Microsporidiosis medical therapy: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Microsporidiosis}} | {{Microsporidiosis}} | ||
{{CMG}};{{AE}}{{AY}} | |||
{{CMG}}; {{AE}}{{AY}} | |||
==Overview== | ==Overview== | ||
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===CDC Guidelines for Prevention and Treatment of Microsporidiosis Infections in HIV-Infected Adults and Adolescents=== | ===CDC Guidelines for Prevention and Treatment of Microsporidiosis Infections in HIV-Infected Adults and Adolescents=== | ||
====Treatment Recommendations==== | ====Treatment Recommendations==== | ||
* [[AIDS antiretroviral drugs|ART]] with immune restoration (an increase of [[CD4 | * [[AIDS antiretroviral drugs|ART]] with immune restoration (an increase of [[CD4+ T cells|CD4<sup>+</sup>T lymphocyte]] count >100 cells/µL) is associated with resolution of symptoms of enteric microsporidiosis, including that caused by E. bieneusi.<ref name="pmid10795595">{{cite journal |author=Maggi P, Larocca AM, Quarto M, Serio G, Brandonisio O, Angarano G, Pastore G |title=Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1 |journal=Eur. J. Clin. Microbiol. Infect. Dis. |volume=19 |issue=3 |pages=213–7 |year=2000 |month=March |pmid=10795595 |doi= |url=http://link.springer.de/link/service/journals/10096/bibs/0019003/00190213.htm |accessdate=2012-04-19}}</ref><ref name="pmid9365777">{{cite journal |author=Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM |title=Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy |journal=AIDS |volume=11 |issue=13 |pages=1658–9 |year=1997 |month=November |pmid=9365777 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=11&issue=13&spage=1658 |accessdate=2012-04-19}}</ref><ref name="pmid9598440">{{cite journal |author=Conteas CN, Berlin OG, Speck CE, Pandhumas SS, Lariviere MJ, Fu C |title=Modification of the clinical course of intestinal microsporidiosis in acquired immunodeficiency syndrome patients by immune status and anti-human immunodeficiency virus therapy |journal=Am. J. Trop. Med. Hyg. |volume=58 |issue=5 |pages=555–8 |year=1998 |month=May |pmid=9598440 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=9598440 |accessdate=2012-04-19}}</ref> | ||
* All patients should be offered [[ART4|ART]] as part of the initial management of their infection ('''AII'''). Nevertheless, data indicate that microsporidia are suppressed but not eliminated.<ref name="pmid9365777">{{cite journal |author=Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM |title=Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy |journal=AIDS |volume=11 |issue=13 |pages=1658–9 |year=1997 |month=November |pmid=9365777 |doi=|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=11&issue=13&spage=1658 |accessdate=2012-04-19}}</ref> | * All patients should be offered [[ART4|ART]] as part of the initial management of their infection ('''AII'''). Nevertheless, data indicate that microsporidia are suppressed but not eliminated.<ref name="pmid9365777">{{cite journal |author=Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM |title=Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy |journal=AIDS |volume=11 |issue=13 |pages=1658–9 |year=1997 |month=November |pmid=9365777 |doi=|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=11&issue=13&spage=1658 |accessdate=2012-04-19}}</ref> | ||
* 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''').<ref name="pmid10930148">{{cite journal |author=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 |title=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 |journal=AIDS |volume=14 |issue=10 |pages=1341–8 |year=2000 |month=July |pmid=10930148 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=14&issue=10&spage=1341 |accessdate=2012-04-19}}</ref><ref name="pmid12075057">{{cite journal |author=Molina JM, Tourneur M, Sarfati C, Chevret S, de Gouvello A, Gobert JG, Balkan S, Derouin F |title=Fumagillin treatment of intestinal microsporidiosis |journal=N. Engl. J. Med. |volume=346 |issue=25 |pages=1963–9 |year=2002 |month=June |pmid=12075057 |doi=10.1056/NEJMoa012924 |url=http://dx.doi.org/10.1056/NEJMoa012924 |accessdate=2012-04-19}}</ref> | * 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''').<ref name="pmid10930148">{{cite journal |author=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 |title=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 |journal=AIDS |volume=14 |issue=10 |pages=1341–8 |year=2000 |month=July |pmid=10930148 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=14&issue=10&spage=1341 |accessdate=2012-04-19}}</ref><ref name="pmid12075057">{{cite journal |author=Molina JM, Tourneur M, Sarfati C, Chevret S, de Gouvello A, Gobert JG, Balkan S, Derouin F |title=Fumagillin treatment of intestinal microsporidiosis |journal=N. Engl. J. Med. |volume=346 |issue=25 |pages=1963–9 |year=2002 |month=June |pmid=12075057 |doi=10.1056/NEJMoa012924 |url=http://dx.doi.org/10.1056/NEJMoa012924 |accessdate=2012-04-19}}</ref> | ||
