Direct Identification of Yeasts from Blood Cultures and Body Fluids Using MALDI-TOF MS with Concurrent Antifungal Susceptibility Testing

Direct Identification of Yeasts from Blood Cultures and Body Fluids Using MALDI-TOF MS with Concurrent Antifungal Susceptibility Testing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Direct Identification of Yeasts from Blood Cultures and Body Fluids Using MALDI-TOF MS with Concurrent Antifungal Susceptibility Testing Arpita Khamrai, Snigdha Reddy, Saikat Paul, Ankita Saroya, Shristi Verma, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6590343/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Aug, 2025 Read the published version in Mycopathologia → Version 1 posted 6 You are reading this latest preprint version Abstract The rising incidence of invasive fungal infections has been accompanied by an increasing prevalence of antifungal resistance among fungal pathogens. Rapid identification of causative agents and their antifungal susceptibility profiles is critical for initiating timely, species-specific targeted therapy. In this context, we evaluated a MALDI-TOF MS-based method for the rapid identification of clinically relevant yeast species directly from blood cultures and body fluids, coupled with direct antifungal susceptibility testing (Direct-AFST). Our study evaluated over 700 yeast isolates, encompassing diverse Candida and non- Candida species, using MALDI-TOF MS. Additionally, antifungal susceptibility was assessed for 250 isolates, demonstrating excellent categorical agreement between Direct-AFST and conventional culture-based AFST (Culture-AFST). Our findings highlight the clinical utility of MALDI-TOF MS for accurate and rapid yeast identification directly from positive blood cultures, irrespective of microbial load or sample preparation method. Furthermore, the successful application of Direct-AFST underscores its potential for early detection of antifungal resistance, significantly reducing diagnostic turnaround times and improving patient management. MALDI-TOF MS Direct-AFST Culture-AFST Rapid Diagnosis Yeast Candida Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Sepsis, an acute infection accompanied by organ dysfunction, is a life-threatening global health problem ( 1 ). In 2017, an estimated 48.9 million sepsis cases and 11 million deaths were reported worldwide, including invasive infections such as bloodstream infections (BSIs) ( 2 ). Globally, including in India, BSIs remain a leading cause of ICU admissions and contribute to significantly higher morbidity and mortality ( 3 – 5 ). Fungal pathogens, particularly Candida species, are increasingly implicated in BSIs and are among the most commonly isolated pathogens ( 6 ). In India, tertiary care centers and ICU settings have reported a rising trend of Candida BSIs (candidemia), associated with high morbidity and mortality ( 4 , 7 , 8 ). Alongside the increasing incidence of Candida BSIs, resistance to commonly used antifungal drugs is also on the rise ( 4 , 9 , 10 ). Since delays in administering appropriate antifungal therapy are linked to higher mortality rates, early and accurate treatment initiation could help reduce infection-related deaths ( 9 , 11 ). Rapid identification of fungal pathogens facilitates prompt antifungal therapy, improving outcomes for high-risk patients ( 12 ). Although conventional phenotypic methods are routinely used for fungal identification, they are labor-intensive, time-consuming, and unable to identify rare yeast species ( 13 ). In contrast, molecular techniques such as rDNA sequencing offer faster and more accurate identification ( 14 ). Despite being the gold standard, sequencing has limitations, including the need for specialized expertise, high costs, labor intensity, and longer turnaround times ( 13 , 15 ). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides a rapid, reliable, and cost-effective alternative for fungal identification, overcoming many limitations of traditional diagnostic methods ( 16 , 17 ). Furthermore, studies have demonstrated species-specific variations in antifungal susceptibility (AFST) profiles. Thus, accurate fungal identification and timely administration of appropriate antifungal therapy are critical for effectively managing invasive candidiasis (IC) ( 11 ). The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) provide standardized guidelines for AFST, widely used in clinical settings ( 18 , 19 ). However, these AFST methods are culture-based, resulting in prolonged turnaround times ( 11 , 13 , 18 , 19 ). In current diagnostic practice, generating a final report on the causative pathogen and its susceptibility profile typically takes 2–5 days. Several studies, including one from our laboratory, have explored rapid yeast identification directly from positive blood cultures using MALDI-TOF MS ( 11 , 20 – 22 ). Additionally, a limited number of studies have documented direct AFST from positive blood cultures ( 11 ). Given this context, there is an urgent need for rapid pathogen identification and AFST profiling to enable prompt, species-specific antifungal therapy. Therefore, we aimed to develop a MALDI-TOF MS-based method for rapid identification of pathogenic yeasts and their AFST profiles directly from blood cultures and body fluids. Methods Sample Collection and Processing Blood culture bottles (BD BACTEC™ Plus Aerobic/F) and body fluid samples from patients with suspected sepsis were collected at the Department of Medical Microbiology, PGIMER, Chandigarh, India (March 2021–March 2024). The institutional ethics committee of the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India approved the study. BACTEC-detected positive bottles underwent Gram staining to assess microbial morphology (Gram-positive/Gram-negative, cocci, bacilli, or oval budding yeast cells). Samples were then inoculated onto Sabouraud dextrose agar (SDA) and blood agar (BA). Only samples with Gram-positive oval budding yeast cells (with/without pseudohyphae) were included in this study. Yeast density was graded by screening 10 oil immersion fields (OIFs): 30 cells/OIF. For mixed infections (yeast with bacteria), bacterial morphology and Gram reaction were similarly recorded. MALDI-TOF MS form Positive Blood Culture Bottles Positive blood culture (BC) broth was processed using our standardized protocol ( 11 ): 4 mL aliquots were centrifuged (13,000 rpm, 10 min), pellets were treated with 0.5% SDS (1 mL, 37°C, 15 min) for RBC lysis, washed twice with sterile water, then spotted (0.5 µL) onto MALDI target plates with 98% formic acid (1:1) and CHCA matrix (1 µL). Spectra were acquired using a Microflex LT Biotyper (Bruker Daltonics) with FlexControl 3.4 and analyzed using Biotyper 3.0 ( 11 , 13 ). For quality control, 110 sterile BC broths (microscopy/SDA/BA-negative) were processed identically as negative controls. In 22 samples, hemocytometer counts of pellets were correlated with Gram stain OIF counts to validate consistency in direct identification. Standardization of Direct Identification of Dense and Less Dense Body Fluid Due to the viscous nature and limited volume (500 µl–2 ml) of these body fluid samples, 1–2 ml of distilled water was added based on density, followed by vortexing to homogenize. For initial characterization, one loopful was Gram-stained and another inoculated onto SDA and BA plates (37°C, 24–48 h) to confirm routine diagnosis. Based on these observations, 2 ml, 4 ml, or the entire sample was selected for processing: centrifugation (3,000 rpm, 5 min), supernatant removal, pellet washing (500 µl sterile water), and resuspension in 50 µl sterile water. MALDI-TOF MS identification was performed by spotting 1, 1.5, and 2 µl aliquots of the processed sample following standard preparation protocols ( 11 ). Yeast Species-Specific Ambiguity of MALDI-TF MS Characterization To evaluate potential identification bias, we standardized both common and rare yeast isolates against our in-house database. Candida glabrata and Candida viswanathii were selected due to their low MALDI-TOF scores during direct identification. For standardization, yeast strains were cultured in BD BACTEC™ bottles at concentrations of 10²-10⁶ CFU/mL (with/without blood) and incubated at 37°C until positivity. Positive bottles were processed to collect pellets, which were washed with sterile distilled water, resuspended in 200 µL water, and identified using the previously described MALDI-TOF MS protocol ( 11 , 13 ). Standardization and Validation of Direct-AFST For standardization, 40 processed blood culture (BC) samples underwent direct antifungal susceptibility testing (direct-AFST) with fluconazole using CLSI M27 microbroth dilution. Processed pellets were rested for 30 min at room temperature; 5 µl of supernatant was microscopically examined for cellular debris and yeast morphology (single/clustered cells). Clustered cells were vortexed before use. Viability was confirmed using Miles-Mishra method (10⁻¹-10⁻⁵ dilutions) on blood agar. Direct-AFST and culture-AFST (reference standard) were performed simultaneously. Validation included 250 yeast-positive BC samples tested against eight antifungals: amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, micafungin, and anidulafungin. Results were compared using: a) Essential agreement (%EA): MICs within ± 1 two-fold dilution of culture-AFST b) Categorical agreement (%CA): concordance in susceptibility categories [sensitive/ intermediate/ resistant (S/I/R)] c) Very major errors (VME): False susceptibility [direct-AFST S, culture-AFST R] d) Major errors (ME): False resistance [direct-AFST R, culture-AFST