Outbreak Of Fungal Infections Research Articles

1422. Surveillance for fungi in hospital environments housing high-risk hosts using culture and culture-independent methods

Abstract Background Nosocomial outbreaks of fungal infections are increasingly reported. There are scant data on fungal burdens in hospital environments. Standardized surveillance methods are lacking. Methods We developed culture and culture-independent (real-time PCR, reference to standard curve) methods for measuring airborne fungal burdens using SAS Super 100 and SASS 3100 Dry Air samplers. We performed serial surveillance in 7 units with high-risk, immunosuppressed patients in 2 hospitals and outside. Results Methods were optimized for multiple variables, including volume, duration, flow of air sampling; culturing techniques (direct impact plates, cultures at different stages of filter processing); filter DNA recovery (extraction protocols, stage of filter processing); PCR (targets, primers, PCR parameters). To date, we have surveyed each unit ≥4 times. Pathogenic moulds were cultured in >50% of outdoor and indoor air, including azole-resistant Aspergillus species [Figures 1A-B]. Fungal burdens were significantly greater outside than inside hospitals, by both positive culture % and DNA burden [Figure 2]. There was no correlation between outside and inside genome equivalents (GEs; R2< 0.06), nor were there significant differences in GEs within a given unit (nurses stations, patient rooms; all p >0.1). GEs were greater in culture-positive than culture-negative samples (Aspergillus, 2.4 vs. 1.5 log10; pan-fungal, 2.8 vs. 1.5 log10GE; p< 0.0001; best results with sonicated filters). Direct impact cultures were less sensitive than filter cultures. Conclusion We developed standardized methods for sampling airborne fungi in hospitals that yield reproducible results. Fungal burdens were significantly lower in hospitals than those immediately outside, but fungal DNA and viable Aspergillus and other moulds were commonly recovered from units housing high-risk patients. Outside fungal burdens could not be used to estimate relative burdens within hospitals. Direct impact cultures, commonly used in surveillance, lacked sensitivity for detecting viable fungi and did not correlate with DNA burdens. We are optimizing direct metagenomic sequencing from airborne samples. We will assess correlations between environmental surveillance data and nosocomial fungal infections. Disclosures Alexander Sundermann, DrPH, CIC, FAPIC, OpGen: Honoraria Graham M. Snyder, MD, SM, Infectious Diseases Connect: Advisor/Consultant

Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management.

Nosocomial clusters of fungal infections, whilst uncommon, cannot be predicted and are associated with significant morbidity and mortality. Here, we review reports of nosocomial outbreaks of invasive fungal disease to glean insight into their epidemiology, risks for infection, methods employed in outbreak detection including genomic testing to confirm the outbreak, and approaches to clinical and infection control management. Both yeasts and filamentous fungi cause outbreaks, with each having general and specific risks. The early detection and confirmation of the outbreak are essential for diagnosis, treatment of affected patients, and termination of the outbreak. Environmental sampling, including the air in mould outbreaks, for the pathogen may be indicated. The genetic analysis of epidemiologically linked isolates is strongly recommended through a sufficiently discriminatory approach such as whole genome sequencing or a method that is acceptably discriminatory for that pathogen. An analysis of both linked isolates and epidemiologically unrelated strains is required to enable genetic similarity comparisons. The management of the outbreak encompasses input from a multi-disciplinary team with epidemiological investigation and infection control measures, including screening for additional cases, patient cohorting, and strict hygiene and cleaning procedures. Automated methods for fungal infection surveillance would greatly aid earlier outbreak detection and should be a focus of research.

A pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, United Kingdom.

