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drug should be discontinued if the blood urea nitrogen reaches 40 mg/dL and resumed when it descends to normal levels Renal tubular acidosis also frequently complicates amphotericin B therapy The addition of ucytosine (150 mg/kg/day) to amphotericin B results in fewer failures or relapses, more rapid sterilization of the CSF, and less nephrotoxicity than the use of amphotericin B alone because it permits the reduction of the amphotericin dose to 03 to 05 mg/kg/day Both medications are usually continued for at least 6 weeks longer if CSF cultures remain positive However, this regimen, which has a success rate of 75 to 85 percent in immunocompetent patients, has proven to be much less effective in patients with AIDS Such patients are also extremely sensitive to ucytosine and about half of them are forced to discontinue this drug because of neutropenia Fluconazole, an oral triazole antifungal agent given in a dosage up to 400 mg daily, or oral itraconazole (up to 200 mg per day) are alternatives to ucytosine in AIDS patients and are considerably more effective in preventing relapse if given inde nitely (Saag et al; Powderly et al) The optimum use of these drugs has not been settled, and some trials have yielded ambiguous results in both AIDS and other patients A current perspective on treatment can be obtained in the reference of Tunkel and Scheld Mortality from cryptococcal meningoencephalitis, even in the absence of AIDS or other disease, is about 40 percent Candidiasis (Moniliasis) Candidiasis is probably the most frequent type of opportunistic fungus infection, but it is far less common then cryptococcosis The most notable antecedents of Candida sepsis are severe burns and the use of total parenteral nutrition, especially in children Urine, blood, skin, and particularly the heart (myocardium and valves) and lungs (alveolar proteinosis) are the usual sites of primary infection No special features distinguish this fungal infection from others; meningitis, meningoencephalitis, and cerebral abscess, usually multiple and small, are the main modes of clinical presentation Lipton and colleagues, who reviewed 2631 autopsy records at the Peter Bent Brigham Hospital (1973 to 1980), found evidence of Candida infection in 28 cases, in half of which the CNS was infected These infections took the form of scattered intraparenchymal microabscesses, noncaseating granulomas, large abscesses, and meningitis and ependymitis (in that order of frequency) In most of these cases, the diagnosis had not been made during life, possibly because of the dif culty of obtaining the organism from the CSF Generally the CSF contains several hundred (up to 2000) cells per cubic millimeter Yeast can be seen on direct microscopy in half the cases Even with treatment (intravenous amphotericin B), the prognosis is extremely grave Aspergillosis In most instances, this fungal infection has presented as a chronic sinusitis (particularly sphenoidal), with osteomyelitis at the base of the skull or as a complication of otitis and mastoiditis Cranial nerves adjacent to the infected bone or sinus may be involved We have also observed brain abscesses and cranial and spinal dural granulomas In one of our patients, the Aspergillus organisms had formed a granulomatous mass that compressed the cervical spinal cord Aspergillosis does not present as a meningitis but hyphal invasion of cerebral vessels may occur, with thrombosis, necrosis, and hemorrhage In some cases the infection is acquired in the hospital, and in most it is preceded by a pulmonary infection that is unresponsive to antibiotics Diagnosis can often be made by nding the organism in a biopsy specimen
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or culturing it directly from a lesion Also, speci c antibodies are detectable Amphotericin B in combination with 5- uorocytosine and imidazole drugs is the recommended treatment, but this regimen is not as effective for aspergillosis as it is for cryptococcal disease The addition of itraconazole, 200 mg bid, in less immunocompromised patients is recommended If amphotericin B is given after surgical removal of the infected material, some patients recover Mucormycosis (Zygomycosis, Phycomycosis) This is a malignant infection of cerebral vessels with one of the Mucorales It occurs as a rare complication in patients with diabetic acidosis, in drug addicts, and in patients with leukemia and lymphoma, particularly those treated with corticosteroids and cytotoxic agents The cerebral infection begins in the nasal turbinates and paranasal sinuses and spreads from there along infected vessels to the retro-orbital tissues (where it results in proptosis, ophthalmoplegia, and edema of the lids and retina) and then to the adjacent brain, causing hemorrhagic infarction Numerous hyphae are present within the thrombi and vessel wall, often invading the surrounding parenchyma The cerebral form of mucormycosis is usually fatal in short order Rapid correction of hyperglycemia and acidosis and treatment with amphotericin B have resulted in recovery in some patients Coccidioidomycosis, Histoplasmosis, Blastomycosis, and Actinomycosis Coccidioidomycosis is a common infection in the southwestern United States It usually causes only a benign, in uenza-like illness with pulmonary in ltrates that mimic those of nonbacterial pneumonia; but in a few individuals (005 to 02 percent), the disease takes a disseminated form, of which meningitis may be a part The pathologic reactions in the meninges and CSF and the clinical features are very much like those of tuberculous meningitis Coccidioides immitis is recovered with dif culty from the CSF but readily from the lungs, lymph nodes, and ulcerating skin lesions Treatment consists of the intravenous administration of amphotericin B coupled with implantation of an Ommaya reservoir into the lateral ventricle, permitting injection of the drug for a period of years Instillation of the drug by repeated lumbar punctures is an alternative albeit cumbersome procedure Even with the most assiduous programs of treatment, only about half the patients with meningeal infections survive A similar type of meningitis may occasionally complicate histoplasmosis, blastomycosis, and actinomycosis These chronic meningitides possess no speci c features except that actinomycosis, like some cases of tuberculosis and nocardiosis, may cause a persistent polymorphonuclear pleocytosis (see page 635) The CSF yields an organism in a minority of patients, so that diagnosis depends upon culture from extraneural sites, biopsy of brain abscesses if present, as well as knowledge of the epidemiology of these fungi Patients with chronic meningitis in whom no cause can be discovered should also have their CSF tested for antibodies to Sporothrix schenkii, an uncommon fungus that is dif cult to culture Several even rarer fungi that must be considered in the diagnosis of chronic meningitis are discussed in the article by Swartz Penicillin is the drug of choice in actinomycosis; amphotericin B and supplemental antifungal agents are used in the others Intrathecal amphotericin is administered in patients who relapse
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