Review Reports - Emergence and Comparative Analysis of Candidozyma auris Versus Candida spp. Candidemia in a Romanian Tertiary Hospital: A 7-Year Study on Resistance, Mortality and Independent Prognostic Factors

Round 1

Reviewer 1 Report

Dear Authors,

Thank you for the opportunity to review this interesting manuscript evaluating Candidozyma auris versus non-auris candidemia in a Romanian tertiary-care center. The topic is timely and clinically relevant, particularly given the increasing global concern regarding C. auris transmission, antifungal resistance, and associated healthcare burden. The manuscript also provides valuable real-world data from Eastern Europe, where published longitudinal data remain limited.

The study has several strengths, including the relatively long study period, the comparison between C. auris and non-auris candidemia, and the detailed antifungal susceptibility analysis. However, in its current form, several important methodological and analytical issues limit the interpretability and overall scientific rigor of the work. Therefore, I recommend major revision before the manuscript can be considered for publication.

Major comments:

Multivariable analysis requires inclusion of Candida species type (Candidozyma auris vs non-auris)
Potential overinterpretation of mortality findings
Sample size and model stability
Heterogeneity of the non-auris group
Statistical reporting
Language and terminology

Minor comments:

Please ensure consistent nomenclature throughout the manuscript regarding Candidozyma auris, Candida auris, and non-auris terminology.
The legends of Figures 1 and 2 could be shortened and made more concise.
The manuscript would benefit from a dedicated subsection discussing infection prevention and control implications of C. auris emergence in prolonged hospitalizations.
Please clarify whether antifungal treatment modifications were guided by susceptibility testing or administered empirically.

Major comments:

Multivariable analysis requires inclusion of Candida species type (Candidozyma auris vs non-auris)

The most important limitation of the current statistical approach is that the infecting pathogen category (C. auris vs non-auris) was not included in the multivariable Cox regression model evaluating mortality predictors.

Given that the entire premise of the manuscript is based on comparing Candidozyma auris with non-auris candidemia, species type represents a clinically central variable and should be incorporated into the multivariable model, regardless of its statistical significance in univariable analysis. The omission of this variable limits the ability to determine whether mortality is independently associated with pathogen type after adjustment for disease severity and other confounders.

In particular, C. auris infections differed substantially from non-auris candidemia regarding:
- hospitalization duration,
- antifungal resistance patterns,
- persistence of candidemia,
- device exposure,
- antifungal treatment selection,
- and healthcare-associated characteristics.
Therefore, it is essential to assess whether pathogen type independently influences survival after adjustment for these variables. I strongly recommend including “Candidozyma auris vs non-auris candidemia” as a covariate in the multivariable Cox proportional hazards model and discussing the results accordingly.
Potential overinterpretation of mortality findings

The conclusion that mortality was “primarily driven by host-related factors and disease severity” may be somewhat overstated given the limited sample size and the absence of pathogen type in the multivariable analysis. Please moderate this interpretation unless supported by an appropriately adjusted model.
Sample size and model stability

The cohort includes only 61 patients and 43 deaths. Please provide clarification regarding variable selection strategy for the multivariable model and discuss the potential risk of model overfitting. The manuscript should specify whether proportional hazards assumptions were formally tested.
Heterogeneity of the non-auris group

The non-auris comparator group combines multiple biologically and clinically distinct Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, etc.). This heterogeneity should be acknowledged more explicitly as a limitation because resistance profiles, virulence, and mortality differ substantially among these species.
Statistical reporting

Several p-values are reported as “p=1”. Please provide exact values whenever possible. Additionally, confidence intervals should be consistently reported throughout the manuscript.
Language and terminology

The manuscript would benefit from careful English language editing. There are multiple grammatical inconsistencies and typographical issues throughout the text (e.g., “contributes” instead of “contribute”, “environmental”, “mortality” misspelled as “morality”, repeated spacing issues, and inconsistent tense usage).