Outbreaks of fungal infections due to emerging and rare species are increasingly reported in healthcare settings. We investigated a pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, UK. We aimed to determine route of healthcare-associated transmission and prevent additional infections. From July 2018 through February 2019, we detected a pseudo-outbreak of R.similis isolated from bronchoalveolar lavage (BAL) fluid samples collected from nine patients who had undergone bronchoscopy in a multispecialty teaching hospital, during a period of 8months. Isolates were identified by MALDI-TOF mass spectrometry. Antifungal susceptibility testing was performed by EUCAST broth microdilution. To determine genetic relatedness among R.similis isolates, we undertook amplified fragment length polymorphism analysis. To determine the potential source of contamination, an epidemiological investigation was carried out. We reviewed patient records retrospectively and audited steps taken during bronchoscopy as well as the subsequent cleaning and decontamination procedures. Fungal cultures were performed on samples collected from bronchoscopes and automated endoscope washer-disinfector systems. No patient was found to have an infection due to R.similis either before or after bronchoscopy. One bronchoscope was identified to be used among all affected patients with positive fungal cultures. Physical damage was found in the index bronchoscope; however, no fungus was recovered after sampling of the affected scope or the rinse water of automated endoscope washer-disinfectors. Use of the scope was halted, and, during the following 12-month period, Rhinocladiella species were not isolated from any BAL specimen. All pseudo-outbreak isolates were identified as R.similis with high genetic relatedness (>90% similarity) on ALFP analysis. The study emphasises the emergence of a rare and uncommon black yeast R.similis, with reduced susceptibility to echinocandins, in a bronchoscope-related pseudo-outbreak with a potential water-related reservoir. Our findings highlight the importance of prolonged fungal culture and species-level identification of melanised yeasts isolated from bronchoscopy samples. Possibility of healthcare-associated transmission should be considered when R.similis is involved in clinical microbiology samples.

Biology of causative agents of crayfish mycoses in connection with environmental protection in crayfish producing reservoirs

In order to prevent outbreaks of fungal infections in reservoirs with crayfish we recommend to (1) performa bioassay on the disease of crayfish with aphanomycosis (crayfish plague); (2) determine the incidence of crayfish with signs of mycosis called burn-spot disease (BSD); (3) check for contamination of coarse grains with agents of mucoriosis; (4) oppose the ingress into the reservoir of waste water from cultivated fields carrying agents of fusariosis; (5) prevent over consolidation of crayfish population. These measures are taking into account the ability of pathogenic oomycetes to quickly infect crayfish with mobile zoospores, long-term viability of chlamydospores (gemmae) of Saprolegniaparasitica and oogoniaof Aphanomyces astaci. These factors support the infection in the reservoir and prevent the recovery of crayfish populations after outbreaks of mycoses.

Outbreaks of fungal infections: a public health perspective

Outbreaks of fungal infections: a public health perspective

Update on Multistate Outbreak of Fungal Infections Associated with Contaminated Methylprednisolone Injections, 2012-2014.

During September 2012, CDC, in collaboration with state and local health departments and the Food and Drug Administration (FDA), investigated a multistate outbreak of fungal meningitis and other infections caused by injections of contaminated methylprednisolone acetate solution (MPA). After this unprecedented outbreak, scientists in the CDC Mycotic Diseases Branch, along with infectious diseases specialists who cared for patients from the outbreak, clinical experts, and public health officials from affected states, have continued to monitor the recovery of affected patients. A long-term follow-up study involving these patients was initiated and is being conducted by the Mycoses Study Group Education and Research Consortium (MSGERC). This update summarizes subsequent information about the current state of the outbreak.

Healthcare‐associated outbreaks due to Mucorales and other uncommon fungi

Healthcare-associated outbreaks of fungal infections, especially with uncommon and emerging fungi, have become more frequent in the past decade. Here, we reviewed the history and definition of healthcare-associated outbreaks of uncommon fungal infections and discussed the principles of investigating, containing and treatment of these outbreaks. In case of these uncommon diseases, occurrence of two or more cases in a short period is considered as an outbreak. Contaminated medical devices and hospital environment are the major sources of these outbreaks. Care must be taken to differentiate a real infection from colonization or contamination. Defining and identifying cases, describing epidemiologic feature of cases, finding and controlling the source of the outbreak, treating patients, and managing asymptomatic exposed patients are main steps for outbreak elimination. These fungal outbreaks are not only difficult to detect but also hard to treat. Early initiation of appropriate antifungal therapy is strongly associated with improved outcomes in infected patients. Choice of antifungal drugs should be made based on spectrum, pharmacodynamic and pharmacokinetic characteristics and adverse effects of available drugs. Combination antifungal therapy and surgical intervention may be also helpful in selected cases. A multidisciplinary approach and close collaboration between all key partners are necessary for successful control of fungal outbreaks.

