What Is New in Candida Infections? T2Candida, Antifungal Stewardship, and Candida auris
Tóm tắt
We review T2Candida panel performance in diagnosing invasive candidiasis, potential roles of T2Candida, and other culture-independent tests in patient management and antifungal stewardship, and diagnosis and treatment of infections by Candida auris, which has emerged globally as a cause of nosocomial outbreaks. In 2 multicenter trials, T2Candida was 90% sensitive and 98% specific for diagnosing candidemia directly from whole blood samples. A subsequent study demonstrated T2Candida sensitivity/specificity of 45%/96% for diagnosing deep-seated candidiasis. Other studies have shown that ongoing T2Candida positivity was associated with poor patient outcomes, and T2Candida targeted to patients at risk for invasive candidiasis was useful in guiding antifungal treatment and stewardship decisions. C. auris is misidentified by commercial biochemical and matrix-assisted laser desorption ionization time-of-flight mass spectrometry systems that do not include the species in their databases. In different studies, a T2Candida research assay was 89% sensitive and 98% specific in identifying C. auris in clinical axilla or groin swab samples, and serum β-D-glucan sensitivity and specificity for diagnosing invasive infections by C. auris and other species were comparable. Fluconazole, amphotericin B, and echinocandin resistance rates among C. auris isolates are > 90%, ~ 30%–40%, and ~ 3%–10%, respectively. Echinocandins are agents of choice against most C. auris infections. Since T2Candida results assign a probability of invasive candidiasis based on pre-test disease likelihood, the test will only have value if directed toward at-risk patients. Rapid and accurate tests for detecting C. auris are needed for surveillance and diagnostic purposes.
Tài liệu tham khảo
Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56(9):1284–92. https://doi.org/10.1093/cid/cit006.
Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis. 2012;54(8):1110–22. https://doi.org/10.1093/cid/cis021.
Vergidis P, Clancy CJ, Shields RK, Park SY, Wildfeuer BN, Simmons RL, et al. Intra-abdominal candidiasis: the importance of early source control and antifungal treatment. PLoS One. 2016;11(4):e0153247. https://doi.org/10.1371/journal.pone.0153247.
Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother. 2005;49(9):3640–5. https://doi.org/10.1128/AAC.49.9.3640-3645.2005.
Clancy CJ, Nguyen MH. The end of an era in defining the optimal treatment of invasive candidiasis. Clin Infect Dis. 2012;54(8):1123–5. https://doi.org/10.1093/cid/cis023.
•• Clancy CJ, Pappas PG, Vazquez J, Judson MA, Kontoyiannis DP, Thompson GR 3rd, et al. Detecting infections rapidly and easily for candidemia trial, part 2 (DIRECT2): a prospective, multicenter study of the T2Candida panel. Clin Infect Dis. 2018;66(11):1678–86. https://doi.org/10.1093/cid/cix1095. This prospective multi-center trial, which used whole blood from patients rather than spiked samples to demonstrate that T2Candida was 89% sensitive for diagnosing candidemia, was the foundation for FDA clearance of the panel.
Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, et al. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis. 2015;60(6):892–9. https://doi.org/10.1093/cid/ciu959.
Clancy CJ, Nguyen MH. Diagnosing invasive candidiasis. J Clin Microbiol. 2018;56(5). https://doi.org/10.1128/JCM.01909-17.
Clancy CJ, Nguyen MH. Emergence of Candida auris: an international call to arms. Clin Infect Dis. 2017;64(2):141–3. https://doi.org/10.1093/cid/ciw696.
Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64(2):134–40. https://doi.org/10.1093/cid/ciw691.
•• Eyre DW, Sheppard AE, Madder H, Moir I, Moroney R, Quan TP, et al. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med. 2018;379(14):1322–31. https://doi.org/10.1056/NEJMoa1714373. This report of the epidemiologic investigation and control of a C. auris outbreak in England due to isolates from the South African clade linked cases to reusable axillary temperature probes, and demonstrated how the organism persists and spreads within health care settings.
Clancy CJ, Nguyen MH. T2 magnetic resonance for the diagnosis of bloodstream infections: charting a path forward. J Antimicrob Chemother. 2018;73(suppl_4):iv2–5. https://doi.org/10.1093/jac/dky050.
Neely LA, Audeh M, Phung NA, Min M, Suchocki A, Plourde D, et al. T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood. Sci Transl Med. 2013;5(182):182ra54. https://doi.org/10.1126/scitranslmed.3005377.
Pfaller MA, Messer SA, Moet GJ, Jones RN, Castanheira M. Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in intensive care unit (ICU) and non-ICU settings in the SENTRY Antimicrobial Surveillance Program (2008–2009). Int J Antimicrob Agents. 2011;38(1):65–9. https://doi.org/10.1016/j.ijantimicag.2011.02.016.