Minor comments:

Please ensure consistent nomenclature throughout the manuscript regarding Candidozyma auris, Candida auris, and non-auris terminology.
The legends of Figures 1 and 2 could be shortened and made more concise.
The manuscript would benefit from a dedicated subsection discussing infection prevention and control implications of C. auris emergence in prolonged hospitalizations.
Please clarify whether antifungal treatment modifications were guided by susceptibility testing or administered empirically.

Author Response

Dear Sir/Madam,

Please find attached the response point by point.

Thank you.

Author Response File: Author Response.pdf

Reviewer 2 Report

The multivariable Cox model appears underspecified, as it does not include several well-established determinants of candidemia mortality, including validated severity scores (SOFA/APACHE II), time to active antifungal therapy, source-control measures (e.g., catheter removal), and Candida species itself. Therefore, residual confounding cannot be excluded, and the conclusion that mortality was primarily driven by host-related factors rather than species-specific effects may be overstated. The authors should acknowledge this limitation more explicitly and interpret the apparent absence of a species effect with greater caution. The discussion would benefit from clarifying that thrombocytopenia was identified as an independent predictor only within the context of the variables available in the retrospective dataset.
The conclusion that C. auris emerged through intra-hospital transmission is based solely on epidemiological observations (temporal clustering and prolonged hospitalization) without molecular typing, whole-genome sequencing, or environmental sampling to confirm clonal relatedness among isolates. Therefore, true nosocomial transmission cannot be distinguished from multiple independent introductions. The authors should acknowledge this limitation more explicitly and interpret the transmission dynamics with greater caution, framing the findings as epidemiologically consistent with healthcare-associated acquisition rather than molecularly confirmed intra-institutional transmission.
The study clearly shows an increase in Candidozyma auris cases and discharge-normalized incidence over time. However, incidence was calculated only per 10,000 discharges, without adjustment for patient-days, ICU-days, device utilization, or other exposure-related denominators commonly recommended for healthcare-associated infection surveillance. Therefore, temporal changes in hospitalization patterns, length of stay, case mix, or blood-culture practices may partly explain the observed increase. The authors should justify the choice of denominator
The reported incidence of C. auris is not adequately discussed in the context of previous studies or regional/international reports, which would help contextualize the magnitude and relevance of the findings.
Candidozyma and Candida are different genera according to current taxonomy; therefore, I suggest changing the denomination of the groups to “Candidozyma auris and Candida” or “C. auris vs Candida spp.”
Figure 2: The figure legend should be revised to improve clarity and consistency. The term “primary endpoint” is ambiguous and should be clearly defined. In addition, the legend does not specify which event was analyzed (e.g., all-cause mortality or in-hospital mortality) or the starting point used for survival-time calculation. Ideally, the authors should also include the total number of patients per group, the p value from the log-rank test, and, if available, the hazard ratio and 95% confidence interval obtained from the Cox analysis.
Tables 4 and Table 5 do not have a legend.
The legends corresponding to each figure and table should be revised and properly formatted for clarity and consistency throughout the manuscript.

