Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Cerebrovascular Complications Associated With Iatrogenic Fungal Meningitis Following Surgical Procedures in Mexico.

BACKGROUND: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with Fusarium solani among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis. METHODS: A retrospective case series of patients diagnosed with fungal meningitis following surgical procedures under contaminated epidural anesthesia who developed a unique pattern of CVC during their hospitalization. RESULTS: Three female patients (mean age, 35 years) with CVC due to iatrogenic fungal meningitis were included. Positive Fungitell ß-D-glucan assay in cerebrospinal fluid was documented in all cases, and F. solani was confirmed by polymerase chain reaction in case 3. All cases were complicated by severe vertebrobasilar circulation vasculopathy and arterial dissections with resultant subarachnoid hemorrhage and intraventricular hemorrhage, ultimately leading to patients' death. CONCLUSIONS: The death toll from the ongoing fungal meningitis outbreak keeps rising, underscoring the need for early recognition and aggressive treatment. We highlight the risk for vertebrobasilar circulation CVC among these patients. The angioinvasive nature of F. solani is yet to be clarified; however, a clear pattern has been observed. Public health awareness should be raised and a strong response should be pursued.

Central nervous system aspergillosis in immunocompetent patients: Case series and literature review.

The aim of this study was to investigate the clinical characteristics of central nervous system (CNS) aspergillosis in immunocompetent patients.This study enrolled six immunocompetent patients diagnosed with CNS aspergillosis. Additionally, we reviewed the clinical profiles for 28 cases reported in the literature. The age, gender, etiology of Aspergillus infection, clinical manifestations, location of the lesion, treatment, and prognosis were analyzed.There were 19 men (average age, 54.6 ±â€Š14.3 years) and 15 women (average age, 47.0 ±â€Š19.4 years). The clinical manifestations included headache (55.9%; n = 19), visual impairment (32.4%; n = 11), diplopia (32.4%; n = 11), hemiplegia (20.6%; n = 7), fever (17.6%; n = 6), and epilepsy (8.8%; n = 3). According to the radiological features, CNS aspergillosis lesions were divided into two subtypes: parenchymal lesions in the cerebral lobes (n = 11), and meningeal lesions in the meninges (n = 23). The patients with meningeal lesions are easy to be complicated with more serious cerebrovascular diseases, such as subarachnoid hemorrhage and massive infarction. Most of the lesions in brain parenchyma were abscess formation, and magnetic resonance imaging showed ring enhancement. The clinical diagnosis of Aspergillus infection was mainly based on brain biopsy (n = 14), autopsy (n = 8), pathological examination of adjacent brain tissues (n = 7), cerebrospinal fluid (CSF) or tissue culture (n = 3), and second-generation sequencing analysis of the CSF (n = 3). Clinical improvement was achieved in 23 cases, and 11 patients succumbed to the disease. Voriconazole treatment was effective in 24 (70.6%) cases.Immunocompetent subjects are also at risk for Aspergillus infections. Concomitant cerebrovascular diseases are common in patients with CNS aspergillosis, especially in patients with meningeal aspergillosis. Parenchymal aspergillosis lesions are usually localized and manifest as brain abscesses with annular enhancement on magnetic resonance imaging. Biopsy, CSF culture, and next-generation sequencing are mainstream diagnostic modalities. Voriconazole is an effective treatment for Aspergillus infection, and early diagnosis and treatment should be highlighted.

Cryptococcosis in HIV-AIDS patients from Southern Brazil: Still a major problem.

INTRODUCTION: Cryptococcus neoformans is an opportunistic pathogen that causes ∼15% mortality in AIDS patients. Rio Grande City, Rio Grande do Sul (RS), Brazil, has the highest national rate of HIV/AIDS, considering cities with population more than 100,000 habitants. OBJECTIVE: We aimed to evaluate the clinical and epidemiological profile of cryptococcosis in a reference service for HIV-AIDS patients in the South region of Brazil, over seven years. Material and methods A retrospective study was performed including all cryptococcosis cases diagnosed at the University Hospital, Federal University of Rio Grande (UH-FURG) between January 2010 and December 2016. RESULTS: Seventy cases of cryptococcosis were diagnosis from 2010 to 2016 in the UH-FURG in the seven years of the study. These numbers were responsible for 2.1% to 8.1% of the hospitalizations/year for HIV patients. All were caused by C. neoformans infection (95% C. neoformans var. grubii VNI and 5% C. neoformans var. grubii VNII). Neurocryptococcosis was the major clinical manifestation and cryptococcosis was the HIV- defining condition in 40% of patients. The period of hospitalization was an average of 39.3 days (SD=31.3), and more than half of patients (53%; 37/70) died after a mean of 82 days. DISCUSSION: The present study showed the importance of cryptococcosis as an AIDS-defining disease in HIV-AIDS patients in a tertiary hospital from Southern Brazil. More investment is necessary to reduce the impact of this opportunistic mycosis in HIV-AIDS patients from southern Brazil.

