Clinical Utility of beta-D-glucan Testing for Detecting Fungal Chorioretinitis and/or Endophthalmitis
Michael J. AmmarRobert M. CarrollAnton M. KolomeyerGui-Shuang YingGideon WhiteheadAlexander J. BruckerBenjamin J. Kim
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Chorioretinitis
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Candida endophthalmitis is a serious infection secondary to hematogenous dissemination or direct inoculation of the organisms following trauma or eye surgery. The diagnosis is based on the characteristic findings in the infected eye and on culture of vitreous samples. Unfortunately, the yield of vitreous cultures is limited. The use of a Candida albicans species-specific polymerase chain reaction (PCR) assay in the diagnosis of Candida endophthalmitis is reported herein. Four patients with suspected fungal endophthalmitis underwent vitrectomy for diagnostic and therapeutic purposes. In 2 of the 4, vitreous cultures were negative. However, characteristic PCR products were generated in all 4 patient specimens, enabling the rapid diagnosis of Candida endophthalmitis in all 4. Clinical response was observed in all cases. These results demonstrate the utility of PCR-mediated detection of C. albicans in vitreous samples.
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Several case reports and cohort studies have examined the use of (1,3)-beta- d -glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta- d -glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta- d -glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded.
Beta-glucan
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Purpose.: Caspofungin is a synthetic echinocandin antifungal agent that inhibits the synthesis of β(1,3)-d-glucan, an essential component of the cell wall of susceptible Aspergillus and Candida species. In this study, retinal toxicity was determined after intravitreal injection of caspofungin in a mouse model to assess its safety profile for the treatment of fungal endophthalmitis. Methods.: Caspofungin acetate was injected intravitreally in the left eyes of male C57BL/6 mice, with final vitreal concentrations corresponding to 0.41, 1.2, 2.5, 4.1, and 41 μM (five mice per cohort). A total of 25 age-matched male C57BL/6 mice injected with balanced salt solution were used as control subjects (five for each of the five different caspofungin acetate concentrations). Electroretinograms (ERGs) were recorded 7 weeks after the injections, and the injected eyes were examined histologically. Results.: Mice injected with caspofungin at vitreal concentrations from 0.41 to 4.1 μM did not have significant alterations in their ERG waveforms, and their retinas had no detectable morphologic changes or loss of cells. At the vitreal concentration of 41 μM, caspofungin reduced the amplitudes of the a-waves, b-waves, and scotopic threshold responses of the ERG and also produced a decrease in the number of cells in the ganglion cell layer. Conclusions.: Caspofungin is a safe antifungal agent at vitreal concentrations of 0.41 to 4.1 μM in mice and consequently shows promise for the treatment of fungal endophthalmitis in humans. Much higher doses produce toxicity and should not be used.
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Invasive candidiasis
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Background Fungal infections are emerging as a major cause of healthcare-associated infection, and invasive fungal infections (IFI) are associated with high mortality in burn patients. The (1,3)-β-D-glucan (BG) assay has been increasingly used for the diagnosis of IFI, but its effectiveness remains uncertain. As such, we evaluated the BG test in patients with severe burn injuries. Methods From July to December 2018, a total of 86 patients with major burn injuries were prospectively tested using a Fungitell assay (Cape Code, East Falmouth, MA). BG levels were measured within the first week of intensive care unit admission and compared with clinical symptoms of patients and results of a fungal culture. Results A total of 11 patients were identified as proven or possible IFI. Thirty seven patients (43.0%) were positive, 5 (5.8%) were intermediate, and 44 (51.2%) were negative based on a 60–80 pg/mL cutoff. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 56.0%, 24.3%, and 95.5%, respectively. A receiver operating characteristic (ROC) analysis showed an area under the curve of 0.725, an optimal cut-off of 124.2 pg/mL, a sensitivity of 81.8%, and a specificity of 74.7%. Conclusion The BG test in burn patients showed moderate accuracy and high negative predictive values but very low positive predictive values. We conclude that the BG test is not useful as a screening tool for IFI, but it is recommended as a follow-up in ruling out the discontinuation of treatment.
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