986.

37. Geraci, J. E., and W. J. Martin. "Antibiotic therapy of bacterial endocarditis: IV. Successful short-term (two weeks) combined penicillin-dihydrostreptomycin therapy," Circulation, 8:494-509, 1953.

38. Geraci, J. E., "Antibiotic therapy of bacterial endocarditis," Medical Clinics of North America, 42:1101-1140, 1958.

39. Ginsburg, C. M., G. H. McCracken Jr., and T. C. Zweighaft, "Serum penicillin concentrations after intramuscular administration of benzathine penicillin G in children," Pediatrics, 69:452-454, 1982.

40. Glassman, H. N., "World incidence of anthrax in man." Public Health Report, 73:22-24, 1958.

41. Gochenour, W. S. Jr., C. A. Gleiser, and W. D. Tigertt, "Observations on penicillin prophylaxis of experimental inhalation anthrax in the monkey," Journal of Hygiene, 60:29-33, 1962.

42. Gold, H., "Anthrax: A report of one hundred seventeen cases," Archives of Internal Medicine, 96:387-396, 1955.

43. Gold, H., "Aureomycin in the treatment of anthrax," American Journal of Medicine, 8:31-33, 1950.

44. Gold, H., "Treatment of anthrax," Federation Proceedings, 26:1563-1568, 1967.

45. Gold, H., and W. P. Boger, "Newer antibiotics in the treatment of anthrax," New England Journal of Medicine, 244:391-394, 1951.

46. Gonciarz, Z. et al., "Plasma penicillin-G parameters in man after intraduodenal or intramuscular administration," International Journal of Clinical Pharmacology, Therapy, and Toxicology, 24:622-624, 1986.

47. Green, R. L. et al., "Elevated plasma procaine concentrations after administration of procaine penicillin G," New England Journal of Medicine, 291:223-226, 1974.

48. Griffin, J. R., R. H. Shanahan, and C. E. DeAngelis, "Treatment of cutaneous anthrax with penicillin," New York State Journal of Medicine, 48:1718-1721, 1948.

49. Grossman, E. R. "Tetracycline and staining of the teeth," Journal of the American Medical Association, 255:2442-2443, 1986.

50. Heaney D., and G. Eknoyan, "Minocycline and doxycycline kinetics in chronic renal failure," Clinical Pharmacology and Therapeutics, 24:233-239, 1978.

51. Henderson, D. W., S. Peacock, and F. C. Belton, "Observations on the prophylaxis of experimental pullmonary anthrax in the monkey," Journal of Hygiene, 54:28-36, 1956.

52. Hoigne, R. et al., "Penicillins," in Meyler's Side Effects of Drugs, ed. M. N. G. Dukes, 12th ed., Amsterdam: Elsevier, 1992, pp. 600-622.

53. Hoigne, R. et al., "Penicillins, Cephalosporins and Other Beta-Lactam Antibiotics," in Meyler's Side Effects of Drugs, ed. M. N. G. Dukes, 12th ed. Amsterdam: Elsevier, 1992, pp. 593-599.

54. Huang, N. N., and R. H. High, "Comparison of serum levels following administration of oral and parenteral preparations of penicillin to infants and children of various age groups," Journal of Pediatrics, 42:657, 1953.

55. International Rheumatic Fever Study Group, "Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever," Lancet, 37:1308-1310, 1991.

56. Inglesby, T. V. et al., "Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense," Journal of the American Medical Association, 281:1735-1745 1999.

57. John, A. B. et al., "Prevention of pneumococcal infection in children with homozygous sickle cell disease," British Medical Journal (Clinical Research Edition), 288:1567-1570, 1984.

58. Jones, M. N. et al., "Antibiotic prophylaxis for inhalation anthrax," Salisbury Medical Bulletin, Suppl 87:127-128, 1996.

59. Joorabchi, B., and E. Kohout. "Apparent penicillin-induced arrest of mature bone marrow elements," British Medical Journal, 2:26-27, 1973.

60. Joshi, N., "Doxycycline revisited," Archives of Internal Medicine, 157:1421-1428, 1997.

61. Kaplan, M. M., "Acute fatty liver of pregnancy," New England Journal of Medicine, 313:367-370, 1985.

62. Karchmer, A. W. et al., "Single-antibiotic therapy for streptococcal endocarditis," Journal of the American Medical Association, 241:1801-1806, 1979.

63. Kaye, D., "Endocarditis," in Cecil Textbook of Medicine, ed. P. B. Beeson, W. McDermott, and J. B. Wyngaarden, 15th ed., Philadelpha: W.B. Saunders Company, 1979, pp. 386-396.

