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Pregnancy risk categories: Table 1 in Antimicrobial Agents.
1. Antibiotics: Metronidazole, tinidazole, trimethoprim/sulfamethoxazole, clindamycin, spiramycin (see Antibacterial Agents).
1) Spectrum of activity: Used as an alternative therapy for prophylaxis or treatment of Pneumocystis jiroveci (formerly carinii) pneumonia in patients who do not tolerate trimethoprim/sulfamethoxazole. It also shows activity against toxoplasmosis and is used in combination therapy with azithromycin for the treatment of babesiosis.
2) Adverse reactions: Hypersensitivity reaction. Gastrointestinal (GI) effects, such as vomiting and diarrhea. Use with caution in patients with severe liver impairment as rare cases of cholestatic hepatitis and liver failure have been reported. Methemoglobinemia.
3) Pregnancy risk: C.
1) Spectrum of activity: Primary therapy for American trypanosomiasis (Chagas disease).
2) Adverse reactions: Angioedema. Cutaneous effects (rash, photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome). Peripheral neuropathy (dose dependent). Hematologic effects, such as bone marrow suppression. A disulfiram-like reaction can occur with concomitant alcohol use (nausea, vomiting, flushing, headache).
3) Pregnancy risk: Not classified. Avoid in pregnancy.
1) Spectrum of activity: Eflornithine is used for the treatment of African trypanosomiasis caused by Trypanosoma brucei gambiense, often in combination with nifurtimox.
2) Adverse reactions: Most common adverse reactions include GI effects (diarrhea, vomiting, abdominal pain), hematologic effects (myelosuppression), fever, and hair loss.
3) Pregnancy risk: Theoretically contraindicated. Use and treatment timing during pregnancy depends on mother’s condition.
1) Spectrum of activity: Fexinidazole is used for the treatment of African trypanosomiasis caused by T brucei gambiense and rhodesiense.
2) Adverse reactions: Neuropsychiatric effects, QT prolongation endocrine effects (hypocalcemia), GI effects, hematologic effects (neutropenia). Do not use in the setting of hepatic impairment or in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30mL/min).
3) Pregnancy risk: Not classified. If required, to be given after the first trimester.
1) Spectrum of activity: A nitrofuran derivative. It is used as alternative therapy for the treatment of resistant Giardia lamblia infection and also considered as alternative therapy for Vibrio cholera infection.
2) Adverse reactions: Hypersensitivity reaction. GI effects, such as vomiting and diarrhea. A disulfiram-like reaction can be seen when taken with alcohol.
3) Pregnancy risk: Safety in the childbearing age has not been established.
1) Spectrum of activity: Iodoquinol is used predominantly for the treatment of noninvasive Entamoeba histolytica infection, Dientamoeba fragilis infection, and considered an alternative treatment for Balantidium coli infection.
2) Adverse reactions: Hypersensitivity reaction. Because iodoquinol contains iodine, caution should be used in patients with thyroid disease. Prolonged use may result in optic neuritis and peripheral neuropathy.
3) Pregnancy risk: Safety in the childbearing age has not been established.
1) Spectrum of activity: Melarsoprol is used for the treatment of second-stage African trypanosomiasis involving the central nervous system (CNS), caused by T brucei gambiense and rhodesiense. For T brucei gambiense, this is often reserved for recurrent relapsed cases, after first-line therapy and rescue therapy have failed. For T brucei rhodesiense, it is a first-line therapy in patients aged <6 years or weighing <20 kg.
2) Adverse reactions: Myocarditis, encephalopathy, and hypersensitivity reactions.
3) Pregnancy risk: Theoretically contraindicated. Use and treatment timing during pregnancy depends on mother’s condition
1) Spectrum of activity: Miltefosine is indicated for the treatment of visceral and cutaneous leishmaniasis.
2) Adverse reactions: GI adverse effects (nausea, vomiting, and diarrhea). CNS effects include headache and vertigo.
3) Pregnancy risk: D.
