Diagnostic challenges and recent advances in the early management of invasive fungal infections

Chandrasekar, Pranatharthi H.

doi:10.1111/j.1600-0609.2009.01391.x

Cited by 45 publications

(31 citation statements)

References 87 publications

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“…uring the last several decades, the impact and frequency of fungal infections have gained importance mainly due to an increasing number of immunocompromised patients (1,2). Fungemia cases are being caused mainly by Candida species, which are the fourth most common microorganisms isolated from the blood samples (3,4,5).…”

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Evaluation of Fluorescent Capillary Electrophoresis for Rapid Identification of Candida Fungal Infections

et al. 2016

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dEarly diagnosis of fungal infection is critical for initiating antifungal therapy and reducing the high mortality rate in immunocompromised patients. In this study, we focused on rapid and sensitive identification of clinically important Candida species, utilizing the variability in the length of the ITS2 rRNA gene and fluorescent capillary electrophoresis (f-ITS2-PCR-CE). The method was developed and optimized on 29 various Candida reference strains from which 26 Candida species were clearly identified, while Candida guilliermondii, C. fermentati, and C. carpophila, which are closely related, could not be distinguished. The method was subsequently validated on 143 blinded monofungal clinical isolates (comprising 26 species) and was able to identify 88% of species unambiguously. This indicated a higher resolution power than the classical phenotypic approach which correctly identified 73%. Finally, the culture-independent potential of this technique was addressed by the analysis of 55 retrospective DNA samples extracted directly from clinical material. The method showed 100% sensitivity and specificity compared to those of the combined results of cultivation and panfungal PCR followed by sequencing used as a gold standard. In conclusion, this newly developed f-ITS2-PCR-CE analytical approach was shown to be a fast, sensitive, and highly reproducible tool for both culture-dependent and culture-independent identification of clinically important Candida strains, including species of the "psilosis" complex. During the last several decades, the impact and frequency of fungal infections have gained importance mainly due to an increasing number of immunocompromised patients (1, 2). Fungemia cases are being caused mainly by Candida species, which are the fourth most common microorganisms isolated from the blood samples (3, 4, 5). Sepsis due to Candida spp. is a very serious condition and has a higher mortality rate that for bacterial pathogens; reaching 54 to 64% in Candida-associated septic shock (6, 7). Moreover, the current changes in the epidemiology of invasive mycoses has highlighted a shift in the Candida species involved with a reduced proportion of Candida albicans and an increase in non-albicans species, which can show different susceptibility to various antifungal therapies (8,9,10).Early initiation of antifungal therapy is a critical step in the treatment of fungal infections. Therefore, quick, successful detection and identification of the etiological agents is crucial for early targeted therapy and favorable clinical patient outcome (11). Correct species identification is mostly based on phenotypic features and is usually time-consuming because a typical diagnostic workflow takes up to several days. Moreover, the phenotypic methods may lead to misidentification, particularly in the case of closely related species (12, 13). A significant improvement occurred when matrix-assisted laser desorption ionizationϪtime of flight mass spectroscopy (MALDI-TOF MS) was introduced as a routine laboratory procedure, enab...

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Evaluation of Fluorescent Capillary Electrophoresis for Rapid Identification of Candida Fungal Infections

et al. 2016

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“…Definitive diagnoses are most often based on direct observation and/or isolation of a fungal organism from a sterile site (4). Fungal cultures have been shown to be insensitive (5), however, and the collection of adequate samples for culture may require invasive procedures (6). Sensitive and rapid serological assays have been approved for the diagnosis of IFD, but many have not been validated using nonserological samples (4).…”

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(1,3)-β- d -Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Meningitis Associated with Contaminated Methylprednisolone Injections

Malani

Singal

Wheat³

et al. 2015

J Clin Microbiol

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Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-␤-D-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturer's cutoff value (>80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed. P rompt diagnosis and administration of appropriate therapy are critical to improving clinical outcomes for patients with invasive fungal disease (IFD) (1, 2); however, the diagnosis of IFD can be difficult (3). Definitive diagnoses are most often based on direct observation and/or isolation of a fungal organism from a sterile site (4). Fungal cultures have been shown to be insensitive (5), however, and the collection of adequate samples for culture may require invasive procedures (6). Sensitive and rapid serological assays have been approved for the diagnosis of IFD, but many have not been validated using nonserological samples (4).In May 2004, the serum Fungitell assay (Associates of Cape Cod Inc., East Falmouth, MA) was approved by the Food and Drug Administration (FDA) for use in the United States. A recent meta-analysis comparing serum (1,3)-␤-D-glucan (BDG) levels among patients with proven or probable IFD versus those without IFD revealed a pooled sensitivity of 76.8% (95% confidence interval [CI], 67.1% to 84.3%) and specificity of 85.3% (95% CI, 79.6% to 89.7%) (7). However, this assay has not been validated or FDA approved for testing of cerebrospinal fluid (CSF), and the appropri...

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“…Culture followed by microscopic examination requires skilled manpower and long assay times for cell culturing, when in vitro growth is feasible. New culture media, lysis centrifugation and automated blood culture systems have decreased the assay time (Chandrasekar, 2010), particularly for detection of Candida spp., but without definitely improving the sensitivity of the detection (Archibald et al, 2000;Chandrasekar, 2010). Direct examination, whenever possible, is simpler, faster and cheaper than culture, but a negative test does not definitely exclude a fungal infection.…”

Section: Limitations Of Conventional Laboratory Diagnosismentioning

confidence: 99%

The future of novel diagnostics in medical mycology

Teles

Seixas

2015

Journal of Medical Microbiology

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Diagnostic challenges and recent advances in the early management of invasive fungal infections

Cited by 45 publications

References 87 publications

Evaluation of Fluorescent Capillary Electrophoresis for Rapid Identification of Candida Fungal Infections

Evaluation of Fluorescent Capillary Electrophoresis for Rapid Identification of Candida Fungal Infections

(1,3)-β- d -Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Meningitis Associated with Contaminated Methylprednisolone Injections

The future of novel diagnostics in medical mycology

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