Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced using a Nextera DNA Flex Kit (Illumina) and the MiseqDx (Illumina) instrument. All isolates harbored the same Msh2p substitution, V239L, associated with multilocus sequence type 7 and a Pdr1p substitution, L825P, that caused azole resistance. Of six isolates with increased AMB MICs (≥2 mg/L), three harboring the Erg6p A158fs mutation had AMB MICs ≥ 8 mg/L, and three harboring the Erg6p R314K, Erg3p G236D, or Erg3p F226fs mutation had AMB MICs of 2–3 mg/L. Four isolates harboring the Erg6p A158fs or R314K mutation had fluconazole MICs of 4–8 mg/L while the remaining six had fluconazole MICs ≥ 256 mg/L. Two isolates with micafungin MICs > 8 mg/L harbored Fks2p (I661_L662insF) and Fks1p (C499fs) mutations, while six isolates with micafungin MICs of 0.25–2 mg/L harbored an Fks2p K1357E substitution. Using WGS, we detected novel mechanisms of AMB and echinocandin resistance; we explored mechanisms that may explain the complex relationship between AMB and azole resistance.

The abilities of the new Vitek 2 AST-YS08 (YS08) and Sensititre YeastOne (SYO) systems to detect the resistances of Candida isolates to azoles and echinocandins were evaluated. In total, 292 isolates, including 28 Candida albicans (6 Erg11 and 2 Fks mutants), 57 Candida parapsilosis (26 Erg11 mutants), 24 Candida tropicalis (10 Erg11 and 1 Fks mutants), and 183 Candida glabrata (39 Pdr1 and 13 Fks mutants) isolates, were tested.

Suhak Jeon, M.D., Jong Hee Shin, M.D., Ph.D., Ha Jin Lim, M.D., Min Ji Choi, Ph.D., Seung A Byun, M.S., Dain Lee, M.S., Seung Yeob Lee, M.D., Eun Jeong Won, M.D., Soo Hyun Kim, M.D., and Myung Geun Shin, M.D.. Ann Lab Med 2021;41:559-67. https://doi.org/10.3343/alm.2021.41.6.559

Young Eun Lee, M.S., Ha Jin Lim, M.D., Ju Heon Park, M.D., Hye Ran Kim, Ph.D., Min-Gu Kang, M.D., Ph.D., Young Kuk Cho, Ph.D., Jong Hee Shin, M.D., Ph.D., and Myung Geun Shin, M.D., Ph.D.. Ann Lab Med 2022;42:585-9. https://doi.org/10.3343/alm.2022.42.5.585

Ha Jin Lim, M.D., Hyunseok Jang, M.D., Ph.D., Naa Lee, M.D., Euisung Jeong, M.D., Yunchul Park, M.D., Younggoun Jo, M.D., Ph.D., Jungchul Kim, M.D., Ph.D., Young Eun Lee, Ph.D., Hyun-Jung Choi, M.D., Ph.D., Seung-Jung Kee, M.D., Ph.D., Jong Hee Shin, M.D., Ph.D., and Myung Geun Shin, M.D., Ph.D.. Ann Lab Med 2024;44:74-81. https://doi.org/10.3343/alm.2024.44.1.74

Background: Timely recognition of sepsis remains a critical clinical challenge, particularly in cancer patients, who are at higher risk due to immunosuppression. Monocyte distribution width (MDW) has emerged as a biomarker with potential utility in the early detection of sepsis. Methods: This retrospective study analyzed 1167 patients who presented to the emergency department of a cancer specialty hospital in Republic of Korea. Patients were classified according to Sepsis-2 and Sepsis-3 criteria, and the diagnostic performance of MDW was compared with conventional biomarkers, including C-reactive protein (CRP) and procalcitonin (PCT). Subgroup analyses were conducted based on malignancy status, leukopenia, and initial signs of infection. Additionally, turnaround times (TATs) were compared among the biomarkers. Results: MDW demonstrated diagnostic accuracy comparable to or exceeding that of CRP and PCT for identifying sepsis and infection across both Sepsis-2 and Sepsis-3 criteria. In the context of diagnosing sepsis using the Sepsis-3 criteria, MDW yielded the highest area under the curve (0.869), sensitivity (91.0%), and negative predictive value (98%). Notably, in cancer patients, MDW maintained strong diagnostic reliability. It also demonstrated high diagnostic capability in patients with leukopenia or presenting with initial signs of infection. Moreover, the TAT was significantly shorter for MDW (median 59 min) than for CRP (105 min) or PCT (111 min). Conclusions: MDW is a rapid and accessible biomarker with demonstrated value for early sepsis detection in emergency settings. Its balanced diagnostic profile and consistent performance across diverse patient subgroups support its integration into routine clinical workflows, especially as part of multimodal sepsis screening strategies.