Minimum concentration of Amphotericin B in serum according to the formulation, dose, and daily or prolonged intermittent therapeutic regimen

Abstract INTRODUCTION: The therapeutic efficacy of daily amphotericin B infusion is related to its maximum concentration in blood; however, trough levels may be useful in intermittent regimens of this antifungal drug. METHODS : High performance liquid chromatography (HPLC) was used to determine the minimum concentration (Cmin) of amphotericin B in the serum of patients receiving deoxycholate (D-Amph) or liposomal amphotericin B (L-AmB) for the treatment of cryptococcal meningitis (n=28), histoplasmosis (n=8), paracoccidioidomycosis (n=1), and leishmaniasis (n=1). RESULTS: Daily use of D-Amph 30 to 50 mg or L-AmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with L-AmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent L-AmB infusions: 357 ng/mL (100 mg 4 to 5 times/week) > 263 ng/mL (50 mg 4 to 5 times/week) > 227 ng/mL (50 mg 1 to 3 times/week). The impact on Cmin was variable in patients whose dose or therapeutic scheme was changed, especially when administered the intermittent infusion of amphotericin B. The mean Cmin for each L-AmB schedule of intermittent therapy was equal or higher than the minimum inhibitory concentration of amphotericin B against Cryptococcus isolates from 10/12 patients. The Cmin of amphotericin B in patients with cryptococcal meningitis was comparable between those that survived or died. CONCLUSIONS: By evaluating the Cmin of amphotericin B, we demonstrated the therapeutic potential of its intermittent use including in the consolidation phase of neurocryptococcosis treatment, despite the great variability in serum levels among patients.

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis / 中华医学杂志(英文版)

BACKGROUND@#Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.@*METHODS@#Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.@*RESULTS@#Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25-12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166-13.269, P = 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548-35.974, P = 0.001) were associated with higher mortality at 8 weeks.@*CONCLUSION@#This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

Criptococosis cerebral, voriconazol, niveles plasmáticos y síndrome de reconstitución inmune: reporte de un caso / Cerebral cryptococcosis and immune reconstitution inflammatory syndrome: case report

We report a 45-year-old male with AIDS who had a Cryptococcus neoformans central nervous system infection. He was treated with amphotericin B deoxycholate subsequently changed to voriconazole due to systemic toxicity of the former. Plasma levels of voriconazole were insufficient with a standard dose (0.7 μg/mL), therefore, the dose was increased thereafter to reach appropriate levels (4.5 μg/mL). Anti-retroviral therapy was started five weeks after voriconazole initiation with non-interacting drugs and he was discharged after a favorable evolution. He was re-admitted three months later due to seizures; a brain magnetic resonance showed new sub-cortical nodules. After excluding alternative causes and demonstrating fungal eradication, an immune reconstitution inflammatory syndrome (IRIS) event was suspected and treated with a short course of steroids. His evolution was satisfactory.

Abordagem cirúrgica de lesão granulomatosa criptocócica cerebral (criptococoma) em paciente imunocompetente / Surgical Approach to an Immunocompetent Patient's Cerebral Granulomatosis (cryptococcoma)

Acriptococose é a principalmicosequeatingeosistemanervosocentral, sendode distribuição mundial, mais prevalente em países em desenvolvimento. Atualmente, são descritas duas subespécies: Cryptococcus neoformans neoformans, associado à imunossupressão, e Cryptococcus neoformans gattii, em pacientes imunocompetentes. A criptococose do sistema nervoso central parenquimatosa em sua forma granulomatosa, ou criptococoma, é extremamente rara, sendo mais frequente a forma meningítica ou meningoencefalítica. Relatamos o caso de um paciente de 35 anos, não portador da síndrome de imunodeficiência adquirida e imunocompetente, com manifestações clínicas iniciais de cefaleia crônica, hemiparesia progressiva, confusão mental aguda e primeiro episódio de crise convulsiva tônico-clônica generalizada. Hipóteses diagnósticas préoperatórias de neoplasia maligna ou abscesso cerebral. Realizado procedimento cirúrgico, remoção completa da lesão maior, diminuindo o efeito de massa. A lesão foi diagnosticada, através de exame anatomopatológico, como criptococoma, o que torna o caso extremamente raro pelo tamanho da lesão e por ser o paciente imunocompetente. Houve melhora completa do déficit neurológico. O paciente encontra-se em seguimento clínico e tratamento medicamentoso com anfotericina-B.