Estimated deaths and illnesses averted during fungal meningitis outbreak associated with contaminated steroid injections, United States, 2012-2013.

During 2012-2013, the US Centers for Disease Control and Prevention and partners responded to a multistate outbreak of fungal infections linked to methylprednisolone acetate (MPA) injections produced by a compounding pharmacy. We evaluated the effects of public health actions on the scope of this outbreak. A comparison of 60-day case-fatality rates and clinical characteristics of patients given a diagnosis on or before October 4, the date the outbreak was widely publicized, with those of patients given a diagnosis after October 4 showed that an estimated 3,150 MPA injections, 153 cases of meningitis or stroke, and 124 deaths were averted. Compared with diagnosis after October 4, diagnosis on or before October 4 was significantly associated with a higher 60-day case-fatality rate (28% vs. 5%; p<0.0001). Aggressive public health action resulted in a substantially reduced estimated number of persons affected by this outbreak and improved survival of affected patients.

Outbreak of fungal infections associated with contaminated methylprednisolone acetate: an update.

In September 2012, an unprecedented outbreak of fungal infections due to preservative-free, injectable methylprednisolone acetate (MPA) was identified. Exserohilum rostratum was quickly identified as the predominant organism involved in disease cases. Prior to this outbreak, little was known about the pathogenesis, treatment, and prognosis of infections due to this unusual brown-black mold. Almost 2years after the onset of this outbreak, numerous epidemiologic and basic science studies have provided some guidance in understanding the epidemiology, clinical findings, diagnosis, and treatment of patients exposed to the contaminated medication. Additionally, this outbreak has directly led to the passage of legislation supporting increased regulation in the industry of pharmaceutical compounding. Many unanswered questions, particularly surrounding the long-term prognosis and outcomes for affected patients remain. However, it is clear that a strong relationship between clinicians caring for patients and public health as well as a rapid, effective public health response was critical in preventing additional cases of disease.

Reply to "not over yet: fungal infections following methyl prednisolone injections smoulder on".

The multistate outbreak of fungal infections in the United States following contaminated methyl prednisolone injection has been well reported ([1][1]). Meningitis was the most frequent consequence, but other infections included arachnoiditis, with local spinal infection and peripheral joint

Hair Loss Is Linked to the Antifungal Voriconazole

The 2012 outbreak of fungal infections associated with injections of contaminated methylprednisolone affected about 750 patients, most of whom

Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain.

Voriconazole is a triazole antifungal medication used for prophylaxis or to treat invasive fungal infections. Inflammation of the periosteum resulting in skeletal pain, known as periostitis, is a reported side effect of long-term voriconazole therapy. The trifluorinated molecular structure of voriconazole suggests a possible link between excess fluoride and periostitis, as elevated blood fluoride has been reported among patients with periostitis who received voriconazole. Two hundred sixty-four patients from Michigan were impacted by the multistate outbreak of fungal infections as a result of contaminated methylprednisolone injections. A retrospective study was conducted among 195 patients who received voriconazole therapy at St Joseph Mercy Hospital during this outbreak. Twenty-eight patients who received both bone scan and plasma fluoride measurements for skeletal pain were included in the statistical analyses. Increased tracer uptake on bone scan was considered positive for periostitis. The primary outcome measure was the correlation between plasma fluoride and bone scan results. Blood fluoride (P < .001), alkaline phosphatase (P = .020), daily voriconazole dose (P < .001), and cumulative voriconazole dose (P = .027) were significantly elevated in patients who had periostitis compared with those who did not. Discontinuation or dose reduction of voriconazole resulted in improvement of pain in 89% of patients. High plasma fluoride levels coupled with skeletal pain among patients who are on long-term voriconazole therapy is highly suggestive of periostitis. Initial measurement of fluoride may be considered when bone scan is not readily available. Early detection should be sought, as discontinuation of voriconazole is effective at reversing the disease.

Spinal and paraspinal fungal infections associated with contaminated methylprednisolone injections.

