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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31817beb78
Letters to the Editor

Resolution of Severe Cryptosporidial Diarrhea With Rifaximin in Patients With AIDS

Gathe, Joseph C Jr MD, FACP*; Mayberry, Carl PA*; Clemmons, John MD†; Nemecek, John MD*

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*Therapeutic Concepts Houston, TX †Private Practice Houston, TX

To the Editor:

Cryptosporidiosis is a parasitic infection of the gastrointestinal tract caused by Cryptosporidium parvum that results in profuse, watery diarrhea1 and may cause life-threatening dehydration and electrolyte abnormalities in individuals with severe immune deficiencies.2 Cryptosporidium infections occur in up to 11% of patients with human immunodeficiency virus (HIV), and patients with advanced immunosuppression (CD4+ count <100 cells/mm3) are at greatest risk for substantial morbidity and mortality from this parasitic infection.3

No definitive therapy has been established for the treatment of cryptosporidial diarrhea in patients with HIV. The oral, nonsystemic antibiotic rifaximin (Xifaxan; Salix Pharmaceuticals, Inc, Morrisville, NC) demonstrates favorable characteristics that makes it a potential treatment option for cryptosporidiosis. Rifaximin is minimally absorbed4 with broad-spectrum in vitro activity against enteric pathogens (eg, Escherichia coli, Clostridium difficile, and Campylobacter jejuni),5,6 placebo-like tolerability in studies of infectious diarrhea,7,8 no known drug-drug interactions, and a lack of clinically relevant antibiotic resistance.9 In an open-label study that evaluated the efficacy of rifaximin therapy in the clearance of protozoan infections in HIV-infected patients (n = 15; CD4+ counts ≥200 cells/mm3), rifaximin 1800 mg/d for 14 days resolved clinical symptoms of infectious diarrhea and eradicated pathogenic protozoa (ie, C. parvum or Blastocystis hominis).10 However, no study to date has evaluated the potential benefit of rifaximin in immunocompromised patients with CD4+ counts <200 cells/mm3. Herein, we report on the efficacy of rifaximin in 5 patients with AIDS (CD4+ count <50 cells/mm3) who were refractory to antiretroviral therapy and were diagnosed with symptomatic cryptosporidial diarrhea. Patients were followed for up to 125 weeks after open-label administration of oral rifaximin 400 mg twice daily (b.i.d.) for up to 8 weeks.

Patient 1 was a 38-year-old male diagnosed with AIDS in 2001. On July 19, 2004, he presented with severe diarrhea and weight loss (Table 1). After failing treatment with systemic antibiotics and multiple HIV therapies and experiencing persistent diarrhea, on October 14, 2004, the patient was prescribed rifaximin 800 mg/d for 8 weeks. Within 3 days, he experienced complete resolution of diarrhea. A stool sample analyzed after completion of rifaximin treatment was negative for cryptosporidial oocysts. At week 105, the patient experienced another cryptosporidial infection and responded to retreatment with rifaximin 800 mg/d; however, the patient died on November 19, 2006, of HIV-related complications.

Table 1
Table 1
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Patient 2 was a 46-year-old male diagnosed with AIDS on July 19, 2002. He was resistant to 3 classes of HIV therapy and refractory to combination therapy with paromomycin and azithromycin. On August 3, 2004, he presented with weight loss and persistent diarrhea (Table 1). On October 19, 2004, the patient began therapy with rifaximin 800 mg/d and reported complete resolution of diarrhea within 48 hours of starting treatment. Within 3 weeks, he gained weight, and a stool sample was negative for cryptosporidial oocysts. At follow-up during week 125, the patient remained asymptomatic despite a persistent CD4+ count <200 cells/mm3.

Patient 3 was a 43-year-old male with AIDS since 1992 who was diagnosed with cryptosporidial diarrhea in July 2004. Despite treatment with oral and intravenous azithromycin, the patient remained severely immunosuppressed and was hospitalized on January 21, 2005, due to persistent diarrhea (Table 1). He received rifaximin 800 mg/d for 8 weeks and experienced complete resolution of diarrhea within 48 hours. A stool sample was negative for cryptosporidial oocysts within 10 days. The patient exhibited no relapse of cryptosporidial diarrhea after 47 weeks of follow-up and died without relapse on December 18, 2005, from other disease-related complications.