S] ( 11 ). Results Screening from blood culture Gram staining of blood culture broth revealed Gram-positive oval/round budding yeast cells (with/without pseudohyphae) under oil immersion (OIF). Among these, 20 samples showed mixed infections with bacteria (Gram-positive cocci or Gram-negative bacilli). Representative smears are shown in Fig. 1 . For 633 yeast-positive samples, we graded yeast cell density per OIF (Table S1 ) to correlate with direct MALDI-TOF MS identification (Direct ID) results. Validation of Direct ID from Blood Culture Bottles Among 754 positive blood cultures, MALDI-TOF MS (Direct ID) correctly identified 713 (94.56%), misidentified 8 (1.06%), and failed to identify 33 (4.38%). All 110 negative controls yielded negative results. The method demonstrated 95.58% sensitivity (95% CI: 93.84–96.94%), 93.22% specificity (95% CI: 87.08–97.03%), 98.89% PPV (95% CI: 97.86–99.43%), and 76.92% NPV (95% CI: 70.41–82.36%), with 95.25% agreement to culture-based identification. Microscopic analysis of Gram-stained cell counts was performed for 633 yeast-positive cultures, revealing no significant correlation between cell counts (> 10 CFU/OIF in 409/633 of samples) and identification accuracy (Table 1 ). Hemocytometer counts of cells from blood samples were evaluated for 22 of the yeast-positive cultures analyzed for cell counts. No association was found between Gram-stain observations and hemocytometer counts, and identification accuracy remained unaffected. (Table S2). Table 1 Correlation Between Gram’s stain yeast cell count and % of correct identification Cells per OIF (n) Not identified Correctly identified Mis-identified 30 (122) 3 (2.45%) 118 (96.7%) 1 (0.81%) Direct Identification of Mono-Yeast Infections Among the 754 positive blood cultures, 724 were identified as mono-yeast infections, while the remaining 30 were mixed infections. Species-wise result of Direct ID in 724 mono-yeast infection cases is shown in Fig. 2 . All isolates of Candida utilis (77), Candida parapsilosis (46), Candida auris ( 12 ), Trichosporon asahii ( 10 ), Candida guillermondii ( 6 ), Cyrptococcus neoformans ( 6 ), Candida lusitaniae ( 5 ), Candida rugosa ( 4 ) Candida metapsilosis ( 3 ) were correctly identified (100%), followed by Candida tropicalis (97.93%; 190/194), Wickerhamomyces anomalus (93.69%; 104/111), Candida albicans (94.89%; 93/98), Candida krusei ( 92.95%; 66/71), Candida glabrata (86.66%; 39/42), Candida orthopsilosis (93.33%; 14/15), Candida fabianii (75%; 3/4), Rhodotorula mucilaginosa (66.66%; 2/3). Three isolate of Candida glabrata was misidentified as Candida guilliermondii , W. anomalus and Candida parapsilosis respectively , two isolate of Candida krusei as Candida orthopsilosis and Candida tropicalis respectively , one isolate of Rhodotorula mucilaginosa as C. guillermondii , one isolate of Wickerhamomyces anomalus as Candida glabrata and one isolate of Candida albicans as Wickerhamomyces anomalus . Identification of Mixed Infections Mixed infections were identified in 30 samples, including combinations of two yeasts (n = 6) and yeast with bacteria (n = 24). Of these, 15 (50%) were correctly identified by Direct ID, 14 (46.7%) were not identified, and 1 (3.3%) was incompletely identified (Table S3). The presence of Gram-positive cocci affected yeast identification, with 10 out of 15 cases (66.7%) correctly identifying the respective yeast by Direct ID. In contrast, the presence of Gram-negative bacilli interfered with yeast identification in 7 out of 9 cases (only 22.2% correct identification). Among the remaining 6 cases with mixed yeast infections, both yeasts were correctly identified in 3 cases. The incomplete identification may have been due to the rare isolate Pichia occidentalis . The remaining two cases, containing Kodamaea ohmeri + Candida krusei and Trichosporon asahii + Lodderomyces elongisporus , were not identified by the Direct ID method. Instead, incorrect identification of S. epidermidis was observed in these cases (Table S3). Screening of Body Fluids Table 2 summarizes the comparative analysis of 21 body fluid samples through microscopic examination, culture identification, and direct MALDI-TOF MS. Gram staining consistently revealed Gram-positive oval budding yeast cells (with/without pseudohyphae) alongside bacterial cells, epithelial cells, RBCs, and pus cells. Routine diagnostic methods identified 18 culture-positive samples (including 4 microscopy-positive), while rapid diagnosis detected 12 culture-positive cases; notably, direct identification via MALDI-TOF MS was unsuccessful in all instances despite the presence of detectable yeast elements in microscopy and culture. Table 2 Details of the body fluid samples received and their diagnosis Fluid type from 21 collected samples Routine Diagnosis Rapid Diagnosis Direct Identification by MALDI-TOF Microscopy Culture Routine Identification Microscopy Culture Culture Identification Dense type Intra OP fluid Epithelial cell+/ Bacteria ++/ No yeast/ No RBC Positive Candida glabrata No yeast/ No RBC/ GPB+++/ PMNLS+/ Epithelial cell++ Negative Not Identified Intra OP fluid Bacteria+/No yeast / RBC+ Positive Candida krusei no yeast/ RBC+/GPB+/PMNLS++ Positive Candida krusei Not Identified PCD fluid Epithelial cell+/ No yeast/ No RBS Positive Candida albicans no yeast/ No RBC/ GPB+++/ PMNLS+/ Epithelial cell++ Positive Candida albicans Not Identified Bile bacteria+/No yeast/ RBC+ Positive Candida albicans no yeast/No RBC/GPC IN PAIRS CLUSTER + + GPB+++/PMNLS+++ Negative - Not Identified Intra op fluid Bacteria ++/ pus+/ No yeast Positive Candida tropicalis no yeast/No RBC/GPC IN PAIRS CLUSTER + + GPB+++/PMNLS+++ Positive Candida tropicalis Not Identified Ascitic fluid Epithelial cell+/ Yeast +/bacteria+ Negative - no yeast/No RBC/GPC in pairs and short chain/PMNLS++/ Epithelial cell++ Negative - Not Identified Drain fluid pus cell +/ No yeast/ No RBC/ Bacteria+ Positive Candida albicans pus cell occ/ no yeast/ no RBC/ GPB + Positive Candida albicans Not Identified PCD fluid pus cell+/ No yeast/ Bacteria + Positive Candida glabrata pus cell+/ no yeast/ GPCB+ Negative - Not Identified Drain fluid pus cell+/ yeast cell +/ pseudo hyphae +/ No RBC/ Bacteria+ Positive Candida albicans pus cell+/ yeast cell +/ no RBC/ GPC+ Positive Candida albicans Not Identified PCD fluid pus cell ++/ yeast cell +/ No RBC Positive Candida tropicalis pus cell +/ yeast cell +/ No RBC Positive Candida tropicalis Not Identified Less dense type Intra OP fluid Epithelial cell +/ No yeast/pus++/RBC+/ Positive Candida glabrata pus++/RBC++/Epithelial+ Negative - Not Identified Bile pus++/ yeast+/ bacteria+ Positive Candida albicans GPCB/ pus++/ yeast+ Positive Candida albicans Not Identified PCD fluid pus+/RBC+/ bacteria +/ No yeast Positive Candida tropicalis pus+++/RBC+/GPCB+ Positive Candida tropicalis Not Identified Intra OP fluid pus++/GPB+/ yeast occ Positive Candida glabrata pus++/GPB+/ yeast occ Positive Candida glabrata Not Identified pleural fluid pus cell +/ yeast occ/ RBC+/ RBC+ Negative - no yeast/no epithelial cell/RBC+/pus cell ++ Negative - Not Identified ascitic fluid pus cell +/yeast +/ No RBC/ Negative - no yeast/no epithelial cell/no RBC/pus cell + Negative - Not Identified pleural fluid pus cell/ RBC+/ yeast occ Positive Wickerhamomyces anomalus pus cells +/no yeast / RBC + Negative - Not Identified pleural fluid pus cell+/ No yeast/ bacteria + Positive Candida tropicalis pus cell+/ no yeast/ GPCB + Positive Candida tropicalis Not Identified pleural fluid pus cell occ/ No yeast/ bacteria + Positive Candida tropicalis pus cell +/ no yeast/ no RBC Positive Candida tropicalis Not Identified PCD fluid pus cell ++/No yeast/ No RBC Positive Candida albicans pus cell +++/no yeast/ no RBC Negative - Not Identified PCD fluid Epithelial cell occ/ pus cell occ/ yeast cell++/ RBC +/ Bacteria + Positive Candida glabrata pus cell +/ yeast cell++/ RBC +/ GPB+ Positive Candida glabrata Not Identified AFST of Yeast Directly from Blood Culture Bottle We have perfumed the viability test to confirm cell growth on blood agar as reported previously (Fig. S1 ) ( 23 ). Among 40 blood culture samples standardized for antifungal susceptibility testing (AFST) against fluconazole, 24 (60%) showed identical MICs between direct AFST and culture AFST methods, while 15 (37.5%) differed by 1 log2 dilution and 1 (2.5%) by 2 log2 dilutions (data not shown). AFST Validation of Yeasts from Blood Culture Bottle We validated direct antifungal susceptibility testing (AFST) using 250 yeast pellets processed from blood cultures. Figure 3 compares MICs obtained by direct AFST versus culture-AFST for each antifungal drug, showing both concordant and divergent results. Direct AFST and culture AFST showed identical MIC values for: fluconazole (168 samples), itraconazole (159), voriconazole (208), posaconazole (168), amphotericin B (178), caspofungin (172), micafungin (185), and anidulafungin (194). Figure 4 displays the frequency of MIC deviations (1, 2, or > 2 log2 dilutions) for each antifungal agent. Comparison between Direct-AFST and Culture-AFST The analysis of AFST revealed excellent categorical agreement between Direct-AFST and Culture-AFST, with posaconazole showing perfect concordance (100%, 250/250), followed by voriconazole (98.4%), amphotericin B (97.6%), anidulafungin (97.2%), micafungin (95.2%), fluconazole (92.8%), itraconazole (87.6%), and caspofungin (88.0%, 107/127). Essential agreement was highest for amphotericin B (98.0%), followed by voriconazole (96.0%) and caspofungin (94.4%). We identified two very major errors (VMEs) with amphotericin B ( Candida