eMedicine Specialties > Neurology > Neurological Infections
HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis: Treatment & Medication
Updated: Feb 23, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Algorithms have been developed for the evaluation and treatment of adult HIV-seropositive patients with neurological symptoms and signs.
- A brain CT scan or MRI with and without contrast is indicated for all patients presenting with altered mental status, headaches, seizures, or focal neurological signs.
- MRI clearly is the superior technique but is not available universally.
- If the initial imaging study is normal or shows atrophy or focal signal abnormalities (but no mass lesion), diagnostic consideration should be given to meningitides, AIDS dementia complex, or progressive multifocal leukoencephalopathy.
- If imaging shows 1 or more focal mass lesions with impending herniation, an open biopsy with decompression is indicated. Treatment for lymphoma, toxoplasmosis, or other opportunistic infections and neoplasms is initiated, depending on biopsy results.
- If imaging shows 1 or more focal mass lesions without impending herniation, additional studies are warranted.
- Where available,201 Th SPECT or 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) can provide high specificity, albeit at low sensitivity, strong evidence that a mass lesion represents a lymphoma; this can be confirmed by stereotactic biopsy.
- When201 Th SPECT or 18FDG-PET cannot be conducted, toxoplasmosis serology in conjunction with imaging results will determine how to proceed.
- In cases of a single mass lesion and negative serologic findings or lack of response after 14 days of empiric therapy, stereotactic brain biopsy is indicated.
- In cases of multiple lesions, whether serologic results are negative or positive, antitoxoplasmosis therapy should be initiated.
Surgical Care
In cases of impending herniation, an open biopsy with decompression is indicated.
Medication
The decision to treat a patient for CNS toxoplasmosis is usually empiric; standard therapy consists of combination pyrimethamine, sulfadiazine, and folinic acid given as primary therapy for 6 weeks, followed by long-term suppressive therapy at reduced doses, with the duration determined by response to potent HAART. The long-term suppressive therapy can be discontinued in patients with persistent elevation of CD4+ counts of greater than 200 cells/µL and resolution of lesions on MRI. TMP-SMZ can be used as an alternative regimen. A recent Cochran data base review failed to find a significant difference between standard therapy and TMP-SMZ. Clindamycin can be used in patients allergic to sulpha drugs. Last but not least, effective antiretroviral therapy is equally important.
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic combinations usually are recommended to circumvent resistance from bacterial subpopulations (which may be resistant to 1 of the antibiotic components) and to provide additive or synergistic effect.
Pyrimethamine (Daraprim)
Folic acid antagonist that selectively inhibits dihydrofolate reductase, highly selective against Plasmodium species and T gondii. Does not destroy gametocytes but arrests sporogony in mosquito.
Adult
100 mg PO bid on day 1, followed by 25-100 mg PO qd for at least 6 wk
Long-term suppressive therapy: Use lower dose of pyrimethamine (50 mg PO qd) plus sulfadiazine at 1 g PO qid
Pediatric
1 mg/kg PO bid for 2-4 d, followed by 0.5 mg/kg PO bid; not to exceed 25 mg qd
Antifolic acids (eg, methotrexate, pyrimethamine) may increase risk of bone marrow suppression; lorazepam may cause mild hepatotoxicity
Documented hypersensitivity, megaloblastic anemia that results from folate deficiency
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Depending on patient response, discontinue or reduce dose if signs of folate deficiency develop; use caution in patients with hepatic or renal impairment; monitor for toxoplasmosis by performing semiweekly blood counts, including platelet counts; may precipitate hemolytic anemia in patients with G-6-PD deficiency, generally in presence of other stressful events
Sulfadiazine (Microsulfon)
Through competitive antagonism of PABA, interferes with microbial growth. Useful for treating toxoplasmosis.
