1704 PART 5 Infectious Diseases

TABLE 222-1 Overview of Agents Used for the Treatment of Parasitic Infections

DRUGS BY CLASS PARASITIC INFECTION(S) ADVERSE EFFECTS

MAJOR DRUG–DRUG

INTERACTIONS

PREGNANCY

CLASSa

BREAST

MILK

Eflornithineh

(difluoromethylornithine,

DFMO)

Trypanosomiasis Frequent: pancytopenia

Occasional: diarrhea, seizures

Rare: transient hearing loss

No major interactions Contraindicated No

information

Emetine and

dehydroemetinef

Amebiasis, fascioliasis Severe: cardiotoxicity

Frequent: pain at injection site

Occasional: dizziness, headache, GI

symptoms

None reported X No

information

Folate antagonists

 Dihydrofolate

reductase inhibitors

 Pyrimethamine Malaria,b

 isosporiasis,

toxoplasmosisb

Occasional: folate deficiency

Rare: rash, seizures, severe skin

reactions (toxic epidermal necrolysis,

erythema multiforme, StevensJohnson syndrome)

Sulfonamides, proguanil,

zidovudine: increased risk of bone

marrow suppression when used

concomitantly

C Yes

 Proguanil and

chlorproguanil

Malaria Occasional: urticaria

Rare: hematuria, GI disturbances

Atazanavir, efavirenz, lopinavir/

ritonavir: plasma levels of

proguanil decreased

C Yes

 Trimethoprim Cyclosporiasis, isosporiasis Hyperkalemia, GI upset, mild

stomatitis

Methotrexate: reduced clearance

Warfarin: effect prolonged

Phenytoin: hepatic metabolism

increased

C Yes

 Dihydropteroate

synthetase inhibitors:

sulfonamides

 Sulfadiazine

 Sulfamethoxazole

 Sulfadoxine

Malaria,b

 toxoplasmosisb Frequent: GI disturbances, allergic

skin reactions, crystalluria

Rare: severe skin reactions (toxic

epidermal necrolysis, erythema

multiforme, Stevens-Johnson

syndrome), agranulocytosis, aplastic

anemia, hypersensitivity of the

respiratory tract, hepatitis, interstitial

nephritis, hypoglycemia, aseptic

meningitis

Thiazide diuretics: increased risk

of thrombocytopenia in elderly

patients

Warfarin: effect prolonged by

sulfonamides

Methotrexate: levels increased by

sulfonamides

Phenytoin: metabolism impaired

by sulfonamides

Sulfonylureas: effect prolonged

by sulfonamides

B Yes

 Dihydropteroate

synthetase inhibitors:

sulfones

 Dapsone Leishmaniasis, malaria,

toxoplasmosis

Frequent: rash, anorexia

Occasional: hemolysis,

methemoglobinemia, neuropathy,

allergic dermatitis, anorexia, nausea,

vomiting, tachycardia, headache,

insomnia, psychosis, hepatitis

Rare: agranulocytosis

Rifampin: lowered plasma levels

of dapsone

C Yes

Fumagillin Microsporidiosis Rare: neutropenia, thrombocytopenia None reported No information No

information

Furazolidone Giardiasis Frequent: nausea/vomiting, brown

urine

Occasional: rectal itching, headache

Rare: hemolytic anemia, disulfiramlike reactions, MAO inhibitor

interactions

Risk of hypertensive crisis when

administered for >5 days with

MAO inhibitors

C No

information

Iodoquinol Amebiasis,b

 balantidiasis, D.

fragilis infection

Occasional: headache, rash, pruritus,

thyrotoxicosis, nausea, vomiting,

abdominal pain, diarrhea

Rare: optic neuritis, peripheral

neuropathy, seizures, encephalopathy

No major interactions C No

information

Lactones

Ivermectin Ascariasis, cutaneous larva

migrans, gnathostomiasis,

loiasis, lymphatic filariasis,

onchocerciasis,b

 scabies,

strongyloidiasis,b

 trichuriasis

Occasional: fever, pruritus, headache,

myalgias

Rare: hypotension

No major interactions C Yesc

 Moxidectin Onchocerciasis Occasional: fever, pruritus, headache,

myalgias

Rare: orthostatic hypotension,

elevated transaminases

No major interactions C Yesc

(Continued)