The multivariable Cox model appears underspecified, as it does not include several well-established determinants of candidemia mortality, including validated severity scores (SOFA/APACHE II), time to active antifungal therapy, source-control measures (e.g., catheter removal), and Candida species itself. Therefore, residual confounding cannot be excluded, and the conclusion that mortality was primarily driven by host-related factors rather than species-specific effects may be overstated. The authors should acknowledge this limitation more explicitly and interpret the apparent absence of a species effect with greater caution. The discussion would benefit from clarifying that thrombocytopenia was identified as an independent predictor only within the context of the variables available in the retrospective dataset.
The conclusion that C. auris emerged through intra-hospital transmission is based solely on epidemiological observations (temporal clustering and prolonged hospitalization) without molecular typing, whole-genome sequencing, or environmental sampling to confirm clonal relatedness among isolates. Therefore, true nosocomial transmission cannot be distinguished from multiple independent introductions. The authors should acknowledge this limitation more explicitly and interpret the transmission dynamics with greater caution, framing the findings as epidemiologically consistent with healthcare-associated acquisition rather than molecularly confirmed intra-institutional transmission.
The study clearly shows an increase in Candidozyma auris cases and discharge-normalized incidence over time. However, incidence was calculated only per 10,000 discharges, without adjustment for patient-days, ICU-days, device utilization, or other exposure-related denominators commonly recommended for healthcare-associated infection surveillance. Therefore, temporal changes in hospitalization patterns, length of stay, case mix, or blood-culture practices may partly explain the observed increase. The authors should justify the choice of denominator
The reported incidence of C. auris is not adequately discussed in the context of previous studies or regional/international reports, which would help contextualize the magnitude and relevance of the findings
Candidozyma and Candida are different genera according to current taxonomy; therefore, I suggest changing the denomination of the groups to “Candidozyma auris and Candida” or “C. auris vs Candida spp.”
Figure 2: The figure legend should be revised to improve clarity and consistency. The term “primary endpoint” is ambiguous and should be clearly defined. In addition, the legend does not specify which event was analyzed (e.g., all-cause mortality or in-hospital mortality) or the starting point used for survival-time calculation. Ideally, the authors should also include the total number of patients per group, the p value from the log-rank test, and, if available, the hazard ratio and 95% confidence interval obtained from the Cox analysis.
Tables 4 and Table 5 do not have a legend.
The legends corresponding to each figure and table should be revised and properly formatted for clarity and consistency throughout the manuscript.

Author Response

09^th June 2026

To Reviewer

Dear Sir/Madam,

Thank you for your very thorough review of our article and your attention and helpful insights. Please find below our point-by-point responses.

Detailed comments

The multivariable Cox model appears underspecified, as it does not include several well-established determinants of candidemia mortality, including validated severity scores (SOFA/APACHE II), time to active antifungal therapy, source-control measures (e.g., catheter removal), and Candida species itself. Therefore, residual confounding cannot be excluded, and the conclusion that mortality was primarily driven by host-related factors rather than species-specific effects may be overstated. The authors should acknowledge this limitation more explicitly and interpret the apparent absence of a species effect with greater caution. The discussion would benefit from clarifying that thrombocytopenia was identified as an independent predictor only within the context of the variables available in the retrospective dataset.

Response:

We thank the reviewer and have addressed this on three levels. First, Candida species type (Candidozyma auris vs non-auris Candida spp.) has been entered as a covariate in the multivariable Cox model; in the final model (species type, ICU admission, and thrombocytopenia), thrombocytopenia remained the only independent predictor of mortality (HR 2.38, p = 0.011), while species type was not significant (HR 0.617, p = 0.136), and the proportional-hazards assumption was verified for all retained variables. Second, we now explicitly acknowledge in the Limitations that validated severity scores (SOFA/APACHE II), time to active antifungal therapy, and source-control measures were not consistently available in this retrospective dataset, so residual confounding cannot be excluded. Third, we have moderated the wording: the Discussion now states that thrombocytopenia was identified as an independent predictor only within the context of the variables available in the retrospective dataset, and the apparent absence of a species effect is interpreted with caution rather than as proof of equivalence.

The corresponding manuscript text reads: “After inclusion of Candidozyma auris versus non-auris Candida species type as a covariate in the multivariable model, thrombocytopenia remained the only independent predictor of mortality (HR 2.38, p = 0.011), while pathogen type was not significantly associated with outcome (HR 0.617, p = 0.136). Proportional hazards assumptions were confirmed for all variables retained in the final model.” We also explicitly acknowledge that thrombocytopenia was identified as an independent predictor only within the limited set of variables available in this retrospective dataset, as validated severity scores (SOFA/APACHE II), time to active antifungal therapy, and source-control measures were not consistently recorded.

The conclusion that C. auris emerged through intra-hospital transmission is based solely on epidemiological observations (temporal clustering and prolonged hospitalisation) without molecular typing, whole-genome sequencing, or environmental sampling to confirm clonal relatedness among isolates. Therefore, true nosocomial transmission cannot be distinguished from multiple independent introductions. The authors should acknowledge this limitation more explicitly and interpret the transmission dynamics with greater caution, framing the findings as epidemiologically consistent with healthcare-associated acquisition rather than molecularly confirmed intra-institutional transmission.

