Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda.

BACKGROUND: Cryptococcal meningitis (CM) remains a major cause of death among people living with HIV in rural sub-Saharan Africa. We previously reported that a CM diagnosis and treatment program (CM-DTP) improved hospital survival for CM patients in rural, northern Uganda. This study aimed to evaluate the impact on long-term survival. METHODS: We conducted a retrospective study at Lira Regional Referral Hospital in Uganda evaluating long-term survival (≥1 year) of CM patients diagnosed after CM-DTP initiation (February 2017-September 2021). We compared with a baseline historical group of CM patients before CM-DTP implementation (January 2015-February 2017). Using Cox proportional hazards models, we assessed time-to-death in these groups, adjusting for confounders. RESULTS: We identified 318 CM patients, 105 in the Historical Group, and 213 in the CM-DTP Group. The Historical Group had a higher 30-day mortality of 78.5% compared to 42.2% in the CM-DTP Group. The overall survival rate for the CM-DTP group at three years was 25.6%. Attendance at follow-up visits (HR:0.13, 95% CI: [0.03-0.53], p <0.001), ART adherence (HR:0.27, 95% CI: [0.10-0.71], p = 0.008), and fluconazole adherence: (HR:0.03, 95% CI: [0.01-0.13], p <0.001), weight >50kg (HR:0.54, 95% CI: [0.35-0.84], p = 0.006), and performance of therapeutic lumbar punctures (HR:0.42, 95% CI: [0.24-0.71], p = 0.001), were associated with lower risk of death. Altered mentation was associated with increased death risk (HR: 1.63, 95% CI: 1.10-2.42, p = 0.016). CONCLUSION: Long-term survival of CM patients improved after the initiation of the CM-DTP. Despite this improved survival, long-term outcomes remained sub-optimal, suggesting that further work is needed to enhance long-term survival.

The Rabbit Model of Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is a fungal disease caused by the invasion of Cryptococcus yeast cells into the central nervous system. The organism is thought to enter the body through the lungs and then escape due to dysregulation of the immune response. Multiple animal species have been used to model the infection and characterize CM including mice, rats, dogs, guinea pigs, and rabbits. The rabbit model has over 40 years of data and has been used to study host-pathogen interactions and the efficacy of antifungal therapeutics. The model begins with immune suppression to eliminate the lymphocytic cell population followed by direct infection of the central nervous system via an injection of a suspension of yeast cells into the cisterna magna. The organism remains in the CNS during the course of infection, and cerebrospinal fluid can be repeatedly sampled to quantify the burden of organism, measure drug levels in the CSF, profile the immune response in the CSF, and/or characterize the yeast cells. The rabbit model of infection is a robust experimental model for better understanding CM and Cryptococcus cellular behavior.

Case report: Experience and insights on the treatment of two cases of cryptococcal meningitis during the later stages of the COVID-19 pandemic.

In the late stages of the COVID-19 pandemic, there's an increasing trend in opportunistic infections, including bacterial and fungal infections. This study discusses the treatment process of two cases of cryptococcal meningitis during the COVID-19 pandemic. It highlights the importance of laboratory testing for these co-infections and stresses the need for vigilance, early diagnosis, and proactive treatment to improve patient outcomes in the post-pandemic era.

[Meningeal cryptococcosis in patients living with HIV. Experience in intensive care]. / Criptococosis meníngea en pacientes viviendo con HIV. Experiencia en cuidados intensivos.