Cryptococcosis is the main mycosis affecting the central nervous system, with worldwide distribution and higher prevalence in developing countries. Currently, two subspecies are described: Cryptococcus neoformans neoformans (associated with immunosuppression) and Cryptococcus neoformans gattii (in immunocompetent patients). Cryptococcosis of the central nervous system as a parenchymal granuloma or cryptococcoma is extremely rare, contrasting to themuchmore frequentmeningitic form. We report a 35 year-old immunocompetent patient with chronic headache, progressive hemiparesis, acute confusion and first episode of tonic-clonic seizures. Preoperative diagnostic hypotheses were malignancy or abscess. A large mass (5.5 cm) was surgically removed from the right parietal lobe relieving the mass effect. This was later diagnosed by pathological examination as cryptococcoma, an extremely rare case in view of lesion size and its occurrence in an immunocompetent subject. The patient evolved with complete resolution of the neurological deficit and is on amphotericin-B treatment.

Puerperal brain cryptococcoma in an HIV-negative woman successfully treated with fluconazole: a case report

Cryptococcus spp. cerebral abscesses are uncommon in immunocompetent subjects. The recommended induction treatment is the administration of amphotericin B plus flucytosine combined with resection for lesions ≥3cm. In this paper, we describe an HIV-negative woman diagnosed with a large cryptococcoma in the immediate postpartum period. The lesion was not resected, and due to amphotericin B intolerance, she received an extended course of fluconazole monotherapy. There was no disease recurrence during the 4 years of follow-up. The abrupt onset of her symptoms following delivery suggests that she developed a postpartum immune reconstitution syndrome. This case also demonstrates that in specific situations fluconazole monotherapy can be attempted in immunocompetent patients with cryptococcoma.

Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.

Cryptococcoma of the brain in an immunocompetent man.

Cryptococcosis is a common opportunistic systemic disease in immunocompromised patients. Pulmonary or brain cryptococcosis is the most common clinical presentation. Immunocompetent patients can also be affected, especially in tropical and subtropical zones where the life cycle of the causal agent, Cryptococcus gattii, is completed. We present a previously healthy man with progressive intracranial hypertension and a right paraventricular mass on CT scan and MRI. Cryptococcus gattii yeasts were isolated from the cerebrospinal fluid. A ventriculoperitoneal shunt was placed and the patient was treated with amphotericin B, fluconazole and dexamethasone. The patient died due to severe intracranial hypertension.

Cryptococcal meningitis associated with tuberculosis in HIV infected patients.

Summary: Opportunistic infections are common complications of advanced immuno-deficiency in individuals with Human Immunodeficiency Virus (HIV) infection. Following involvement of the lung, the central nervous system (CNS) is the second most commonly affected organ. We report two cases of concurrent cryptococcal meningitis and tuberculosis (TB) in HIV infected persons. A high suspicion of multiple opportunistic infections should be kept in mind in HIV seropositive individuals.

Strategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin America

Latin America is the region with the third most AIDS-related cryptococcal meningitis infections globally. Highly active antiretroviral therapy (HAART) has reduced the number of infections; however, the number of deaths and the case-fatality rate continues to be unacceptable. In this review, we focus on the burden of AIDS-related cryptococcosis in Latin America and discuss potential strategies to reduce early mortality from Cryptococcus. In this review, we highlight the importance of: (1) earlier HIV diagnosis and HAART initiation with retention-in-care to avoid AIDS; (2) pre-HAART cryptococcal antigen (CRAG) screening with preemptive fluconazole treatment; (3) better diagnostics (e.g. CRAG testing); and (4) optimal treatment with aggressive management of intracranial pressure and induction therapy with antifungal combination. Implementation of these strategies can reduce cryptococcal-related deaths, improve care, and reduce healthcare costs.

