The Other Side of the Incubator: A Preemie Turns 40 Years Old.

Deb Discenza interviews Geoff, a preemie born almost 40 years ago, and gets unique insight into his birth, his NICU stay, and life afterward.

[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.

Chronic Candida albicans meningitis following critical COVID-19 and serial measurements of (1,3)-ß-D-glucan in cerebrospinal fluid.

Co-infections with invasive candidiasis have been reported to be overrepresented in severe COVID-19. This report presents an unusual case of chronic Candida meningitis following intensive care for COVID-19.

Case Report: Successful Treatment of Recurrent Candida Albicans Meningitis with Kimura's Disease Using Amphotericin B Colloidal Dispersion Combined with Fluconazole.

Background: Candida albicans meningitis is a fungal infectious disease of the central nervous system that most often occurs in immunodeficient populations. Kimura's disease is an IgE-mediated inflammatory reactive disease that is a chronic immune disorder with predominantly lymph node, soft tissue, and salivary gland damage, the treatment of which is hormone-based. The combination of Kimura's disease with C. albicans meningitis is relatively uncommon. Herein, we report a case of C. albicans meningitis in combination with Kimura's disease. Case Presentation: The case is a 26-year-old male with a medical history of Kimura, who presented with symptoms of dizziness, headache, and double vision. Lumbar puncture and cerebrospinal fluid examination revealed an increased white blood cell count. Further analysis through cerebrospinal fluid culture and metagenomic second-generation sequencing (mNGS) led to the final diagnosis of C. albicans meningitis. The patient was treated with fluconazole after the onset of C. albicans meningitis and had a good response. During the treatment, changes in the pathogen genome sequences were monitored dynamically using metagenomic next-generation sequencing. After 1 year, the patient had a recurrence of Candida meningitis. Treatment with fluconazole alone was ineffective, while antifungal treatment with amphotericin B colloidal dispersion was effective with no detectable renal injury. Conclusion: Candida meningitis can occur in the context of Kimura disease. In patients with mild disease, the possibility of recurrence exists with fluconazole treatment alone, and the efficacy of amphotericin B colloidal dispersion combined with fluconazole is better than fluconazole alone in patients with a recurrence. No nephrotoxicity was observed during amphotericin B colloidal dispersion treatment. The mNGS allows dynamic monitoring of pathogen sequencing reads, and for Candida meningitis, there may be a mismatch between peak sequencing reads and disease during treatment, the basis for which is unclear.

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.

Candida albicans meningitis in AIDS patient: A case report and literature review.

Candida albicans is found to be part of the normal flora in human skin, oral, and respiratory tract, and is known to be an opportunistic infection in immunocompromised populations; rarely is it a cause of meningitis. This case of a patient with Acquired Immune Deficiency Syndrome (AIDS) and Candida albicans meningitis illustrates the subtle symptoms and insidious onset of fungal meningitis. This case and review of literature identify the importance of early identification and therapy.

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.

Chronic Candida dubliniensis meningitis in a lung transplant recipient.

Candida spp. are common colonizers of the oral mucosa and respiratory tract in lung transplant recipients. Although thought to be non-pathogenic in most cases, donor derived infections related to Candida spp. have been described. Among the manifestations of invasive candidiasis, chronic meningitis is one of the rarest and one of the most challenging to diagnose, due to the indolence of the disease and the low yield of the CSF cultures. It is associated with severe morbidity and a high mortality. Fungal PCR and BD glucan assays can be assistance in its diagnosis, although these tests are not widely available. We report a case of a possible donor derived Candida dubliniensis infection in a lung transplant recipient, who initially presented with empyema that was treated successfully, but subsequently developed chronic meningitis. Diagnosis was delayed due to the low yield of CSF cultures, and was confirmed with fungal PCR and BD glucan assay.

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

PURPOSE: 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. METHODOLOGY: 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. RESULTS: 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). CONCLUSION: 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.