eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Chorioretinitis: Treatment & Medication

Author: Ayesha Mirza, MD, Assistant Professor, Pediatric Infectious Diseases, University of Florida College of Medicine Jacksonville
Coauthor(s): Diana E Guinazu, MD, Fellow in Pediatric Infectious Diseases, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: Oct 16, 2009

Treatment

Medical Care

  • Medical care in chorioretinitis (CR) focuses on the establishment of specific therapies for treatable etiologies and on the stabilization of the patient with chorioretinitis to prevent further loss of vision especially in immunocompromised infants and children.
  • Care for individuals with chorioretinitis is complex and requires thorough consideration of short-term and long-term care and goals to maintain quality of life.
  • Available treatment options for specific causes of chorioretinitis are as follows:
    • Antivirals: Four drugs have been licensed for the systemic treatment of cytomegalovirus (CMV) infection. These include ganciclovir, valganciclovir (oral prodrug of ganciclovir), foscarnet, and cidofovir. Fomivirsen is licensed for intravitreal administration to treat CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Newer drugs such as maribavir, which has the potential to be useful in ganciclovir-resistant strains of CMV, are under clinical investigation.8,23
    • For children with human immunodeficiency virus (HIV) infection, the drug of choice for initial treatment for CMV retinitis is intravenous ganciclovir. Oral valganciclovir is an option primarily for older children who are able to receive the adult dose and tablet formulation of valganciclovir. An alternative to treat CMV disease or for use in ganciclovir-resistant CMV infections in children with HIV is foscarnet. Combination therapy with ganciclovir and foscarnet delays progression of retinitis in certain patients failing monotherapy and can be used as initial therapy among children with sight-threatening disease. Intravenous ganciclovir and foscarnet may also be considered in initial therapy of CMV CNS disease. However, combination therapy is associated with substantial rates of adverse effects.
    • Several agents are used to treat toxoplasmosis. Treatment with antiparasitic drugs is effective for active infections but not for the encysted form. The classic treatment includes triple drug therapy with pyrimethamine (0.5-1 mg/kg/d), sulfadiazine (120-150 mg/kg/d), and prednisone. Concurrent folinic acid helps to minimize bone marrow toxicity produced by the pyrimethamine. High-performance liquid chromatography with ultraviolet and mass spectrometric detection has been developed for monitoring the plasma levels of pyrimethamine and sulfadiazine during treatment using a small amount of plasma (25 mcL). This may be helpful in determining the relationship between plasma concentrations and treatment efficacy.24
    • Alternative antibiotic treatments include atovaquone (40 mg/kg/d has been used in adults, no dosage for children), azithromycin (5 mg/kg/d) and trimethoprim-sulfamethoxazole (40 mg/kg/d sulfamethoxazole, 8 mg/kg/d trimethoprim). Adjunctive clindamycin (20 mg/kg/d) is used for coverage against the encysted form. Treatment duration for congenital infection is typically 1 year.
    • Prevention of fetal infection after maternal Toxoplasma seroconversion during pregnancy is attempted with spiramycin administration. A 60% decrease has been reported in the congenital infection rate in patients who received this treatment; however, it does not ameliorate the fate of infants who are infected.
    • Catscratch disease is usually a self-limited disease in immunocompetent patients. B henselae is sensitive to many antibiotics in vitro, but only aminoglycosides have bactericidal activity. In immunocompetent patients, doxycycline at 200 mg/d is usually administered because of its property to cross the blood-brain and blood-ocular barrier. Caution should be used if administered to children because it may cause dental changes. Ciprofloxacin (1.5 g/d), gentamicin (3-5 mg/kg/d), erythromycin (20-50 mg divided into 3 doses; adults, 2 g/d), trimethoprim-sulfamethoxazole (40 mg/kg/d sulfamethoxazole, 8 mg/kg/d trimethoprim) are good alternatives and, like doxycycline, are usually given for 14-28 days. Immunodeficient patients need a more prolonged course of treatment, usually as long as 4 months. Steroids are also indicated for ocular disease.25,26
    • Treatment of chorioretinitis due to fungal infections can be difficult and prolonged. Intravitreous amphotericin B (5-10 mcg) has been used to treat serious fungal chorioretinitis.
      • Candida species infection: Fluconazole (6-12 mg/kg/d) and amphotericin B (0.75-1 mg/kg/d) has been recommended as preferred antifungals for treatment of Candida endophthalmitis. New-generation triazoles (eg, voriconazole, posaconazole, ravuconazole) are changing the conventional approach to fluconazole-resistant Candida strains, as well as the approach to fungal endophthalmitis. Caspofungin is the first echinocandin approved to treat fungal endophthalmitis. Concomitant systemic caspofungin and voriconazole therapy has successfully treated endophthalmitis due to Candida albicans.27,28,29,30 Experimental intraocular voriconazole (£ 25 mcg/mL) has been used for azole-resistant Candida infection with some success.
      • Ocular histoplasmosis: Treatment is limited to photocoagulation of neovascular membranes, particularly when the macula is threatened. Antifungal therapy has no role in treatment of this disease because no actively replicating organisms are present. Amphotericin B is used to treat systemic disease (0.75-1 mg/kg/d).31
      • Cryptococcus species infection: Amphotericin B (0.75-1 mg/kg/d) is used.
    • Antituberculosis drugs are administered in patients with M tuberculosis (MTB) and include isoniazid (10-30 mg/kg/d), rifampicin (10-20 mg/kg/d), pyrazinamide (30 mg/kg/d), and ethambutol (15 mg/kg/d). Other drugs, such as aminoglycosides and quinolones, may be used for treatment of drug-resistant organisms. Duration of therapy depends on the extent of the disease and on the immune status of the host.
    • Anthelmintics, including diethylcarbamazine (6 mg/kg/d), albendazole (400 mg PO bid), and mebendazole (100-200 mg PO bid), are usually administered with corticosteroids in patients with toxocariasis or baylisascariasis.
    • Etiologic treatments may not alter the clinical course of chorioretinitis because the pathologic changes may be due to an inflammatory and/or immunologic response instead of infection.
    • Treatment of other infectious etiologies, such as syphilis, yersiniosis, neuroborreliosis, depends on extent of disease but is likely to be successful in most patients.
  • Eye symptoms can be treated as follows:
    • Steroids may have a role in the acute management of many vasculitides, collagen vascular diseases, or sarcoidosis; in some infectious processes (eg, MTB); or in some cases infections caused by Toxoplasma species.
    • Laser treatment of retinal lesions is used in certain conditions with good results.

