Thirty six clinical isolates of Cryptococcus neoformans were tested for their susceptibility to 5-fluorocytosine and amphotericin B by the determination of minimum inhibitory concentrations and minimum fungicidal concentrations. 22.2% of the isolates were resistant to 5-fluorocytosine and 36.1% indicated 5-fluorocytosine tolerance. All strains were sensitive to amphotericin B.
Cryptococcal infection uncommonly presents with pulmonary manifestations and even more rarely so as massive bilateral effusions. Pleural involvement is usually associated with underlying pulmonary parenchymal lesions and is unusual while on antifungal therapy. We report a patient with cryptococcal meningitis who, while on intravenous 5-flucytosine and amphotericin B, developed life-threatening bilateral massive pleural effusions with evidence of spontaneous resolution, consistent with prior hypothesis of antigenic stimulation as the cause of pleural involvement.
We review our experience with 27 cases of pulmonary and meningeal cryptococcosis at the University Hospital, (Kuala Lumpar, Malaysia) where this is the most common cause of adult meningitis in patients without debilitating illnesses. Of the 27 cases analysed, six presented primarily with pulmonary symptomatology which usually were mainly cough, chest pain and low grade fever. The rest presented with primarily central nervous system (CNS) symptomatology of which headaches and fever were the most consistent symptoms although a third of these patients also had pulmonary lesions noted on chest radiographs. Treatment in all cases was with amphotericin B and 5-fluorocytosine and usually till a total cumulative dose of 1.5 g of amphotericin had been reached (an average of 10 weeks). Primary pulmonary presentations, if symptomatic, were treated as per CNS cryptococcosis due to the high likelihood of CNS dissemination. Incidental pulmonary cryptococcoma found on routine chest radiographs were confirmed by biopsy under ultrasound or fluoroscopy guidance and booked for surgical resection. Death usually occurred early in patients who presented late. Once patients responded to therapy, mortality was usually avoided. The only cause of morbidity in survivors was visual impairment or blindness, and this was attributed mainly to intracranial hypertension with residual deficits determined by the measures taken to lower intracranial pressures. Our experience suggests that: (i) symptomatic patients should have combination therapy with 5-fluorocytosine and amphotericin B till at least a cumulative dose of 1.5 g amphotericin B is reached irrespective of whether they have primary CNS or pulmonary symptomatology; (ii) non-symptomatic pulmonary cryptococcoma could be treated primarily by surgical resection; (iii) visual failure or papilloedema should be treated aggressively; and (iv) prognosis is good with adequate therapy and early presentation.
Cryptococcal infection of the brain as encountered in a tropical country is reviewed. The meningitic form is not uncommon and there has been, in the last decade, an apparent, if not real, rise in incidence in Malaysia as in Singapore. Only exceptionally was there overt evidence of immunological deficiency. Hydrocephalus was present in about three-quarters of the patients with meningitis and shunts were employed readily. The presence of multiple small intracerebral cysts could be suspected clinically but treatment for this complication was ineffective. The antifungal agent used most frequently was 5-fluorocytosine. Resistance to this drug developed in about one patient in four. There is a need for further epidemiological studies and for a continuing search for new antifungal agents.
The in vitro susceptibilities of Malaysian clinical isolates of Cryptococcus neoformans var. grubii and C . gattii to five antifungal drugs (amphotericin B, flucytosine, fluconazole, itraconazole and ketoconazole) were determined using the Etest method. None of the Malaysian isolates was resistant to amphotericin B and ketoconazole. Isolates resistant to flucytosine, fluconazole and itraconazole were observed in this study. Minimum inhibition concentrations (MICs) of > or = 32 microg ml(-1) against flucytosine, > or = 64 microg ml(-1) against fluconazole and > or = 1 microg ml(-1) against itraconazole were noted in four (8.3%), two (4.2%) and one (2.1%) isolates respectively. There was no significant difference in the MICs for both Cryptococcus species (P > 0.05), indicating that C. gattii was as susceptible as var. grubii to all the antifungal drugs tested. No significant difference in the MICs for both Cryptococcus species collected from 1980 to 1990 and 2002 to 2004 were observed (P > 0.05).
We describe a Malay girl with disseminated cryptococcosis affecting the lungs, liver, lymph nodes and bones. The diagnosis was made by culture of the bone marrow. Tests of immune function showed that she was HIV-negative but the CD4 percentage was persistently low. Idiopathic CD4+ T-lymphocytopenia was diagnosed. The child died despite two courses of anti-fungal therapy.
Cryptococcal meningitis is a central nervous system infection cause by Cryptococcus neoformans. Although Cryptococcus is found in bird droppings, it has never been reported for those ranchers involved in the niche swiftlet ranching industry despite having close proximity with the bird droppings. We present here a case of a 41-year-old healthy swiftlet rancher who presents with a history of prolonged fever, headache and altered behaviour of a month duration. Cerebral spinal fluid analysis revealed the presence of Cryptococcus. He was treated with intravenous amphotericin B and flucytosine and discharged well with fluconazole consolidation therapy for 8 weeks, followed by maintenance therapy for 1 year. We believe this is the first reported case of Cryptococcal meningitis (CM) occurring in an immunocompetent swiftlet rancher. This case should highlight the needs to wear a proper personal protective equipment inside a swiftlet ranch due to the constant exposure to the potential cryptococcal-rich environment. A high index of suspicion, careful history taking and physical examination focusing on neurologic assessment is key to early diagnosis and timely management of CM.