(Continued)

1705CHAPTER 222 Agents Used to Treat Parasitic Infections

TABLE 222-1 Overview of Agents Used for the Treatment of Parasitic Infections

DRUGS BY CLASS PARASITIC INFECTION(S) ADVERSE EFFECTS

MAJOR DRUG–DRUG

INTERACTIONS

PREGNANCY

CLASSa

BREAST

MILK

Macrolides

Azithromycin Babesiosis Occasional: nausea, vomiting,

diarrhea, abdominal pain

Rare: angioedema, cholestatic

jaundice

Cyclosporine and digoxin: levels

increased by azithromycin

Nelfinavir: increased levels of

azithromycin

B Yes

Spiramycinh Toxoplasmosis Occasional: GI disturbances, transient

skin eruptions

Rare: thrombocytopenia, QT

prolongation in an infant, cholestatic

hepatitis

No major interactions Not assignedd Yesc

Mefloquine Malariab Frequent: lightheadedness, nausea,

headache

Occasional: confusion; nightmares;

insomnia; visual disturbance; transient

and clinically silent ECG abnormalities,

including sinus bradycardia, sinus

arrhythmia, first-degree AV block,

prolongation of QTc interval, and

abnormal T waves

Rare: psychosis, convulsions,

hypotension

Administration of halofantrine <3

weeks after mefloquine use may

produce fatal QTc prolongation.

Mefloquine may lower plasma

levels of anticonvulsants. Levels

are decreased and clearance

is accelerated by artesunate.

Mefloquine decreases plasma

levels of ritonavir and possibly

other protease inhibitors.

C Yes

Melarsoprolf Trypanosomiasis Frequent: myocardial injury,

encephalopathy, peripheral

neuropathy, hypertension

Occasional: G6PD-induced hemolysis,

erythema nodosum leprosum

Rare: hypotension

No major interactions Not assigned No

information

Metrifonate Schistosomiasis Frequent: abdominal pain, nausea,

vomiting, diarrhea, headache, vertigo,

bronchospasm

Rare: cholinergic symptoms

No major interactions B No

Miltefosine Leishmaniasis,b

 primary

amebic meningoencephalitis

Frequent: mild and transient (1–2 days)

GI disturbances within first 2 weeks

of therapy (resolve after treatment

completion); motion sickness

Occasional: reversible elevations of

creatinine and aminotransferases

No major interactions Not assigned No

information

Niclosamide Intestinal cestode infectionsb Occasional: nausea, vomiting,

dizziness, pruritus

No major interactions B No

information

Nifurtimoxf Chagas disease Frequent: nausea, vomiting, abdominal

pain, insomnia, paresthesias,

weakness, tremors

Rare: seizures (all reversible and

dose-related)

No major interactions Not assigned No

information

Nitazoxanide Cryptosporidiosis,b

 giardiasisb Occasional: abdominal pain, diarrhea

Rare: vomiting, headache

Increases plasma levels of

highly protein-bound drugs (e.g.,

phenytoin, warfarin)

B No

information

Nitroimidazoles

Metronidazole Amebiasis,b

 balantidiasis,

dracunculiasis, giardiasis,

trichomoniasis,b D. fragilis

infection

Frequent: nausea, headache,

anorexia, metallic aftertaste

Occasional: vomiting, insomnia,

vertigo, paresthesias, disulfiram-like

effects

Rare: seizures, peripheral neuropathy

Warfarin: effect enhanced by

metronidazole

Disulfiram: psychotic reaction

Phenobarbital, phenytoin:

accelerate elimination of

metronidazole

Lithium: serum levels elevated by

metronidazole

Cimetidine: prolonged half-life of

metronidazole

Oral solutions of antiretrovirals

containing alcohol: disulfiram

effect due to alcohol

B Yes

Tinidazole Amebiasis,b

 giardiasis,

trichomoniasis

Occasional: nausea, vomiting, metallic

taste

See metronidazole C Yes

(Continued)