• Arendrup MC, Andersen JS, Holten MK, Krarup KB, Reiter N, Schierbeck J, et al. Diagnostic performance of T2Candida among ICU patients with risk factors for invasive candidiasis. Open Forum Infect Dis. 2019;6(5):ofz136. https://doi.org/10.1093/ofid/ofz136. This is the first study to describe the performance of T2Candida in diagnosing blood culture-negative, deep-seated candidiasis.
Munoz P, Vena A, Machado M, Gioia F, Martinez-Jimenez MC, Gomez E, et al. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study. J Antimicrob Chemother. 2018;73(suppl_4):iv6–iv12. https://doi.org/10.1093/jac/dky047 This study showed that T2Candida has prognostic utility, as positive results among patients receiving empiric antifungal therapy was predictive of poor outcomes.
• Munoz P, Vena A, Machado M, Martinez-Jimenez MC, Gioia F, Gomez E, et al. T2MR contributes to the very early diagnosis of complicated candidaemia. A prospective study. J Antimicrob Chemother. 2018;73(suppl_4):iv13–iv9. https://doi.org/10.1093/jac/dky048. This study, a companion to the study in reference 16, showed that T2Candida-positivity among patients receiving antifungal agents for treatment of candidemia was predictive of poor outcomes.
He S, Hang JP, Zhang L, Wang F, Zhang DC, Gong FH. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-beta-D-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect. 2015;48(4):351–61. https://doi.org/10.1016/j.jmii.2014.06.009.
Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. Beta-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–70. https://doi.org/10.1093/cid/ciq206.
Onishi A, Sugiyama D, Kogata Y, Saegusa J, Sugimoto T, Kawano S, et al. Diagnostic accuracy of serum 1,3-beta-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol. 2012;50(1):7–15. https://doi.org/10.1128/JCM.05267-11.
Clancy CJ, Nguyen MH. Non-culture diagnostics for invasive candidiasis: promise and unintended consequences. J Fungi (Basel). 2018;4(1). https://doi.org/10.3390/jof4010027.
• Patch ME, Weisz E, Cubillos A, Estrada SJ, Pfaller MA. Impact of rapid, culture-independent diagnosis of candidaemia and invasive candidiasis in a community health system. J Antimicrob Chemother. 2018;73(suppl_4):iv27–30. https://doi.org/10.1093/jac/dky046. The use of T2Candida by a US healthcare system’s stewardship program was associated with shorter times to diagnosis of candidemia and decreased durations of empiric antifungal therapy.
Kullberg BJ, Arendrup MC. Invasive Candidiasis. N Engl J Med. 2016;374(8):794–5. https://doi.org/10.1056/NEJMc1514201.
Kordalewska M, Perlin DS. Identification of drug resistant Candida auris. Front Microbiol. 2019;10:1918. https://doi.org/10.3389/fmicb.2019.01918.
Lockhart SR, Berkow EL, Chow N, Welsh RM. Candida auris for the clinical microbiology laboratory: not your grandfather’s Candida species. Clin Microbiol Newsl. 2017;39(13):99–103. https://doi.org/10.1016/j.clinmicnews.2017.06.003.
Mizusawa M, Miller H, Green R, Lee R, Durante M, Perkins R, et al. Can multidrug-resistant Candida auris be reliably identified in clinical microbiology laboratories? J Clin Microbiol. 2017;55(2):638–40. https://doi.org/10.1128/JCM.02202-16.
Spivak ES, Hanson KE. Candida auris: an emerging fungal pathogen. J Clin Microbiol. 2018;56(2). https://doi.org/10.1128/JCM.01588-17.
Welsh RM, Bentz ML, Shams A, Houston H, Lyons A, Rose LJ, et al. Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic health care surface. J Clin Microbiol. 2017;55(10):2996–3005. https://doi.org/10.1128/JCM.00921-17.
Chibabhai V, Fadana V, Bosman N, Nana T. Comparative sensitivity of 1,3 beta-D-glucan for common causes of candidaemia in South Africa. Mycoses. 2019. https://doi.org/10.1111/myc.12982. The performance of serum BDG testing for the diagnosis of C. auris bloodstream infections was comparable to that for the diagnosis of candidemia by other species.
Sexton DJ, Bentz ML, Welsh RM, Litvintseva AP. Evaluation of a new T2 magnetic resonance assay for rapid detection of emergent fungal pathogen Candida auris on clinical skin swab samples. Mycoses. 2018;61(10):786–90. https://doi.org/10.1111/myc.12817.