Meningoencefalitis por Criptococo neoformans: reporte de caso y revisión del tema / Meningoencephalitis by Cryptococcus neoformans: case report and subject revision

Se presenta el caso de una paciente femenina de 60 años, procedente de área urbana, con antecedentes de hipertensión arterial y artritis psoriásica, que lleva tratamiento con metrotexate, quien ingresó en la Unidad de Cuidados Intensivos por cefalea gradual generalizada y constante, seguida de pérdida de la conciencia, convulsiones generalizadas tónico-clónicas, estupor, afasia mixta, hiperreflexia osteotendinosa en los 4 miembros, Babinnsky bilateral y rigidez de nuca. La tomografía de cráneo informó hemorragia cerebral intraparenquimatosa. El estudio del líquido cefalorraquídeo fue incoloro, transparente, con 50 células solamente a predominio de linfocitos, por lo que se sospechó meningoencefalitis por hongos, que se confirmó al realizar tinción con tinta china (Cryptococo neoformans). Fueron estudiadas las excretas de su mascota (cotorra Amazona leucocephala leucocephala) que demostró ser el agente causal. Se aplicó tratamiento con amfotericin B, pero finalmente falleció ocho semanas después.

Meningitis por Cryptococcus neoformans en niños y adolescentes infectados por virus de la inmunodeficiencia humana / Cryptococcus neoformans meningitis in children and adolescentes infected with HIV

Three cases of meningitis due to criptococcus in children infected with HIV are reported. All patients had severe immunodeficiency. The first case occurred before antiretroviral therapy. The second case had poor adherence to treatment. The third case is a teenager with prolonged fever, who did not have a clear source of transmission of HIV and was immunodeficient at the time of diagnosis. Examination of cerebrospinal fluid with India ink dye was essential for making the diagnosis in all three cases. The disease course was adequate in all three patients despite flucytosine not being available.

Se presentan tres casos de meningitis por Cryptococcus sp. en niños infectados con VIH e inmunodeficiencia grave. El primero fue en la época en que no se disponía de TAR. El segundo fue un paciente no adherente al tratamiento. La tercera fue una adolescente en la que se hizo diagnóstico por una enfermedad febril prolongada, donde no fue posible encontrar la fuente de transmisión de VIH y que en el momento del diagnóstico estaba con inmunosupresión grave. En los tres fue fundamental para el diagnóstico rápido la tinción de LCR con tinta china. La evolución de la enfermedad fue adecuada en los tres pacientes aunque no se contó en ninguno de los casos con flucitosina.

Meningite criptocócica na gravidez: revisão de aspectos terapêuticos / Cryptococcal meningitis in pregnancy: review of the therapeutic aspects

A criptococose é uma infecção fúngica, cujo envolvimento do sistema nervoso central é caracteristicamente insidioso, apresentando sinais de irritação meníngea, sequelas neurológicas e alta mortalidade. A gestação, condição que leva a certo grau de imunossupressão, pode dificultar a resposta ao tratamento. Objetivando determinar a estratégia de tratamento mais efetiva para meningite criptocócica em grávidas sem outras condições de imunossupressão, o presente trabalho realizou um levantamento bibliográfico acerca do tema. Foram revisados cinco artigos, os quais evidenciaram ampla utilização de anfotericina B em monoterapia ou associada à flucitosina, inclusive no primeiro, segundo e terceiro trimestre de gestação. Também foi relatada a utilização de fluconazol e itraconazol. Em todos os relatos, os resultados foram favoráveis tanto para mãe quanto para a criança. Existem poucos dados disponíveis na literatura acerca do tema proposto. Preferencialmente, a conduta a ser realizada envolve internação da gestante como gravidez de alto risco e administração de anfotericina B. Embora os resultados apresentados tenham sido favoráveis tanto para a monoterapia com anfotericina B quanto para sua associação com flucitosina, ou para monoterapia com fluconazol ou itraconazol, são necessários estudos prospectivos, controlados e randomizados para determinar o esquema terapêutico significativamente mais eficaz para o tratamento da criptococose em gestantes

