Candida Meningitis Research Articles

Monitoring of the cerebrospinal fluid voriconazole level in a patient with recurrent Candida meningitis after pituitary surgery

Monitoring of the cerebrospinal fluid voriconazole level in a patient with recurrent Candida meningitis after pituitary surgery

A case of Candida meningitis in a patient with CARD9 deficiency: an autopsy report

Here we present the case of a 23-year-old female with a history of onychomycosis and oral thrush since childhood. She presented with a gradual onset of headache, and cerebrospinal fluid (CSF) analysis on admission revealed an elevated mononuclear cell count. Hydrocephalus was observed on brain MRI. Candida albicans (C. albicans) was detected in the CSF, and antifungal treatment was initiated to diagnose of Candida meningitis. Due to an insufficient therapeutic response, intraventricular administration of liposomal amphotericin B initiated; however, the lesions persisted. Subsequently, the patient experienced repeated occlusions of the ventriculoperitoneal shunt tube, ultimately dying from a bacterial shunt infection. Autopsy findings revealed diffuse fungal proliferation on the surface of the brainstem and ventricular walls. Genetic testing confirmed a diagnosis of CARD9 deficiency. Although CARD9 deficiency is a rare disease, genetic testing should be considered when primary immunodeficiency is suspected.

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

Background: Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods: Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine®) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC0-24, plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions: The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood-brain barrier reaching therapeutic levels in CSF.

Flucytosine and its clinical usage.

Flucytosine is an antifungal agent first licensed in the 1970's. However, its clinical value has long been overlooked and its availability across the globe is limited. This review highlights the important clinical and pharmacological aspects of flucytosine. This a narrative review of the clinical and in vitro susceptibility literature, with a focus on clinical uses for flucytosine. Detailed literature review including early literature related to primary and acquired resistance to flucytosine. Flucytosine has good antifungal activity against Cryptococcus species, Candida species, and dematiaceous fungi. Its water solubility enables good penetration into the eye, urinary tract, central nervous system (CNS), cardiac vegetations and fungal biofilms. In combination with amphotericin B, it shows early fungicidal activity against Cryptococcus species, and this translates to ~20% improved survival in cryptococcal meningitis. Combination therapy also reduces the mortality of Candida meningitis, and should be used in neonatal candidiasis because of the high frequency of CNS infection. Monotherapy for urinary candidiasis is under-studied, but is usually effective. It is probably valuable in the treatment of Candida endocarditis and endophthalmitis: there are few data. It is not effective for aspergillosis or mucormycosis. Flucytosine monotherapy of urinary candidiasis resulted in 22% developing resistance on therapy and failing therapy, and in 29% of 21 patients with cryptococcosis. Certain regions of the world still do not have access to flucytosine compromising the management of certain severe fungal infections. Flucytosine has an important role in combination therapy for yeast and dematiaceous infections and probably as monotherapy for urinary candidiasis, with a modest risk of resistance emergence. Facilitating access to flucytosine in those regions (especially low-income countries) might alleviate the mortality of invasive fungal diseases.

Neonatal Candidiasis: Clinical Spectrum and Epidemiology at a Tertiary Care Centre, Bhopal, India

Introduction: Neonatal candidiasis is one of the leading causes of sepsis amongst newborns admitted to newborn care unit, especially premature and Low Birth Weight (LBW) babies. It is one of the significant contributors to neonatal morbidity and mortality. Aim: To describe the spectrum and epidemiology of fungal sepsis in Neonatal Intensive Care Unit (NICU) at a tertiary care level. Materials and Methods: A longitudinal study was conducted from January 2018- December 2019 in NICU of Chirayu Medical College and Hospital, a tertiary level hospital in Bhopal, Central India. All neonates, who had positive fungal blood culture were included in the study, their demographic data was analysed (age, birth weight, predisposing factors etc.,), maternal history, their response to the antifungal treatment documented and complications. Statistical analysis was done using the Chi- square test with the help of Statistical Package for Social Sciences (SPSS) software version 2.0. Results: A total of 409 neonates admitted in the NICU during the study period, were suspected clinically to have sepsis and their blood culture was done, of which 110 samples were culture positive. Amongst the 110 neonates, 41(37.2%) were positive for fungal infection {29 showed Candida albicans, 12 Non Albicans Candida (NAC)}. Total 25 neonates were preterm (60.97%). The mean age of admission was 3.02 days, 51.2% (21/41) of the neonates had a history of respiratory distress and related symptoms at birth. There was no significant maternal history. Amongst the risk factors, lower birth weight (<2.5 kg), preterm (<34 weeks), and presence of invasive central lines were statistically associated with morbidity. Urine for candidial hyphae was positive in 12 out of 41 cases (29.27%). Incidence of candidal meningitis was seen in four neonates (13.33%). Thrombocytopenia was the most common laboratory finding amongst these cases (32/41). Among the different regimens used the combination regimen of Lipid based amphotericin B and voriconazole was associated with a better survival. Conclusion: Candida sepsis was found to be the most common cause of septicaemia in the NICU. LBW and preterm babies are especially at greater risk of candida sepsis. Candida albicans still continues to be a dominant aetiology for fungal sepsis, as compared to non candida species.

