Cerebrospinal Fluid and Plasma (1→3)-β-<scp>d</scp>-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous<i>Candida</i>Meningoencephalitis

Petraitienė, Rūta; Petraitis, Vidmantas; Hope, William; Mickiene, Diana; Kelaher, Amy M.; Murray, Heidi; Mya-San, Christine; Hughes, Johanna E.; Cotton, Margaret P.; Bacher, John; Walsh, Thomas J.

doi:10.1128/aac.00674-08

Cited by 57 publications

(37 citation statements)

References 32 publications

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“…With respect to studies in other central nervous system mycoses, a study in rabbits with experimental Candida meningitis found that CSF ␤-glucan was more sensitive than CSF culture (19). These authors also noted that CSF ␤-glucan correlated with the tissue burden and response to therapy, in contrast to the results of our rabbit coccidioidal studies.…”

Section: Discussioncontrasting

confidence: 55%

“…␤-Glucan is stable, and slow clearance from the CSF compartment may occur in coccidioidal meningitis. The lack of correlation with the organism burden and response to therapy is in contrast with the experience with Candida meningitis in rabbits (19), cryptococcal meningitis in humans (16), pediatric central nervous system infections (12), and serum ␤-glucan results in other clinical mycoses (15). However, the serum ␤-glucan value and even its early kinetics did not correlate with outcomes in other mycoses in some studies (20).…”

Section: Discussioncontrasting

confidence: 41%

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Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

et al. 2016

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c Diagnosing coccidioidal meningitis (CM) can be problematic owing to its infrequency and/or a delay in the positivity of a cerebrospinal fluid (CSF) culture or CSF antibody, particularly if the primary coccidioidal infection is unrecognized. We tested 37 CSF specimens, 26 from patients with confirmed CM and 11 from patients with suspected microbial meningitis without fungal diagnosis, for (1,3)-beta-glucan (BG). BG in CM CSF specimens ranged from 18 to 3,300 pg/ml and in controls ranged from <3.9 to 103 pg/ml. Diagnostic performance was determined using a 31-pg/ml cutoff (the bottom of the serum range according to the directions for the commercial kit, although further serial dilutions of the standard indicated linearity to 3.9). Sensitivity was 96%, specificity was 82%, positive and negative predictive values were 93% and 90%, and the area under the receiver operating characteristic curve was 0.937. Fifteen of 15 samples of >103 pg/ml were CM. The one false-negative specimen was from a patient with a pseudosyrinx, without inflammatory evidence of meningitis activity. Serial samples from some patients were positive at <8 years, indicating no loss of positivity with chronicity. Samples stored frozen since 2000 included those with 2 of the 3 highest values, indicating that fresh samples not required. A previous study indicated serum sensitivities of 53% in acute, 50% in resolved, and 83% in disseminated and meningeal coccidioidomycosis. Three studies of other fungal meningitides ranged from 86 to 1,524 pg/ml CSF, with 37 controls of <4 to 115 pg/ml CSF. CSF BG analysis had good diagnostic performance in CM. CSF BG testing can be useful in CM, and a commercial kit is available. It will be of interest to correlate this with course, treatment, outcome, inflammation, and antigen. The only mycoses with common central nervous system (CNS) involvement are cryptococcal and coccidioidal, so CSF BG screening can be useful in meningitis diagnosis. C occidiodal meningitis, the most feared complication of coccidioidomycosis, has a documented mortality if untreated of 90% in 1 year and 100% in 2 years. It is estimated that there are 200 to 500 new cases per year. It is a granulomatous meningitis, usually involving the basilar meninges. The spinal cord is often involved. It may have an acute, a subacute, or a chronic type of presentation. It may be accompanied by parenchymal abscesses. Complications include hydrocephalus, cerebral infarction, vasculitis, arachnoiditis, cranial nerve palsy, syringomyelia, transverse myelitis, cord compression, seizures, and hyponatremia owing to inappropriate antidiuretic hormone secretion (1).Definitive diagnosis rests on isolating Coccidioides from cerebrospinal fluid (CSF) or other central nervous system (CNS) specimens, although results are only positive in about one-third of patients. A presumptive diagnosis has classically been made by identifying anticoccidioidal antibodies in the CSF; however, antibody results may be negative early in the disease, and false-positive results can occur wit...

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Section: Discussioncontrasting

confidence: 55%

Section: Discussioncontrasting

confidence: 41%

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

et al. 2016

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“…There are limited data to guide dosing of anidulafungin. Neonatal data are needed for all the echinocandins in four major areas: optimal dose, resistance patterns with regards to C parapsilosis, safety, and central nervous system penetration 31,35,36 . Their role in treatment or prophylaxis will depend on these findings and the general principle to use one agent for prophylaxis and a different agent for treatment.…”