tropicalis , Wickerhamomyces anomalus , Candida auris ) and fluconazole ( C. parapsilosis, C. krusei ), one VME with caspofungin ( C. tropicalis ), and three major errors (MEs) with amphotericin B ( C. tropicalis, W. anomalus ), plus single MEs with anidulafungin ( C. tropicalis ), itraconazole ( C. tropicalis ), and micafungin ( C. auris ). Complete agreement metrics and error rates across isolates are presented in Table 3 . Yeast Species-Specific Ambiguity of Mass Spectra The MALDI-TOF MS spectra of Candida glabrata (data not shown) and Candida viswanathii showed high similarity between culture isolates and direct blood culture processing (with or without blood), showing only minor spectral variations. Figure 5 presents a representative spectral comparison for C. viswanathii , demonstrating consistent peak profiles across preparation methods. Discussion The present study evaluated the efficacy of MALDI-TOF MS for direct identification (Direct-ID) of yeast species from positive blood cultures along with body fluids and assessed the impact of yeast cell counts, sample preparation protocols, and antifungal susceptibility testing (AFST). Our findings reinforce the robustness of MALDI-TOF MS for rapid microbial identification and its potential role in complementing or replacing traditional culture-based methods. Our data demonstrated that yeast cell count, as determined by Gram staining, did not significantly impact MALDI-TOF MS identification accuracy. This aligns with prior research showing that microbial load variations above a threshold level do not compromise MALDI-TOF MS efficacy ( 24 , 25 ). A key advantage of this approach is the ability to identify pathogens directly from blood cultures, facilitating rapid diagnosis and early antifungal therapy initiation. Zhou et al. reported a 60.87% concordance rate for fungal species at a log score threshold of ≥ 1.700, reinforcing the reliability of MALDI-TOF MS for yeast identification ( 26 ). In comparison with other rapid identification methods, Idelevich et al. demonstrated that PNA-FISH had a 96% success rate, Gram staining had a 76% success rate, and MALDI-TOF MS achieved 76% when optimized with in-house parameters ( 27 ). These findings underscore the necessity of protocol optimization, particularly with regard to sample preparation and data interpretation, to enhance MALDI-TOF MS performance. The effectiveness of Direct-ID was significantly enhanced by an optimized sample preparation protocol ( 11 ). The incorporation of SDS-mediated lysis, centrifugation, and washing steps improved red blood cell removal, leading to high identification accuracy (94.56%) and excellent sensitivity (95.58%) and specificity (93.22%). This aligns with previous reports emphasizing that efficient host protein removal is crucial for obtaining high-quality spectra ( 24 , 25 ). While Direct-ID performed well across most Candida species, we observed lower identification rates for Candida glabrata, Candida krusei and Rhodotorula mucilaginosa . This is consistent with Cassagne et al., who noted variability in identification accuracy due to species-specific differences in cell wall composition affecting protein extraction efficiency ( 17 ). This suggests that database expansion and pretreatment modifications could further improve identification outcomes. A comparison between visual Gram stain counts and quantitative haemocytometer measurements revealed significant discrepancies, with some samples displaying low Gram stain counts but high haemocytometer counts (≥ 10⁶ cells/mL). Despite this variability, Direct-ID and culture-based methods maintained high identification accuracy. This reinforces the observation that microbial load estimation is less critical for MALDI-TOF MS once a sufficient analyte threshold is met ( 24 , 25 ). Our findings suggest that while haemocytometric measurements provide objective quantification, Gram staining remains useful as a rapid screening tool in microbiology laboratories. The development of a direct antifungal susceptibility testing (Direct-AFST) method represents a significant advancement in rapid antifungal resistance detection. Our study found high essential agreements (EA) and categorical agreements (CA) between Direct-AFST and conventional culture-AFST for most antifungal agents. Notably, EA was highest for amphotericin B (98.0%) and voriconazole (96.0%), while CA reached 100% for posaconazole. This level of agreement mirrors findings by Chang et al., Oz and Gokbolat, and Vecchione et al., who reported similarly high correlations between rapid and conventional AFST methods ( 28 – 30 ). Importantly, our study showed minimal very major errors (VMEs) and major errors (MEs), confirming the sensitivity and specificity of Direct-AFST. Previous studies have noted challenges in itraconazole MIC interpretation, with slightly lower EA (91.6%) and CA (87.6%) observed in our dataset, consistent with Guinea et al. ( 31 ). The direct method's ability to reduce turnaround time by at least 24 hours has significant clinical implications, allowing earlier antifungal therapy adjustments, which is crucial given that delayed treatment is associated with increased mortality in candidemia ( 32 ). The standardization of Direct ID from body fluids demonstrated the feasibility of using MALDI-TOF MS for yeast identification. However, limitations were observed, particularly in directly identifying yeast from body fluid samples. The higher identification rate from cultured samples, compared to the lack of Direct ID, highlights both the potential and the limitations of MALDI-TOF MS for rapid fungal diagnostics across diverse sample types. Further refinements in sample processing and analysis are needed to enhance its direct detection capabilities. One critical challenge in MALDI-TOF MS yeast identification is the dependence on comprehensive reference databases. Our study evaluated potential biases by comparing spectral data from culture-based and Direct-ID methods. While Candida viswanathii showed consistent spectral profiles regardless of sample preparation, Candida glabrata exhibited few unique peaks in Direct-ID spectra. This suggests that variations in sample preparation can influence spectral outputs, reinforcing the need for expanded in-house reference databases ( 17 , 33 ). Previous studies have highlighted that yeast cell wall variability affects protein extraction efficiency, leading to species-specific differences in spectral patterns ( 17 ). Our findings support this notion, particularly regarding lower identification rates for certain species, emphasizing the importance of refining sample preparation protocols. Future research should focus on database expansion and standardization efforts to mitigate these identification discrepancies. Conclusion Our study demonstrates MALDI-TOF MS as an accurate, rapid method for direct yeast identification from blood cultures, performing consistently across varying microbial loads and processing conditions. The successful Direct-AFST application enables early resistance detection, significantly reducing diagnostic delays from days to hours while maintaining reliability comparable to conventional methods. This dual approach (Direct-ID and Direct-AFST) offers a transformative solution for timely antifungal therapy decisions in critical care settings. Declarations Conflict of Interest The authors declare no competing interests to disclose. Funding The authors duly acknowledge the Indian Council of Medical Research (ICMR), Government of India for financial supports. Data Availability The datasets analyzed and used during the study are available from the corresponding authors upon reasonable request. 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Rapid antifungal susceptibility determination for yeast isolates by use of Etest performed directly on blood samples from patients with fungemia. J Clin Microbiol. 2010;48(6):2205–12. Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43(1):25–31. Marklein G, Josten M, Klanke U, Muller E, Horre R, Maier T, et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and reliable identification of clinical yeast isolates. J Clin Microbiol. 2009;47(9):2912–7. Supplementary Files SupplementoryInformation05112025.docx Cite Share Download PDF Status: Published Journal Publication published 25 Aug, 2025 Read the published version in Mycopathologia → Version 1 posted Reviewers agreed at journal 23 May, 2025 Reviewers invited by journal 15 May, 2025 Editor invited by journal 12 May, 2025 Editor assigned by journal 12 May, 2025 First submitted to journal 11 May, 2025 Editorial decision: Minor revisions 07 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6590343","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":456927403,"identity":"fadc8f83-9b8d-4377-8163-69ae931ccca3","order_by":0,"name":"Arpita Khamrai","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Arpita","middleName":"","lastName":"Khamrai","suffix":""},{"id":456927404,"identity":"6dac2b19-91ec-4434-81ad-a78791f9cfa4","order_by":1,"name":"Snigdha Reddy","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Snigdha","middleName":"","lastName":"Reddy","suffix":""},{"id":456927405,"identity":"8f8859d4-ab7c-416e-b308-8003335f0755","order_by":2,"name":"Saikat Paul","email":"","orcid":"","institution":"The University of Tennessee Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Saikat","middleName":"","lastName":"Paul","suffix":""},{"id":456927406,"identity":"251113df-90a7-44cb-aede-dea69db32dfc","order_by":3,"name":"Ankita