Background. A nationwide outbreak of fungal infections was traced to injection of Exserohilum-contaminated methylprednisolone. We describe our experience with patients who developed spinal or paraspinal infection after injection of contaminated methylprednisolone.Methods. Data were assembled from the Michigan Department of Community Health, electronic medical records, and magnetic resonance imaging (MRI) reports.Results. Of 544 patients who received an epidural injection from a contaminated lot of methylprednisolone at a pain clinic in southeastern Michigan, 153 (28%) were diagnosed at our institution with probable or confirmed spinal or paraspinal fungal infection at the injection site. Forty-one patients had both meningitis and spinal or paraspinal infection, and 112 had only spinal or paraspinal infection. Magnetic resonance imaging abnormalities included abscess, phlegmon, arachnoiditis, and osteomyelitis. Surgical debridement in 116 patients revealed epidural phlegmon and epidural abscess most often. Among 26 patients with an abnormal MRI but with no increase or change in chronic pain, 19 (73%) had infection identified at surgery. Fungal infection was confirmed in 78 patients (51%) by finding hyphae in tissues, positive polymerase chain reaction, or culture. Initial therapy was voriconazole plus liposomal amphotericin B in 115 patients (75%) and voriconazole alone in 38 patients (25%). As of January 31, 2014, 20 patients remained on an azole agent. Five patients died of infection.Conclusions. We report on 153 patients who had spinal or paraspinal fungal infection at the site of epidural injection of contaminated methylprednisolone. One hundred sixteen (76%) underwent operative debridement in addition to treatment with antifungal agents.

Fungal Infections Associated with Contaminated Methylprednisolone Injections

BackgroundFungal infections are rare complications of injections for treatment of chronic pain. In September 2012, we initiated an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy.MethodsThree lots of methylprednisolone acetate were recalled by the pharmacy; examination of unopened vials later revealed fungus. Notification of all persons potentially exposed to implicated methylprednisolone acetate was conducted by federal, state, and local public health officials and by staff at clinical facilities that administered the drug. We collected clinical data on standardized case-report forms, and we tested for the presence of fungi in isolates and specimens by examining cultures and performing polymerase-chain-reaction assays and histopathological and immunohistochemical testing.ResultsBy October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of July 1, 2013, there were 749 reported cases of infection in 20 states, with 61 deaths (8%). Laboratory evidence of Exserohilum rostratum was present in specimens from 153 case patients (20%). Additional data were available for 728 case patients (97%); 229 of these patients (31%) had meningitis with no other documented infection. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 15 to 97), and the median incubation period (the number of days from the last injection to the date of the first diagnosis) was 47 days (range, 0 to 249); 40 patients (5%) had a stroke.ConclusionsAnalysis of data from a large, multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.

Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

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.