Surgical Care

  • Vitrectomy is usually not needed and is reserved for severe cases that are resistant to conservative medical treatment. 
  • Ocular cytology used to detect the presence of eosinophils, ocular antibody, and immunoglobulin E (IgE) levels should always be performed to differentiate toxocaral ocular larva migrans from malignant retinoblastoma to prevent unnecessary enucleations.

Consultations

  • Involvement of the following specialists is helpful in performing a diagnostic workup, determining the length of treatment, and planning the total management of a child with chorioretinitis:
    • Ophthalmologist - For determination of eye damage, treatment, and long-term follow-up care 
    • Infectious disease specialist - For diagnostic workup, selection of therapeutic agents and options, investigation of potential drug toxicities, and determination of treatment length in consultation with the ophthalmologist
  • Other specialists include the following:
    • Neurologist - For seizure control and long-term follow-up care of neurologic deficits 
    • Allergy and immunology/rheumatology specialist - To treat other associated conditions (ie, juvenile rheumatoid arthritis)
    • Audiologist - For assessment and corrective measures to detect and treat deafness (if possible)
    • Physical therapist - For maximization of functions and range of motions of muscles and joints and for referral to an orthopedist for surgical intervention if needed
  • Occasionally, genetic testing is required to investigate possible dysmorphic syndromes.

Medication

Over the last few years the list of therapeutic options available has grown. This section includes information on specific treatment options available.

Antivirals

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.


Foscarnet (Foscavir)

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.

Adult

Prehydration (infusion pump): Long-term IV access
Induction: 90 mg/kg q12h for 14-21 d
Maintenance: 90-120 mg/kg IV qd
Intravitreal injection: 2400 mcg/0.1 mL q72h
Decrease dose in renal failure

Pediatric

Administer as in adults

Avoid administration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine < 0.4 mL/min/kg); hydration may reduce nephrotoxicity
Carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures; granulocytopenia and anemia may occur (regularly monitor CBC count)
Infuse foscarnet solutions into veins with adequate blood flow to avoid local irritation; to avoid toxicity do not administer by rapid or bolus IV injection


Valganciclovir (Valcyte)

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.

Adult

Induction (active CMV retinitis): 900 mg PO bid with food for 21 d
Maintenance: 900 mg PO once daily with food

Pediatric

Not established

Interactions are similar to those reported with ganciclovir; coadministration with cytotoxic drugs such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity of rapidly dividing cell populations including bone marrow, spermatogonia, germinal layers of skin and GI mucosa (coadminister only if benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if benefits outweigh risks); serum creatinine may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in presence of ganciclovir

Documented hypersensitivity; severe renal dysfunction or hemodialysis; pregnancy, breastfeeding women; absolute neutrophil count is <500 cells/mcL, platelet count is <25,000/mcL, or hemoglobin is <8 g/dL

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Strict adherence to dosage guidelines essential to avoid overdose; valganciclovir tablets may not be substituted for ganciclovir capsules on one-to-one basis; adjust dose according to CrCl in impaired renal function; may cause granulocytopenia, anemia and thrombocytopenia; not indicated for CMV disease prevention in liver transplantation (higher CMV disease incidence in liver transplantation compared to prophylaxis with ganciclovir)


Acyclovir (Zovirax, Avirax)

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.