Single and Repeated Episodes of Candida Species Isolated From Cerebrospinal Fluid for Diagnosing Probable Candida meningitis.

Background: The clinical relevance of single or repeated episodes of Candida spp. in cerebrospinal fluid (CSF) in adult patients is debatable.Methods: Forty-two patients with positive Candida episodes in CSF were enrolled in this retrospective study.Results: A total of 42.9% (18/42) were determined to have probable Candida meningitis (PCM). Neurosurgery [odds ratio (OR) (95% confidence interval), OR: 14.4 (1.6–126.1), P = 0.004], lumbar drainage [OR: 5.8 (1.5–23.3), P = 0.009], VP shunt [(OR: 5.6 (1.2–25.8), P = 0.020)], external ventricular drainage [OR: 4.7 (1.3–17.7), P = 0.018], CRP ≥ 10.0 mg/L [OR: 4.9 (1.3–18.1), P = 0.034], and postsurgical broad-spectrum antibiotics [OR: 9.5 (1.8–50.5), P = 0.004] were risk factors associated with PCM. A single CSF Candida episode for the diagnosis of PCM had 7.7% (0.4–37.9%) sensitivity and 20.7% (8.7–40.3%) specificity, whereas repeated episodes of Candida had 66.7% (41.2–85.6%) sensitivity and 95.8% (76.9–99.8%) specificity. No significant difference was found in radiological imaging or CSF profiles between PCM and non-PCM patients. A total of 37.5% (9/24) of patients without PCM received empirical antifungal treatment, and 88.9% (16/18) of patients with PCM received preemptive antifungal treatment. PCM patients had hospitalized mortality rates of 50.0% (9/18). The odds ratio of mortality was 23.0 (2.5–208.6) for PCM patients compared with non-PCM patients (P = 0.001).Conclusion: Both single and repeated positive CSF samples have low validity for the diagnosis of PCM, suggesting that novel strategies for diagnosis algorithms of PCM are urgently needed. Empirical antifungal treatment should be started immediately for suspicious patients with risk factors.

Candidal meningitis in disseminated candidiasis by Candida tropicalis - A rare case report from India

Introduction: Candida spp. are the normal flora of human body and do not cause CNS disease unless there is some immune disturbance. The prevalence of non albicans species differed significantly in various geographic areas. Candida tropicalis is a species that is now recognized as an important pathogen of debilitated individuals. Case Report: A 70 year old female complaining of altered sensorium since 7 days with neck stiffness. The patient was also had white plaques in the oral cavity and pharynx. MRI scan showed bilateral cerebral infarcts in pre and post central gyral regions and left thalamus. Thick curvilinear leptomeningeal enhancement along the bilateral parietal regions. Gram stain of centrifused CSF, throat swab showed presence of gram positive, yeast budding cells. Growth was curdy white on Saboraud’s dextrose agar and was negative for germ tube test. Blue colored colonies were obtained on Candida chrome agar and considered as Candida tropicalis. HIV status was negative. The patient was administered intravenous liposomal amphotericin B along with regular insulin, levitiracetam lobazam, pheytoin and potassium supplementation along with I.V. fluids. She was discharged from hospital with fluconazole maintenance dose. Conclusion: Candida tropicalis is now recognized as an important pathogen of debilitated individuals. Subclinical candidal colonization can make the individual more prone to develop systemic infection and disease. Candida tropicalis infects meningeal layers, brain parenchyma and also involves vasculature of brain. Even though Systemic infections with Candida tropicalis may occur as terminal complications, timely evaluation, accurate diagnosis, administration of specific and supportive treatment gives good prognosis. Keywords: Candida tropicalis, Disseminated, Meningoencephalitis, Amphotericin B.

Candida meningitis in neurosurgical patients: a single-institute study of nine cases over 7 years.

Candida meningitis in neurosurgical patients is relatively unusual but is associated with a high mortality rate. We present our experience with this infection and discuss the clinical characteristics, treatment options and outcomes. We retrospectively reviewed neurosurgical patients with multiple positive cerebrospinal fluid (CSF) culture results in our hospital from January 2013 to December 2019. Nine patients were available for review according to our inclusion and exclusion criteria. Four species of Candida were isolated from the CSF samples and Candida albicans accounted for half of all infections. Eight infections were associated with ventricle peritoneal shunt, lumbar cistern peritoneal shunt or external ventricular drain. All of these foreign intracranial materials were removed or changed and all the patients received antifungal treatment, including fluconazole and/or voriconazole. It is associated with severe long-term outcomes in survivors and a mortality rate that reaches 11.1%. Prior treatments with broad-spectrum and high-grade antibiotics and anaemia are possible risk factors for Candida meningitis. We advise that foreign intracranial material should be removed or changed as early as possible and the timing of re-shunt operation can be 1 month after control of Candida meningitis has been achieved, with several negative CSF culture results.