Cryptococcosis is an infection caused by a fungus, whose involvement in the central nervous system is characteristically insidious, presenting signs of meningitis, neurological sequelae, and high mortality. The pregnancy, a condition that leads to a certain degree of immunosupression, may hinder the response to treatment. With the aim of determining the most effective treatment for cryptococcal meningitis in pregnant women without other causes of immunodeficiency, this paper carried out a survey about the subject. Five articles were analyzed and they showed a wide utilization of amphotericin B as monotherapy or associated with flucytosine in the treatment of cryptococcal meningitis in pregnant women, which includes the usage during the first, second and third trimesters of pregnancy. It was also reported the usage of itraconazole and fluconazol. The results were positive in all articles for both mother and fetus. There are few data available in the literature about this theme. Preferably, the physician should proceed with the admission of the patient as a high-risk pregnancy and should administer amphotericin B. Although the presented results were favorable to monotherapy with amphotericin B and to its association with flucytosine, as well as to monotherapy with fluconazole or itraconazole, only randomized controlled trials will be able to determine the best significantly effective therapeutics for cryptococcosis in pregnant women

An analysis of three opportunistic infections in an outpatient HIV Clinic in Jamaica / Análisis de tres infecciones oportunistas en un paciente externo de la Clínica de VIH en Jamaica

OBJECTIVES: To determine the occurrence of opportunistic infection (OI) in HIV-positive patients and to identify any risk factors which may be associated with such. METHODS: A cross-sectional study of all patients attending the HIV out-patient clinic was conducted. Their hospital notes were examined between January 1 and December 31, 2007 inclusive, to identify any occurrence of opportunistic infection. In addition, the patient list was also cross-referenced with all patients hospitalized on the medical wards during the same time period. Clinical and demographic data were collected for all participants. The occurrence of opportunistic infections and the variables of age, gender, CD4 counts and viral loads: (first ever, last in 2007 and at diagnosis of OI [or within six months]), the use of primary and secondary prophylaxis, the discontinuation of prophylactic regimens and the HAART regime at diagnosis of an OI and the diagnostic and treatment protocols of these infections were calculated. RESULTS: Six hundred and three patients participated in the study and 4.7% (n = 28) were found to have experienced at least one opportunistic infection in 2007. Significant associations were found between first and last CD4 cell count, viral load in 2007, year of entry into the clinic and death (p < 0.05). CONCLUSIONS: Opportunistic infections continue to cause significant morbidity and mortality in the HIV-patient population in this study. Earlier entry to treatment facilities and the use of HAART and appropriate prophylaxis can reduce this impact and lead to improved quality of life for HIV-positive individuals.

OBJETIVOS: Determinar la ocurrencia de infecciones oportunistas (IO) en pacientes VIH-positivos e identificar factores de riesgo que puedan estar asociados con ellas. MÉTODOS: Se llevó a cabo un estudio transversal de todos los pacientes que asisten a la clínica externa de VIH. Sus apuntes de hospital fueron examinados entre el 1 de enero y el 31 de diciembre de 2007 inclusive, a fin de identificar cualquier manifestación de infección oportunista. Además, la lista de pacientes fue creada con referencias cruzadas en relación con todos los pacientes hospitalizados en las salas del hospital durante el periodo en cuestión. Se recogieron los datos clínicos y demográficos de todos los participantes. Se realizaron cálculos de la ocurrencia de infecciones oportunistas y las variables de edad, género, conteos de CD4 y las cargas virales: (la primeray la última en 2007 y en el diagnóstico de IO [o dentro de seis meses]), el uso de profilaxis primaria y secundaria, la descontinuación de los regimenes profilácticos y el régimen de TARGA en el diagnóstico de una IO, así como los protocolos de diagnóstico y tratamiento de estas infecciones. RESULTADOS: Seiscientos tres pacientes participaron en el estudio y se halló que 4.7% (n = 28) habían parecido por lo menos una infección oportunista en 2007. Se hallaron asociaciones significativas entre elprimer y el último conteo celular CD4, la carga viral en el 2007, el ano de entrada en la clínica y la muerte (p < 0.05). CONCLUSIONES: Las infecciones oportunistas continúan siendo la causa de morbilidad y mortalidad significativas entre la población de pacientes de VIH de acuerdo a este estudio. El ingreso temprano a los centros de tratamiento y el uso de la terapia de TARGA así como una profilaxis adecuada, puede reducir este impacto y llevar a una mejor calidad de vida de los individuos VIH positivos.