* 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.<ref name="pmid10602740">{{cite journal |author=Bicart-Sée A, Massip P, Linas MD, Datry A |title=Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS |journal=Antimicrob. Agents Chemother. |volume=44 |issue=1 |pages=167–8 |year=2000 |month=January |pmid=10602740 |pmc=89645 |doi= |url= |accessdate=2012-04-19}}</ref> | * 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.<ref name="pmid10602740">{{cite journal |author=Bicart-Sée A, Massip P, Linas MD, Datry A |title=Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS |journal=Antimicrob. Agents Chemother. |volume=44 |issue=1 |pages=167–8 |year=2000 |month=January |pmid=10602740 |pmc=89645 |doi= |url= |accessdate=2012-04-19}}</ref> | ||
* 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. | * 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.<ref name="pmid9210681">{{cite journal |author=Didier ES |title=Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro |journal=Antimicrob. Agents Chemother. |volume=41 |issue=7 |pages=1541–6 |year=1997 |month=July |pmid=9210681 |pmc=163955 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9210681 |accessdate=2012-04-19}}</ref><ref name="pmid9420047">{{cite journal |author=Katiyar SK, Edlind TD |title=In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives |journal=Antimicrob. Agents Chemother. |volume=41 |issue=12 |pages=2729–32 |year=1997 |month=December |pmid=9420047 |pmc=164197 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9420047 |accessdate=2012-04-19}}</ref><ref name="pmid9593027">{{cite journal |author=Molina JM, Chastang C, Goguel J, Michiels JF, Sarfati C, Desportes-Livage I, Horton J, Derouin F, Modaï J |title=Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial |journal=J. Infect. Dis. |volume=177 |issue=5 |pages=1373–7 |year=1998 |month=May |pmid=9593027 |doi= |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9593027 |accessdate=2012-04-19}}</ref><ref name="pmid9262551">{{cite journal |author=Gritz DC, Holsclaw DS, Neger RE, Whitcher JP, Margolis TP |title=Ocular and sinus microsporidial infection cured with systemic albendazole |journal=Am. J. Ophthalmol. |volume=124 |issue=2 |pages=241–3 |year=1997 |month=August |pmid=9262551 |doi= |url= |accessdate=2012-04-19}}</ref><ref name="pmid8117342">{{cite journal |author=Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT |title=Treatment of microsporidial keratoconjunctivitis with topical fumagillin |journal=Am. J. Ophthalmol. |volume=115 |issue=3 |pages=293–8 |year=1993 |month=March |pmid=8117342 |doi= |url= |accessdate=2012-04-19}}</ref> | * [[Albendazole]] and [[fumagillin]] have demonstrated consistent activity against other microsporidia in vitro and in vivo.<ref name="pmid9210681">{{cite journal |author=Didier ES |title=Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro |journal=Antimicrob. Agents Chemother. |volume=41 |issue=7 |pages=1541–6 |year=1997 |month=July |pmid=9210681 |pmc=163955 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9210681 |accessdate=2012-04-19}}</ref><ref name="pmid9420047">{{cite journal |author=Katiyar SK, Edlind TD |title=In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives |journal=Antimicrob. Agents Chemother. |volume=41 |issue=12 |pages=2729–32 |year=1997 |month=December |pmid=9420047 |pmc=164197 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9420047 |accessdate=2012-04-19}}</ref><ref name="pmid9593027">{{cite journal |author=Molina JM, Chastang C, Goguel J, Michiels JF, Sarfati C, Desportes-Livage I, Horton J, Derouin F, Modaï J |title=Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial |journal=J. Infect. Dis. |volume=177 |issue=5 |pages=1373–7 |year=1998 |month=May |pmid=9593027 |doi= |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9593027 |accessdate=2012-04-19}}</ref><ref name="pmid9262551">{{cite journal |author=Gritz DC, Holsclaw DS, Neger RE, Whitcher JP, Margolis TP |title=Ocular and sinus microsporidial infection cured with systemic albendazole |journal=Am. J. Ophthalmol. |volume=124 |issue=2 |pages=241–3 |year=1997 |month=August |pmid=9262551 |doi= |url= |accessdate=2012-04-19}}</ref><ref name="pmid8117342">{{cite journal |author=Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT |title=Treatment of microsporidial keratoconjunctivitis with topical fumagillin |journal=Am. J. Ophthalmol. |volume=115 |issue=3 |pages=293–8 |year=1993 |month=March |pmid=8117342 |doi= |url= |accessdate=2012-04-19}}</ref> | ||