64. Kees, F. et al., "The bioavailability of doxycycline." Arzneimittel-Forschung (Aulendorf), 40:1039-1043, 1990.

65. Kelly, D. J. et al., "Serum concentrations of penicillin, doxycycline, and ciprofloxacin during prolonged therapy in Rhesus monkeys," Journal of Infectious Diseases, 166:1184-1187, 1992.

66. Kendall, C. E., "Occupational anthrax in the United States," Journal of Occupational Medicine, 1:174-177, 1959.

67. Klein, J. O. et al., "Levels of penicillin in serum of newborn infants after single intramuscular doses of benzathine penicillin G," Journal of Pediatrics, 82:1065-1968, 1973.

68. Klempner, M. S. et al., "Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease," New England Journal of Medicine, 345:85-92, 2001.

69. Kunelis, C. T., J. L. Peters, and H. A. Edmonson, "Fatty liver of pregnancy and its relationship to tetracycline therapy," American Journal of Medicine, 38:359-377, 1965.

70. LaBoccetta, A. C., "Anthrax: 36 human cases of the external type treated successfully with penicillin," American Journal of the Medical Sciences, 216:407-410, 1948.

71. Levy, P. Y. et al., "Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis," Antimicrobial Agents and Chemotherapy, 35:533-537, 1991.

72. Lew, H. T., and S. W. French, "Tetracycline nephrotoxicity and nonoliguric acute renal failure," Archives of Internal Medicine, 118:123-128, 1966.

73. Lightfoot, N. F., R. J. D. Scott, and P. C. B. Turnbull, "Antimicrobial susceptibility of Bacillus anthracis," Salisbury Medical Bulletin, 68 Suppl:95-98, 1990.

74. Maesen, F. P., B. I. Davies, and J. J. van den Bergh, "Doxycycline and minocycline in the treatment of respiratory infections: a double-blind comparative clinical, microbiological and pharmacokinetic study," Journal of Antimicrobial Chemotherapy, 23:123-129, 1989.

75. Malacoff, R. F., E. Frank, and V. T. Andriole, "Streptococcal endocarditis (nonenterococcal, non-group A): single vs combination therapy," Journal of the American Medical Association, 241:1807-1810, 1979.

76. Malmborg, A. S., "Bioavailability of doxycycline monohydrate. A comparison with equivalent doses of doxycycline hydrochloride," Chemotherapy, 30:76-80, 1984.

77. Mandell, Gerald L., and William A. Petri, "Antimicrobial Agents," in Goodman & Gilman's the Pharmacological Basis of Therapeutics, ed. Joel G. Hardman, et al., 9th ed., New York: McGraw-Hill, pp. 1073-1101, 1996.

78. McCracken, G. H., Jr. et al., "Clinical pharmacology of penicillin in newborn infants," Journal of Pediatrics, 82:692-698, 1973.

79. Menke, H. E., and L. Pepplinkhuizen, "Letter: Acute non-allergic reaction to aqueous procaine penicillin," Lancet, 2:723-724, 1974.

80. Meselson, M. et al., "The Sverdlovsk anthrax outbreak of 1979," Science, 266:1202-1208, 1994.

81. Misago, C. et al., "Out-patient drug treatment of pneumonia among children under two years of age in Fortaleza, Brazil," Cadernos de Saúde Pública, 13:37-43, 1997.

82. Muller-Vahl, H., "Adverse reactions after intramuscular injections," Lancet, 1:1050, 1983.

83. Neu, H. C., "A symposium on the tetracyclines: a major appraisal," Bulletin of the New York Academy of Medicine, 54:141-155, 1978.

84. Nguyen, V. X. et al., "Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline," Antimicrobial Agents and Chemotherapy, 33:434-436, 1989.

85. Odendaal, M. W. et al., "The antibiotic sensitivity patterns of Bacillus anthracis isolated from the Kruger National Park," Onderstepoort Journal of Veterinary Research, 58:17-19, 1991.

86. Olaison, L. et al., "Incidence of beta-lactam-induced delayed hypersensitivity and neutropenia during treatment of infective endocarditis," Archives of Internal Medicine, 159:607-615, 1999.

87. Overturf, G. D., "American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis," Pediatrics, 106:367-376, 2000.

88. Pai, V. B., and M. C. Nahata, "Duration of penicillin prophylaxis in sickle cell anemia: issues and controversies," Pharmacotherapy, 20:110-117, 2000.

89. Patra, G. et al., "Molecular characterization of Bacillus strains involved in outbreaks of anthrax in France in 1997," Journal of Clinical Microbiology, 36:3412-3414, 1998.