Criptococosis meníngea y lupus eritematoso sistémico: reporte de un caso y revisión de la literatura / Cryptococcal meningitis and systemic lupus erythematosus: a case report and review

Cryptococcal meningitis is an uncommon but well-known and frequently fatal complication of systemic lupus erythematosus (SLE). The clinical manifestations are unspecific and frequently are confused with lupus activity. A patient with cryptococcal meningitis and SLE, who responded well to amphotericin deoxycolate therapy, is reported. In a review through MEDLINE of the Spanish and English literature, 57 cases of SLE and cryptococcal meningitis were found. Simultaneous presentation of both diseases has been reported in only three cases. This temporal coexistence suggests that specific underlying immune defects associated with SLE directly predisposes to mycotic infections.

La meningitis por Cryptococcu neoformans es una inusual pero reconocida fatal complicación en los pacientes con lupus eritematoso sistémico (LES). Se presenta con un cuadro clínico inespecífico y frecuentemente se confunde con la actividad lúpica. Se reporta un caso de un paciente diagnosticado con meningitis por C. neoformans, al comienzo de LES, que fue tratada satisfactoriamente con anfotericina B deoxicolato. En la revisión de la literatura en español e inglés a través de MEDLINE, se encontró que han sido reportados 57 casos de pacientes con LES y criptococosis meníngea, de los cuales hay solamente 3 casos cuya infección se presentó simultáneamente con el LES. La presentación simultánea de criptococosis meníngea y LES enfatiza la posibilidad de que defectos inmunológicos intrínsecos en pacientes con LES sean los directamente responsables de la predisposición a adquirir infecciones micóticas.

Cryptococcal meningitis in HIV negative pregnant women: case report and review of literature / Meningite criptocóccica em gestante HIV negativa: relato de caso e revisão da literatura

INTRODUCTION: Cryptococcosis has become an important entity due to the epidemic of AIDS and therefore it is a significant opportunistic infection. However, there are case reports of cryptococcal meningitis in immune competent pregnant women. Since pregnancy is considered a period of relative immunosuppression, which likely prevents fetal rejection, this could explain the occurrence of opportunistic infections. OBJECTIVE: To report a case of cryptococcosis, and review all cases involving pregnancy and neurocryptococcal infection in immune competent pregnant patients. METHODS: Case report and systematic review of the literature using the MEDLINE and SciELO databases. DISCUSSION: A total of 27 patients were analyzed from 19 studies. The mean age at diagnosis was 26.4 years. There were six patients in their first trimester of pregnancy, 10 in the second, eight in the third and three post-partum. The most prevalent symptoms were headache (85.2 percent), altered vision (44.4 percent), altered mental status (44.4 percent), nausea (40.7 percent) and fever (33.3 percent). There were nine deaths (33.3 percent). Most of the patients received intravenous amphotericin B as treatment (77.8 percent). The majority (66.6 percent) of the patients accomplished a term delivery with healthy infants. CONCLUSION: Cryptococcal meningitis should be considered during pregnancy in cases of unexplained headache, altered vision, altered mental status, nausea and fever. Patients with a confirmed diagnosis should be admitted and treated with amphotericin B.

INTRODUÇÃO: Com a epidemia da AIDS, a neurocriptococose foi melhor estudada e considerada infecção fúngica oportunista. No entanto, há casos descritos de gestantes acometidas, apesar de imunocompetentes. A gestação, por si só, pode ser considerada um período de imunossupressão, para adaptação materno-fetal, o que poderia predispor à instalação de certas infecções. OBJETIVOS: Relato de caso de gestante com neurocriptococose e revisão sistemática dos casos descritos na literatura desta patologia durante a gestação, em pacientes imunocompetentes. METODOLOGIA: Revisão sistemática com busca MEDLINE e SciELO. RESULTADOS: Foram analisadas 27 pacientes com diagnóstico de neurocriptococse na gestação. A média de idade foi 26,4 anos. Seis pacientes estavam no primeiro trimestre de gravidez ao diagnóstico, 10 no segundo, oito no terceiro e três eram puérperas. O sintoma mais prevalente foi cefaléia (85,2 por cento), seguido por alteração visual (44,4 por cento), confusão mental (44,4 por cento), náusea (40,7 por cento) e febre (33 por cento). Houve nove óbitos maternos (33,3 por cento). Vinte e uma pacientes foram tratadas com anfotericina B (77,8 por cento). A maioria dos casos evoluiu com gestação a termo, com recém-nascidos saudáveis (66,6 por cento). CONCLUSÕES: Neurocriptococose deve ser um diagnóstico a se considerar na gestação, nos casos de cefaléia, alteração visual, confusão mental, náusea e febre persistentes, sendo indicada terapia intensiva e uso de anfotericina B.