Use of Cerebrospinal Fluid (1,3)-β-d-Glucan to Monitor Treatment Response in Candida albicans Meningitis in an HIV-infected Patient

Abstract Candida meningitis is rare in the setting of human immunodeficiency virus (HIV) infection and often presents a diagnostic challenge. Its clinical features typically mimic those of cryptococcal or tuberculous meningitis and Candida can be difficult to culture from cerebrospinal fluid. Furthermore, optimal treatment and monitoring parameters are not well defined. Cerebrospinal fluid levels of (1,3)-β-d-glucan, which is a component of the fungal cell wall, have been used to diagnose and monitor response to therapy in other cases of fungal meningitis, but its utility in the setting of Candida meningitis and HIV infection is less clear. Here, we present a case of spontaneous Candida albicans meningitis in a woman with advanced HIV infection and report on the clinical utility of cerebrospinal fluid (1,3)-β-d-glucan for diagnosis and monitoring of chronic infection.

Prevalence, healthcare resource utilization and overall burden of fungal meningitis in the United States.

Previous epidemiological and cost studies of fungal meningitis have largely focused on single pathogens, leading to a poor understanding of the disease in general. We studied the largest and most diverse group of fungal meningitis patients to date, over the longest follow-up period, to examine the broad impact on resource utilization within the United States. The Truven Health Analytics MarketScan database was used to identify patients with a fungal meningitis diagnosis in the United States between 2000 and 2012. Patients with a primary diagnosis of cryptococcal, Coccidioides, Histoplasma, or Candida meningitis were included in the analysis. Data concerning healthcare resource utilization, prevalence and length of stay were collected for up to 5 years following the original diagnosis. Cryptococcal meningitis was the most prevalent type of fungal meningitis (70.1 % of cases over the duration of the study), followed by coccidioidomycosis (16.4 %), histoplasmosis (6.0 %) and candidiasis (7.6 %). Cryptococcal meningitis and candidiasis patients accrued the largest average charges ($103 236 and $103 803, respectively) and spent the most time in the hospital on average (70.6 and 79 days). Coccidioidomycosis and histoplasmosis patients also accrued substantial charges and time in the hospital ($82 439, 48.1 days; $78 609, 49.8 days, respectively). Our study characterizes the largest longitudinal cohort of fungal meningitis in the United States. Importantly, the health economic impact and long-term morbidity from these infections are quantified and reviewed. The healthcare resource utilization of fungal meningitis patients in the United States is substantial.

Systemic Candidiasis in Extremely Low Birthweight (ELBW) Neonates Despite the Routine Use of Topical Miconazole Prophylaxis: Trends, Risk Factors and Outcomes over an 11-Year Period

This study aims to determine the incidence, trends of systemic candidiasis and meningitis in extremely low birthweight (ELBW) neonates (<1000 gms) despite the routine use of topical miconazole prophylaxis and to compare the risk factors, adverse outcomes and comorbidities with controls. Retrospective cohort study of ELBW neonates with systemic candidiasis and meningitis over an 11-year period (1997 to 2007). Matched case control analyses were performed to determine the risk factors and comorbidities which were severe intraventricular haemorrhage (IVH), severe retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) requiring treatment, necrotising enterocolitis (NEC), chronic lung disease (CLD) and cholestatic jaundice. Mortality and end organ involvement secondary to systemic candidiasis were identified as adverse outcomes. Of the 757 ELBW neonates, 51 (6.7%) had evidence of systemic candidiasis with a significant 3-fold increase in trend noted in 2007 as compared against 1997 (12.1% vs 3.8%) (RR 1.2, 95% CI, 1.06 to 1.36, P <0.001). This corresponds to a significant increasing trend of preceding or co-existent bacterial blood stream infections (BSI) in neonates with systemic candidiasis (0% in 1997 vs 7.1% in 2007, RR 1.40, 95% CI, 1.04 to 1.25, P = 0.005). On logistic regression analysis, decreasing gestational age was an independent risk factor for systemic candidiasis (OR 2.0, 95% CI, 1.52 to 2.63, P <0.001). Candida meningitis was detected in 4/38 (10.5%) and end organ involvement in 17 (33%). The organisms isolated were Candida parapsilosis 31 (61%), Candida albicans 17 (33%) and Candida glabrata 3 (5.8%). Significantly higher mortality was seen in cases when compared to controls 10/51 (19.6%) vs 76/706 (10.7%) (OR 2.02, 95% CI, 1.02 to 4.40, P <0.001). Increasing trend in the incidence of systemic candidiasis despite routine use of topical miconazole prophylaxis is of concern and future studies comparing the use of systemic fl uconazole versus oral nystatin may need to be considered.