Patient 4 was a 38-year-old male diagnosed with AIDS on November 9, 2004. Despite treatment with oral trimethoprim-sulfamethoxazole and oral azithromycin, he was hospitalized on April 15, 2005, with weight loss, fatigue, and diarrhea (Table 1). The patient was prescribed rifaximin 800 mg/d for 14 days and experienced complete resolution of diarrhea within 3 days and weight gain within 10 days. A stool sample indicated organism eradication by day 18. After 100 weeks of follow-up, the patient remained asymptomatic without relapse despite a CD4+ count <200 cells/mm3.

Patient 5 was a 40-year-old male with AIDS since 1991 and resistance to 4 classes of HIV therapy. He was hospitalized on April 16, 2005, with profound immunosuppression, complaints of diarrhea for >12 weeks, and weight loss (Table 1). Rifaximin 800 mg/d was administered for 3 weeks, and the patient experienced complete resolution of diarrhea within 5 days after initiation of treatment. No stool sample was available to confirm organism eradication. However, the patient remained free of all gastrointestinal symptoms until he died 9 months later due to sequelae of immune reconstitution syndrome.

The incidence of enteric protozoan infections has increased substantially with the rapid spread of HIV, and certain infectious pathogens (eg, Cryptosporidium) are associated with increased morbidity in these immunocompromised patients.4 Although no definitive treatment has been established, antimicrobial therapy is often administered for the treatment of cryptosporidial diarrhea in HIV-infected patients. The nonsystemic antibiotic rifaximin is a potential treatment option for cryptosporidiosis in immunocompromised individuals. Results of a published study (n = 15) showed that rifaximin was beneficial in reducing clinical symptoms and eradicating protozoan enteric infection in HIV-infected patients (CD4+ count ≥200 cells/mm3) coinfected with C. parvum.10 This is the first published report of rifaximin for treatment of cryptosporidial diarrhea in patients with AIDS and severe immunosuppression. Despite prolonged gastrointestinal symptoms, profound resistant immunosuppression, and failure of prior anticryptosporidial interventions, patients experienced a robust response with rifaximin 800 mg/d. These findings demonstrate the substantial clinical benefit of rifaximin in the treatment of cryptosporidial diarrhea in patients with HIV and warrant additional confirmatory clinical trials.

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ACKNOWLEDGMENTS

Study supported by Salix Pharmaceuticals, Inc.

Joseph C. Gathe, Jr., MD, FACP*

Carl Mayberry, PA*

John Clemmons, MD†

John Nemecek, MD*

*Therapeutic Concepts Houston, TX

†Private Practice Houston, TX

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REFERENCES

1. Reeders JW, Yee J, Gore RM, et al. Gastrointestinal infection in the immunocompromised (AIDS) patient. Eur Radiol. 2004;14(Suppl 3):E84-E102.

2. Dionisio D. Cryptosporidiosis in HIV-infected patients. J Postgrad Med. 2002;48:215-216.

3. Miao YM, Awad-El-Kariem FM, Franzen C, et al. Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy. J Acquir Immune Defic Syndr. 2000;25:124-129.

4. Jiang Z-D, Ke S, Palazzini E, et al. In vitro activity and fecal concentration of rifaximin after oral administration. Antimicrob Agents Chemother. 2000;44:2205-2206.

5. Gomi H, Jiang Z-D, Adachi JA, et al. In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing traveler's diarrhea in four geographic regions. Antimicrob Agents Chemother. 2001;45:212-216.

6. Ripa S, Mignini F, Prenna M, et al. In vitro antibacterial activity of rifaximin against Clostridium difficile, Campylobacter jejuni and Yersinia spp. Drugs Exp Clin Res. 1987;13:483-488.

7. DuPont HL, Jiang Z-D, Okhuysen PC, et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers' diarrhea. Ann Intern Med. 2005;142:805-812.

8. Steffen R, Sack DA, Riopel L, et al. Therapy of travelers' diarrhea with rifaximin on various continents. Am J Gastroenterol. 2003;98:1073-1078.

9. Jiang Z-D, DuPont HL. Rifaximin: in vitro and in vivo antibacterial activity-a review. Chemotherapy. 2005;51(Suppl 1):67-72.

10. Amenta M, Dalle Nogare ER, Colomba C, et al. Intestinal protozoa in HIV-infected patients: effect of rifaximin in Cryptosporidium parvum and Blastocystis hominis infections. J Chemother. 1999;11:391-339.

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