On 2013 Dec 20, Raphael Stricker commented:

Fatal Clostridium Difficile Colitis Following Treatment for Lyme Disease: The Wrong Message.

Raphael B. Stricker, MD* and Lorraine Johnson, JD, MBA*

*International Lyme and Associated Diseases Society, P.O. Box 341461, Bethesda, MD 20827-1461. www.ILADS.org

Holzbauer and colleagues (1) describe a case of fatal Clostridium difficile colitis in a patient treated with ten weeks of oral antibiotics for chronic Lyme disease. Rather than focusing on patient-specific risk factors and prevention of antibiotic-related complications, the authors preach about the dangers of treating Lyme disease outside the controversial guidelines of the Infectious Diseases Society of America (IDSA), which were the subject of an antitrust investigation by the Connecticut Attorney General (2,3). In doing so, the authors exaggerate the risks of treating Lyme disease and ignore the risks of failing to treat an ongoing spirochetal infection that may cause disability equivalent to congestive heart failure, and even death (4,5). Consequently the emphasis of the case report is misguided and ultimately detrimental to patient care.

In the single case described here, no information is given about cellular or humoral immune dysfunction that may have contributed to the rapid demise of the 52-year-old patient. This rapid demise is unusual in patients less than 80 years old with C. difficile colitis (6) and suggests the presence of a hypervirulent C. difficile ribotype that might explain the clinical course. Furthermore, the authors fail to mention whether the patient received probiotic therapy during the extended oral antibiotic treatment. Probiotic therapy appears to be effective in avoiding antibiotic-induced complications, and evidence suggests that certain probiotics may neutralize C. difficile toxin (7,8). The lack of probiotic therapy may have been a significant factor in this patient’s demise.

As for the appropriateness of antibiotic therapy in a patient with clinical and laboratory evidence of chronic Lyme disease, two points should be considered. First, two approaches to treatment of this tickborne illness have been described in the medical literature. The approach promulgated by IDSA proscribes extended antibiotic therapy for persistent symptoms related to infection with Borrelia burgdorferi, the spirochetal agent of Lyme disease (2). In contrast, the competing approach of the International Lyme and Associated Diseases Society (ILADS) considers this therapy to be appropriate based on evidence of persistent spirochetal infection (4,9,10). Second, the patient described in the report received a course of oral antibiotics that is shorter than the antibiotic courses endorsed or accepted by IDSA for chronic conditions such as tuberculosis, leprosy, complicated actinomycosis, Whipple’s disease, Q fever endocarditis, alveolar echinococcosis, osteomyelitis and asplenia prophylaxis; the risks of prolonged antibiotic therapy are considered acceptable for these conditions (11-18). While several clinical studies have demonstrated the safety of extended oral and intravenous antibiotic therapy for patients diagnosed with Lyme disease (19-22), caution should always be exercised in administering extended antibiotic therapy to any patient with a chronic infectious disease.

References

1. Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis 2010;51:369-70.

2. Johnson L, Stricker RB. The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about development of clinical practice guidelines. Philos Ethics Humanit Med 2010;5:9.

3. Johnson L, Stricker RB. Final report of the Lyme Disease Review Panel of the Infectious Diseases Society of America: A Pyrrhic victory? Clin Infect Dis 2010;51:1108-9.

4. Cameron DJ. Proof that chronic Lyme disease exists. Interdiscip Perspect Infect Dis 2010;2010:876450.

5. Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep. 2013;62:993-6.

6. Kotila SM, Virolainen A, Snellman M, Ibrahem S, Jalava J, Lyytikäinen O. Incidence, case fatality and genotypes causing Clostridium difficile infections, Finland, 2008. Clin Microbiol Infect 2011;17:888-93.

7. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812-22.

8. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 1999;67:302-7.

9. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis 2007;45:149-57.

10. Stricker RB, Johnson L. Lyme disease: The next decade. Infect Drug Resist 2011;4:1–9.

11. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001;345:189-200.

12. Cox H, Kebede Y, Allamuratova S, Ismailov G, Davletmuratova Z, Byrnes G, Stone C, Niemann S, Rüsch-Gerdes S, Blok L, Doshetov D. Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance. PLoS Med 2006;3:e384.

13. Garner JP, Macdonald M, Kumar PK. Abdominal actinomycosis. Int J Surg 2007;5:441-8.

14. Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol 2009;15:2078-80.

15. Liu YH, Wang XG, Gao JS, Qingyao Y, Horton J. Continuous albendazole therapy in alveolar echinococcosis: long-term follow-up observation of 20 cases. Trans R Soc Trop Med Hyg 2009;103:768-78.

16. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis 2005;9:127-38.

17. Price VE, Blanchette VS, Ford-Jones EL.The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 2007;21:697-710, viii-ix.

18. Beytout J, Tournilhac O, Laurichesse H. Antibiotic prophylaxis in splenectomized adults. Presse Med 2003;32(28 Suppl):S17-9.

19. Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997;25 Suppl 1:S52-6.

20. Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003;9:PI136-42.

21. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med 2010; 101:1–7.

22. Stricker RB, Delong AK, Green CL, Savely VR, Chamallas SN, Johnson L. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med 2011;4:639-46.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.