* [[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]], a [[benzimidazole]] that binds to b-[[tubulin]], has activity against many species of microsporidia, but it is not effective for [[Enterocytozoon bieneusi|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'''). | * [[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 disseminated disease when combined with [[albendazole]] especially in infections caused by Trachipleistophora or Brachiola ('''CIII'''). | * [[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''').<ref name="pmid8117342">{{cite journal |author=Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT |title=Treatment of microsporidial keratoconjunctivitis with topical fumagillin |journal=Am. J. Ophthalmol. |volume=115 |issue=3 |pages=293–8 |year=1993 |month=March |pmid=8117342 |doi= |url= |accessdate=2012-04-19}}</ref> Topical fumagillin is the only formulation available for treatment in the United States and is investigational. | * Ocular infections caused by [[microsporidia]] should be treated with [[topical]] Fumidil B [[Fumagillin|(fumagillin]] bicylohexylammonium) in [[saline]] (to achieve a concentration of 70 mg/mL of fumagillin)('''BII''').<ref name="pmid8117342">{{cite journal |author=Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT |title=Treatment of microsporidial keratoconjunctivitis with topical fumagillin |journal=Am. J. Ophthalmol. |volume=115 |issue=3 |pages=293–8 |year=1993 |month=March |pmid=8117342 |doi= |url= |accessdate=2012-04-19}}</ref> 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'''). | * 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'''). | * [[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|Malnutrition and wasting]] should be treated with nutritional supplementation ('''AIII'''). | ||
{| class="wikitable" | {| class="wikitable" | ||
!Rating | !Rating | ||
| Line 26: | Line 29: | ||
|- | |- | ||
|A | |A | ||
|Both strong evidence for efficacy and substantial | |Both strong [[evidence]] for [[efficacy]] and substantial | ||
clinical benefit support recommendation for use. | clinical benefit support recommendation for use. | ||
| Line 32: | Line 35: | ||
|- | |- | ||
|B | |B | ||
|Moderate evidence for | |Moderate evidence for [[efficacy]]—or strong | ||
evidence for efficacy but only limited clinical | evidence for efficacy but only limited clinical | ||
| Line 40: | Line 43: | ||
|- | |- | ||
|C | |C | ||
|Evidence for efficacy is insufficient to support a | |Evidence for [[efficacy]] is insufficient to support a | ||
recommendation for or against use | recommendation for or against use or evidence | ||
for efficacy might not outweigh adverse conse- | for [[efficacy]] might not outweigh adverse conse- | ||
quences (e.g. drug toxicity, drug interactions) or the | quences (e.g. [[drug toxicity]], [[Drug interaction|drug interactions]]) or the | ||
cost of the treatment or alternative approaches. | cost of the treatment or alternative approaches. | ||
| Line 52: | Line 55: | ||
|- | |- | ||
|D | |D | ||
|Moderate evidence for lack of efficacy or for | |Moderate [[evidence]] for lack of [[efficacy]] or for | ||
adverse outcome supports a recommendation | [[adverse outcome]] supports a recommendation | ||
against use. | against use. Generally, treatment should not be offered. | ||
|- | |- | ||
|E | |E | ||
|Good evidence for lack of efficacy or for adverse | |Good [[evidence]] for lack of [[efficacy]] or for [[adverse | ||
outcome supports a recommendation against use. | outcome]] supports a recommendation against use. | ||
Should never be offered. | Should never be offered. | ||
|- | |- | ||
|'''Rating''' | |'''Rating''' | ||
|'''Quality of the evidence supporting''' | |'''Quality of the [[evidence]] supporting''' | ||
'''the recommendation''' | '''the recommendation''' | ||
|- | |- | ||
|I | |I | ||
|Evidence from at least one properly-designed | |[[Evidence]] from at least one properly-designed | ||
randomized, controlled trial. | randomized, controlled trial. | ||
|- | |- | ||
|II | |II | ||
|Evidence from at least one well-designed clinical | |[[Evidence]] from at least one well-designed clinical | ||
trial without randomization, from cohort or case- | trial without randomization, from cohort or case- | ||