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.

Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey.

OBJECTIVES: To identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden. METHODS: The study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016. RESULTS: In total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100 000 (2005-2006) to 4.7/100 000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C. albicans and between 0% and 100%, in non-albicans species other than C. glabrata and C. krusei. Resistance to voriconazole was rare, except for C. glabrata, C. krusei and C. tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B. CONCLUSIONS: We report an overall increase in candidaemia but a minor decrease of C. albicans while C. glabrata and C. parapsilosis remain constant over this 10-year period.

Aspergillus sinusitis complicated with meningitis and multiple cerebral infarctions in immunocompetent patient.

This is a case of a 33-year-old male complaining of severe headache, neck pain, photophobia, vomiting and high-grade fever of several days. He had history of nasal polyp removal and recurrent sinusitis in the last 8 years. On examination: conscious with glasco coma scale (GCS) 15/15 and normal limbs strength but with positive Babinski sign. For further observation, he was admitted and full work-up was done. Even though full empirical antibiotics were started, there was no immediate improvement and he deteriorated dramatically developing ocular deficit, hydrocephalus and lower level of consciousness with multiple infarctions found at different areas in brain. After that point, a decompressive craniectomy was done, and multiple antibiotics and antifungal medications were prescribed. However, he deteriorated to GCS 3/15; cardiopulmonary resuscitations were not successful, as he demised next day. It shall be noted that aspergillosis can lead to difficult complications, so diagnosis and treatments should not be delayed.

Candida Meningitis After Transsphenoidal Surgery: A Single-Institution Case Series and Literature Review.

Candida meningitis after neurosurgical procedures is a rare but potentially devastating complication. The presentation of meningitis can be insidious in immunosuppressed patients and thus can be easily overlooked. Cerebrospinal fluid studies often resemble bacterial profiles, and cultures can be falsely negative. Candida albicans is the most common species identified in postsurgical Candida meningitis, and delay in diagnosis and treatment can be devastating. The standard induction therapy for Candida meningitis has been amphotericin B combined with flucytosine. A high index of suspicion is needed in any patient with risk factors such as abdominal surgery, bowel perforation, recent broad spectrum antibiotic therapy, intravenous drug use, extremes of age, indwelling catheters, and immunosuppression such as AIDS, malignancy, antineoplastic therapy, and steroid use. Here, we describe 3 case presentations of patients with giant skull base tumors who developed postsurgical Candida meningitis, each with vastly different clinical courses and outcomes, ranging from benign to catastrophic. We performed a literature review with special focus on common risk factors, Candida species, diagnostic criteria, and treatment.

Fungal Contamination of Methylprednisolone Causing Recurrent Lumbosacral Intradural Abscess.

Fungal meningitis transmitted through injections of methylprednisolone contaminated with Exserohilum rostratum affected 753 persons and caused 61 deaths in the United States in 2012. We report a case of infection recurrence after 24-months with the unique manifestation of an intradural fungal abscess. Fungal disease should remain on the differential diagnosis list for previously exposed patients.

Candida meningitis in an immunocompetent patient detected through (1→3)-beta-d-glucan.

A 44-year-old female presented with a 3-month history of headache, dizziness, nausea, and vomiting. Her past medical history was significant for long-standing intravenous drug abuse. Shortly after admission, the patient became hypertensive and febrile, with fever as high as 38.8°C. The lumbar puncture profile supported an infectious process; however multiple cultures of blood and cerebrospinal fluid (CSF) did not initially show growth of organisms. Finally after 9 days of incubation, a CSF culture showed evidence of a few colonies of Candida albicans. To confirm the diagnosis, preserved CSF from that sample was tested for (1→3)-ß-d-glucan, showing levels >500pg/ml. This report illustrates a rare complication of intravenous drug use in an immunocompetent patient and demonstrates the utility of (1→3)-ß-d-glucan testing in possible Candida meningitis.

[Imported histoplasmosis]. / Importierte Histoplasmose.