Culture-negative Candida meningitis diagnosed by detection of Candida mannan antigen in CSF

We present a patient with chronic culture-negative Candida meningitis, in whom the diagnosis was made by detection of the mannan antigen (Mn) and anti-mannan antibodies (A-Mn) in the CSF.

Neurodevelopmental Outcome of Extremely Low Birth Weight Infants with Candida Infection

Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

Favorable Outcome of Neonatal Cerebrospinal Fluid Shunt-Associated Candida Meningitis with Caspofungin

Invasive Candida infections associated with medical devices are very difficult to cure without device removal. We present a case of neonatal cerebrospinal fluid shunt-associated Candida meningitis, in which removal of the device was precluded, that was successfully treated with caspofungin. Pharmacokinetic assessment of caspofungin concentrations in cerebrospinal fluid showed that exposure was adequate in the presence of a high systemic exposure. In complex cases of neonatal Candida infections involving medical devices, the addition of caspofungin might be beneficial.

Neonatal bacterial meningitis in Turkey: epidemiology, risk factors, and prognosis

We aimed to determine the incidence, etiology, risk factors and outcome of bacterial meningitis in neonates. Neonates who developed bacterial meningitis between 2003 and 2010 in a tertiary hospital in Turkey were included in the study. Patients born in our hospital were defined as Group 1 and patients referred from other centres were defined as Group 2. Patients with evidence of congenital infections or central nervous system malformations were excluded. Demographic features, delivery type, time of onset of meningitis, co-morbidities, clinical features, blood and cerebrospinal fluid (CSF) analysis, cranial sonographic findings, and outcome of patients were recorded. The study comprised 325 meningitis cases identified from 38,023 hospitalised patients in the neonatology unit among 11,8091 live births. Mean gestational age, birth weight, and hospital stay were 36.8 ± 3.7 weeks, 2.480 ± 924 g, and 26 ± 12.4 days, respectively. Almost half (48%) of the patients were diagnosed in the first seven postnatal days and 52% at 8-30 days after birth. CSF culture findings were positive in 59 (18%) patients (28 in Group 1 and 31 in Group 2). Gram-positive bacteria were the responsible agents in 30 (51%) patients, whereas 26 (44%) patients had Gram-negative bacterial meningitis and 3 (5%) had Candida meningitis. Gram-negative bacteria were predominant in Group 1 whereas Gram positive bacteria were predominant in Group 2. Transfontanel ultrasonography revealed pathologic findings in 17.5% of patients. The total mortality rate was 2.5%. This large-scale study provides essential information about the etiology, characteristics, and outcome of neonatal bacterial meningitis in Turkey.

Efficacy of CG3R6TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for the Treatment of Candida albicans Meningitis in Rabbits

Background: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG₃R₆TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis. Methods: In vitro activity of CG₃R₆TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG₃R₆TAT nanoparticles (n = 6; 0.25 mg/kg/day) or fluconazole (n = 6; 100 mg/kg/day) began 3 days after infection and continued for 11 consecutive days; the efficacy was assessed following 11 days of treatment by yeast counting in cerebrospinal fluid (CSF), the leukocyte concentrations in CSF and the histopathology of brain parenchyma. Results: At a concentration three times higher than the minimum inhibitory concentration (8.1 µmol/l), the nanoparticles complete- ly sterilized C. albicans after 5 h of incubation. In addition, there was a significant reduction in fungal counts and leukocyte concentrations in the CSF from rabbits treated with CG₃R₆TAT nanoparticles or fluconazole versus those from untreated control rabbits (p < 0.05, ANCOVA). The median number of days of treatment required to sterilize CSF cultures was 8.5 days for CG₃R₆TAT nanoparticle therapy (p = 0.022, vs. control) and 9.7 days for fluconazole therapy (p > 0.05, vs. control). The histopathologic severity of rabbits was significantly attenuated after CG₃R₆TAT treatment (p = 0.001, vs. control). Conclusion: This study suggests that CG₃R₆TAT nanoparticles may be a promising therapeutic agent for candidal meningitis.

Candida infections in non-neutropenic children after the neonatal period

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.

7 Candidiasis

7 Candidiasis

Candida parapsilosis meningitis as the first manifestation of AIDS: case report

Candida meningitis is a rare condition that occurs more frequently in premature infants, immunocompromised patients or patients after neurosurgery. We describe a case of a previously healthy 41-year-old man with Candida parapsilosis meningitis associated with oropharyngeal candidiasis as the first manifestation of AIDS.

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