INTRODUCTION: Meningeal cryptococcosis (MC) is a frequent cause of meningoencephalitis in people living with HIV (PLHIV), leading to substantial morbidity (20-55%). Clinical characteristics, lethality and adverse prognostic factors in PLHIV with MC admitted to intensive care units (ICUs) are described. METHODS: A retrospective observational study. Period from 11/21/2006 to 05/24/2023. It involved 154 adult PLHIV diagnosed with MC and admitted to ICUs. Percentages and absolute values were compared by Chi-Square or Fisher's test and medians by Mann-Whitney test. The association with mortality was assessed by logistic regression. SPSS 23.0 software was used. A p-value <0.05 was considered significant. RESULTS: Patients who died and those who survived were comparable in age and sex (p>0.05). Univariate analysis showed that impaired functional and nutritional status, lack of previous highly active antiretroviral therapy, CD4 <100 cells, APACHE II ≥ 13 and a PLHIV prognostic score ≥ 8 points, requiring mechanical ventilation (MV), respiratory failure, renal failure, neurological dysfunction or sepsis could be associated (p<0.05) with mortality. Logistic regression established that impaired functional and nutritional status, a PLHIV prognostic score ≥ 8, need for MV and presence of sepsis would be independent variables associated with mortality. CONCLUSION: The results indicate that altered functional and nutritional status, a PLHIV prognostic score ≥ 8 points, requiring MV and suffering sepsis on admission to the ICU are more frequent in deceased patients, and they could therefore serve as independent variables to predict a higher risk of mortality.

Introducción: La criptococosis meníngea (CM) es una causa frecuente de meningoencefalitis en personas que viven con HIV (PVHIV) y produce una importante morbimortalidad (20-55%). Se describen las características clínicas, la letalidad y las variables de mal pronóstico en PVHIV con CM, en unidades de cuidados intensivos (UCI). Métodos: Estudio observacional y retrospectivo. Período 21/11/2006 a 24/05/2023. Población evaluada: 154 PVHIV adultos, admitidos en UCI con diagnóstico de CM. Los porcentajes y valores absolutos, fueron comparados mediante Chi-Cuadrado o test de Fisher y las medianas mediante test de Mann-Whitney. La asociación con mortalidad se evaluó por regresión logística. Se utilizó el programa SPSS 23.0. Un valor p<0.05 fue considerado significativo. Resultados: Los pacientes que fallecieron y los que sobrevivieron fueron comparables en edad y sexo (p>0.05). El análisis univariado, observó que un estado funcional y nutricional alterado, falta de tratamiento antirretroviral previo (TARV), CD4 <100 células/µl, APACHE II ≥ 13 y un score pronóstico de PVHIV ≥ 8 puntos, requerir ventilación mecánica (VM), sufrir insuficiencia respiratoria, renal, disfunción neurológica o sepsis, podrían estar asociados (p<0.05) con mortalidad. La regresión logística estableció que un estado funcional y nutricional alterado, un score pronóstico PVHIV ≥ 8, necesitar VM y sufrir sepsis serían variables independientes asociadas a mortalidad. Conclusión: Los resultados indican que el estado funcional y nutricional alterado, un score pronóstico PVHIV ≥ 8 puntos, requerir VM y sufrir sepsis al ingreso a UCI podrían servir como variables independientes para predecir un mayor riesgo de mortalidad.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Polymerase chain reaction negative cryptococcal meningitis.

A 61-year-old male with subacute headache was found to have cryptococcal meningitis despite a negative BioFire FilmArray meningitis/encephalitis panel. This case underscores the importance of liberal cryptococcal antigen testing, and that a negative FilmArray panel is inadequate in excluding cryptococcal meningitis, particularly in a HIV-negative host.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

BACKGROUND: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection. METHODS AND RESULTS: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine. CONCLUSION: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals.

[Cryptococcal meningitis associated with hydrocephalus in an immunocompetent patient].

Cryptococcal meningitis is an infrequent infection with high morbidity and mortality. Its presentation in immunocompetent patients is rare. We present the case of a 67-year-old male who was admitted for subacute symptoms of gait disturbance and urinary incontinence. Neurological examination revealed inability to stand and memory impairment. Cranial imaging showed obstructive tetraventricular hydrocephalus with areas of gliosis in the cerebellar peduncles. Endoscopic treatment of hydrocephalus was performed and cerebrospinal fluid samples taken revealing the growth of Cryptococcus neoformans. The patient improved with the endoscopic treatment and after completing intravenous antifungal therapy with liposomal amphotericin B and fluconazole for ten weeks. Antifungals are used to treat cryptococcal meningitis in immunocompetent patients. On rare occasions, it presents with hydrocephalus, a situation that requires surgical treatment using cerebrospinal fluid diversions or endoscopic techniques.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

BACKGROUND: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. METHODS: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. RESULTS: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. CONCLUSION: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.

