- Author: Ayesha Mirza, MD; Chief Editor: Russell W Steele, MD more...
Over the last few years the list of therapeutic options available has grown. This section includes information on specific treatment options available.
Treatment of congenital viral infections with chorioretinitis, such as HSV (CNS, mucocutaneous, sepsis), CMV, or varicella-zoster virus, has resulted in lower mortality rates. Older children may benefit from intravitreal administration, which requires consultation with an ophthalmologist.
Analog of pyrophosphate. Inhibits DNA polymerase of CMV and reverse transcriptase of HIV. Virostatic with renal excretion. As effective as ganciclovir. Median time to relapse is 53 d.
In the foscarnet and ganciclovir CMV retinitis trial, 234 newly diagnosed patients were randomized. Same efficacy was reported for controlling retinitis and preserving vision. Survival with foscarnet was 12.6 mo versus 8.5 for ganciclovir group; mortality risk was 1.79x. Controlling for antiretroviral use, still better survival with foscarnet. Foscarnet has anti-HIV activity but has more dose-limiting toxicity.
L-valyl ester prodrug of ganciclovir used to treat CMV retinitis in patients with AIDS. Ganciclovir is synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Inhibits viral activity by inhibiting viral DNA synthesis. Has the advantage of once daily or bid PO administration. Achieves levels comparable to those obtained with IV ganciclovir.
Indicated for neonatal HSV and varicella-zoster infections. Treatment is most efficacious when started earlier in disease course. More effective in younger children than in adults.
Indicated for CMV retinitis. Synthetic guanine derivative active against CMV. An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold more than in CMV-infected cells than in uninfected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells. For patients who experience progression of CMV retinitis while receiving a maintenance treatment with either dosage form of ganciclovir, the reinduction regimen should be administered.
Used for CMV retinitis. Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.
Pyrimethamine and sulfadiazine are synergistic against Toxoplasma species. Spiramycin is used to treat pregnant women. Clindamycin has occasionally been administered to patients with AIDS and CNS toxoplasmosis. It is also used in patients who are unable to tolerate pyrimethamine and sulfadiazine due to side effects. Other treatments with atovaquone and newer macrolide antibiotics are being investigated.
Folic acid antagonist that selectively inhibits plasmodial dihydrofolate reductase. Highly selective against plasmodia and T gondii. Length of treatment is not well documented. Some infants with active chorioretinitis have been treated for more than 6 mo. Most often combined with sulfadiazine or clindamycin.
Used synergistically with pyrimethamine. Length of treatment is not well documented. Some infants with active chorioretinitis have been treated for more than 6 mo. Administer with pyrimethamine.
Used in European countries to lower risk of vertical transmission of toxoplasmosis in primoinfections of pregnant women by 60% but does not ameliorate fate of infants who are infected. Not commercially available in the US (obtain from FDA). Take on an empty stomach.
Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. As an alternative to sulfonamides, clindamycin may be beneficial when used with pyrimethamine in acute treatment of CNS toxoplasmosis in patients with AIDS.
Bactericidal and bacteriostatic against mycobacteria; mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.
Amphotericin B and its various lipid forms are the principal drugs for parenteral use. For synergy, 5 flucytosine (5FC) could be administered with amphotericin B. Azoles (chiefly fluconazole, itraconazole, and voriconazole) are agents of choice for long-term oral therapy. Both voriconazole and caspofungin are being increasingly used in patients with susceptible fungal infections as well as those resistant to conventional antifungal agents
Produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.
Particularly active against Candida, Cryptococcus, and Aspergillus species.
Fungal endophthalmitis has been treated with intraocular injection of amphotericin B. An infectious diseases specialist should be consulted regarding the appropriate protocol and dosage. Several studies have shown poor intravitreal penetration when administered systemically.
Special attention is required when making the dilutions and injecting in gas-filled eyes because it has a narrow therapeutic range and can cause retinal toxicity. Subconjunctival injections of amphotericin B have no role in fungal ocular infections.
Although the exact mode of action is unknown, flucytosine is believed to act directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and is believed to act indirectly by intracellular metabolism, in which it is converted to 5-fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species; generally used in combination with amphotericin B.
Use in combination with another agent because acquired resistance develops frequently when flucytosine is administered alone.
Well absorbed PO but should be administered IV to critically ill patients.
Synthetic PO antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tablets for PO administration, as a powder for PO susp, and as a sterile solution for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles.
Effective against Candida, Cryptococcus, and Aspergillus species. Bioavailability following PO administration is comparable with parenteral administration. Good CSF and intravitreal penetration is achieved after systemic administration.
Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Used for primary treatment of invasive aspergillosis and treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Has also proven to be effective for the treatment of disseminated Candida infections as well as other fungal infections (eg, cryptococcus, Blastomyces).
Used to treat refractory invasive aspergillosis. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall. Also approved for the treatment of candidemia and general invasive candidiasis in adult patients. Emerging role in treating fungal endophthalmitis with or without voriconazole.
Parasite biochemical pathways are different from those of the human host; thus, the toxicity is directed to the parasite, egg, or larvae. The mechanism of action varies within the drug class. Antiparasitic actions may include the following:
- Inhibition of microtubules, which causes irreversible block of glucose uptake
- Tubulin polymerization inhibition
- Depolarizing neuromuscular blockade
- Cholinesterase inhibition
- Increased cell membrane permeability, resulting in intracellular calcium loss
- Vacuolization of the schistosome tegument
- Increased cell membrane permeability to chloride ions via chloride channels alteration
A benzimidazole carbamate drug that inhibits tubulin polymerization, resulting in degeneration of cytoplasmic microtubules. Decreases ATP production in worms, causing energy depletion, immobilization, and, finally, death. Converted in the liver to its primary metabolite, albendazole sulfoxide. Less than 1% of the primary metabolite is excreted in the urine. Plasma level is noted to significantly rise (as much as 5-fold) when ingested after high-fat meal. Experience with patients < 6 y is limited.
To avoid inflammatory response in CNS, patients must also be started on anticonvulsants and high-dose glucocorticoids.
A piperazine derivative, diethylcarbamazine has effects on the 5-lipoxygenase pathway, targets the cyclooxygenase pathway and COX-1, and enhances the phagocytosis of the parasite.
Exerts inhibitory effect on tubulin polymerization resulting in loss of cytoplasmic microtubules in the parasite.
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