Response:

We agree and have modified the wording throughout. The temporal clustering and prolonged hospitalisation are now described as epidemiologically consistent with healthcare-associated acquisition rather than as molecularly confirmed clonal transmission, and we state explicitly that, without molecular typing, whole-genome sequencing, or environmental sampling, true nosocomial transmission cannot be distinguished from multiple independent introductions.

The corresponding sentence in the Discussion now reads: “The delayed onset of Candidozyma auris bloodstream infection is consistent with prior colonization preceding invasive disease; however, clonal relatedness and the exact transmission pathway cannot be confirmed in the absence of molecular typing or environmental sampling.”

The study clearly shows an increase in Candidozyma auriscases and discharge-normalized incidence over time. However, incidence was calculated only per 10,000 discharges, without adjustment for patient-days, ICU-days, device utilization, or other exposure-related denominators commonly recommended for healthcare-associated infection surveillance. Therefore, temporal changes in hospitalization patterns, length of stay, case mix, or blood-culture practices may partly explain the observed increase. The authors should justify the choice of denominator

Response:

We clarified that incidence was calculated per 10,000 discharges because this denominator was consistently available throughout the study period. We also added that patient-days, ICU-days, and device-utilization data were not available, which limits direct comparison with surveillance studies using exposure-adjusted denominators.

The justification has been added to the Discussion: “Incidence was expressed per 10,000 hospital discharges because this denominator was consistently available across the full study period; however, patient-days, ICU-days, and device-utilization data were not available, which limits direct comparison with surveillance studies using exposure-adjusted denominators.” We acknowledge that, because of this, changes in length of stay, case mix, or blood-culture practice could contribute to the observed trend, and we have tempered the wording accordingly; discharge-based normalisation nonetheless provides a stable, hospital-wide denominator that was uniformly captured across all seven epidemiological years.

The reported incidence of C. auris is not adequately discussed in the context of previous studies or regional/international reports, which would help contextualize the magnitude and relevance of the findings

Response

We expanded the Discussion to place our incidence findings in a broader epidemiologic context and to emphasize the relevance of the observed increase over time.

Specifically, the absolute number of C. auris cases rose from none in 2018–2021 to 11 in the final study year, with a concordant rise in hospital-wide incidence per 10,000 discharges (Table 1, Figure 1). We now situate this trend against national data: the first Romanian C. auris cases were reported in 2022, and whole-genome sequencing assigned all isolates to the South Asian clade (clade I), consistent with clonal dissemination within and between healthcare facilities (doi: 10.1186/s13756-023-01297-x); a subsequent analysis of 102 patients (2022–2023) confirmed ongoing spread of clade I strains carrying multiple resistance markers, with a crude mortality of 68.18% (doi: 10.1128/spectrum.02809-24). Our seven-year, single-centre comparative dataset adds to this emerging body of evidence and indicates that the local increase parallels the documented regional emergence of the pathogen.

Candidozyma and Candida are different genera according to current taxonomy; therefore, I suggest changing the denomination of the groups to “Candidozyma auris and Candida” or “C. auris vs Candida spp.”

Response:

We agree and standardized the terminology throughout the manuscript to Candidozyma auris and non-auris Candida spp. We retained the qualifier “non-auris” before “Candida spp.” so that the comparator group remains unambiguous for the reader.

Figure 2: The figure legend should be revised to improve clarity and consistency. The term “primary endpoint” is ambiguous and should be clearly defined. In addition, the legend does not specify which event was analyzed (e.g., all-cause mortality or in-hospital mortality) or the starting point used for survival-time calculation. Ideally, the authors should also include the total number of patients per group, the p value from the log-rank test, and, if available, the hazard ratio and 95% confidence interval obtained from the Cox analysis.

Response:

We have revised the Figure 2 legend accordingly. It now defines the analysed event as all-cause in-hospital mortality, states that survival time was calculated from the date of the first positive blood culture, and reports the number of patients per group, the log-rank p value (p = 0.150), and the hazard ratio with 95% confidence interval from the univariable Cox analysis (HR 0.638, 95% C.I. = 0.340–1.195, p = 0.160). The ambiguous term “primary endpoint” has been replaced by this explicit definition, and the abbreviations “OS” (overall survival) and “Cumulative Survival” are now spelled out at first use.