On 2013 Dec 20, Raphael Stricker commented:

Fatal Clostridium Difficile Colitis Following Treatment for Lyme Disease: The Wrong Message.

Raphael B. Stricker, MD* and Lorraine Johnson, JD, MBA*

*International Lyme and Associated Diseases Society, P.O. Box 341461, Bethesda, MD 20827-1461. www.ILADS.org

Holzbauer and colleagues (1) describe a case of fatal Clostridium difficile colitis in a patient treated with ten weeks of oral antibiotics for chronic Lyme disease. Rather than focusing on patient-specific risk factors and prevention of antibiotic-related complications, the authors preach about the dangers of treating Lyme disease outside the controversial guidelines of the Infectious Diseases Society of America (IDSA), which were the subject of an antitrust investigation by the Connecticut Attorney General (2,3). In doing so, the authors exaggerate the risks of treating Lyme disease and ignore the risks of failing to treat an ongoing spirochetal infection that may cause disability equivalent to congestive heart failure, and even death (4,5). Consequently the emphasis of the case report is misguided and ultimately detrimental to patient care.

In the single case described here, no information is given about cellular or humoral immune dysfunction that may have contributed to the rapid demise of the 52-year-old patient. This rapid demise is unusual in patients less than 80 years old with C. difficile colitis (6) and suggests the presence of a hypervirulent C. difficile ribotype that might explain the clinical course. Furthermore, the authors fail to mention whether the patient received probiotic therapy during the extended oral antibiotic treatment. Probiotic therapy appears to be effective in avoiding antibiotic-induced complications, and evidence suggests that certain probiotics may neutralize C. difficile toxin (7,8). The lack of probiotic therapy may have been a significant factor in this patient’s demise.

As for the appropriateness of antibiotic therapy in a patient with clinical and laboratory evidence of chronic Lyme disease, two points should be considered. First, two approaches to treatment of this tickborne illness have been described in the medical literature. The approach promulgated by IDSA proscribes extended antibiotic therapy for persistent symptoms related to infection with Borrelia burgdorferi, the spirochetal agent of Lyme disease (2). In contrast, the competing approach of the International Lyme and Associated Diseases Society (ILADS) considers this therapy to be appropriate based on evidence of persistent spirochetal infection (4,9,10). Second, the patient described in the report received a course of oral antibiotics that is shorter than the antibiotic courses endorsed or accepted by IDSA for chronic conditions such as tuberculosis, leprosy, complicated actinomycosis, Whipple’s disease, Q fever endocarditis, alveolar echinococcosis, osteomyelitis and asplenia prophylaxis; the risks of prolonged antibiotic therapy are considered acceptable for these conditions (11-18). While several clinical studies have demonstrated the safety of extended oral and intravenous antibiotic therapy for patients diagnosed with Lyme disease (19-22), caution should always be exercised in administering extended antibiotic therapy to any patient with a chronic infectious disease.

References

1. Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis 2010;51:369-70.

2. Johnson L, Stricker RB. The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about development of clinical practice guidelines. Philos Ethics Humanit Med 2010;5:9.

3. Johnson L, Stricker RB. Final report of the Lyme Disease Review Panel of the Infectious Diseases Society of America: A Pyrrhic victory? Clin Infect Dis 2010;51:1108-9.

4. Cameron DJ. Proof that chronic Lyme disease exists. Interdiscip Perspect Infect Dis 2010;2010:876450.

5. Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep. 2013;62:993-6.

6. Kotila SM, Virolainen A, Snellman M, Ibrahem S, Jalava J, Lyytikäinen O. Incidence, case fatality and genotypes causing Clostridium difficile infections, Finland, 2008. Clin Microbiol Infect 2011;17:888-93.

7. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812-22.

8. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 1999;67:302-7.

9. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis 2007;45:149-57.

10. Stricker RB, Johnson L. Lyme disease: The next decade. Infect Drug Resist 2011;4:1–9.

11. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001;345:189-200.

12. Cox H, Kebede Y, Allamuratova S, Ismailov G, Davletmuratova Z, Byrnes G, Stone C, Niemann S, Rüsch-Gerdes S, Blok L, Doshetov D. Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance. PLoS Med 2006;3:e384.

13. Garner JP, Macdonald M, Kumar PK. Abdominal actinomycosis. Int J Surg 2007;5:441-8.

14. Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol 2009;15:2078-80.

15. Liu YH, Wang XG, Gao JS, Qingyao Y, Horton J. Continuous albendazole therapy in alveolar echinococcosis: long-term follow-up observation of 20 cases. Trans R Soc Trop Med Hyg 2009;103:768-78.

16. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis 2005;9:127-38.

17. Price VE, Blanchette VS, Ford-Jones EL.The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 2007;21:697-710, viii-ix.

18. Beytout J, Tournilhac O, Laurichesse H. Antibiotic prophylaxis in splenectomized adults. Presse Med 2003;32(28 Suppl):S17-9.

19. Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997;25 Suppl 1:S52-6.

20. Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003;9:PI136-42.

21. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med 2010; 101:1–7.

22. Stricker RB, Delong AK, Green CL, Savely VR, Chamallas SN, Johnson L. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med 2011;4:639-46.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.