Diloxanide furoate is a dichloroacetamide derivative. It is an effective luminal amebicide but is not active against trophozoites. In the gut, diloxanide furoate is split into diloxanide and furoic acid; about 90% of the diloxanide is rapidly absorbed and then conjugated to form the glucuronide, which is promptly excreted in the urine. The unabsorbed diloxanide is the active antiamebic substance. Diloxanide furoate is not available commercially in the USA but can be obtained from some compounding pharmacies. It does not produce serious adverse effects. Flatulence is common, but nausea and abdominal cramps are infrequent and rashes are rare. The drug is not recommended in pregnancy.
Paromomycin sulfate is an aminoglycoside antibiotic (see also Chapter 45) that is not significantly absorbed from the gastrointestinal tract. It is used as a luminal amebicide and has no effect against extraintestinal organisms. The small amount absorbed is slowly excreted unchanged, mainly by glomerular filtration. However, the drug may accumulate with renal insufficiency and contribute to renal toxicity. Paromomycin appears to have similar efficacy and less toxicity than other luminal agents; in one study it was superior to diloxanide furoate in clearing asymptomatic infections. As it is readily available, paromomycin can be considered the antiamebic luminal agent of choice in the USA. Adverse effects include occasional abdominal distress and diarrhea. Parenteral paromomycin is now used to treat visceral leishmaniasis and is discussed separately in the text that follows.
Emetine, an alkaloid derived from ipecac, and dehydroemetine, a synthetic analog, are effective against tissue trophozoites of E histolytica, but because of major toxicity concerns their use is limited to unusual circumstances in which severe amebiasis requires effective therapy and metronidazole cannot be used. Dehydroemetine is preferred because of its somewhat better toxicity profile. The drugs should be used for the minimum period needed to relieve severe symptoms (usually 3–5 days) and administered subcutaneously (preferred) or intramuscularly in a supervised setting. Adverse effects, which are generally mild with use for 3–5 days but increase over time, include pain, tenderness, and sterile abscesses at the injection site; diarrhea, nausea, and vomiting; muscle weakness and discomfort; and minor electrocardiographic changes. Serious toxicities include cardiac arrhythmias, heart failure, and hypotension.
The primary drugs used to treat African trypanosomiasis are listed in Table 52–6, and those for other protozoal infections are listed in Table 52–7. Important antiprotozoal drugs that are not covered elsewhere are discussed below.
Pentamidine has activity against trypanosomatid protozoans and against P jiroveci, but toxicity is significant.
Pentamidine is an aromatic diamidine (Figure 52–3) formulated as an isethionate salt. The drug is only administered parenterally. It leaves the circulation rapidly, with an initial half-life of about 6 hours, but is bound avidly by tissues. Pentamidine thus accumulates and is eliminated very slowly, with a terminal elimination half-life of about 12 days. Only trace amounts of pentamidine appear in the central nervous system, so it is not effective against CNS African trypanosomiasis. Pentamidine can also be inhaled as a nebulized powder for the prevention of pneumocystosis. Absorption into the systemic circulation after inhalation appears to be minimal. The mechanism of action of pentamidine is unknown.