(Continued)

1706 PART 5 Infectious Diseases

TABLE 222-1 Overview of Agents Used for the Treatment of Parasitic Infections

DRUGS BY CLASS PARASITIC INFECTION(S) ADVERSE EFFECTS

MAJOR DRUG–DRUG

INTERACTIONS

PREGNANCY

CLASSa

BREAST

MILK

Oxamniquine Schistosomiasis Occasional: dizziness, drowsiness,

headache, orange urine, elevated

aminotransferases

Rare: seizures

No major interactions C No

information

Pentamidine isethionate Leishmaniasis,

trypanosomiasis

Frequent: hypotension, hypoglycemia,

pancreatitis, sterile abscesses at

IM injection sites, GI disturbances,

reversible renal failure

Occasional: hepatotoxicity,

cardiotoxicity, delirium

Rare: anaphylaxis

No major interactions C No

information

Piperazine and

derivatives

Piperazine Ascariasis, enterobiasis Occasional: nausea, vomiting,

diarrhea, abdominal pain, headache

Rare: neurotoxicity, seizures

None reported C No

information

Diethylcarbamazinef Lymphatic filariasis,

loiasis, tropical pulmonary

eosinophilia

Frequent: dose-related nausea,

vomiting

Rare: fever, chills, arthralgias,

headache

None reported Not assignedd No

information

Praziquantel Clonorchiasis,b

 cysticercosis,

diphyllobothriasis,

hymenolepiasis, taeniasis,

opisthorchiasis, intestinal

trematodes, paragonimiasis,

schistosomiasisb

Frequent: abdominal pain, diarrhea,

dizziness, headache, malaise

Occasional: fever, nausea

Rare: pruritus, singultus

No major interactions B Yes

Pyrantel pamoate Ascariasis, eosinophilic

enterocolitis, enterobiasis,b

hookworm, trichostrongyliasis

Occasional: GI disturbances,

headache, dizziness, elevated

aminotransferases

No major interactions C No

information

Pyronaridine Malaria Occasional: headache, nausea None reported to date B Yes

Quinacrineh Giardiasisb Frequent: headache, nausea, vomiting,

bitter taste

Occasional: yellow-orange

discoloration of skin, sclerae, urine;

begins after 1 week of treatment

and lasts up to 4 months after drug

discontinuation

Rare: psychosis, exfoliative dermatitis,

retinopathy, G6PD-induced hemolysis,

exacerbation of psoriasis, disulfiramlike effects

Primaquine: toxicity potentiated

by quinacrine

C No

information

Quinine and quinidine Malaria, babesiosis Frequent: cinchonism (tinnitus, hightone deafness, headache, dysphoria,

nausea, vomiting, abdominal pain,

visual disturbances, postural

hypotension), hyperinsulinemia

resulting in life-threatening

hypoglycemia

Occasional: deafness, hemolytic

anemia, arrhythmias, hypotension due

to rapid IV infusion

Carbonic anhydrase inhibitors,

thiazide diuretics: reduced renal

elimination of quinidine

Amiodarone, cimetidine:

increased quinidine levels

Nifedipine: decreased quinidine

levels; quinidine slows

metabolism of nifedipine

Phenobarbital, phenytoin,

rifampin: accelerated hepatic

elimination of quinidine

Verapamil: reduced hepatic

clearance of quinidine

Diltiazem: decreased clearance

of quinidine

X Yesc

Quinolones

Ciprofloxacin Cyclosporiasis, isosporiasis Occasional: nausea, diarrhea,

vomiting, abdominal pain/discomfort,

headache, restlessness, rash

Rare: myalgias/arthralgias, tendon

rupture, CNS symptoms (nervousness,

agitation, insomnia, anxiety,

nightmares, or paranoia); convulsions

Probenecid: increased serum

levels of ciprofloxacin

Theophylline, warfarin: serum

levels increased by ciprofloxacin

C Yes

(Continued)

