Update: Treatment of Cryptosporidiosis in Patients with Acquired Immunodeficiency Syndrome (AIDS)

In November 1982, 21 patients with acquired immunodeficiency syndrome (AIDS) and severe, protracted diarrhea caused by cryptosporidiosis were reported; the report concluded that no effective treatment for cryptosporidiosis was known at that time (1). Since then, 91 additional AIDS patients with chronic cryptosporidiosis have been reported to CDC. Although no therapy has been consistently effective in treating them, preliminary reports suggest that a few may have responded to treatment with spiramycin (Rovamycine,* Rhone-Poulenc Pharma, Montreal) or the combination of quinine and clindamycin.

Since December 1982, physicians at the University of Miami, Florida, have used spiramycin to treat seven AIDS patients with chronic cryptosporidiosis; six other AIDS patients with cryptosporidiosis have been treated with spiramycin at five other institutions; and one non-AIDS patient with chronic cryptosporidiosis associated with a bone marrow transplant has received the drug. Thirteen of the 14 patients were adults; they received 1 g of spiramycin orally three or four times a day. The 14th patient, a 2-year-old child, received 500 mg orally twice a day. No adverse effects were attributed to the drug.

Three of the 13 AIDS patients were apparently cured after 3-4 weeks of spiramycin therapy (i.e., all three improved symptomatically, and intestinal biopsies and three successive stool examinations after therapy were negative). Follow-up 6-7 months after discontinuation of spiramycin revealed that all three remained asymptomatic. Two have subsequently died from causes related to their underlying immunodeficiency--one with Kaposi's sarcoma, the other with Pneumocystis carinii pneumonia.

In an additional three AIDS patients, gastrointestinal symptoms improved rapidly with spiramycin (in two cases, within 48 hours of starting the drug), but these patients continued to have Cryptosporidium in their stools. Spiramycin was continued for variable periods of time, but when therapy was stopped, diarrhea in each patient promptly recurred. On reinitiation of spiramycin, two of the three again improved, but the third continued to have severe diarrhea and has since died. One of the two surviving patients had Cryptosporidium detected in his stool at weekly intervals for the first 3H months of therapy. The patient recently had three negative stools, and spiramycin was stopped; he now has been off therapy for 2 weeks and remains asymptomatic.

The remaining seven AIDS patients did not respond symptomatically or parasitologically to spiramycin. Three, however, died within 2-7 days after starting spiramycin. None of the deaths was attributed to spiramycin.

A non-AIDS patient with chronic cryptosporidiosis, acquired after receiving a bone marrow transplant, also improved with spiramycin therapy. She began spiramycin after suffering from severe, watery diarrhea and abdominal cramps for 6 weeks; within 24 hours, her cramps had resolved and her diarrhea had improved, and 2 weeks later, she was having one bowel movement a day. After 3 weeks of therapy, a stool examination was negative for Cryptosporidium.

CDC has also received six reports of AIDS patients and one bone marrow transplant patient with cryptosporidiosis who were treated with a combination of quinine and clindamycin, both given orally. Two patients did not respond after 7-14 days of therapy. In three others, the drugs were discontinued because of adverse effects; one developed a severe rash; another, severe vomiting; the third, thrombocytopenia. Symptoms improved in two of these three patients during the first few days of therapy. The sixth patient had acute cholecystitis and diarrhea associated with Cryptosporidium of the cystic duct and intestines. He received 300 mg of clindamycin and 250 mg of quinine, given orally four times a day. Within 2 days of initiating therapy, the patient's diarrhea resolved, but stool examinations after therapy continued to show occasional Cryptosporidium. A seventh patient, who developed chronic cryptosporidiosis after receiving a bone marrow transplant, also received oral quinine and clindamycin; the patient showed no clinical improvement despite 2 weeks of therapy. Reported by M Whiteside, MD, C MacLeod, MD, M Fischl, MD, G Scott, MD, Miami, Florida; J Cain, MD, M Wolfe, MD, Washington, DC; T Brasitus, MD, Chicago, Illinois; B Blazar, MD, Minneapolis, Minnesota; R Glickman, MD, New York City, R Soave, MD, D Kaufman, MD, New York; E Buckley, MD, Durham, North Carolina; G Poporad, MD, Elkins Park, S Gluckman, MD, W Lipshutz, MD, R Kaplan, MD, Philadelphia, Pennsylvania; D Portnoy, MD, M Zaklos, MD, Montreal, Quebec, Canada; AIDS Activity, Div of Host Factors, Protozoal Diseases Br, Div of Parasitic Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Cryptosporidium is a protozoan parasite that causes severe, protracted diarrhea in immune suppressed patients. The first patient with human cryptosporidiosis was reported in 1976, and before 1982, only seven cases of human cryptosporidiosis had been published. During 1982 and 1983, however, the number of reported cases has increased steadily (2).