CDC Probes New Outbreak Associated With Compounded Steroids

PUBLIC HEALTH AUTHORITIES IN THE United States are investigating what appears to be a second outbreak of fungal infections associated with compounded steroid injections. The compounding pharmacy being investigated has recalled all lots of products that are intended to be sterile. Thesuspectedoutbreakhas spurreda multistate investigation by authorities fromtheUSFoodandDrugAdministration (FDA), the US Centers for Disease Control and Prevention (CDC), and localpublichealthauthorities fromIllinois, NorthCarolina,Florida, andTennessee. The investigation comes on the heels of an ongoing outbreak of fungal meningitis cases causedbycontaminatedsteroid injectionsproducedbyaMassachusettsbased compounding pharmacy that beganlastfallandthatcausedillnessinmore than 740 patients, killing 55 of them. On May 24, the FDA announced that it had received several reports of infections among patients who received methylprednisolone acetate injections compounded by the Main Street Family Pharmacy in Newbern, Tenn. (http: //1.usa.gov/13QsH4K). The agency advised clinicians not to use any sterile products produced by the pharmacy, and the pharmacy recalled all sterile products with a “use by” date on or before November 20, 2013. By May 30, the CDC reported that 20 cases of suspected infections associated with these products had been reported in 3 states (http://1.usa.gov /12mqOzc). Most of the patients have developed skin or soft tissue infections without a clear cause after receiving a methylprednisolone acetate injection, according to the CDC. No cases of meningitis had been reported at press time, but according to the FDA, at least 1 infection appeared to have a fungal cause. The suspect methylprednisolone injections were distributed in 17 states. The original fungal meningitis was identified inSeptember2012,whenpublic health officials linked cases of fungal meningitistocontaminatedlotsofmethylprednisolone acetate steroid injections produced by the New England Compounding Center (NECC) in Framingham, Mass. More than 13 000 patients werepotentiallyexposedviaspinal injectionsofthecontaminatedproducts.Cases of localizedinfectionsassociatedwiththe contaminated injectionshavecontinued to emerge over the past several months, leading the CDC to urge continued vigilance. Additionally, CDC scientists recently reported a case of fungal meningitis relapse in 1 patient who was exposed to contaminated steroids from the NECC (Smith RM et al. N Engl J Med. doi: 10.1056/NEJMc1306560 [published online May 29, 2013]). The 80-year-old man was treated with voriconazole for 4.5 months and discontinued therapy after the infection had apparently resolved.However, aboutamonth later, the man presented with headache and neck pain, an elevated white cell count, and a positive specimen for Exserohilum rostratum. The man’s physician resumed treatment with voriconazole. “Because Exserohilum rostratum meningitis is a new clinical entity, it is not known whether the current treatment guidance is sufficient,” noted the authors. “Some patients with central nervous system infection may require prolonged antifungal therapy owing to the chronic nature of fungal diseases and the difficulty in maintaining adequate drug concentrations in the cerebrospinal fluid.” Clinical guidance from the CDC is available at http://1.usa.gov/RdXGz1. news@JAMA From JAMA’s Daily News Site

Detection of Fungal DNA in Human Body Fluids and Tissues during a Multistate Outbreak of Fungal Meningitis and Other Infections

Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak.

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.

Fungal Infections Associated with Contaminated Methylprednisolone in Tennessee

BackgroundWe investigated an outbreak of fungal infections of the central nervous system that occurred among patients who received epidural or paraspinal glucocorticoid injections of preservative-free methylprednisolone acetate prepared by a single compounding pharmacy.MethodsCase patients were defined as patients with fungal meningitis, posterior circulation stroke, spinal osteomyelitis, or epidural abscess that developed after epidural or paraspinal glucocorticoid injections. Clinical and procedure data were abstracted. A cohort analysis was performed.ResultsThe median age of the 66 case patients was 69 years (range, 23 to 91). The median time from the last epidural glucocorticoid injection to symptom onset was 18 days (range, 0 to 56). Patients presented with meningitis alone (73%), the cauda equina syndrome or focal infection (15%), or posterior circulation stroke with or without meningitis (12%). Symptoms and signs included headache (in 73% of the patients), new or worsening back pain (in 50%), neurologic symptoms (in 48%), nausea (in 39%), and stiff neck (in 29%). The median cerebrospinal fluid white-cell count on the first lumbar puncture among patients who presented with meningitis, with or without stroke or focal infection, was 648 per cubic millimeter (range, 6 to 10,140), with 78% granulocytes (range, 0 to 97); the protein level was 114 mg per deciliter (range, 29 to 440); and the glucose concentration was 44 mg per deciliter (range, 12 to 121) (2.5 mmol per liter [range, 0.7 to 6.7]). A total of 22 patients had laboratory confirmation of Exserohilum rostratum infection (21 patients) or Aspergillus fumigatus infection (1 patient). The risk of infection increased with exposure to lot 06292012@26, older vials, higher doses, multiple procedures, and translaminar approach to epidural glucocorticoid injection. Voriconazole was used to treat 61 patients (92%); 35 patients (53%) were also treated with liposomal amphotericin B. Eight patients (12%) died, seven of whom had stroke.ConclusionsWe describe an outbreak of fungal meningitis after epidural or paraspinal glucocorticoid injection with methylprednisolone from a single compounding pharmacy. Rapid recognition of illness and prompt initiation of therapy are important to prevent complications. (Funded by the Tennessee Department of Health and the Centers for Disease Control and Prevention.)