Adult

30 mg/kg/d IV divided tid

Pediatric

Neonates: 60 mg/kg/d IV divided tid
Children: 30 mg/kg/d IV divided tid
Optimal therapy duration has not been determined; 14 d recommended minimum

Increased CNS adverse effects with probenecid

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Infants require optimal fluid management to avoid potential crystallization in the renal tubules; exercise caution in patients with renal disease, dehydration, and underlying neurologic disease


Ganciclovir (Cytovene)

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.

Adult

Induction: 5 mg/kg IV infused over 1 h q12h for 14-21 d (do not use PO ganciclovir for induction treatment)
Maintenance PO: 500 mg q4h or 1 g tid for life
Maintenance IV: 5 mg/kg qd; alternatively, 6 mg/kg/d for 5 d/wk

Pediatric

<3 months: Not established
>3 months: Administer as in adults

Concomitant administration with cytotoxic drugs such as dapsone, vinblastine, doxorubicin (Adriamycin), pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine levels may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, whereas bioavailability of zidovudine is increased in presence of ganciclovir

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Clinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia; since PO ganciclovir is associated with higher rate of CMV retinitis progression than IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations of ganciclovir may be increased as a result of reduced renal clearance; dosages >6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration of ganciclovir should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur


Cidofovir (Vistide)

Used for CMV retinitis. Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Adult

Induction: 5 mg/kg IV infused over 1 h once per wk for 2 wk
Maintenance: 5 mg/kg infused over 1 h once every other wk

Pediatric

Induction: 5 mg/kg IV infused over 1 h as a single dose
Maintenance: 3 mg/kg IV infused over 1 h qwk

Coadministration of aminoglycosides, amphotericin B, IV pentamidine, and foscarnet may increase nephrotoxicity

Documented hypersensitivity; coadministration with other nephrotoxic agents; serum creatinine level >1.5 mg/dL; CrCl <55 mL/min; urine protein level >100 mg/dL

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor neutrophil counts; renal toxicity is major adverse effect; prehydrate with normal saline IV and coadminister probenecid with each infusion to minimize nephrotoxicity (monitor renal function); monitor serum creatinine and urine protein levels 48 h prior to treatment (adjust dose accordingly); granulocytopenia may occur

Antitoxoplasmosis agents

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.


Pyrimethamine (Daraprim)

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.

Adult

25-50 mg/d PO for 4 wk

Pediatric

2 mg/kg/d PO in loading dose, then 0.5-1 mg/kg/d PO

Concurrent use of antifolic acids (eg, methotrexate) and pyrimethamine may increase risk of bone marrow suppression; discontinue therapy if signs of folate deficiency develop; mild hepatotoxicity possible with concomitant administration of lorazepam and pyrimethamine

Documented hypersensitivity; megaloblastic anemia resulting from folate deficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If signs of folate deficiency develop, reduce dose or discontinue drug depending on patient response; caution in hepatic or renal impairment; may precipitate hemolytic anemia in G-6-PD deficiency, generally in presence of other stressful events


Sulfadiazine (Microsulfon)

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.

Adult

0.5-1.5 g PO q6h

Pediatric

120-150 mg/kg/d PO divided q6h

Documented hypersensitivity; porphyria; patients <2 mo; pregnancy in third trimester

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hepatic or renal impairment; may precipitate hemolytic anemia in G-6-PD deficiency, generally in presence of other stressful events


Spiramycin

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.

Adult

3 g/d PO divided bid/qid for 3 wk, discontinue for 2 wk, then repeat cycle

Pediatric

50-100 mg/kg/d for 3-4 wk

Coadministration may increase toxicity of theophylline, digoxin, fluconazole, pimozide, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis; arrhythmias and increase in QTc intervals occur with disopyramide

Documented hypersensitivity; hepatic impairment

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease or obstruction of bile ducts


Clindamycin (Cleocin)

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.

Adult

600 mg PO/IV q6-8h

Pediatric

20 mg/kg/d PO/IV divided q6-8h

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin

Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile


Dapsone (Avlosulfon)

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.