Survival time of HIV-infected patients with cryptococcal meningitis.

OBJECTIVE: To study survival time and risk factors of mortality among HIV-infected patients who had cryptococcal meningitis. DESIGN: Retrospective cohort study. MATERIAL AND METHOD: Patients' medical records of those who had HIV-infection with newly diagnosed cryptoccocal meningitis between January 2002 and December 2004 were reviewed. Each patient was classified into one of two groups, according to their anti-retroviral status (ART). RESULTS: Five hundred and forty nine patients enrolled in the present study: 281 (51.2%) in the ART+ group and 268 (48.8%) in the ART-group. The mean age was 33.4 +/- 6.9 years old in the ART + group and 33.6 +/- 7.0 years old in the ART-group. There were more male in both groups: 207 males and 74 females in the ART+ group, and 195 males and 73 females in the ART-group. Baseline CD4 cell count of both groups was 20 (6-74) cells/mL and 24 (9-72) cells/ml. About 30% of both groups of patients experienced major opportunistic infection before cryptococcal meningitis. All patients were treated by standard amphotericin B for a 2-week duration followed by fluconazole for an additional 8 weeks. There were no differences of baseline characteristics between the two groups (p > 0.05). The survival rates at 12, 24, and 36 months were 92.8%, 87.4%, and 85.4% in the ART+ group and 55.3%, 42.2%, and 36.8% in the ART- group, respectively (p < 0.01). The median survival time in the ART- group was 15 months. From the Cox regression model, the hazard ratio for "not received ART" was 4.87 (95%CI = 2.48-9.44, p < 0.01). CONCLUSION: The present study demonstrated the substantial increasing of survival time of HIV-infected patients with cryptococcal meningitis by initiated ART even in a resource limited setting (no flucytosine, local combined antiretroviral drugs with NVP based regimens).

Efficacy of amphotericin B in a fat emulsion for the treatment of cryptococcal meningitis in AIDS patients

Several formulae have been developed in an attempt to reduce the toxicity of amphotericin B (AmB), but their high costs preclude widespread use. The aim of this study was to evaluate the efficacy of amphotericin B in a fat emulsion, i.e. Intralipid (AmB-IL), in 37 AIDS patients with cryptococcal meningitis (CM). We retrospectively reviewed data collected in a non-comparative open study between January 1999 and December 2001. The therapeutic cure was defined as complete resolution or improvement of the clinical symptoms or complete absence or improvement of the mycological alterations of the CSF. The outcomes were evaluated at 2 weeks, induction phase (IP), and at the end of treatment or consolidation phase (CP) with the last available CSF. Prior to the diagnosis of CM, 72 percent of patients had had one or more OI and 67.57 percent had a concomitant OI. The median CD4-cell count was 32 cells/mm³, the median leukocyte count in the CSF was 29 cells/mm³ and the median cumulative dose of AmB-IL was 1,200 mg (300-2,500). The therapeutic cure was 57.14 percent in the IP and 64.86 percent in the CP. During IP, 9 patients died (24.32 percent) and 4 (10.81 percent) during the CP (p=0.2). Thus, the overall mortality rate was 35.14 percent. AmB-IL, an inexpensive preparation, might be an alternative to conventional AmB. Some questions remain such as its compatibility, stability and level of toxicity. The benefit is especially important in developing countries, where no drugs other than AmB are available to treat systemic fungal infections.

Human immunodeficiency virus (HIV) related cryptococcal meningitis in rural central Thailand--treatment difficulties and prevention strategies.

In 2000, cryptococcal meningitis was a common HIV related opportunistic infection in central Thailand requiring inpatient management but few patients suffering from it could afford a full course of treatment once infection had occurred. Since then, the production of generic fluconazole and highly active antiretroviral therapy (HAART) in Thailand (and national guidelines regarding their use) is reducing the incidence of this condition and such a strategy of prevention appears much more effective than treating established disease. There remains a continuing need for health education in the region and the removal of stigma associated with this disease so that earlier detection of HIV infection and the implementation of these national guidelines can have their greatest impact.