Tables 4 and Table 5 do not have a legend.

Reponse:

We apologise for the omission. Legends have been added to Tables 4 and 5. Table 4 is now titled “Comparative analysis of laboratory parameters between non-auris Candida spp. and Candidozyma auris groups at the moment of diagnosis,” and Table 5 now carries a corresponding descriptive legend defining its content (antifungal susceptibility patterns) and the groups compared.

The legends corresponding to each figure and table should be revised and properly formatted for clarity and consistency throughout the manuscript.

We have reviewed and reformatted all figure legends and table titles/footnotes for clarity and consistency, harmonizing the nomenclature (Candidozyma auris / non-auris Candida spp.), defining all abbreviations at first use, and ensuring that each legend specifies the comparison made, the statistical test applied, and the relevant effect estimates where applicable.

Best regards,

Simona Tetradov,

Corresponding author,

On behalf of all co-authors.

Reviewer 3 Report

In this manuscript, Smadu at al compare C auris and non-C auris candidemia epidemiology, including mortality, resistance, and treatment over a 7-year period. This paper offers insight into the rising numbers of candidemia cases at medical centers all over the world, and corresponding increases in C auris prevalence as well and how this impacts patient outcomes. The study is well-designed and important, with a number of clinical variables discussed and appropriate limitations considered. Some additional comments for consideration.

-The sentence in the early Results: "Being initially hospitalized for a bacterial infection, candidemia has occurred overall after a median of 18 days (16-54 IQR)," is awkwardly phrased and confusing to interpret. Please re-word.

-Table 2 mentions "Other conditions" but no further detail. These should be outlined in the Table, or in a Table footnote.

-The authors comment on persistent candidemia only briefly, and these patients had a high mortality. Are there any other factors that were associated with persistent disease that the authors can elaborate on? (e.g., inability to remove source, retained central venous catheter, antifungal resistance, etc)

-Limitations should also mention that this was a single-center study and thus not necessarily generalizable to all institutions/geographic areas.

-Would consider formatting for the figure legends/tables and footnotes. As they stand, they initially appear to be part of the main text and thus confusing for the reader.

-In the Discussion, the authors reference the "morality rate" (line 484), which should be correct to "mortality rate."

-Would consider consolidating the Conclusion - this is meant to be a briefer summary of the overall document and many of the points highlighted are redundant from the Results and Discussion Section

As above

Author Response

09^th June 2026

To Reviewer

Dear Sir/Madam,

Thank you for your very thorough review of our article and your attention and helpful insights. Please find below our point-by-point responses.

Comment 1

The sentence in the early Results: "Being initially hospitalized for a bacterial infection, candidemia has occurred overall after a median of 18 days (16-54 IQR)," is awkwardly phrased and confusing to interpret. Please re-word.

Response: We thank the reviewer. We rephrased the sentence to improve readability and clarity. The revised sentence reads: “Among patients initially hospitalized for bacterial infections, candidemia developed after a median of 18 days (IQR: 12–34.5; 95% C.I. = 21.43–35.59) from admission.”

Comment 2

Table 2 mentions "Other conditions" but no further detail. These should be outlined in the Table, or in a Table footnote.

Response:

We agree. We added a footnote specifying the diagnoses included under “Other conditions.