Saroya","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Ankita","middleName":"","lastName":"Saroya","suffix":""},{"id":456927407,"identity":"e7203f3f-0c02-4b00-8fe6-24571f937e29","order_by":4,"name":"Shristi Verma","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Shristi","middleName":"","lastName":"Verma","suffix":""},{"id":456927408,"identity":"f582ca90-6c5d-47e1-9cc0-fd930656f6f2","order_by":5,"name":"Diksha Bhangot","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Diksha","middleName":"","lastName":"Bhangot","suffix":""},{"id":456927409,"identity":"67f9f6b1-fe40-46ea-82d3-f4767d79aa61","order_by":6,"name":"Shivaprakash M Rudramurthy","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Shivaprakash","middleName":"M","lastName":"Rudramurthy","suffix":""},{"id":456927410,"identity":"746a9399-d2cc-414c-afc3-c784cb41a6eb","order_by":7,"name":"Harsimran Kaur","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Harsimran","middleName":"","lastName":"Kaur","suffix":""},{"id":456927411,"identity":"721d5002-402a-4ae0-ac13-112104536076","order_by":8,"name":"Neelam Taneja","email":"","orcid":"","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Neelam","middleName":"","lastName":"Taneja","suffix":""},{"id":456927412,"identity":"e0ad0ca3-a310-42b6-ad30-550dd2676855","order_by":9,"name":"anup K ghosh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYJACxgaGGjkQ48ADErQcMwZrSSBBC3NiA4hFlBb+2T1mD2f8YkufH3b4IdAWOzndBgJaJO6cMTfc2CeTu/F2mgFQS7Kx2QFC1tzIMZN82MOWu3F2AkjLgcRthLTIQ7QwpxvOTv9AnBYDkJYNP5gT5KVziLTF8EZaueHMhmOGG6RzCg4kGBDhF7kbydse9vypkZefnb75w4cKOznC3mdgYGNgbAO6EKzSgLByiBaGP8BwaCBO9SgYBaNgFIxAAACdWEo0qNwOoAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-0341-6680","institution":"Post Graduate Institute of Medical Education and Research","correspondingAuthor":true,"prefix":"","firstName":"anup","middleName":"K","lastName":"ghosh","suffix":""}],"badges":[],"createdAt":"2025-05-04 22:33:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6590343/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6590343/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11046-025-00987-x","type":"published","date":"2025-08-25T15:57:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83142777,"identity":"8dd72bac-34e5-48df-9b30-e4270d5c100c","added_by":"auto","created_at":"2025-05-20 12:34:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1507306,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentativeGram’s staining under OIF with various cell counts\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/005b1be8f1e683e86d314ee0.png"},{"id":83144012,"identity":"009298a2-168b-4295-b58a-40a9d7069160","added_by":"auto","created_at":"2025-05-20 12:42:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":34075,"visible":true,"origin":"","legend":"\u003cp\u003eSpecies-wise Direct ID results of mono-yeast infection cases\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/e29322cdc14d84a3210bfe6d.png"},{"id":83142784,"identity":"65542821-398e-4eea-88e0-bf386ab20440","added_by":"auto","created_at":"2025-05-20 12:34:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":141936,"visible":true,"origin":"","legend":"\u003cp\u003eAntifungal drug-wise correlation of MICs by Direct AFST (y-axis) and Culture AFST (x-axis) showing the number of isolates in the cells between the axes. Gray color shows identical MICs between Direct AFST and Culture AFST [Caspo= caspofungin; Mica= micafungin; Ani= anidulafungin; AmB= amphotericin B; Flu= fluconazole; Itra= itraconazole; Vori= voriconazole; Posa= Posaconazole]\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/5f944741674dbc122119f538.png"},{"id":83144014,"identity":"cafc3ddf-6352-4b8a-9feb-8bd2b9f65ab3","added_by":"auto","created_at":"2025-05-20 12:42:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":27397,"visible":true,"origin":"","legend":"\u003cp\u003eGraph representing the number of samples showing identical MICs by Direct AFST and Culture AFST, followed by deviation in the MICs by log\u003csub\u003e2\u003c/sub\u003e dilution of 1, 2 or \u0026gt;2.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/7c60e44692c44795f56600ec.png"},{"id":83142785,"identity":"4c7d088d-0e54-4d44-aeba-8969849046fc","added_by":"auto","created_at":"2025-05-20 12:34:13","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":148162,"visible":true,"origin":"","legend":"\u003cp\u003eMALDI-TOF mass spectral profile analysis of \u003cem\u003eC. viswanathii identified\u003c/em\u003e directly from processed blood cultures and from culture isolates. (A) Culture spectra, (B) blood culture without blood spectra and (c) blood culture with blood spectra.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/23eccdbf7e9efebdd6043722.png"},{"id":90344998,"identity":"80f6b3b9-d8e0-494d-8f02-c38b8a1b44ee","added_by":"auto","created_at":"2025-09-01 16:09:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2545301,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/392792fe-ceaf-43f9-b7f9-4817ceab9665.pdf"},{"id":83145478,"identity":"4dbffb5c-c715-4359-acef-6110f3b9a0aa","added_by":"auto","created_at":"2025-05-20 12:58:13","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":200917,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementoryInformation05112025.docx","url":"https://assets-eu.researchsquare.com/files/rs-6590343/v1/b04541a24d14bae8a3b1e259.docx"}],"financialInterests":"","formattedTitle":"Direct Identification of Yeasts from Blood Cultures and Body Fluids Using MALDI-TOF MS with Concurrent Antifungal Susceptibility Testing","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSepsis, an acute infection accompanied by organ dysfunction, is a life-threatening global health problem (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 2017, an estimated 48.9\u0026nbsp;million sepsis cases and 11\u0026nbsp;million deaths were reported worldwide, including invasive infections such as bloodstream infections (BSIs) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Globally, including in India, BSIs remain a leading cause of ICU admissions and contribute to significantly higher morbidity and mortality (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Fungal pathogens, particularly \u003cem\u003eCandida\u003c/em\u003e species, are increasingly implicated in BSIs and are among the most commonly isolated pathogens (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In India, tertiary care centers and ICU settings have reported a rising trend of \u003cem\u003eCandida\u003c/em\u003e BSIs (candidemia), associated with high morbidity and mortality (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Alongside the increasing incidence of \u003cem\u003eCandida\u003c/em\u003e BSIs, resistance to commonly used antifungal drugs is also on the rise (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Since delays in administering appropriate antifungal therapy are linked to higher mortality rates, early and accurate treatment initiation could help reduce infection-related deaths (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Rapid identification of fungal pathogens facilitates prompt antifungal therapy, improving outcomes for high-risk patients (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough conventional phenotypic methods are routinely used for fungal identification, they are labor-intensive, time-consuming, and unable to identify rare yeast species (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In contrast, molecular techniques such as rDNA sequencing offer faster and more accurate identification (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Despite being the gold standard, sequencing has limitations, including the need for specialized expertise, high costs, labor intensity, and longer turnaround times (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides a rapid, reliable, and cost-effective alternative for fungal identification, overcoming many limitations of traditional diagnostic methods (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, studies have demonstrated species-specific variations in antifungal susceptibility (AFST) profiles. Thus, accurate fungal identification and timely administration of appropriate antifungal therapy are critical for effectively managing invasive candidiasis (IC) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) provide standardized guidelines for AFST, widely used in clinical settings (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). However, these AFST methods are culture-based, resulting in prolonged turnaround times (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn current diagnostic practice, generating a final report on the causative pathogen and its susceptibility profile typically takes 2\u0026ndash;5 days. Several studies, including one from our laboratory, have explored rapid yeast identification directly from positive blood cultures using MALDI-TOF MS (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Additionally, a limited number of studies have documented direct AFST from positive blood cultures (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Given this context, there is an urgent need for rapid pathogen identification and AFST profiling to enable prompt, species-specific antifungal therapy. Therefore, we aimed to develop a MALDI-TOF MS-based method for rapid identification of pathogenic yeasts and their AFST profiles directly from blood cultures and body fluids.