Infections with Histoplasma capsulatum are rare in Germany, and mostly imported from endemic areas. Infections can present as localized or disseminated diseases in immunocompromised as well as immunocompetent hosts. A travel history may be a major clue for diagnosing histoplasmosis. Diagnostic tools include histology, cultural and molecular detection as well as serology. Here we present four cases of patients diagnosed and treated in Freiburg between 2004 and 2013 that demonstrate the broad range of clinical manifestations of histoplasmosis: an immunocompetent patient with chronic basal meningitis; a patient with HIV infection and fatal disseminated disease; a patient with pulmonary and cutaneous disease and mediastinal and cervical lymphadenopathy; and an immunosuppressed patient with disseminated involvement of lung, bone marrow and adrenal glands.

How gaps in regulation of compounding pharmacy set the stage for a multistate fungal meningitis outbreak.

OBJECTIVE: To provide an overview of the regulation issues surrounding compounding pharmacy that allowed the United States fungal meningitis outbreak to occur and the changes in regulation that ensued. SUMMARY: In September 2012, a single case report sparked an investigation into a nationwide outbreak of fungal meningitis due to contaminated injectable drugs. The source of the contamination, New England Compounding Center (NECC), was in violation of several state and federal laws and had a history of such violations. The regulation of compounding pharmacies has historically been left to the states, while manufacturing fell under the jurisdiction of the Food and Drug Administration. However, as more compounders took part in large-scale interstate distribution of drugs, the current state-based regulatory system became less equipped to provide oversight. The lack of a clear definition of "compounding pharmacy" further obscures proper oversight and regulation. Congress and several states have taken steps to build safeguards against large-scale compounding by increasing inspections, adopting stricter licensing requirements, and enacting the Drug Quality and Security Act of 2013. CONCLUSION: While the current compounding regulation changes are a necessary step forward, it remains to be seen how effective they will be in safeguarding the public.

Description of outbreaks of health-care-associated infections related to compounding pharmacies, 2000-12.

PURPOSE: Outbreaks of health-care-associated infections related to compounding pharmacies from 2000 through 2012 are described. METHODS: PubMed and the websites for the Centers for Disease Control and Prevention and the Food and Drug Administration were searched to identify infectious outbreaks associated with compounding pharmacies outside the hospital setting between January 2000 and November 2012. RESULTS: Between January 2000 and before the 2012 fungal meningitis outbreak, 11 outbreaks were identified, involving 207 infected patients and 17 deaths after exposure to contaminated compounded drugs. The 2012 meningitis outbreak had a similar mortality rate but increased these totals almost fivefold. Half of the outbreaks involved patients in more than one state. Three outbreaks involved ophthalmic drugs. The remaining outbreaks involved corticosteroids, heparin flush solutions, cardioplegia solution, i.v. magnesium sulfate, total parenteral nutrition, and fentanyl. The outbreaks were caused by pathogens commonly associated with health-care-associated infections, common skin commensals, and organisms that rarely cause infection. Morbidity was substantial, including vision loss. Half the outbreaks resulted in recall of all sterile drugs from the pharmacy due to systemic problems with sterile procedures. CONCLUSION: Before the nationwide 2012 fungal meningitis outbreak, drugs produced by compounding pharmacies were associated with 11 other smaller, but equally serious, outbreaks that occurred sporadically over the past 12 years. Lapses in sterile compounding procedures led to contamination of compounded drugs, exposure to patients, and a threat to public health in these outbreaks. Recognition and subsequent public health investigation were usually triggered by the occurrence of illness among multiple patients in a single health care setting.

A hybrid strategy for surveillance of individuals potentially exposed to contaminated methylprednisolone acetate--Virginia, 2012.

In September 2012, a multistate outbreak of fungal infections associated with the use of contaminated steroid products resulted in 675 exposed persons in Virginia and 53 cases of fungal infections, including 2 deaths. This article describes the design and implementation of a "hybrid" active public health surveillance system and related communication activities in partnership with key clinical stakeholders in Virginia. Strong collaboration with clinical partners is critical in establishing and implementing a surveillance system for an evolving outbreak. While clinicians focused on diagnosis, treatment, and routine follow-up of patients who presented with symptoms consistent with the outbreak case definition, public health took on the responsibility of weekly surveillance phone calls to all exposed persons who did not enter clinical care. Communication between clinical partners and public health was essential and included the somewhat atypical role of public health actively performing assessment and referral to care functions during an outbreak.