Microsporidiosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]


Overview

The mainstay of therapy for microsporidiosis in immunocompromised patients is highly active antiretroviral therapy (HAART). Albendazole and fumagillin have demonstrated consistent activity against other microsporidia in vitro and in vivo.

Medical Therapy

CDC Guidelines for Prevention and Treatment of Microsporidiosis Infections in HIV-Infected Adults and Adolescents

Treatment Recommendations

  • ART with immune restoration (an increase of CD4+T lymphocyte count >100 cells/µL) is associated with resolution of symptoms of enteric microsporidiosis, including that caused by E. bieneusi.[1][2][3]
  • All patients should be offered ART as part of the initial management of their infection (AII). Nevertheless, data indicate that microsporidia are suppressed but not eliminated.[2]
  • No specific therapeutic agent is active against E. bieneusi infection. A controlled clinical trial suggests that E. bieneusi might respond to oral fumagillin (60 mg/day), a water insoluble antibiotic made by Aspergillus fumigatus (BII).[4][5]
  • However, fumagillin is not available for systemic use in the United States. One report indicates that 60 days of nitazoxanide might resolve chronic diarrhea caused by E. bieneusi in the absence of ART.[6]
  • However, the effect might be minimal among patients with low CD4+ T cell counts. Nitazoxanide is approved for use among children and is expected to be approved by the FDA for use among adults.
  • Albendazole and fumagillin have demonstrated consistent activity against other microsporidia in vitro and in vivo.[7][8][9][10][11]
  • Albendazole, a benzimidazole that binds to b-tubulin, has activity against many species of microsporidia, but it is not effective for Enterocytozoon infections, although fumagillin has activity in vitro and in vivo.
  • Albendazole is recommended for initial therapy of intestinal and disseminated (not ocular) microsporidiosis caused by microsporidia other than E. bieneusi (AII).
  • Itraconazole also might be useful in the disseminated disease when combined with albendazole especially in infections caused by Trachipleistophora or Brachiola (CIII).
  • Ocular infections caused by microsporidia should be treated with topical Fumidil B (fumagillin bicylohexylammonium) in saline (to achieve a concentration of 70 mg/mL of fumagillin)(BII).[11] Topical fumagillin is the only formulation available for treatment in the United States and is investigational.
  • Although clearance of microsporidia from the eye can be demonstrated, the organism often is still present systemically and can be detected in the urine or in nasal smears. In such cases, the use of albendazole as a companion systemic agent is recommended (BIII).
  • Metronidazole and atovaquone are not active in vitro or in animal models and should not be used to treat microsporidiosis (DII). Fluid support should be offered if diarrhea has resulted in dehydration (AIII). Malnutrition and wasting should be treated with nutritional supplementation (AIII).
Rating Strength of recommendation
A Both strong evidence for efficacy and substantial

clinical benefit support recommendation for use.

Should always be offered

B Moderate evidence for efficacy—or strong

evidence for efficacy but only limited clinical

benefit—supports the recommendation for use.

Should generally be offered.

C Evidence for efficacy is insufficient to support a

recommendation for or against use or evidence

for efficacy might not outweigh adverse conse-

quences (e.g. drug toxicity, drug interactions) or the

cost of the treatment or alternative approaches.

Optional.

D Moderate evidence for lack of efficacy or for

adverse outcome supports a recommendation

against use. Generally, treatment should not be offered.

E Good evidence for lack of efficacy or for [[adverse

outcome]] supports a recommendation against use.

Should never be offered.

Rating Quality of the evidence supporting

the recommendation

I Evidence from at least one properly-designed

randomized, controlled trial.

II Evidence from at least one well-designed clinical

trial without randomization, from cohort or case-

controlled analytic studies (preferably from more

than one center), or from multiple time-series

studies, or dramatic results from uncontrolled

experiments.

III Evidence from opinions of respected authorities

based on clinical experience, descriptive studies,

or reports of expert committees.

Monitoring and Adverse Events

Albendazole side effects are rare but the following adverse effects should be watched for:

Fumagillin side effects:

Management of Treatment Failure

Supportive treatment and optimizing ART to attempt to achieve full virologic suppression are the only feasible approaches to the management of treatment failure (CIII).