Complex Decisions in HIV-Related Cryptococcosis: Addressing Second Episodes of Cryptococcal Meningitis.

PURPOSE OF REVIEW: This review highlights the difficulties in diagnosing and treating persons with a prior history of cryptococcal meningitis who improve but suffer from a recurrence of symptoms. This scenario is well known to those who frequently care for patients with cryptococcal meningitis but is not well understood. We highlight major gaps in knowledge. RECENT FINDINGS: We recently summarized our experience with 28 persons with paradoxical immune reconstitution inflammatory syndrome (IRIS) and 81 persons with microbiological relapse. CD4 count and cerebrospinal fluid white blood cell count were higher in IRIS than relapse but neither was reliable enough to routinely differentiate these conditions. Second-episode cryptococcal meningitis remains a difficult clinical scenario as cryptococcal antigen, while excellent for initial diagnosis has no value in differentiating relapse of infection from other causes of recurrent symptoms. Updated research definitions are proposed and rapid, accurate diagnostic tests are urgently needed.

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study.

BACKGROUND: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25-30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. METHODS: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018-21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. FINDINGS: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1-99·5) and of the QSP1 assay was 90·4% (85·2-94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55-75) and 68% (57-73), respectively, and lower C gattii rates of 21% (14-31) and 8% (4-14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). INTERPRETATION: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear. FUNDING: European and Developing Countries Clinical Trials Partnership; Swedish International Development Cooperation Agency; Wellcome Trust/UK Medical Research Council/UKAID Joint Global Health Trials; and UK National Institute for Health Research.

A comparison of the surgical outcomes of ventriculoperitoneal versus lumbar peritoneal shunts in the management of intracranial hypertension secondary to cryptococcal meningitis in HIV infected adult patients.

OBJECTIVE: Cryptococcal meningitis (CM), an AIDS-defining illness, significantly impacts morbidity and mortality. This study aims to compare complications arising from ventriculoperitoneal shunt (VPS) and lumbar peritoneal shunt (LPS) procedures used to manage refractory intracranial hypertension (IH) secondary to CM in HIV-infected patients. METHODS: Retrospective data were collected from January 2003 to January 2015 for HIV-infected adults diagnosed with refractory IH secondary to CM and subsequently shunted. Demographics, clinical characteristics, antiretroviral therapy, laboratory findings (including CD4 count and CSF results), CT brain scan results, shunt-related complications, and mortality were compared between VPS and LPS groups. RESULTS: This study included 83 patients, with 60 (72%) undergoing VPS and 23 (28%) receiving LPS. Mean ages were comparable between VPS (32.5) and LPS (32.2) groups (p = 0.89). Median CD4+ counts were 76 cells/µl (IQR= 30-129) in VPS versus 54 cells/µl (IQR= 31-83) in LPS (p=0.45). VPS group showed a higher mean haemoglobin of 11.5 g/dl compared to 9.9 g/dl in the LPS group (p=0.001). CT brain scans showed hydrocephalus in 55 VPS and 13 LPS patients respectively. Shunt complications were observed in 17 (28%) VPS patients versus 10 (43.5%) LPS patients (p=0.5). Patients developing shunt sepsis in the VPS group exhibited a median CD4+ count of 117 cells/µl (IQR= 76-129) versus 48 cells/µl (IQR= 31- 66) in the LPS group (p=0.03). Early shunt malfunction occurred more frequently in the LPS group compared to VPS group (p=0.044). The mean hospital stay was 6.2 days for VPS versus 5.4 days for LPS patients (p=0.9). In-hospital mortality was 6%, occurring in three VPS and two LPS patients respectively. CONCLUSION: Shunting procedures remain important surgical interventions for refractory IH secondary to HIV-related CM. However, cautious consideration is warranted for patients with CD4 counts below 200 cells/µL due to increased shunt complications. This study suggests a trend toward higher complication rates in patients undergoing LPS insertion.

