A 2014 retrospective, single-center analysis examined the epidemiology of Candida kefyr (also known as Kluyveromyces marxianus) colonization and infection among patients with hematologic malignancies at Johns Hopkins Hospital between January 2004 and December 2010. All patients with a culture positive for C. kefyr, those admitted to two dedicated hematology wards who underwent routine weekly surveillance cultures, and a sub-cohort of patients with acute myelogenous leukemia (AML) receiving intensive induction chemotherapy were included. A nested case-control study within the AML subcohort demonstrated that 9.6% (8/83) of HM patients with positive C. kefyr cultures developed invasive candidiasis (IC), all of whom had a prior history of colonization. A notable seasonal pattern emerged: colonization and bloodstream infections peaked in the summer months (July to September), independent of year or treatment setting, a trend corroborated by parallel data from a Montreal-based tertiary care center. Among AML patients, colonization was significantly associated with summertime hospital admission (odds ratio [OR], 3.1; p= 0.03), while antifungal exposure to azoles (OR, 0.06; p<0.001) and amphotericin B (OR, 0.35; p= 0.05) conferred protective effects. Breakthrough infections occurred in five episodes during antifungal therapy, with isolates demonstrating resistance to the ongoing agents (fluconazole, micagungin, amphotericin B, and flucytosine; one isolate was pan-resistant and resulted in patient death). Fingerprinting revealed high genetic diversity among isolates, excluding a clonal outbreak. C. kefyr isolates consistently appeared genetically distinct, suggesting multiple sources rather than nosocomial transmission. These data indicate an emerging pattern of C. kefyr as a clinically significant pathogen in immunocompromised populations, with implications for empiric antifungal strategies and infection control practices. [1]
A 2020 retrospective study analyzed 69 clinical isolates of Kluyveromyces marxianus (Candida kefyr) obtained between 2011 and 2018 from a variety of specimen types, including 18 from sputum. The study assessed antifungal susceptibility and interpreted results according to CLSI breakpoints for Candida albicans due to the absence of species-specific breakpoints for C. kefyr. Among 63 evaluable isolates, 5 (7.8%) exhibited reduced susceptibility to amphotericin B, 1 (1.6%) to fluconazole, 1 (1.6%) to voriconazole, and 1 (1.6%) to caspofungin, with the other isolates demonstrating low MICs to fluconazole, voriconazole, amphotericin B, and caspofungin. Notably, the study did not provide specific treatment recommendations; however, it emphasized that susceptibility testing was performed and noted emerging resistance among certain isolates. [2]
A 2014 short communication reported a retrospective analysis of bloodstream infections caused by uncommon opportunistic yeasts in a single tertiary care hospital in Qatar over a six-year period (2004–2010). Seventeen cases of fungemia were identified among 187 patients with confirmed Candida bloodstream infections, accounting for 201 episodes in total. The aged extremes of the population were disproportionately affected, with 10 of 17 cases occurring in patients under 15 years and 5 cases in those over 65. Yeast isolates included species not frequently reported in clinical practice, such as Kluyveromyces marxianus (1 case in 1970), Lodderomyces elongisporus, Lindnera fabianii, Meyerozyma guilliermondii, Yarrowia lipolytica, and Wickerhamomyces anomalus. Species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which demonstrated 100% concordance with molecular sequencing of the D1/D2 and ITS regions, indicating high diagnostic accuracy (κ = 1.0). Antifungal susceptibility testing utilized the Clinical and Laboratory Standards Institute (CLSI) M27-A3 broth microdilution method, with MIC interpretive breakpoints applied per M27-S4 guidelines where available. [3]
Results revealed low minimum inhibitory concentrations (MICs) for isavuconazole and voriconazole across all isolates, with values ranging from ≤0.016 to 0.25 µg/mL. Notably, Meyerozyma guilliermondii displayed MICs of 1–2 µg/mL for echinocandins, suggesting reduced susceptibility, while Pichia kudriavzevii exhibited resistance to fluconazole (MIC 32–64 µg/mL) and borderline resistance to caspofungin (MIC = 1 µg/mL). A 30-day all-cause mortality rate of 41% was observed, underscoring the clinical significance of these rare pathogens despite antifungal therapy. Pharmacokinetic properties of isavuconazole, including a peak serum concentration exceeding 1.85 µg/mL in healthy volunteers, support its potential utility as a treatment option against these uncommon yeasts whose MICs remain below this threshold. Of note, Candida appears primarily isolated from blood cultures irrespective of antifungal therapy. [3]
A 2024 in vitro study investigated the inhibitory capacity of 28 antibiotics belonging to multiple pharmacologic classes, including aminoglycosides, beta-lactams, macrolides, quinolones, tetracyclines, and sulfonamides, against Kluyveromyces marxianus using a turbidimetric microplate bioassay. Kluyveromyces marxianus ATCC 8554 was cultured in a semi-synthetic whey matrix fortified to a final composition of 0.9% protein and 5.0% lactose at pH 7.0. The assay employed 16 replicates across 12 antibiotic concentrations per compound, spanning aqueous solutions prepared at 1000 mg/L. Results demonstrated that cephalosporins, quinolones, and tetracyclines significantly inhibited K. marxianus growth at concentrations nearing their Maximum Residue Limits (MRLs) as defined for milk. Notably, IC50 values for agents such as cephalexin (100 mcg/L), ciprofloxacin (178 mcg/L), and oxytetracycline (62 mcg/L) approximated or matched established MRL thresholds (e.g., 100 mcg/L for tetracyclines and 100 mcg/L for some fluoroquinolones). In contrast, beta-lactams such as ampicillin and aminoglycosides, including neomycin, exhibited IC50 levels substantially exceeding MRLs, suggesting minimal inhibitory activity at physiologically relevant concentrations. The authors attributed the observed resistance to certain beta-lactams to potential penicillinase activity in K. marxianus. These findings underscore the need for pre-treatment of dairy whey containing antimicrobial residues prior to its industrial application in fermentation processes, particularly when employing K. marxianus for bioethanol or probiotic production. [4]
A 2021 cross-sectional laboratory investigation evaluated the in vitro antifungal susceptibility profiles of Kluyveromyces marxianus and Clavispora lusitaniae strains isolated from diverse clinical specimens. The analysis included 21 K. marxianus and eight C. lusitaniae isolates obtained from bronchoalveolar lavage fluid, urine, peritoneal fluid, and blood cultures of hospitalized patients with suspected invasive fungal infections. K. marxianus demonstrated the highest geometric mean MIC to amphotericin B (1.0 mcg/mL after 24 hours) and the lowest to voriconazole (0.010 mcg/mL). Voriconazole exhibited potent activity against both species, with C. lusitaniae strains showing a geometric mean MIC of 0.011 mcg/mL. Fluconazole, itraconazole, and posaconazole also displayed favorable activity against K. marxianus, with MIC90 values remaining at or below 0.06 mcg/mL. In contrast, C. lusitaniae isolates exhibited significantly reduced susceptibility to flucytosine, with MICs reaching as high as 64 mcg/mL and a geometric mean MIC of 8 mcg/mL, indicating considerable variability in susceptibility, potentially limiting its therapeutic utility. Echinocandins demonstrated consistent activity against both organisms: micafungin, anidulafungin, and caspofungin showed MIC90 values ≤0.5 μg/mL for both species. These data suggest that while azoles and echinocandins maintain robust in vitro activity against both non-albicans Candida species, amphotericin B and flucytosine demonstrated reduced potency for K. marxianus and C. lusitaniae, respectively. The results underscore the clinical importance of susceptibility testing when managing infections caused by emerging fungal pathogens. [5]