The case reports described here are the first to offer encouragement in the treatment of cryptosporidiosis in immune suppressed patients. However, these reports must be viewed cautiously for several reasons. Most of the patients have had no response to spiramycin or the combination of clindamycin and quinine, and many of the patients who have responded symptomatically have not had parasitologic cures. Furthermore, treatment with clindamycin and quinine was associated frequently with adverse effects. Little is known about spiramycin's antiprotozoal activity. There are no published reports evaluating the efficacy of spiramycin against cryptosporidiosis in animals, and preliminary results by investigators at Auburn University, Alabama, suggest that spiramycin does not inhibit Cryptosporidium growth in tissue culture (3). Spiramycin is used in Europe and Canada to treat infections caused by another protozoan parasite, Toxoplasma gondii, but studies of spiramycin's efficacy for human toxoplasmosis have not included appropriate control groups, and animal studies have produced equivocal results (4-7).

Spiramycin is a macrolide antibiotic with an antimicrobial activity similar to erythromycin and clindamycin. It has been used in Europe and Canada for over 20 years to treat bacterial infections. Serious adverse effects from spiramycin are apparently rare, and no drug-associated deaths have been reported. Two patients have been reported who complained of nausea, sweating, giddiness, and paresthesia 1 hour after a single oral dose of 3 g; the symptoms subsided spontaneously within an hour (8). Mild to moderate diarrhea, including bloody diarrhea in two cases, has been reported in patients receiving various doses of spiramycin (8-12). Other reports of adverse reactions include one patient who developed a mild rash and others who developed contact dermatitis after handling spiramycin in animal feed (13-16).

The U.S. Food and Drug Administration (FDA) has not approved spiramycin for routine use, and therefore, the drug is not commercially available in the United States. Physicians in the United States who wish to obtain spiramycin should contact the FDA's Division of Anti-infective Drug Products, telephone (301) 443-4310.

References

1. CDC. Cryptosporidiosis: assessment of chemotherapy of males with acquired immune deficiency syndrome (AIDS). MMWR 1982;31:589-92.

2. Navin TR, Juranek DD. Cryptosporidiosis: clinical, epidemiologic and parasitologic review. Rev Infect Dis (in press).

3. Current WL. Auburn University. Unpublished data.

4. Beverley JKA, Freeman AP, Henry L, Whelan JPF. Prevention of pathologic changes in experimental congenital toxoplasma infections. Lyon Medical 1973;230:491-8.

5. Thiermann E, Apt W, Atias A, Lorca M, Olguin J. A comparative study of some combined treatment regimens in acute toxoplasmosis in mice. Am J Trop Med Hyg 1978;27:747-50.

6. Coradello H, Kretschmer S. Vergleichende Untersuchung der Wirksamkeit von Ultrax, Diazil, Baktrim und Spiramycin auf die experimentelle Toxoplasmose der Maus. Wien Klin Wochenschr 1978;90:25-9.

7. Desmonts G, Couvreur J. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N Engl J Med 1974;290:1110-6.

8. Kamme C, Kahlmeter G, Melander A. Evaluation of spiramycin as a therapeutic agent for elimination of nasopharyngeal pathogens. Possible use of spiramycin for middle ear infections and for gonococcal and meningococcal nasopharyngeal carriage. Scand J Infect Dis 1978;10:135-42.

9. Hudson DG, Yoshihara GM, Kirby WM. Spiramycin: clinical and laboratory studies. AMA Arch Intern Med 1956;97:57-61.

10. Kamme C, Kahlmeter G. Evaluation of spiramycin in meningococcal carriage. Scand J Infect Dis 1979;11:229-32.

11. Di Febo G, Milazzo G, Gizzi G, Biasco G, Miglioli M. Antibiotic-associated colitis: always pseudomembranous? Endoscopy 1982;14:128-30.

12. Decaux GM, Devroede C. Acute colitis related to spiramycin. Lancet (letter) 1978;II:993.

13. Macfarlane JA, Mitchell AA, Walsh JM, Robertson JJ. Spiramycin in

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