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.

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.

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.

The index case for the fungal meningitis outbreak in the United States.

Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.

Early clinical observations in prospectively followed patients with fungal meningitis related to contaminated epidural steroid injections.

UNLABELLED: Chinese translation BACKGROUND: Administration of epidural steroid injections (ESIs) with contaminated methylprednisolone resulted in an outbreak of fungal meningitis in many locations in the United States. OBJECTIVE: To characterize early clinical findings and initial response to treatment. DESIGN: Case series with standardized observation studied from 4 October to 31 October 2012. SETTING: An 800-bed hospital in Virginia. PATIENTS: 172 patients who presented to the hospital with exposure to contaminated ESI. INTERVENTION: Standardized approach to screening, case definition, treatment, and data collection. MEASUREMENTS: Clinical findings, cerebrospinal fluid (CSF) values, magnetic resonance imaging (MRI), serum and CSF voriconazole concentrations, and clinician assessment of response to therapy. RESULTS: Of 172 patients presenting to the hospital who had had ESI, 131 had lumbar puncture because of symptoms or signs consistent with central nervous system disease. Twenty-five (19%) had neutrophilic meningitis. All were started on voriconazole therapy alone. Three patients developed stroke during treatment. Ten patients had arachnoiditis, another had an epidural abscess, and 9 had urine retention. Fifteen continued to receive voriconazole, and 10 were switched to amphotericin B. Cerebrospinal fluid leukocyte counts began to decrease by day 13 of treatment. Findings on MRI included ventriculitis, leptomeningeal enhancement, infarction, hemorrhage, and arachnoiditis. Serum voriconazole levels varied, and CSF concentrations of voriconazole were approximately 50% those of serum. Exserohilum rostratum and Cladosporium species have been cultured. LIMITATIONS: This is an observational study of an evolving outbreak. Not all exposed patients presented for evaluation. Follow-up is too short to determine final outcomes. CONCLUSION: Meningitis after receipt of contaminated ESI has been diagnosed in many exposed patients presenting to 1 hospital. Most patients have improved on receipt of empirical voriconazole therapy. The full natural history and long-term sequelae of this infection are currently unknown. PRIMARY FUNDING SOURCE: None.

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.

Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings.

An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

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.

Multistate fungal meningitis outbreak -- interim guidance for treatment.

CDC and the Food and Drug Administration (FDA) continue to work closely with state and local public health departments on the multistate meningitis outbreak investigation of fungal infections among patients who received a steroid injection of a potentially contaminated product into the spinal area. The investigation also includes possible fungal infections associated with injections in a peripheral joint space. These cases are associated with a potentially contaminated steroid medication prepared by New England Compounding Center (NECC) in Framingham, Massachusetts.

Multistate outbreak of fungal infection associated with injection of methylprednisolone acetate solution from a single compounding pharmacy - United States, 2012.

On September 18, 2012, the Tennessee Department of Health was alerted by a clinician regarding a patient with culture-confirmed Aspergillus fumigatus meningitis diagnosed 46 days after epidural steroid injection at a Tennessee ambulatory surgical center. By September 27, the initial investigation, carried out by the Tennessee Department of Health in collaboration with CDC and the North Carolina Department of Health and Human Services, had identified an additional eight patients with clinically diagnosed, culture-negative meningitis: seven in Tennessee and one in North Carolina. All nine patients had received epidural steroid injection with preservative-free methylprednisolone acetate solution (MPA), compounded at New England Compounding Center (NECC) in Framingham, Massachusetts. All nine patients had received one or more injections from three lots of MPA (lot numbers 05212012@68; 06292012@26; and 08102012@51). As of October 10, a multistate investigation led by CDC in collaboration with state and local health departments and the Food and Drug Administration (FDA) had identified 137 cases and 12 deaths associated with this outbreak in 10 states. Active case-finding efforts and extensive investigation into medications and medication lot numbers received by patients have confirmed that, as of October 10, no cases were associated with other lots of MPA, nor were any associated with other NECC products. This report describes the ongoing investigation by CDC and state and local health departments, and includes important recommendations for physicians and patients.

Battlefront. Michigan hospital at forefront in national fight against outbreak from tainted injections.

A hospital in Michigan has found itself at the epicenter of a spiraling fungal meningitis outbreak that has turned the facility into a learning laboratory and tested its emergency preparedness. "Disasters usually have a defined time period, and we quickly realized we were going from a sprint to marathon," says Rob Casalou, CEO of St. Joseph Mercy Ann Arbor.

Candida meningitis post Gliadel wafer placement successfully treated with intrathecal and intravenous amphotericin B.

OBJECTIVE: To report a case of Candida meningitis post Gliadel wafer (polifeprosan 20 with carmustine implant) placement successfully treated with the combination of intrathecal and intravenous amphotericin B. CASE SUMMARY: A 33-year-old white female with a history of recurrent oligodendroglioma was admitted to the neuroscience intensive care unit with acute mental status changes. Computed tomography of the head demonstrated a cystic dilation of the right frontoparietal tumor resection cavity with Gliadel wafers in place and the presence of a large fluid collection. The cavity was debrided surgically and a ventriculostomy catheter was left in place. Cerebrospinal fluid (CSF) cultures were positive for Candida albicans and methicillin-resistant coagulase-negative Staphylococcus spp. Antiinfective therapy with intrathecal and intravenous amphotericin B as well as flucytosine and vancomycin was started. The patient had subsequent improvement in clinical manifestations, resolution of CSF leukocytosis, and mycologic cure. DISCUSSION: Candida meningitis occurs primarily in the setting of immunosuppression, intravenous drug abuse and following neurosurgical procedures. Secondary bacterial and fungal infections have been reported following Gliadel wafer placement in patients with brain tumor resection. Candida meningitis has traditionally been treated with intravenous amphotericin B with or without oral flucytosine. There have been reports of treatment with intrathecal amphotericin B with variable clinical outcomes. CONCLUSIONS: This case demonstrates successful treatment of Candida meningitis post Gliadel wafer placement with the combination of intrathecal and intravenous amphotericin B. This treatment modality may provide an effective therapeutic option for other patients with Candida meningitis, especially those unresponsive to intravenous therapy.