(Continued)

1707CHAPTER 222 Agents Used to Treat Parasitic Infections

TABLE 222-1 Overview of Agents Used for the Treatment of Parasitic Infections

DRUGS BY CLASS PARASITIC INFECTION(S) ADVERSE EFFECTS

MAJOR DRUG–DRUG

INTERACTIONS

PREGNANCY

CLASSa

BREAST

MILK

Suraminf Trypanosomiasis Frequent: immediate: fever, urticaria,

nausea, vomiting, hypotension;

delayed (up to 24 h): exfoliative

dermatitis, stomatitis, paresthesias,

photophobia, renal dysfunction

Occasional: nephrotoxicity, adrenal

toxicity, optic atrophy, anaphylaxis

No major interactions Not assigned No

information

Tetracyclines Balantidiasis, D. fragilis

infection, malaria; lymphatic

filariasis (doxycycline)

Frequent: GI disturbances

Occasional: photosensitivity dermatitis

Rare: exfoliative dermatitis,

esophagitis, hepatotoxicity

Warfarin: effect prolonged by

tetracyclines

D Yes

a

Based on U.S. Food and Drug Administration (FDA) pregnancy categories of A–D, X. b

Approved by the FDA for this indication. c

Not believed to be harmful. d

Use in

pregnancy is recommended by international organizations outside the United States. e

Only AmBisome has been approved by the FDA for this indication. f

Available through

the CDC. g

Only artemether (in combination with lumefantrine) and artesunate have been approved by the FDA for this indication. h

Available through the manufacturer.

Abbreviations: ACTH, adrenocorticotropic hormone; AV, atrioventricular; CNS, central nervous system; ECG, electrocardiogram; G6PD, glucose 6-phosphate dehydrogenase;

GI, gastrointestinal; MAO, monoamine oxidase.

nearly 36 h. This slower phase may be due to conversion of pentavalent

antimony to a trivalent form that is the likely cause of the side effects

often seen with prolonged therapy.

Artemisinin Derivatives* Artesunate, artemether, artemotil, and

the parent compound artemisinin are sesquiterpene lactones derived

from the wormwood plant Artemisia annua. These agents are at least

10-fold more potent in vivo than other antimalarial drugs and presently

show no cross-resistance with known antimalarial drugs; thus they

have become first-line agents for the treatment of severe falciparum

malaria. The artemisinin compounds are rapidly effective against the

asexual blood forms of Plasmodium species but are not active against

intrahepatic forms. With the exception of artesunate, artemisinin and

its derivatives are highly lipid soluble and readily cross both host and

parasite cell membranes. One factor that explains the drugs’ highly

selective toxicity against malaria is that parasitized erythrocytes concentrate artemisinin and its derivatives to concentrations 100-fold

higher than those in uninfected erythrocytes. The antimalarial effect

of these agents results primarily from the active metabolite dihydroartemisinin; in the presence of heme or molecular iron, the endoperoxide

moiety of dihydroartemisinin decomposes, generating free radicals

and other metabolites that damage parasite proteins. The compounds

are available for oral, rectal, IV, or IM administration, depending on

the derivative. In the United States, IV artesunate is available for the

treatment of severe, quinidine-unresponsive malaria through the CDC

malaria hotline (770-488-7788 or 855-856-4713 [toll-free], M–F, 0800–

1630 EST; 770-488-7100 after hours). Artemisinin and its derivatives

are cleared rapidly from the circulation. Their short half-lives limit

their value for prophylaxis and monotherapy. Side effects appear to

be minor, although sinus bradycardia and transient first-degree heart

block have been reported. Although seen in animal models, embryotoxicity and neurotoxicity have not been identified in humans despite

active investigation. These agents should be used only in combination

with another, longer-acting agent (e.g., artesunate-mefloquine, dihydroartemisinin-piperaquine). While artesunate is only available in the