Prevalence, treatment, and factors associated with cryptococcal meningitis post introduction of integrase inhibitors antiretroviral based regimens among People Living with HIV in Tanzania.

OBJECTIVE: This study aimed to assess the prevalence of Cryptococcal Meningitis (CM), treatment practice, and the associated factors post-introduction of Tenofovir Lamivudine and Dolutegravir (TLD) regimen among People Living with HIV (PLHIV) in Tanzania. METHODS: This was an analytical cross-sectional study, and the data was collected retrospectively in three public regional referral hospitals (RRHs) in Dar es Salaam, Tanzania. A total of 405 files of the PLHIV admitted in the medical wards on the TLD regimen from January 2019 to December 2022 were reviewed. The collected information includes the patient's demographic characteristics, Cryptococcal status, CD4 level at the time of CM diagnosis, status of using ART, CM treatment approach, and outcome. Data was analyzed using SPSS software version 23. RESULTS: Out of 405 patients, the majority 267(65.9%) were female, 224(55.3%) were aged between 36-55 years, and 293(72.3%) were married. ART defaulters were found to be 37(9.1%). The prevalence of CM was found to be 48(11.9%), out of which 42(87.5%) received fluconazole alone. ART defaulter and marital status significantly (p-value < 0.05) were associated with those who tested CM positive. CONCLUSION: The study found the prevalence of CM among PLHIV to be significantly high and the majority were treated with fluconazole alone. ART defaulters and marital status were significantly associated with one being CM positive. Responsible authorities and stakeholders should enforce guideline adherence and PLHIV should be encouraged on medication adherence.

Brain glucose induces tolerance of Cryptococcus neoformans to amphotericin B during meningitis.

Antibiotic tolerance is the ability of a susceptible population to survive high doses of cidal drugs and has been shown to compromise therapeutic outcomes in bacterial infections. In comparison, whether fungicide tolerance can be induced by host-derived factors during fungal diseases remains largely unknown. Here, through a systematic evaluation of metabolite-drug-fungal interactions in the leading fungal meningitis pathogen, Cryptococcus neoformans, we found that brain glucose induces fungal tolerance to amphotericin B (AmB) in mouse brain tissue and patient cerebrospinal fluid via the fungal glucose repression activator Mig1. Mig1-mediated tolerance limits treatment efficacy for cryptococcal meningitis in mice via inhibiting the synthesis of ergosterol, the target of AmB, and promoting the production of inositolphosphorylceramide, which competes with AmB for ergosterol. Furthermore, AmB combined with an inhibitor of fungal-specific inositolphosphorylceramide synthase, aureobasidin A, shows better efficacy against cryptococcal meningitis in mice than do clinically recommended therapies.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.

OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

Case Report: Cryptococcal Meningitis in a Previously Immunocompetent Patient with Coronavirus Disease 2019.

Cryptococcus neoformans infections occur most frequently in immunocompromised patients. Here, we report a case of cryptococcal meningitis in a previously immunocompetent 78-year-old female patient after treatment of COVID-19. Underlying diseases included hypertension, hyperlipidemia, and diabetes. The patient was critically ill and was treated with remdesivir, baricitinib, and dexamethasone. During hospitalization, her mental state changed, and C. neoformans was detected in the cerebrospinal fluid. She died despite receiving antifungal treatment. Treatment of COVID-19 may be a predisposing factor for C. neoformans infection. There is a need for concern and countermeasures for opportunistic fungal infections that may accompany COVID-19.

The prognostic factors for cryptococcal meningitis in non-human immunodeficiency virus patients: An observational study using nationwide database.

BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.

Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.