1) Spectrum of activity: Nitazoxanide is used for the treatment of Cryptosporidium infection. It also has activity against E histolytica and G lamblia.
2) Adverse reactions: Hypersensitivity reaction. GI effects, such as abdominal pain, vomiting, and diarrhea.
3) Pregnancy risk: B.
1) Spectrum of activity: Primary therapy for American trypanosomiasis (Chagas disease). It can also be used in combination with elfornithine for the treatment of African trypanosomiasis due to T brucei gambiense.
2) Adverse reactions: GI adverse effects are common and include abdominal pain, nausea, vomiting, and diarrhea. CNS effects are also common and include insomnia, irritability, depression, tremors, and peripheral neuropathy. Cutaneous effects (erythema, pruritus). Avoid alcohol use during treatment as it may increase the risk of adverse effects.
3) Pregnancy risk: Theoretically contraindicated. Use and treatment timing during pregnancy depends on mother’s condition.
12. Paromomycin (oral, topical):
1) Spectrum of activity: Paromomycin is an aminoglycoside antibiotic showing no GI absorption. It is used in the treatment of noninvasive E histolytica and to eliminate luminal cysts after treatment of invasive disease. It also has activity against D fragilis, Cryptosporidium parvum, and G lamblia. As topical therapy, it has been used for the treatment of cutaneous leishmaniasis.
2) Adverse reactions: Hypersensitivity reaction. GI effects, such as abdominal pain, vomiting, and diarrhea.
3) Pregnancy risk: B.
13. Pentamidine (IV, inhaled):
1) Spectrum of activity: Inhaled and parenteral pentamidine is used for prophylaxis and treatment of P jiroveci pneumonia. It is also active against Leishmania spp, T brucei gambiense (West African sleeping sickness), and free-living amoebas (Acanthamoeba and Balamuthia).
2) Adverse reactions: Hypersensitivity reaction. Because pentamidine may cause QT prolongation, avoid it in patients with underlying risk factors for prolonged QT; other cardiac effects include hypotension and arrhythmias. Reversible nephrotoxicity and electrolyte abnormalities, including hyponatremia, hyperkalemia, hypomagnesemia, and hypocalcemia. Hematologic effects (neutropenia, thrombocytopenia). Pentamidine can be toxic to pancreatic islet beta cells, causing hypoglycemia and pancreatitis.
3) Pregnancy risk: C.
14. Pentavalent antimonials: Sodium stibogluconate (IV, IM) and meglumine antimoniate (IV, IM):
1) Spectrum of activity: These agents are indicated for the treatment of visceral and cutaneous leishmaniasis.
2) Adverse reactions: GI effects, such as nausea and vomiting, hepatitis, and pancreatitis. Arthralgias and myalgias. Cardiotoxicity including QT prolongation. Bone marrow suppression.
3) Pregnancy risk: Not classified.
1) Spectrum of activity: Pyrimethamine in combination therapy is used for the treatment of toxoplasmosis (pyrimethamine/sulfadiazine) and prophylaxis of Pneumocystis pneumonia (pyrimethamine/dapsone). It also has activity against Cystoisospora belli.
2) Adverse reactions: Hypersensitivity reaction. Hematologic effects, such as hemolytic anemia (especially in patients with glucose-6-phosphate dehydrogenase deficiency), megaloblastic anemia (in those with folate deficiency), neutropenia, and thrombocytopenia. In patients receiving high doses of pyrimethamine, administer concomitant folinic acid.
3) Pregnancy risk: C.
1) Spectrum of activity: Suramin is used for the treatment of early-stage African trypanosomiasis caused by T brucei rhodesiense.
2) Adverse reactions: Cutaneous eruptions, fever, hemolytic anemia, vomiting, paresthesia, photophobia, peripheral neuropathy, hypersensitivity reactions, and nephrotoxicity. Avoid in patients with severe kidney disease.
3) Pregnancy risk: Theoretically contraindicated. Use and treatment timing during pregnancy depends on mother’s condition.
17. Antifungal agents: Fluconazole and amphotericin B (see Antifungal Agents).