Special Considerations During Pregnancy

  • Among animals (i.e., rats and rabbits), albendazole is embryotoxic and teratogenic at dosages of 30 mg/kg body weight. Therefore, albendazole is not recommended for use among pregnant women (DIII). However, well-controlled studies in human pregnancy have not been performed.
  • Systemic fumagillin has been associated with increased resorption and growth retardation in rats. No data on use in human pregnancy are available. However, because of the antiangiogenic effect of fumagillin, this drug should not be used among pregnant women (EIII).
  • Topical fumagillin has not been associated with embryotoxic or teratogenic effects among pregnant women and might be considered when therapy with this agent is appropriate (CIII).

Antimicrobial Regimen

  • Microsporidiosis
  • 2. Intestinal (diarrhea)[13]
  • Preferred regimen:
  • Adult: Albendazole 400 mg PO bid for 3 weeks for E. intestinalis.
  • Pediatric: Albendazole 15 mg/kg per day divided into 2 daily doses for 7 days for E. intestinalis.
  • Note: Fumagillin 20 mg PO tid is the only reported effective treatment for E. bieneusi.
  • Preferred regimen: Albendazole 400 mg po bid for 3 weeks.

References

  1. Maggi P, Larocca AM, Quarto M, Serio G, Brandonisio O, Angarano G, Pastore G (2000). "Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1". Eur. J. Clin. Microbiol. Infect. Dis. 19 (3): 213–7. PMID 10795595. Retrieved 2012-04-19. 
  2. 2.0 2.1 Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM (1997). "Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy". AIDS. 11 (13): 1658–9. PMID 9365777. Retrieved 2012-04-19. 
  3. Conteas CN, Berlin OG, Speck CE, Pandhumas SS, Lariviere MJ, Fu C (1998). "Modification of the clinical course of intestinal microsporidiosis in acquired immunodeficiency syndrome patients by immune status and anti-human immunodeficiency virus therapy". Am. J. Trop. Med. Hyg. 58 (5): 555–8. PMID 9598440. Retrieved 2012-04-19. 
  4. Molina JM, Goguel J, Sarfati C, Michiels JF, Desportes-Livage I, Balkan S, Chastang C, Cotte L, Maslo C, Struxiano A, Derouin F, Decazes JM (2000). "Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA". AIDS. 14 (10): 1341–8. PMID 10930148. Retrieved 2012-04-19. 
  5. Molina JM, Tourneur M, Sarfati C, Chevret S, de Gouvello A, Gobert JG, Balkan S, Derouin F (2002). "Fumagillin treatment of intestinal microsporidiosis". N. Engl. J. Med. 346 (25): 1963–9. PMID 12075057. doi:10.1056/NEJMoa012924. Retrieved 2012-04-19. 
  6. Bicart-Sée A, Massip P, Linas MD, Datry A (2000). "Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS". Antimicrob. Agents Chemother. 44 (1): 167–8. PMC 89645Freely accessible. PMID 10602740. 
  7. Didier ES (1997). "Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro". Antimicrob. Agents Chemother. 41 (7): 1541–6. PMC 163955Freely accessible. PMID 9210681. Retrieved 2012-04-19. 
  8. Katiyar SK, Edlind TD (1997). "In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives". Antimicrob. Agents Chemother. 41 (12): 2729–32. PMC 164197Freely accessible. PMID 9420047. Retrieved 2012-04-19. 
  9. Molina JM, Chastang C, Goguel J, Michiels JF, Sarfati C, Desportes-Livage I, Horton J, Derouin F, Modaï J (1998). "Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial". J. Infect. Dis. 177 (5): 1373–7. PMID 9593027. Retrieved 2012-04-19. 
  10. Gritz DC, Holsclaw DS, Neger RE, Whitcher JP, Margolis TP (1997). "Ocular and sinus microsporidial infection cured with systemic albendazole". Am. J. Ophthalmol. 124 (2): 241–3. PMID 9262551. 
  11. 11.0 11.1 Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT (1993). "Treatment of microsporidial keratoconjunctivitis with topical fumagillin". Am. J. Ophthalmol. 115 (3): 293–8. PMID 8117342. 
  12. Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843. 
  13. Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843. 
  14. Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843. 

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