Adult
1-2 g PO qid for at least 6 wk
Long-term suppressive therapy: Use lower dose of pyrimethamine (50 mg PO qd) plus sulfadiazine at 1 g PO qid
Pediatric
75 mg/kg PO initial loading dose, followed by 150 mg/kg/d divided q4-6h; not to exceed 6 g/dose
Increases effects of oral anticoagulants and oral hypoglycemic agents; effects decreased by PABA or PABA metabolites of drugs (eg, proparacaine, tetracaine, sunscreens, procaine)
Documented hypersensitivity
Pregnancy
D - Unsafe in pregnancy
Precautions
Use caution in patients with impaired renal or hepatic function or G-6-PD deficiency; adjust dose in patients with renal insufficiency
Clindamycin (Cleocin)
Inhibits bacterial protein synthesis by its action at bacterial ribosome. Antibiotic binds preferentially to 50S ribosomal subunit and affects process of peptide chain initiation. As alternative to sulfonamides, may be beneficial in combination with pyrimethamine in acute treatment of CNS toxoplasmosis in AIDS.
Adult
1200-4800 mg/d PO/IV/IM divided q6-8h
Pediatric
20-40 mg/kg/d IV/IM divided tid
Increases duration of neuromuscular blockade induced by tubocurarine or pancuronium
Documented hypersensitivity, regional enteritis, hepatic impairment, ulcerative colitis, antibiotic-associated colitis
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
May be necessary to adjust dose in patients with severe hepatic dysfunction; no adjustment necessary in patients with renal insufficiency; has been associated with severe and possibly fatal colitis
Clarithromycin (Biaxin)
Reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl tRNA from ribosomes.
Adult
2 g PO qd or divided bid
Pediatric
7.5 mg/kg PO bid
Fluconazole may increase levels significantly; pimozide may result in toxic levels and possibly death; rifabutin or rifampin may decrease antimicrobial effects or increase frequency of adverse GI effects; important to monitor anticoagulant function in patients receiving anticoagulants and any macrolide antibiotic; taking with astemizole may cause adverse cardiovascular effects (eg, death, cardiac arrest, torsades de pointes, other ventricular effects); taking with cisapride may cause serious cardiac arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT interval prolongation); may increase disopyramide plasma levels, causing arrhythmias and increasing QTc intervals; may increase plasma levels of certain benzodiazepines, prolonging CNS depressant effects
May increase carbamazepine concentrations; may increase serum digoxin concentrations as a result of effects on gut flora, which metabolize digoxin in more than 10% of patients; may cause acute ergot toxicity, characterized by severe peripheral vasospasm and dysesthesia (important to monitor patients who are receiving ergot alkaloids and any macrolide antibiotic); increases risk of severe myopathy or rhabdomyolysis associated with HMG CoA inhibitors; coadministration of omeprazole and clarithromycin may increase plasma levels of both drugs; may elevate serum tacrolimus levels, increasing risk of adverse effects such as nephrotoxicity
Documented hypersensitivity, concurrent pimozide, astemizole (recalled from US market), cisapride, or terfenadine (recalled from US market)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Concurrent ranitidine/bismuth citrate therapy not recommended in patients with CrCl <25 mL/min; may be administered without dosage adjustment to patients with hepatic impairment and normal renal function; in severe renal impairment (CrCl <30 mL/min) with or without coexisting hepatic impairment, dosage should be halved or dosing interval doubled; like nearly all antibacterial agents, may cause mild to severe pseudomembranous colitis— consider this diagnosis in patients who present with diarrhea after receiving antibacterial agents; antibiotic use, especially prolonged or repeated, may result in bacterial or fungal overgrowth of nonsusceptible organisms, possibly leading to a secondary infection (take appropriate measures if superinfection occurs)
Corticosteroids
These agents have anti-inflammatory properties and may decrease intracranial pressure. They cause profound and varied metabolic effects and modify the body's immune response to diverse stimuli. They should be used only when warranted in cases of impending brain herniation. Their use may complicate the interpretation of a response to antitoxoplasmosis therapy.
Dexamethasone (Decadron, Dexone)
Used in treatment of various inflammatory diseases, decreases inflammation by suppressing migration of polymorphonuclear leukocytes, inhibiting proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, and IFN-gamma), and down-regulating recruitment of inflammatory cells.