| Line 91: | Line 94: | ||
====Monitoring and Adverse Events==== | ====Monitoring and Adverse Events==== | ||
Albendazole side effects are rare but the following adverse effects should be watched for: | [[Albendazole]] side effects are rare but the following [[adverse effects]] should be watched for: | ||
* Hypersensitivity ([[rash]], [[pruritus]], [[fever]]) | * [[Hypersensitivity]] ([[rash]], [[pruritus]], [[fever]]) | ||
* [[ | * [[Neutropenia]] (reversible) | ||
* CNS effects ([[dizziness]], [[headache]]) | * CNS effects ([[dizziness]], [[headache]]) | ||
* Gastrointestinal disturbances ([[abdominal pain]], [[diarrhea]], [[nausea]], [[vomiting]]) | * [[Gastrointestinal]] disturbances ([[abdominal pain]], [[diarrhea]], [[nausea]], [[vomiting]]) | ||
* [[Hair loss]] (reversible) | * [[Hair loss]] (reversible) | ||
* Elevated liver enzymes (reversible) have been reported. | * Elevated [[liver enzymes]] (reversible) have been reported. | ||
==== Fumagillin side effects: ==== | ==== Fumagillin side effects: ==== | ||
| Line 104: | Line 107: | ||
====Management of Treatment Failure==== | ====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'''). | Supportive treatment and optimizing [[ART4|ART]] to attempt to achieve full virologic suppression are the only feasible approaches to the management of treatment failure ('''CIII'''). | ||
===Special Considerations During Pregnancy=== | ===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. | * 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'''). | * 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'''). | * 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'''). | ||
| Line 118: | Line 121: | ||
:* '''2. Intestinal (diarrhea)'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref> | :* '''2. Intestinal (diarrhea)'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref> | ||
::* Preferred regimen: | ::* Preferred regimen: | ||
:::* Adult: [[Albendazole]] 400 mg PO bid for 3 weeks | :::* 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 | :::* 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. | ::* Note: [[Fumagillin]] 20 mg PO tid is the only reported effective treatment for E. bieneusi. | ||
:* '''3. Disseminated'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref> | :* '''3. Disseminated'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref> | ||
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==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Emergency mdicine]] | |||
[[Category:Disease]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | |||
[[Category:Ophthalmology]] | |||
[[Category:Neurology]] | |||
[[Category:Dermatology]] | |||
[[Category:Gastroenterology]] | [[Category:Gastroenterology]] | ||
Latest revision as of 22:43, 29 July 2020
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Microsporidiosis Microchapters |
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Microsporidiosis medical therapy On the Web |
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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:
- Hypersensitivity (rash, pruritus, fever)
- Neutropenia (reversible)
- CNS effects (dizziness, headache)
- Gastrointestinal disturbances (abdominal pain, diarrhea, nausea, vomiting)
- Hair loss (reversible)
- Elevated liver enzymes (reversible) have been reported.
Fumagillin side effects:
- Topical fumagillin has not been associated with substantial side effects.
- Oral fumagillin has been associated with thrombocytopenia, which is reversible on stopping the drug.
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
- 1. Ocular[12]
- Preferred regimen: Albendazole 400 mg PO bid for 3 weeks AND Fumagillin eye drops.
- 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.
- 3. Disseminated[14]
- Preferred regimen: Albendazole 400 mg po bid for 3 weeks.
References
- ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. doi:10.1056/NEJMoa012924. PMID 12075057. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ 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 89645. PMID 10602740. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Didier ES (1997). "Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro". Antimicrob. Agents Chemother. 41 (7): 1541–6. PMC 163955. PMID 9210681. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ 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 164197. PMID 9420047. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ 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. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.