90. Pelletier, Lawrence L., and Robert G. Petersdorf, "Infective Endocarditis," in Harrison's Principles of Internal Medicine, ed. Robert G. Petersdorf et al., 10th ed., New York: McGraw-Hill, 1983, pp. 1418-23.

91. "Penicillin G (Pen G)," in The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, and Antiviral Drugs, ed. A. Kucers et al., 5th ed., Oxford: Butterworth-Heinemann, 1997, pp. 3-70.

92. "Penicillin G Procaine," in AHFS Drug Information 2000, ed. G. K. McEvoy, Bethesda, MD: American Society of Health-System Pharmacists, 2000, pp. 336-338.

93. Pile, J. et al., "Anthrax as a Potential Biological Warfare Agent," Archives of Internal Medicine, 158:429-434, 1998.

94. Plotkin, S. A. et al., "An epidemic of inhalation anthrax, the first in the twentieth century I. Clinical features," American Journal of Medicine, 29:992-1001, 1960.

95. Raoult, D. et al., "Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine," Archives of Internal Medicine, 159:167-173, 1999.

96. Resnick, L., and L. Cohen, "Antibiotic treatment of penicillin-sensitive streptococcal endocarditis," Journal of the American Medical Association, 241:1826-1827, 1979.

97. Ronaghy, H. A. et al., "Penicillin therapy of human cutaneous anthrax," Current Therapeutic Research, Clinical and Experimental, 14:721-725, 1972.

98. Ross, J. M., "The pathogenesis of anthrax following the administration of spores by the respiratory route," Journal of Pathology and Bacteriology, 73:485-494, 1957.

99. Rumble, R. H., M. S. Roberts, and A. R. Scott, "The effects of posture on the pharmacokinetics of intramuscular benzylpenicillin," European Journal of Clinical Pharmacology, 33:629-635, 1988.

100. Saivin, S., and G. Houin, "Clinical pharmacokinetics of doxycycline and minocycline," Clinical Pharmacokinetics, 15:355-366, 1988.

101. Sande, M. A., and W. M. Scheld, "Combination antibiotic therapy of bacterial endocarditis," Annals of Internal Medicine, 92:390-395, 1980.

102. Sande, Merle A., and Peter M. Small, "Infective Endocarditis," in Internal Medicine, ed. Jay H. Stein, et al., 3rd ed., Boston: Little, Brown and Company, 1990, pp. 140-149.

103. Saux, M. C. et al., "Pharmacokinetic study of doxycycline polyphosphate (PPD), hydrochloride (CHD) and base (DB)," European Journal of Drug Metabolism and Pharmacokinetics, 6:3-10, 1981.

104. Scheife, R. T., M. Levy, and D. J. Greenblatt, "Antimicrobial Agents: Tetracyclines," in Drug Effects in Hospitalized Patients, ed. R. R. Miller and D. J. Greenblatt, New York: John Wiley & Sons, 1976, pp. 263-264.

105. Scheld, W. Michael, and Merle A. Sande, "Cardiovascular Infections: Endocarditis & Intravascular Infections," in Principles and Practice of Infectious Diseases, ed. G. L. Mandell, G. Douglas, Jr., and J. E. Bennett, 3rd ed, New York: Churchill Livingstone, Inc., 1990, pp. 670-706.

106. Schreiner, A., and A. Digranes, "Pharmacokinetics of lymecycline and doxycycline in serum and suction blister fluid," Chemotherapy, 31:261-265, 1985.

107. Seow, W. K., "Enamel hypoplasia in the primary dentition: A review," ASDC Journal of Dentistry for Children, 58:441-452, 1991.

108. Shann, F., V. Linnemann, and M. Gratten, "Serum concentrations of penicillin after intramuscular administration of procaine, benzyl, and benethamine penicillin in children with pneumonia," Journal of Pediatrics, 110:299-302, 1987.

109. Shapiro, L. E., S. R. Knowles, and N. H. Shear, "Comparative safety of tetracycline, minocycline, and doxycycline," Archives of Dermatology, 133:1224-1230, 1997.

110. Shils, M. E., "Renal disease and the metabolic effects of tetracycline," Annals of Internal Medicine, 58:389-408, 1963.

111. Silber, T. J., and L. J. D'Angelo, "Panic attack following injection of aqueous procaine penicillin G (Hoigne syndrome)," Journal of Pediatrics, 107:314-315, 1985.

112. Silber, T. J., and L. D'Angelo, "Psychosis and seizures following the injection of penicillin G procaine. Hoigne's syndrome," American Journal of Diseases of Children, 139:335-337, 1985.

113. Simon, H. J. et al., "Clinical pharmacology of antimicrobials in premature infants. 3. Alpha-6-deoxyoxytetracycline (doxycycline)," Antimicrobial Agents and Chemotherapy, 6:121-126, 1966.