Adult
16 mg/d PO/IV divided q6h starting dose; continue until patient improves; taper to cessation or minimum effective dose
Much higher doses (up to 100 mg/d divided) may be indicated in treatment of intraspinal lymphoma
Pediatric
0.15 mg/kg/d PO/IV divided q6h
Barbiturates, phenytoin, and rifampin can decrease effects; decreases effect of salicylates and vaccines used for immunization
Infection, peptic ulcer disease, psychosis, hypertension
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
With impending herniation that is not amenable to decompression, treat patient carefully and watch for adverse sequelae; important to monitor for adrenal insufficiency when tapering drug; commonly elevates serum glucose and blood pressure; may inhibit normal immune response, contribute to formation of peptic ulcers, and cause myopathy and behavioral changes; because of risk of adverse effects, use cautiously in elderly, in smallest possible dose and for shortest possible time; adverse effects include infections, hyperglycemia, hypokalemia, osteoporosis, aseptic hip necrosis, headaches, anxiety, psychosis, insomnia, myalgia, steroid myopathy, cataracts, glaucoma, acne, hirsutism, facial plethora
Folic acid derivative
These agents are used to rescue cells from the deteriorating effects of folic acid antagonists.
Folic acid (Wellcovorin, Folinic acid)
Reduced form of folic acid, does not require reduction reaction by enzyme for activation. Allows for purine and pyrimidine synthesis, which is needed for normal erythropoiesis. It prevents bone marrow suppression.
Adult
10-15 mg PO qd
Pediatric
Administer as in adults
None reported
Documented hypersensitivity, pernicious anemia, vitamin-deficient megaloblastic anemias, intrathecal or intraventricular administration
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Do not administer intrathecally or intraventricularly
More on HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis |
| Overview: HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis |
| Differential Diagnoses & Workup: HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis |
 Treatment & Medication: HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis |
| Follow-up: HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis |
| Multimedia: HIV-1 Associated Opportunistic Infections - CNS Toxoplasmosis |
| References |
| « Previous Page | Next Page » |
References
AAN Quality Standards Subcommittee. Evaluation and management of intracranial mass lesions in AIDS. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Jan 1998;50(1):21-6. [Medline].
Behbahani R, Moshfeghi M, Baxter JD. Therapeutic approaches for AIDS-related toxoplasmosis. Ann Pharmacother. Jul-Aug 1995;29(7-8):760-8. [Medline].
Bertschy S, Opravil M, Cavassini M, et al. Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy. Clin Microbiol Infect. 2006;12(7):666-71. [Medline].
Dedicoat M, Livesley N. Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings). Cochrane Database Syst Rev. 2006;3:CD005420. [Medline].
Fung HB, Kirschenbaum HL. Treatment regimens for patients with toxoplasmic encephalitis. Clin Ther. Nov-Dec 1996;18(6):1037-56; discussion 1036. [Medline].
Klepser ME, Klepser TB. Drug treatment of HIV-related opportunistic infections. Drugs. Jan 1997;53(1):40-73. [Medline].
Marra MC. Infections of the central nervous sytem in patients infected with human immunodeficiency virus. Continuum. 2006;12:111-32.
Offiah CE, Turnbull IW. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients. Clinical Radiology. 2006;61:393-401. [Medline].
Verma A. Neurological manifestations of human immunodeficiency virus infection in adults. In: Neurology in Clinical Practice. Vol 2. 2004:1581-1601.
Walker M, Zunt JR. Parasitic central nervous system infections in immunocompromised hosts. Clin Infect Dis. Apr 1 2005;40(7):1005-15. [Medline].
de Gans J, Portegies P. Neurological complications of infection with human immunodeficiency virus type 1. A review of literature and 241 cases. Clin Neurol Neurosurg. 1989;91(3):199-219. [Medline].
Further Reading
Keywords
acquired immunodeficiency syndrome, AIDS, intracellular parasite, Toxoplasma gondii, T gondii, CNS disease in AIDS, HIV infection, complication of HIV, complication of AIDS, advanced HIV infection