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eSample Collection and Processing\u003c/p\u003e \u003cp\u003eBlood culture bottles (BD BACTEC\u0026trade; Plus Aerobic/F) and body fluid samples from patients with suspected sepsis were collected at the Department of Medical Microbiology, PGIMER, Chandigarh, India (March 2021\u0026ndash;March 2024). The institutional ethics committee of the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India approved the study. BACTEC-detected positive bottles underwent Gram staining to assess microbial morphology (Gram-positive/Gram-negative, cocci, bacilli, or oval budding yeast cells). Samples were then inoculated onto Sabouraud dextrose agar (SDA) and blood agar (BA). Only samples with Gram-positive oval budding yeast cells (with/without pseudohyphae) were included in this study. Yeast density was graded by screening 10 oil immersion fields (OIFs): \u0026lt;10 cells/OIF, 10\u0026ndash;20 cells/OIF, 20\u0026ndash;30 cells/OIF, \u0026gt;\u0026thinsp;30 cells/OIF. For mixed infections (yeast with bacteria), bacterial morphology and Gram reaction were similarly recorded.\u003c/p\u003e \u003cp\u003eMALDI-TOF MS form Positive Blood Culture Bottles\u003c/p\u003e \u003cp\u003ePositive blood culture (BC) broth was processed using our standardized protocol (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e): 4 mL aliquots were centrifuged (13,000 rpm, 10 min), pellets were treated with 0.5% SDS (1 mL, 37\u0026deg;C, 15 min) for RBC lysis, washed twice with sterile water, then spotted (0.5 \u0026micro;L) onto MALDI target plates with 98% formic acid (1:1) and CHCA matrix (1 \u0026micro;L). Spectra were acquired using a Microflex LT Biotyper (Bruker Daltonics) with FlexControl 3.4 and analyzed using Biotyper 3.0 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). For quality control, 110 sterile BC broths (microscopy/SDA/BA-negative) were processed identically as negative controls. In 22 samples, hemocytometer counts of pellets were correlated with Gram stain OIF counts to validate consistency in direct identification.\u003c/p\u003e \u003cp\u003eStandardization of Direct Identification of Dense and Less Dense Body Fluid\u003c/p\u003e \u003cp\u003eDue to the viscous nature and limited volume (500 \u0026micro;l\u0026ndash;2 ml) of these body fluid samples, 1\u0026ndash;2 ml of distilled water was added based on density, followed by vortexing to homogenize. For initial characterization, one loopful was Gram-stained and another inoculated onto SDA and BA plates (37\u0026deg;C, 24\u0026ndash;48 h) to confirm routine diagnosis. Based on these observations, 2 ml, 4 ml, or the entire sample was selected for processing: centrifugation (3,000 rpm, 5 min), supernatant removal, pellet washing (500 \u0026micro;l sterile water), and resuspension in 50 \u0026micro;l sterile water. MALDI-TOF MS identification was performed by spotting 1, 1.5, and 2 \u0026micro;l aliquots of the processed sample following standard preparation protocols (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eYeast Species-Specific Ambiguity of MALDI-TF MS Characterization\u003c/p\u003e \u003cp\u003eTo evaluate potential identification bias, we standardized both common and rare yeast isolates against our in-house database. \u003cem\u003eCandida glabrata\u003c/em\u003e and \u003cem\u003eCandida viswanathii\u003c/em\u003e were selected due to their low MALDI-TOF scores during direct identification. For standardization, yeast strains were cultured in BD BACTEC\u0026trade; bottles at concentrations of 10\u0026sup2;-10⁶ CFU/mL (with/without blood) and incubated at 37\u0026deg;C until positivity. Positive bottles were processed to collect pellets, which were washed with sterile distilled water, resuspended in 200 \u0026micro;L water, and identified using the previously described MALDI-TOF MS protocol (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStandardization and Validation of Direct-AFST\u003c/p\u003e \u003cp\u003eFor standardization, 40 processed blood culture (BC) samples underwent direct antifungal susceptibility testing (direct-AFST) with fluconazole using CLSI M27 microbroth dilution. Processed pellets were rested for 30 min at room temperature; 5 \u0026micro;l of supernatant was microscopically examined for cellular debris and yeast morphology (single/clustered cells). Clustered cells were vortexed before use. Viability was confirmed using Miles-Mishra method (10⁻\u0026sup1;-10⁻⁵ dilutions) on blood agar. Direct-AFST and culture-AFST (reference standard) were performed simultaneously. Validation included 250 yeast-positive BC samples tested against eight antifungals: amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, micafungin, and anidulafungin. Results were compared using: a) Essential agreement (%EA): MICs within \u0026plusmn;\u0026thinsp;1 two-fold dilution of culture-AFST b) Categorical agreement (%CA): concordance in susceptibility categories [sensitive/ intermediate/ resistant (S/I/R)] c) Very major errors (VME): False susceptibility [direct-AFST S, culture-AFST R] d) Major errors (ME): False resistance [direct-AFST R, culture-AFST S] (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eScreening from blood culture\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eGram staining of blood culture broth revealed Gram-positive oval/round budding yeast cells (with/without pseudohyphae) under oil immersion (OIF). Among these, 20 samples showed mixed infections with bacteria (Gram-positive cocci or Gram-negative bacilli). Representative smears are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. For 633 yeast-positive samples, we graded yeast cell density per OIF (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e) to correlate with direct MALDI-TOF MS identification (Direct ID) results.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eValidation of Direct ID from Blood Culture Bottles\u003c/p\u003e \u003cp\u003eAmong 754 positive blood cultures, MALDI-TOF MS (Direct ID) correctly identified 713 (94.56%), misidentified 8 (1.06%), and failed to identify 33 (4.38%). All 110 negative controls yielded negative results. The method demonstrated 95.58% sensitivity (95% CI: 93.84\u0026ndash;96.94%), 93.22% specificity (95% CI: 87.08\u0026ndash;97.03%), 98.89% PPV (95% CI: 97.86\u0026ndash;99.43%), and 76.92% NPV (95% CI: 70.41\u0026ndash;82.36%), with 95.25% agreement to culture-based identification. Microscopic analysis of Gram-stained cell counts was performed for 633 yeast-positive cultures, revealing no significant correlation between cell counts (\u0026gt;\u0026thinsp;10 CFU/OIF in 409/633 of samples) and identification accuracy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Hemocytometer counts of cells from blood samples were evaluated for 22 of the yeast-positive cultures analyzed for cell counts. No association was found between Gram-stain observations and hemocytometer counts, and identification accuracy remained unaffected. (Table S2).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation Between Gram\u0026rsquo;s stain yeast cell count and % of correct identification\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCells per OIF (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot identified\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCorrectly identified\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMis-identified\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10 (224)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e205 (91.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2(0.89%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u0026ndash;20 (191)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.04%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186 (97.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3(1.57%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;30 (96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 (99%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1(1.04%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30 (122)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118 (96.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (0.81%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDirect Identification of Mono-Yeast Infections\u003c/p\u003e \u003cp\u003eAmong the 754 positive blood cultures, 724 were identified as mono-yeast infections, while the remaining 30 were mixed infections. Species-wise result of Direct ID in 724 mono-yeast infection cases is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. All isolates of \u003cem\u003eCandida utilis (77), Candida parapsilosis (46), Candida auris\u003c/em\u003e (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), \u003cem\u003eTrichosporon asahii\u003c/em\u003e (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), \u003cem\u003eCandida guillermondii\u003c/em\u003e (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), \u003cem\u003eCyrptococcus neoformans\u003c/em\u003e (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), \u003cem\u003eCandida lusitaniae\u003c/em\u003e (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), \u003cem\u003eCandida rugosa\u003c/em\u003e (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) \u003cem\u003eCandida metapsilosis\u003c/em\u003e (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) were correctly identified (100%), followed by \u003cem\u003eCandida tropicalis\u003c/em\u003e (97.93%; 190/194), \u003cem\u003eWickerhamomyces anomalus\u003c/em\u003e (93.69%; 104/111), \u003cem\u003eCandida albicans\u003c/em\u003e (94.89%; 93/98), \u003cem\u003eCandida krusei\u003c/em\u003e ( 92.95%; 66/71), \u003cem\u003eCandida glabrata\u003c/em\u003e (86.66%; 39/42), \u003cem\u003eCandida orthopsilosis\u003c/em\u003e (93.33%; 14/15), Candida fabianii (75%; 3/4), \u003cem\u003eRhodotorula mucilaginosa\u003c/em\u003e (66.66%; 2/3). Three isolate of \u003cem\u003eCandida glabrata\u003c/em\u003e was misidentified as \u003cem\u003eCandida guilliermondii\u003c/em\u003e, \u003cem\u003eW. anomalus and Candida parapsilosis respectively\u003c/em\u003e, two isolate of \u003cem\u003eCandida krusei\u003c/em\u003e as \u003cem\u003eCandida orthopsilosis and Candida tropicalis respectively\u003c/em\u003e, one isolate of \u003cem\u003eRhodotorula mucilaginosa\u003c/em\u003e as \u003cem\u003eC. guillermondii\u003c/em\u003e, one isolate of \u003cem\u003eWickerhamomyces anomalus\u003c/em\u003e as \u003cem\u003eCandida glabrata\u003c/em\u003e and one isolate of \u003cem\u003eCandida albicans\u003c/em\u003e as \u003cem\u003eWickerhamomyces anomalus\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIdentification of Mixed Infections\u003c/p\u003e \u003cp\u003eMixed infections were identified in 30 samples, including combinations of two yeasts (n\u0026thinsp;=\u0026thinsp;6) and yeast with bacteria (n\u0026thinsp;=\u0026thinsp;24). Of these, 15 (50%) were correctly identified by Direct ID, 14 (46.7%) were not identified, and 1 (3.3%) was incompletely identified (Table S3). The presence of Gram-positive cocci affected yeast identification, with 10 out of 15 cases (66.7%) correctly identifying the respective yeast by Direct ID. In contrast, the presence of Gram-negative bacilli interfered with yeast identification in 7 out of 9 cases (only 22.2% correct identification). Among the remaining 6 cases with mixed yeast infections, both yeasts were correctly identified in 3 cases. The incomplete identification may have been due to the rare isolate \u003cem\u003ePichia occidentalis\u003c/em\u003e. The remaining two cases, containing \u003cem\u003eKodamaea ohmeri\u003c/em\u003e\u0026thinsp;+\u0026thinsp;\u003cem\u003eCandida krusei\u003c/em\u003e and \u003cem\u003eTrichosporon asahii\u003c/em\u003e\u0026thinsp;+\u0026thinsp;\u003cem\u003eLodderomyces elongisporus\u003c/em\u003e, were not identified by the Direct ID method. Instead, incorrect identification of \u003cem\u003eS. epidermidis\u003c/em\u003e was observed in these cases (Table S3).\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eScreening of Body Fluids\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the comparative analysis of 21 body fluid samples through microscopic examination, culture identification, and direct MALDI-TOF MS. Gram staining consistently revealed Gram-positive oval budding yeast cells (with/without pseudohyphae) alongside bacterial cells, epithelial cells, RBCs, and pus cells. Routine diagnostic methods identified 18 culture-positive samples (including 4 microscopy-positive), while rapid diagnosis detected 12 culture-positive cases; notably, direct identification via MALDI-TOF MS was unsuccessful in all instances despite the presence of detectable yeast elements in microscopy and culture.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetails of the body fluid samples received and their diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eFluid type from 21 collected\u003c/p\u003e \u003cp\u003esamples\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eRoutine Diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eRapid Diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDirect Identification by MALDI-TOF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMicroscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCulture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRoutine Identification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMicroscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCulture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCulture Identification\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003e\u003cb\u003eDense type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntra OP fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEpithelial cell+/ Bacteria ++/ No yeast/ No RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo yeast/ No RBC/ GPB+++/ PMNLS+/ Epithelial cell++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntra OP fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBacteria+/No yeast / RBC+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida krusei\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/ RBC+/GPB+/PMNLS++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida krusei\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePCD fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEpithelial cell+/ No yeast/ No RBS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/ No RBC/ GPB+++/ PMNLS+/ Epithelial cell++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ebacteria+/No yeast/ RBC+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/No RBC/GPC IN PAIRS CLUSTER\u0026thinsp;+\u0026thinsp;+\u0026thinsp;GPB+++/PMNLS+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntra op fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBacteria ++/ pus+/ No yeast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/No RBC/GPC IN PAIRS CLUSTER\u0026thinsp;+\u0026thinsp;+\u0026thinsp;GPB+++/PMNLS+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAscitic fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEpithelial cell+/ Yeast +/bacteria+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/No RBC/GPC in pairs and short chain/PMNLS++/ Epithelial cell++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDrain fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell +/ No yeast/ No RBC/ Bacteria+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell occ/ no yeast/ no RBC/ GPB +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePCD fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell+/ No yeast/ Bacteria +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell+/ no yeast/ GPCB+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDrain fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell+/ yeast cell +/ pseudo hyphae +/ No RBC/ Bacteria+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell+/ yeast cell +/ no RBC/ GPC+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePCD fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell ++/ yeast cell +/ No RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell +/ yeast cell +/ No RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e \u003cp\u003e\u003cb\u003eLess dense type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntra OP fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEpithelial cell +/ No yeast/pus++/RBC+/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus++/RBC++/Epithelial+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus++/ yeast+/ bacteria+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGPCB/ pus++/ yeast+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePCD fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus+/RBC+/ bacteria +/ No yeast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus+++/RBC+/GPCB+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntra OP fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus++/GPB+/ yeast occ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus++/GPB+/ yeast occ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epleural fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell +/ yeast occ/ RBC+/ RBC+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/no epithelial cell/RBC+/pus cell ++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eascitic fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell +/yeast +/ No RBC/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno yeast/no epithelial cell/no RBC/pus cell +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epleural fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell/ RBC+/ yeast occ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eWickerhamomyces anomalus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cells +/no yeast / RBC +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epleural fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell+/ No yeast/ bacteria +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell+/ no yeast/ GPCB +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epleural fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell occ/ No yeast/ bacteria +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell +/ no yeast/ no RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePCD fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epus cell ++/No yeast/ No RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell +++/no yeast/ no RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePCD fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEpithelial cell occ/ pus cell occ/ yeast cell++/ RBC +/ Bacteria +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epus cell +/ yeast cell++/ RBC +/ GPB+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCandida glabrata\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot Identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAFST of Yeast Directly from Blood Culture Bottle\u003c/p\u003e \u003cp\u003eWe have perfumed the viability test to confirm cell growth on blood agar as reported previously (Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Among 40 blood culture samples standardized for antifungal susceptibility testing (AFST) against fluconazole, 24 (60%) showed identical MICs between direct AFST and culture AFST methods, while 15 (37.5%) differed by 1 log2 dilution and 1 (2.5%) by 2 log2 dilutions (data not shown).\u003c/p\u003e \u003cp\u003eAFST Validation of Yeasts from Blood Culture Bottle\u003c/p\u003e \u003cp\u003eWe validated direct antifungal susceptibility testing (AFST) using 250 yeast pellets processed from blood cultures. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e compares MICs obtained by direct AFST versus culture-AFST for each antifungal drug, showing both concordant and divergent results.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDirect AFST and culture AFST showed identical MIC values for: fluconazole (168 samples), itraconazole (159), voriconazole (208), posaconazole (168), amphotericin B (178), caspofungin (172), micafungin (185), and anidulafungin (194). Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e displays the frequency of MIC deviations (1, 2, or \u0026gt;\u0026thinsp;2 log2 dilutions) for each antifungal agent.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComparison between Direct-AFST and Culture-AFST\u003c/p\u003e \u003cp\u003eThe analysis of AFST revealed excellent categorical agreement between Direct-AFST and Culture-AFST, with posaconazole showing perfect concordance (100%, 250/250), followed by voriconazole (98.4%), amphotericin B (97.6%), anidulafungin (97.2%), micafungin (95.2%), fluconazole (92.8%), itraconazole (87.6%), and caspofungin (88.0%, 107/127). Essential agreement was highest for amphotericin B (98.0%), followed by voriconazole (96.0%) and caspofungin (94.4%). We identified two very major errors (VMEs) with amphotericin B (\u003cem\u003eCandida tropicalis\u003c/em\u003e, \u003cem\u003eWickerhamomyces anomalus\u003c/em\u003e, \u003cem\u003eCandida auris\u003c/em\u003e) and fluconazole (\u003cem\u003eC. parapsilosis, C. krusei\u003c/em\u003e), one VME with caspofungin (\u003cem\u003eC. tropicalis\u003c/em\u003e), and three major errors (MEs) with amphotericin B (\u003cem\u003eC. tropicalis, W. anomalus\u003c/em\u003e), plus single MEs with anidulafungin (\u003cem\u003eC. tropicalis\u003c/em\u003e), itraconazole (\u003cem\u003eC. tropicalis\u003c/em\u003e), and micafungin (\u003cem\u003eC. auris\u003c/em\u003e). Complete agreement metrics and error rates across isolates are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \n\u003cp\u003e\u003cimg 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\" height=\"564\" width=\"657\"\u003e\u003c/p\u003e\n\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eYeast Species-Specific Ambiguity of Mass Spectra\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe MALDI-TOF MS spectra of \u003cem\u003eCandida glabrata\u003c/em\u003e (data not shown) and \u003cem\u003eCandida viswanathii\u003c/em\u003e showed high similarity between culture isolates and direct blood culture processing (with or without blood), showing only minor spectral variations. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e presents a representative spectral comparison for \u003cem\u003eC. viswanathii\u003c/em\u003e, demonstrating consistent peak profiles across preparation methods.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study evaluated the efficacy of MALDI-TOF MS for direct identification (Direct-ID) of yeast species from positive blood cultures along with body fluids and assessed the impact of yeast cell counts, sample preparation protocols, and antifungal susceptibility testing (AFST). Our findings reinforce the robustness of MALDI-TOF MS for rapid microbial identification and its potential role in complementing or replacing traditional culture-based methods.\u003c/p\u003e \u003cp\u003eOur data demonstrated that yeast cell count, as determined by Gram staining, did not significantly impact MALDI-TOF MS identification accuracy. This aligns with prior research showing that microbial load variations above a threshold level do not compromise MALDI-TOF MS efficacy (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). A key advantage of this approach is the ability to identify pathogens directly from blood cultures, facilitating rapid diagnosis and early antifungal therapy initiation. Zhou et al. reported a 60.87% concordance rate for fungal species at a log score threshold of \u0026ge;\u0026thinsp;1.700, reinforcing the reliability of MALDI-TOF MS for yeast identification (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn comparison with other rapid identification methods, Idelevich et al. demonstrated that PNA-FISH had a 96% success rate, Gram staining had a 76% success rate, and MALDI-TOF MS achieved 76% when optimized with in-house parameters (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). These findings underscore the necessity of protocol optimization, particularly with regard to sample preparation and data interpretation, to enhance MALDI-TOF MS performance.\u003c/p\u003e \u003cp\u003eThe effectiveness of Direct-ID was significantly enhanced by an optimized sample preparation protocol (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The incorporation of SDS-mediated lysis, centrifugation, and washing steps improved red blood cell removal, leading to high identification accuracy (94.56%) and excellent sensitivity (95.58%) and specificity (93.22%). This aligns with previous reports emphasizing that efficient host protein removal is crucial for obtaining high-quality spectra (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile Direct-ID performed well across most \u003cem\u003eCandida\u003c/em\u003e species, we observed lower identification rates for \u003cem\u003eCandida glabrata, Candida krusei\u003c/em\u003e and \u003cem\u003eRhodotorula mucilaginosa\u003c/em\u003e. This is consistent with Cassagne et al., who noted variability in identification accuracy due to species-specific differences in cell wall composition affecting protein extraction efficiency (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This suggests that database expansion and pretreatment modifications could further improve identification outcomes.\u003c/p\u003e \u003cp\u003eA comparison between visual Gram stain counts and quantitative haemocytometer measurements revealed significant discrepancies, with some samples displaying low Gram stain counts but high haemocytometer counts (\u0026ge;\u0026thinsp;10⁶ cells/mL). Despite this variability, Direct-ID and culture-based methods maintained high identification accuracy. This reinforces the observation that microbial load estimation is less critical for MALDI-TOF MS once a sufficient analyte threshold is met (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Our findings suggest that while haemocytometric measurements provide objective quantification, Gram staining remains useful as a rapid screening tool in microbiology laboratories.\u003c/p\u003e \u003cp\u003eThe development of a direct antifungal susceptibility testing (Direct-AFST) method represents a significant advancement in rapid antifungal resistance detection. Our study found high essential agreements (EA) and categorical agreements (CA) between Direct-AFST and conventional culture-AFST for most antifungal agents. Notably, EA was highest for amphotericin B (98.0%) and voriconazole (96.0%), while CA reached 100% for posaconazole. This level of agreement mirrors findings by Chang et al., Oz and Gokbolat, and Vecchione et al., who reported similarly high correlations between rapid and conventional AFST methods (\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eImportantly, our study showed minimal very major errors (VMEs) and major errors (MEs), confirming the sensitivity and specificity of Direct-AFST. Previous studies have noted challenges in itraconazole MIC interpretation, with slightly lower EA (91.6%) and CA (87.6%) observed in our dataset, consistent with Guinea et al. (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The direct method's ability to reduce turnaround time by at least 24 hours has significant clinical implications, allowing earlier antifungal therapy adjustments, which is crucial given that delayed treatment is associated with increased mortality in candidemia (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe standardization of Direct ID from body fluids demonstrated the feasibility of using MALDI-TOF MS for yeast identification. However, limitations were observed, particularly in directly identifying yeast from body fluid samples. The higher identification rate from cultured samples, compared to the lack of Direct ID, highlights both the potential and the limitations of MALDI-TOF MS for rapid fungal diagnostics across diverse sample types. Further refinements in sample processing and analysis are needed to enhance its direct detection capabilities.\u003c/p\u003e \u003cp\u003eOne critical challenge in MALDI-TOF MS yeast identification is the dependence on comprehensive reference databases. Our study evaluated potential biases by comparing spectral data from culture-based and Direct-ID methods. While \u003cem\u003eCandida viswanathii\u003c/em\u003e showed consistent spectral profiles regardless of sample preparation, \u003cem\u003eCandida glabrata\u003c/em\u003e exhibited few unique peaks in Direct-ID spectra. This suggests that variations in sample preparation can influence spectral outputs, reinforcing the need for expanded in-house reference databases (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePrevious studies have highlighted that yeast cell wall variability affects protein extraction efficiency, leading to species-specific differences in spectral patterns (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Our findings support this notion, particularly regarding lower identification rates for certain species, emphasizing the importance of refining sample preparation protocols. Future research should focus on database expansion and standardization efforts to mitigate these identification discrepancies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study demonstrates MALDI-TOF MS as an accurate, rapid method for direct yeast identification from blood cultures, performing consistently across varying microbial loads and processing conditions. The successful Direct-AFST application enables early resistance detection, significantly reducing diagnostic delays from days to hours while maintaining reliability comparable to conventional methods. This dual approach (Direct-ID and Direct-AFST) offers a transformative solution for timely antifungal therapy decisions in critical care settings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests to disclose.