United States from the CDC drug service, a combined formulation of

artemether and lumefantrine is widely available for the treatment of

acute uncomplicated falciparum malaria acquired in areas where Plasmodium falciparum is resistant to chloroquine and antifolates.

Atovaquone Atovaquone is a hydroxynaphthoquinone that exerts

broad-spectrum antiprotozoal activity via selective inhibition of parasite mitochondrial electron transport. This agent exhibits potent activity

against toxoplasmosis and babesiosis when used with pyrimethamine

and azithromycin, respectively. Atovaquone possesses a novel mode of

action against Plasmodium species, inhibiting the electron transport

system at the level of the cytochrome bc1 complex. The drug is active

against both the erythrocytic and the exoerythrocytic stages of Plasmodium species; however, because it does not eradicate hypnozoites

from the liver, patients with P. vivax or P. ovale infections must be given

radical prophylaxis.

Malarone is a fixed-dose combination of atovaquone and proguanil used for malaria prophylaxis as well as for the treatment of acute,

uncomplicated P. falciparum malaria. Malarone has been shown to be

effective in regions with multidrug-resistant P. falciparum. Resistance

to atovaquone develops rapidly via mutations in the parasite’s mitochondrial cytochrome b complex. However, the mutations result in

sterility of female parasites; thus atovaquone-resistant parasites cannot

be transmitted to another person. This situation may explain why clinical resistance has yet to be reported.

The bioavailability of atovaquone varies considerably. Absorption

after a single oral dose is slow, increases two- to three-fold with a fatty

meal, and is dose-limited above 750 mg. The elimination half-life is

increased in patients with moderate hepatic impairment. Because of

the potential for drug accumulation, the use of atovaquone is generally

contraindicated in persons with a creatinine clearance rate <30 mL/min.

No dosage adjustments are needed in patients with mild to moderate

renal impairment.

Azithromycin See Table 222-1 and Chap. 144.

Azoles See Table 222-1 and Chap. 211.

Benznidazole* This oral nitroimidazole derivative is used to treat

Chagas disease, with cure rates of 80–90% recorded in acute infections.

Benznidazole is believed to exert its trypanocidal effects by generating

oxygen radicals to which the parasites are more sensitive than mammalian cells because of a relative deficiency in antioxidant enzymes.

Benznidazole also appears to alter the balance between pro- and antiinflammatory mediators by downregulating the synthesis of nitrite, interleukin (IL) 6, and IL-10 in macrophages. Benznidazole is highly lipophilic

and readily absorbed. The drug is extensively metabolized; only 5% of the

dose is excreted unchanged in the urine. Benznidazole is well tolerated;

adverse effects are rare and usually manifest as GI upset or pruritic rash.

Chloroquine This 4-aminoquinoline has marked, rapid schizonticidal and gametocidal activity against blood forms of P. ovale and P.

malariae and against susceptible strains of P. vivax and P. falciparum.

It is not active against intrahepatic forms (P. vivax and P. ovale). Parasitized erythrocytes accumulate chloroquine in significantly greater

concentrations than do normal erythrocytes. Chloroquine, a weak

base, concentrates in the food vacuoles of intraerythrocytic parasites

because of a relative pH gradient between the extracellular space and

the acidic food vacuole. Once it enters the acidic food vacuole, chloroquine is rapidly converted to a membrane-impermeable protonated

form and is trapped. Continued accumulation of chloroquine in the

parasite’s acidic food vacuoles results in drug levels that are 600-fold

higher at this site than in plasma. The high accumulation of chloroquine results in an increase in pH within the food vacuole to a level