Adult

100 mg PO qd

Pediatric

1 mg/kg/d PO qd; not to exceed 100 mg/d

May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine [monitor for agranulocytosis during the second and third months of therapy]); probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of an increase in renal clearance, dapsone levels may significantly decrease when administered concurrently with rifampin

Documented hypersensitivity; known G-6-PD deficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform weekly blood counts (first month); then perform WBC counts monthly (6 mo); then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is observed; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M due to high risk of hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light

Antifungals

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


Amphotericin B (Amphocin, Fungizone)

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.

Adult

5-10 mcg intravitreally; levels remain above MIC for 11 d following injection in a nonvitrectomized eye compared with 2 d in vitrectomized eyes

Pediatric

Not established

With systemic administration, antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

With systemic administration, monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock


Flucytosine (Ancobon)

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.

Adult

50-150 mg/kg/d PO/IV divided q6h

Pediatric

Not established; limited data suggest dose is similar as in adults

Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in bone marrow suppression; adjust dose in renal impairment


Fluconazole (Diflucan)

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.

Adult

400 mg PO loading dose, followed by 200 mg PO qd

Pediatric

12 mg/kg PO loading dose, followed by 6 mg/kg/d; not exceed 600 mg/d

CYP450 2C19 and 3A4 inhibitor; levels may increase with hydrochlorothiazide; fluconazole levels may decrease with chronic coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications; not recommended for breastfeeding mothers
Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with PO fluconazole versus intravaginal agents


Itraconazole (Sporanox)

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.

Adult

200 mg PO tid loading dose, followed by 200-400 mg PO qd

Pediatric

5-10 mg/kg/d PO

Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death
May increase digoxin levels; coadministration may increase midazolam or triazolam levels; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hepatic insufficiencies


Voriconazole (VFEND)

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).

Adult

Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h; switch to 200 mg PO q12h when able to tolerate; may increase to 300 mg PO q12h if inadequate response
<40 kg: Average maintenance dose is 100 mg PO q12h (may increase to 150 mg PO q12h)
Take on an empty stomach

Pediatric

Not established; limited data suggest to administer as in adults

CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by as much as 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)

Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc


Caspofungin (Cancidas)

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.

Adult

50 mg IV qd

Pediatric

Not established; limited data exist in pediatrics to treat aspergillosis using 1 mg/kg/d

Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus; rifampin decreases caspofungin levels by 30% (ie, adjust dose to 70 mg/d)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression.

Anthelmintics

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


Albendazole (Albenza)

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.

Adult

10 mg/kg PO qd for up to 4 wk

Pediatric

<2 years: Not established
>2 years: 400 mg PO bid for 3-5 d

Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue use if LFT results significantly increase (resume when levels decrease to pretest values); abdominal pain, nausea, vomiting, diarrhea, dizziness, vertigo, fever, increased intracranial pressure, and alopecia may occur


Diethylcarbamazine (Hetrazan)

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.

Adult

6 mg/kg/d PO divided tid for 7-10 d

Pediatric

Administer as in adults

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause headaches, itching, skin rash, joint pain, and rarely vision impairment


Mebendazole (Vermox)

Exerts inhibitory effect on tubulin polymerization resulting in loss of cytoplasmic microtubules in the parasite.

Adult

100-200 mg PO bid for 5 d

Pediatric

Administer as in adults

Carbamazepine and phenytoin may decrease effects of mebendazole; cimetidine may increase mebendazole levels

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in hepatic impairment

More on Chorioretinitis

Overview: Chorioretinitis
Differential Diagnoses & Workup: Chorioretinitis
Treatment & Medication: Chorioretinitis
Follow-up: Chorioretinitis
Multimedia: Chorioretinitis
References

References

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Further Reading

Keywords

chorioretinitis, CR, retinochoroiditis, choroidoretinitis, congenital toxoplasmosis, CTP, congenital cytomegalovirus, CMV, congenital lymphocytic choriomeningitis virus, fungal infections, retinal vessels, infection, West Nile virus, Epstein-Barr virus, varicella-zoster virus, intrauterine growth retardation, microcephaly, microphthalmia, cataract, uveitis, hearing defect, osteomyelitis, hepatosplenomegaly, lymphadenopathy, dermal erythropoiesis, carditis, congenital heart disease, herpes simplex virus, ocular bartonellosis, infections, treatment, diagnosis

Contributor Information and Disclosures

Author

Ayesha Mirza, MD, Assistant Professor, Pediatric Infectious Diseases, University of Florida College of Medicine Jacksonville
Ayesha Mirza, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Tropical Medicine and Hygiene, HIV Medicine Association of America, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Sanofi Pasteur Honoraria Speaking and teaching

Coauthor(s)

Diana E Guinazu, MD, Fellow in Pediatric Infectious Diseases, University of Florida College of Medicine
Diana E Guinazu, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota Medical School
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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