114. Snavely, S. R. et al., "Profound neutropenia associated with benzylpenicillin," Southern Medical Journal, 76:1299-1302, 1983.

115. Solera, J. et al., "Treatment of human brucellosis with doxycycline and gentamicin," Antimicrobial Agents & Chemotherapy, 41:80-84, 1997.

116. St. Clair, E. W. et al., "The effects of intravenous doxycycline therapy for rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial," Arthritis and Rheumatism, 44:1043-1047, 2001.

117. Swartz, Morton N, Bernadine P. Healy, and Daniel M Musher, "Late Syphillis," in Sexually Transmitted Diseases, ed. K. K. Holmes et al., 3rd ed., New York: McGraw-Hill, 1999, pp. 487-509.

118. Tahernia, A. C., "Treatment of anthrax in children," Archives of Disease in Childhood, 42:181-182, 1967.

119. Tahernia, A. C., and G. Hashemi, "Survival in anthrax meningitis," Pediatrics, 50:329-333, 1972.

120. Tastepe, A. I. et al., "Thoracic actinomycosis," European Journal of Cardio-Thoracic Surgery, 14:578-583, 1998.

121. "Tetracyclines," in The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, and Antiviral Drugs, ed. A. Kucers et al., 5th ed., Oxford: Butterworth-Heinemann, 1997, pp. 719-762.

122. "Tetracyclines and the teeth," Lancet, 1:917-918, 1966.

123. Tilley, B. C. et al., "Minocycline in rheumatoid arthritis: A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group," Annals of Internal Medicine, 122:81-89, 1995.

124. Ullman, R. F. et al., "Streptococcus mutans endocarditis: report of three cases and review of the literature," Heart and Lung, 17:209-212, 1988.

125. Utley, P. M., J. B. Lucas, and T. E. Billings, "Acute psychotic reactions to aqueous procaine penicillin," Southern Medical Journal, 59:1271-1274, 1966.

126. Vancurik, J., "Causes of the failure of antibiotic prophylaxis of inhalation anthrax and clearance of the spores from the lungs," Folia Microbiologica (Praha), 11:459-464, 1966.

127. Wenk, R. E. et al., "Tetracycline-associated fatty liver of pregnancy, including possible pregnancy risk after chronic dermatologic use of tetracycline," Journal of Reproductive Medicine, 26:135-141, 1981.

128. Whalley, P. J., R. H. Adams, and B. Combes, "Tetracycline toxicity in pregnancy," Journal of the American Medical Association, 189:357-362, 1964.

129. Willcox, R. R., "Mass treatment campaigns against the endemic treponematoses," Reviews of Infectious Diseases, 7 Suppl 2:s278-s283, 1985.

130. Wilson, W. R. et al., "Short-term intramuscular therapy with procaine penicillin plus streptomycin for infective endocarditis due to viridans streptococci," Circulation, 57:1158-1161, 1978.

131. Wilson, W. R. et al., "Short-term therapy for streptococcal infective endocarditis. Combined intramuscular administration of penicillin and streptomycin," Journal of the American Medical Association, 245:360-363, 1981.

132. Wilson, W. R. et al., "Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association," Journal of the American Medical Association, 274:1706-1713, 1995.

133. Wilson, W. R. et al., "Treatment of streptomycin-susceptible and streptomycin-resistant enterococcal endocarditis," Annals of Internal Medicine, 100:816-823, 1984.

134. Witkop, C. J., and R. O. Wolf, "Hypoplasia and intrinsic staining of enamel following tetracycline therapy," Journal of the American Medical Association, 185:1008-1011, 1963.

135. Wojcicki, J., W. Kalinowski, and B. Gawronska-Szklarz, "Comparative pharmacokinetics of doxycycline and oxytetracycline in patients with hyperlipidemia," Arzneimittel-Forschung (Aulendorf), 35:991-993, 1985.

136. Wolfe, J. C., and W. D. Johnson. "Penicillin-sensitive streptococcal endocarditis: In-vitro and clinical observations on penicillin-streptomycin therapy," Annals of Internal Medicine, 81:178-181, 1974.

137. Wolff, A. H., and H. Heimann. "Industrial anthrax in the United States: An epidemiologic study," American Journal of Hygiene, 53:80-109, 1951.

138. Wollenhaupt, J., "A double-blind, placebo-controlled comparison of 2 weeks versus 4 months treatment with doxycycline in chlamydia-induced reactive arthritis," Arthritis and Rheumatism, 40 Suppl:S143, 1997.

139. Wright, A. J., and C. J. Wilkowske, "The penicillins," Mayo Clinic Proceedings, 66:1047-1063, 1991.