(Continued)

1708 PART 5 Infectious Diseases

above that required for the acid proteases’ optimal activity, inhibiting

parasite heme polymerase; as a result, the parasite is effectively killed

with its own metabolic waste. Compared with susceptible strains,

chloroquine-resistant plasmodia transport chloroquine out of intraparasitic compartments more rapidly and maintain lower chloroquine

concentrations in their acid vesicles. Hydroxychloroquine, a congener

of chloroquine, is equivalent to chloroquine in its antimalarial efficacy

but is preferred to chloroquine for the treatment of autoimmune disorders because it produces less ocular toxicity when used in high doses.

Chloroquine is well absorbed. However, because it exhibits extensive tissue binding, a loading dose is required to yield effective plasma

concentrations. A therapeutic drug level in plasma is reached 2–3 h

after oral administration (the preferred route). Chloroquine can be

administered IV, but excessively rapid parenteral administration can

result in seizures and death from cardiovascular collapse. The mean

half-life of chloroquine is 4 days, but the rate of excretion decreases

as plasma levels decline, making once-weekly administration possible

for prophylaxis in areas with sensitive strains. About one-half of the

parent drug is excreted in urine, but the dose should not be reduced for

persons with acute malaria and renal insufficiency.

Ciprofloxacin See Table 222-1 and Chap. 144.

Clindamycin See Table 222-1 and Chap. 144.

Dapsone See Table 222-1 and Chap. 181.

Dehydroemetine Emetine is an alkaloid derived from ipecac;

dehydroemetine is synthetically derived from emetine and is considered less toxic. Both agents are active against Entamoeba histolytica

and appear to work by blocking peptide elongation and thus inhibiting

protein synthesis. Emetine is rapidly absorbed after parenteral administration, rapidly distributed throughout the body, and slowly excreted

in the urine in unchanged form. Both agents are contraindicated in

patients with renal disease.

Diethylcarbamazine* A derivative of the antihelminthic agent

piperazine with a long history of successful use, diethylcarbamazine

(DEC) remains the treatment of choice for lymphatic filariasis and

loiasis and has also been used for visceral larva migrans. Although

piperazine itself has no antifilarial activity, the piperazine ring of DEC

is essential for the drug’s activity. DEC’s mechanism of action remains

to be fully defined. Proposed mechanisms include immobilization

due to inhibition of parasite cholinergic muscle receptors, disruption

of microtubule formation, and alteration of helminthic surface membranes resulting in enhanced killing by the host’s immune system. DEC

enhances adherence properties of eosinophils. The development of

resistance under drug pressure (i.e., a progressive decrease in efficacy

when the drug is used widely in human populations) has not been

observed, although DEC has variable effects when administered to

persons with filariasis. Monthly administration provides effective prophylaxis against both bancroftian filariasis and loiasis.

DEC is well absorbed after oral administration, with peak plasma

concentrations reached within 1–2 h. No parenteral form is available.

The drug is eliminated largely by renal excretion, with <5% found in

feces. If more than one dose is to be administered to an individual with

renal dysfunction, the dose should be reduced commensurate with the

reduction in creatinine clearance rate. Alkalinization of the urine prevents renal excretion and increases the half-life of DEC. Use in patients

with onchocerciasis can precipitate a Mazzotti reaction, with pruritus,

fever, and arthralgias. Like other piperazines, DEC is active against

Ascaris species. Patients co-infected with this nematode may expel live

worms after treatment.

Diloxanide Furoate Diloxanide furoate, a substituted acetanilide,

is a luminally active agent used to eradicate the cysts of E. histolytica.

After ingestion, diloxanide furoate is hydrolyzed by enzymes in the

lumen or mucosa of the intestine, releasing furoic acid and the ester

diloxanide; the latter acts directly as an amebicide.

Diloxanide furoate is given alone to asymptomatic cyst passers.