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors duly acknowledge the Indian Council of Medical Research (ICMR), Government of India for financial supports.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e \u003cp\u003eThe datasets analyzed and used during the study are available from the corresponding authors upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSinger M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). 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Clin Microbiol Infect. 2010;16(5):493\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLacroix C, Gicquel A, Sendid B, Meyer J, Accoceberry I, Francois N, et al. Evaluation of two matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems for the identification of Candida species. Clin Microbiol Infect. 2014;20(2):153\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassagne C, Cella AL, Suchon P, Normand AC, Ranque S, Piarroux R. Evaluation of four pretreatment procedures for MALDI-TOF MS yeast identification in the routine clinical laboratory. Med Mycol. 2013;51(4):371\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePfaller MA, Castanheira M, Messer SA, Rhomberg PR, Jones RN. Comparison of EUCAST and CLSI broth microdilution methods for the susceptibility testing of 10 systemically active antifungal agents when tested against Candida spp. Diagn Microbiol Infect Dis. 2014;79(2):198\u0026ndash;204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlastruey-Izquierdo A, Cuenca-Estrella M, EUCAST. How to Assess in Vitro Susceptibility and Clinical Resistance. Curr Fungal Infect Rep. 2012;6(3):229\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIdelevich EA, Grunastel B, Becker K. Rapid Detection and Identification of Candidemia by Direct Blood Culturing on Solid Medium by Use of Lysis-Centrifugation Method Combined with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). J Clin Microbiol. 2017;55(1):97\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLavergne RA, Chauvin P, Valentin A, Fillaux J, Roques-Malecaze C, Arnaud S, et al. An extraction method of positive blood cultures for direct identification of Candida species by Vitek MS matrix-assisted laser desorption ionization time of flight mass spectrometry. Med Mycol. 2013;51(6):652\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerroni A, Suarez S, Beretti JL, Dauphin B, Bille E, Meyer J, et al. Real-time identification of bacteria and Candida species in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol. 2010;48(5):1542\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHedges AJ. Estimating the precision of serial dilutions and viable bacterial counts. Int J Food Microbiol. 2002;76(3):207\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eProd'hom G, Bizzini A, Durussel C, Bille J, Greub G. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets. J Clin Microbiol. 2010;48(4):1481\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarnini S, Ghelardi E, Brucculeri V, Morici P, Lupetti A. Rapid and reliable identification of Gram-negative bacteria and Gram-positive cocci by deposition of bacteria harvested from blood cultures onto the MALDI-TOF plate. BMC Microbiol. 2015;15:124.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou M, Yang Q, Kudinha T, Sun L, Zhang R, Liu C, et al. An Improved In-house MALDI-TOF MS Protocol for Direct Cost-Effective Identification of Pathogens from Blood Cultures. Front Microbiol. 2017;8:1824.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIdelevich EA, Schule I, Grunastel B, Wullenweber J, Peters G, Becker K. Rapid identification of microorganisms from positive blood cultures by MALDI-TOF mass spectrometry subsequent to very short-term incubation on solid medium. Clin Microbiol Infect. 2014;20(10):1001\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang HC, Chang JJ, Chan SH, Huang AH, Wu TL, Lin MC, et al. Evaluation of Etest for direct antifungal susceptibility testing of yeasts in positive blood cultures. J Clin Microbiol. 2001;39(4):1328\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOz Y, Gokbolat E. Evaluation of direct antifungal susceptibility testing methods of Candida spp. from positive blood culture bottles. J Clin Lab Anal. 2018;32(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVecchione A, Florio W, Celandroni F, Barnini S, Lupetti A, Ghelardi E. A Rapid Procedure for Identification and Antifungal Susceptibility Testing of Yeasts From Positive Blood Cultures. Front Microbiol. 2018;9:2400.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuinea J, Recio S, Escribano P, Torres-Narbona M, Pelaez T, Sanchez-Carrillo C, et al. Rapid antifungal susceptibility determination for yeast isolates by use of Etest performed directly on blood samples from patients with fungemia. J Clin Microbiol. 2010;48(6):2205\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43(1):25\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarklein G, Josten M, Klanke U, Muller E, Horre R, Maier T, et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and reliable identification of clinical yeast isolates. J Clin Microbiol. 2009;47(9):2912\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"mycopathologia","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"myco","sideBox":"Learn more about [Mycopathologia](https://www.springer.com/journal/11046)","snPcode":"11046","submissionUrl":"https://submission.nature.com/new-submission/11046/3","title":"Mycopathologia","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"MALDI-TOF MS, Direct-AFST, Culture-AFST, Rapid, Diagnosis, Yeast, Candida","lastPublishedDoi":"10.21203/rs.3.rs-6590343/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6590343/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe rising incidence of invasive fungal infections has been accompanied by an increasing prevalence of antifungal resistance among fungal pathogens. Rapid identification of causative agents and their antifungal susceptibility profiles is critical for initiating timely, species-specific targeted therapy. In this context, we evaluated a MALDI-TOF MS-based method for the rapid identification of clinically relevant yeast species directly from blood cultures and body fluids, coupled with direct antifungal susceptibility testing (Direct-AFST). Our study evaluated over 700 yeast isolates, encompassing diverse \u003cem\u003eCandida\u003c/em\u003e and non-\u003cem\u003eCandida\u003c/em\u003e species, using MALDI-TOF MS. Additionally, antifungal susceptibility was assessed for 250 isolates, demonstrating excellent categorical agreement between Direct-AFST and conventional culture-based AFST (Culture-AFST). Our findings highlight the clinical utility of MALDI-TOF MS for accurate and rapid yeast identification directly from positive blood cultures, irrespective of microbial load or sample preparation method. Furthermore, the successful application of Direct-AFST underscores its potential for early detection of antifungal resistance, significantly reducing diagnostic turnaround times and improving patient management.\u003c/p\u003e","manuscriptTitle":"Direct Identification of Yeasts from Blood Cultures and Body Fluids Using MALDI-TOF MS with Concurrent Antifungal Susceptibility Testing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-20 12:34:08","doi":"10.21203/rs.3.rs-6590343/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-05-23T06:21:29+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-15T07:51:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Mycopathologia","date":"2025-05-12T15:59:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-12T05:17:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Mycopathologia","date":"2025-05-11T16:16:57+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor revisions","date":"2025-05-07T13:17:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"mycopathologia","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"myco","sideBox":"Learn more about [Mycopathologia](https://www.springer.com/journal/11046)","snPcode":"11046","submissionUrl":"https://submission.nature.com/new-submission/11046/3","title":"Mycopathologia","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"810fd44f-779f-4ac0-8bc6-4178225b1ad5","owner":[],"postedDate":"May 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T16:04:26+00:00","versionOfRecord":{"articleIdentity":"rs-6590343","link":"https://doi.org/10.1007/s11046-025-00987-x","journal":{"identity":"mycopathologia","isVorOnly":false,"title":"Mycopathologia"},"publishedOn":"2025-08-25 15:57:25","publishedOnDateReadable":"August 25th, 2025"},"versionCreatedAt":"2025-05-20 12:34:08","video":"","vorDoi":"10.1007/s11046-025-00987-x","vorDoiUrl":"https://doi.org/10.1007/s11046-025-00987-x","workflowStages":[]},"version":"v1","identity":"rs-6590343","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6590343","identity":"rs-6590343","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}