Section: Treatment Of Invasive Fungal Infectionsmentioning

confidence: 99%

Challenging issues in neonatal candidiasis

Kaufman

2010

Current Medical Research and Opinion

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In an era of quality improvement and 'getting to zero (infections and/or related mortality),' neonatal candidiasis is ripe for evidence-based initiatives. Knowledge of each institution's invasive Candida infection (ICI) incidence and infection-related mortality is critical to evaluate disease burden and effective interventions. Evidenced-based interventions include: antifungal prophylaxis, starting with appropriate dosing, and prompt removal of central venous catheters (CVC). There is A-I evidence supporting antifungal prophylaxis with fluconazole, and it should be considered in every neonatal intensive care unit (NICU). The literature supports targeting infants51000 g and/or 27 weeks, because this group has high infection-related mortality and neurodevelopmental impairment in 57% of survivors. Antifungal prophylaxis has been shown to nearly eliminate infection-related mortality. Interventions start with prenatal initiatives, with women being treated for vaginal candidiasis, especially with preterm labor or complications. Targeting modifiable risk factors, including restriction policies for use of third-and fourth-generation cephalosporins, carbapenems, H2-antagonists, proton pump inhibitors, and postnatal steroids; guidelines for CVC care and removal; and feeding practices, with promotion of early feedings and breast milk, may also reduce risk. A few studies have emerged on empiric antifungal therapy with sepsis evaluations for preterm infants 51500 g and other high-risk patients that have shown favorable effects of eliminating mortality, but these have not been compared to appropriate antifungal therapy and central line removal. Further study of empiric therapy, prospective treatment studies with higher targeted dosing of amphotericin B preparations, fluconazole, and new antifungals with prompt CVC removal may contribute to a 100% survival rate for those infants41000 g and 28 weeks not receiving antifungal prophylaxis. Evaluation of ICI incidence and mortality by gestational age and birth week should be followed in each NICU, to evaluate infection control and prevention.

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“…Conversely, we found that the BDG level was significantly higher in CSF than in serum in three cases of proven/probable CNS fungal infection. This could suggest isolated CNS infection without significant spillover into venous blood or that BDG may be more rapidly cleared in blood than in CSF, as indicated in the fungal meningitis rabbit model (5), and it suggests that serum values may not be helpful in determining invasion of the CNS by a fungal pathogen.…”

mentioning

confidence: 99%

Utility of Measuring (1,3)-β- d -Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection

Lyons

Thakur²,

Lee

et al. 2015

J Clin Microbiol

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(1-3)-␤-D-Glucan (BDG) from cerebrospinal fluid (CSF) is a promising marker for diagnostic and prognostic aid of central nervous system (CNS) fungal infection, but its relationship to serum values has not been studied. Herein, we detected BDG from CSF at levels 2-fold lower than those in serum in patients without evidence of fungal disease but 25-fold higher than those in in serum in noncryptococcal CNS fungal infections. CSF BDG may be a useful biomarker in the evaluation of fungal CNS disease.is a fungal cell wall polysaccharide (Cryptococcus and mucoralean fungi generally excepted). Circulating BDG is sometimes detectable at low levels (Ͻ60 pg/ml) in blood of asymptomatic individuals and is elevated in patients with invasive fungal infections (1). The U.S. Food and Drug Administration (FDA) has approved testing of BDG in serum to aid in diagnosis of invasive fungal infections. Clinical studies have demonstrated that the test marketed in the United States has a sensitivity of 75 to 77% and a specificity of 60 to 80% in the diagnosis of candidiasis in intensive care unit patients and aspergillosis in lung transplant patients with a cutoff value of Յ60 pg/ml as negative and Ն80 pg/ml as positive (2-4).Cerebrospinal fluid (CSF) BDG measurement has not been validated. Its utility was first described for a nonneutropenic rabbit model of experimental hematogenous Candida meningoencephalitis (5). Lyons et al. (6) and Litvintseva et al. (7) showed its diagnostic and prognostic utility during the 2012 U.S. fungal central nervous system (CNS) infection outbreak. Our study further explores the utility of CSF BDG and the relationship between serum and CSF BDG in CNS fungal and nonfungal disease.We selected CSF and serum samples collected for routine care between 2007 and 2013 and frozen as part of a research protocol approved by Johns Hopkins Institutional Review Board. We selected subjects whose CSF and serum were collected within 24 h of one another. There was only one serum and one CSF specimen available per patient. Diagnoses were confirmed by chart review and were simultaneous with the timing of sample acquisition.Demographic information, including gender, age, race, clinical diagnosis, and indication for lumbar puncture, was documented. Pertinent clinical information gathered included history of fungal infection or other CNS infection, HIV status, and history of organ transplantation or other evidence of immunosuppression. Culture, serology, histopathology, and neuroimaging data were collected for diagnostic purposes. Fungal infections were defined as proven, probable, or possible based on EORTC/MSG criteria (8) or CDC definitions for outbreak-associated meningitis (9).Sterilely collected CSF and serum specimens had been frozen to Ϫ80°C and were shipped on dry ice to the Beacon Diagnostics Laboratory for testing via the Fungitell assay (Associates of Cape Cod, Inc., East Falmouth, MA). All assays were performed in a biosafety cabinet that had not been used to manipulate fungal cultures. Glucan-free dilution tubes an...

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Cerebrospinal Fluid and Plasma (1→3)-β-d-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental HematogenousCandidaMeningoencephalitis

Cited by 57 publications

References 32 publications

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

Cerebrospinal Fluid (1,3)-Beta- d -Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

Challenging issues in neonatal candidiasis

Utility of Measuring (1,3)-β- d -Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection

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