For patients with active amebic infections, diloxanide is generally

administered in combination with a 5-nitroimidazole such as metronidazole or tinidazole. Diloxanide furoate is rapidly absorbed after

oral administration. When coadministered with a 5-nitroimidazole,

diloxanide levels peak within 1 h and disappear within 6 h. About 90%

of an oral dose is excreted in the urine within 48 h, chiefly as the glucuronide metabolite. Diloxanide furoate is contraindicated in pregnant

and breast-feeding women and in children <2 years of age.

Eflornithine* Eflornithine (difluoromethylornithine, or DFMO) is

a fluorinated analogue of the amino acid ornithine. Although originally

designed as an antineoplastic agent, eflornithine has proven effective

against some trypanosomatids.

Eflornithine has specific activity against all stages of infection

with Trypanosoma brucei gambiense; however, it is inactive against

T. b. rhodesiense. The drug acts as an irreversible suicide inhibitor of

ornithine decarboxylase, the first enzyme in the biosynthesis of the

polyamines putrescine and spermidine. Polyamines are essential for the

synthesis of trypanothione, an enzyme required for the maintenance of

intracellular thiols in the correct redox state and for the removal of

reactive oxygen metabolites. However, polyamines are also essential

for cell division in eukaryotes, and ornithine decarboxylase is similar

in trypanosomes and mammals. The selective antiparasitic activity of

eflornithine is partly explained by the structure of the trypanosomal

enzyme, which lacks a 36-amino-acid C-terminal sequence found on

mammalian ornithine decarboxylase. This difference results in a lower

turnover of ornithine decarboxylase and a more rapid decrease of

polyamines in trypanosomes than in the mammalian host. The diminished effectiveness of eflornithine against T. b. rhodesiense appears to

be due to the parasite’s ability to replace the inhibited enzyme more

rapidly than T. b. gambiense.

Eflornithine is less toxic but more costly than conventional therapy.

It can be administered IV or PO. The dose should be reduced in renal

failure. Eflornithine readily crosses the blood–brain barrier; CSF levels

are highest in persons with the most severe central nervous system

(CNS) involvement.

Fumagillin† Originally discovered as an anti-angiogenic compound derived from the fungus Aspergillus fumigatus, fumagillin is a

water-insoluble antibiotic that is active against microsporidia and is

used topically to treat ocular infections due to Encephalitozoon species.

When given systemically, fumagillin was effective but caused thrombocytopenia in all recipients in the second week of treatment; this

side effect was readily reversed when administration of the drug was

stopped. Fumagillin acts by binding to methionine aminopeptidase 2,

thus inhibiting microsporidial replication by irreversibly blocking the

active site.

Furazolidone This nitrofuran derivative is an effective alternative

agent for the treatment of giardiasis and also exhibits activity against

Isospora belli. Because it is the only agent active against Giardia that

is available in liquid form, it is most often used to treat young children. Furazolidone undergoes reductive activation in Giardia lamblia

trophozoites—an event that, unlike the reductive activation of metronidazole, involves an NADH oxidase. The killing effect correlates

with the toxicity of reduced products, which damage important

cellular components, including DNA. Although furazolidone had

been thought to be largely unabsorbed when administered orally, the

occurrence of systemic adverse reactions indicates that this is not the

case. More than 65% of the drug dose can be recovered from the urine

as colored metabolites. Omeprazole reduces the oral bioavailability of

furazolidone.

Furazolidone is a monoamine oxidase (MAO) inhibitor; thus

caution should be used in its concomitant administration with other

drugs (especially indirectly acting sympathomimetic amines) and in

the consumption of food and drink containing tyramine during treatment. However, hypertensive crises have not been reported in patients

receiving furazolidone, and it has been suggested that—because

furazolidone inhibits MAOs gradually over several days—the risks

are small if treatment is limited to a 5-day course. Because hemolytic

anemia can occur in patients with glucose-6-phosphate dehydrogenase