Background Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with poor clinical response despite antifungal therapy and negative CSF cultures. Data on effective treatment are limited. Methods Between March 2015 and March 2020, 15 consecutive previously healthy patients with CM and PIIRS were treated with adjunctive pulse corticosteroid taper therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/d, tapered based on clinical and radiological response plus oral fluconazole. Montreal Cognitive Assessments (MOCA), Karnofsky Performance scores, MRI brain scanning, ophthalmic and audiologic exams, CSF parameters including cellular and soluble immune responses were compared at PIIRS diagnosis and after methylprednisolone completion. Results The median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were altered mental status and vision changes. All patients demonstrated significant improvements in MOCA and Karnofsky scores at 1 month (p<0.0003), which was accompanied by improvements in CSF glucose, WBC, protein, cellular and soluble inflammatory markers 1 week after receiving corticosteroids (CS) (p<0.003). All patients with papilledema and visual field deficits also exhibited improvement (p<0.0005). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement. Brain MRI showed significant improvement of radiological findings (p=0.001). CSF cultures remained negative. Conclusions PCT in this small cohort of PIIRS was associated with improvements in CM-related complications with minimal toxicity in the acute setting.

Background: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) may fail to improve with standard monotherapy, particularly in patients with multifocal infection, incomplete source control, or persistent bacteremia. Synergy observed in vitro between ceftaroline (CPT) and daptomycin (DAP) or vancomycin (VAN) may translate into clinical benefit. Here, we describe our experience with DAP/CPT and VAN/CPT for complicated MRSA-B after monotherapy failure. Methods: Single-center, retrospective review of consecutive patients treated with DAP/CPT or VAN/CPT for MRSA-B after monotherapy failure from 1 January 2016 to 30 November 2018. Results: We identified 11 instances of combination therapy in 10 patients (DAP/CPT = 6, VAN/CPT = 5) with 1 patient receiving VAN/CPT followed by DAP/CPT. Rates of multifocal infection, incomplete source control, persistent bacteremia, and infective endocarditis were high (100%, 80%, 60%, and 60%, respectively). Combination therapy was initiated most commonly for persistent bacteremia (60%). When patients were persistently bacteremic, median preceding duration was 13 days and median time to clearance was 3 days. Total microbiologic cure rate was 100%. There were zero instances of bacteremia relapse at 30 days (30D) or 60 days (60D). All-cause 30D and 60D mortality rates were 11.1% and 33.3%, respectively. Conclusions: Combination therapy demonstrated success in diverse cases of refractory MRSA-B, including instances of persistent bacteremia paired with incomplete source control. Optimal timing and therapeutic cadence for combination therapy remain unclear. Our findings suggest that DAP/CPT and VAN/CPT can be considered for complicated MRSA bacteremia when other treatment options fail or are unavailable. We propose persistent bacteremia with incomplete source control to be a clinical niche particularly worthy of further investigation.

Infection caused by novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been associated with coagulopathy. We present a case of a previously healthy 49year-old female who was admitted to the hospital for coronavirus disease 2019 (COVID-19) pneumonia and later found to have extensive deep vein thrombosis (DVT) in all four extremities. This was accompanied by a steep rise in D-dimer levels and positive antiphospholipid antibodies (APLA) on further testing. She clinically improved on hydroxychloroquine and therapeutic anticoagulation. This is one of the first case reports describing APLA-associated DVT in a patient with COVID-19 pneumonia. Transient elevation of APLA from the viral illness may play a role in thrombosis associated with COVID-19.

The C. neoformans and C. gattii species complex causes cryptococcosis. The C. neoformans species complex is known as an opportunistic pathogen since it primarily infects immunocompromised patients. C. gattii species complex has been referred to as a primary pathogen due to its high infection frequency in apparently immunocompetent people.

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Twenty-seven previously healthy (of 36 consecutive eligible patients), HIV-negative cryptococcal meningoencephalitis (CM) patients underwent comprehensive neuropsychological evaluation during the late post-treatment period (1.3–4 years post diagnosis), assessing attention, language, learning, memory, visuospatial, executive function, information processing, psychomotor functioning, as well as mood symptoms. Seven of eight domains (all except attention) showed increased percentages of CM patients scoring in the less than 16th percentile range compared to standardized normative test averages, adjusted for education level and age. Comparison with a matched archival dataset of mild cognitive impairment/Alzheimer’s disease patients showed that CM patients exhibited relative deficits in psychomotor and executive function with fewer deficits in memory and learning, consistent with a frontal-subcortical syndrome. MRI evaluation at the time of testing demonstrated an association of lower neuropsychological functioning with ventriculomegaly. These studies suggest that CM should be included in the list of treatable causes of dementia in neurological work ups. Future studies are needed to identify diagnostic and treatment regimens that may enhance neurological function after therapy.

Cryptococcal meningoencephalitis (CM) continues to cause major morbidity and mortality in a range of patients such as those immunosuppressed from HIV and with biologic immunosuppressants, including treatments of autoimmunity, malignancies, and conditioning regimens for transplantation. It is currently the most common cause of non-viral meningitis in the United States. Infections in previously healthy patients also develop with autoantibodies to granulocyte-macrophage colony stimulating factor or with monogenetic defects. In all populations, mortality and significant long-term morbidity occur in 30–50% despite therapy, and immune reconstitution and post-infectious inflammatory response syndromes complicate management. To help with these difficult cases, we present here a practical tutorial of the care of a range of patients with CM in the absence of HIV/AIDS.