The added footnote to Table 2 reads: “Patients with other conditions (N = 21) were as follows: 11 patients (52.4%) with SARS-CoV-2 infection, 6 patients (28.6%) with HIV infection, and 4 patients (19%) with tuberculous meningitis”

Comment 3

The authors comment on persistent candidemia only briefly, and these patients had a high mortality. Are there any other factors that were associated with persistent disease that the authors can elaborate on? (e.g., inability to remove source, retained central venous catheter, antifungal resistance, etc)

Response:

We revised the Discussion to clarify that the retrospective design did not allow identification of a definite source in these cases, so a causal role of a specific focus or retained device cannot be established. Notably, all recommended measures for the prevention and control of healthcare-associated infections were applied throughout the study period, in accordance with local (National Institute of Public Health, Romania) and international guidelines. However, because the patients with persistent candidemia were critically ill and dependent on intensive-care support, removal of central venous catheters and other indwelling devices was frequently not feasible, which may have contributed to the persistence of bloodstream infection. Antifungal resistance, a further factor associated with persistence, was documented within the manuscript (Table 3), including near-universal azole resistance in C. auris (95.8%). These factors – inability to achieve source control in device-dependent critically ill patients and documented antifungal resistance – are the most plausible contributors to persistent disease, even though the retrospective design excluded attribution of a single definite source.

The corresponding manuscript sentence reads: “Persistent candidemia was observed in a small subset of patients, but no definite source was identified in the retrospective analysis; therefore, a causal role of a specific focus or retained device cannot be established. . All recommended measures for the prevention and control of healthcare-associated infections were applied in accordance with local and international guidelines; however, in these critically ill, intensive-care-dependent patients, removal of indwelling central venous catheters was frequently not feasible, and the documented antifungal resistance may have further contributed to the persistence of bloodstream infection.”

Comment 4

Limitations should also mention that this was a single-center study and thus not necessarily generalizable to all institutions/geographic areas.

Response

We added this explicitly to the Limitations section and note that the findings may not be fully generalizable to other institutions or geographic settings.

We have also added why this single-center experience is informative despite its limited generalizability. The study reports one of the first seven-year, head-to-head comparisons of C. auris and non-auris candidemia from a Romanian tertiary infectious-diseases referral center, capturing the local emergence of the pathogen in real time. The single-center design ensured uniform case definitions, microbiological methods, and management across the whole cohort, which strengthens the internal validity of the comparison and of the prognostic signal for thrombocytopenia. For other centers, the data provide a practical benchmark – the incidence trajectory, the resistance profile, the predominance of ward (non-ICU) onset, and the prognostic value of thrombocytopenia – that can be used to calibrate screening and infection-control policies and to inform empirical echinocandin use in settings facing a similar emergence of C. auris.

The Limitations text now reads: “As a single-center retrospective analysis, our results should be interpreted with caution and may not be generalizable to institutions with different patient populations, referral patterns, or infection-control practices.”

Comment 5

Would consider formatting for the figure legends/tables and footnotes. As they stand, they initially appear to be part of the main text and thus confusing for the reader.

Response

We revised the formatting to separate legends and footnotes more clearly from the main text.

Comment 6

In the Discussion, the authors reference the "morality rate" (line 484), which should be correct to "mortality rate."

Response

Thank you for this observation. Our apologies. We corrected this to “mortality rate.”

Comment 7

Would consider consolidating the Conclusion - this is meant to be a briefer summary of the overall document and many of the points highlighted are redundant from the Results and Discussion Section

Response

We agree and have consolidated the Conclusion into a single, concise paragraph. We removed the passages that merely restated material already presented in the Results and Discussion — subgroup-specific mortality figures, repeated risk-factor lists, and methodological detail — and retained only the principal take-home messages: that Candidozyma auris is a clinically distinct, highly resistant healthcare-associated pathogen; that in-hospital mortality was comparably high in both groups, with thrombocytopenia — rather than pathogen identity — as the sole independent predictor of death; that the disease burden extended beyond the ICU; and the resulting practical recommendations (enhanced infection control, empirical echinocandin therapy where C. auris is epidemiologically plausible, and early risk stratification). We additionally added a single closing sentence stating the practical value of this single-center experience for other centers, which complements rather than lengthens the summary.

The conclusions states now: This 7-year comparative analysis distinguishes Candidozyma auris as a unique, highly resistant healthcare-associated pathogen. Notably, mortality remained comparably high in both Candidozyma auris and non-auris Candida spp, with thrombocytopenia—not pathogen identity—emerging as the only independent predictor of mortality. Persistent infection led to poor outcomes, with a significant disease burden observed outside the ICU. These findings underscore a critical need for interventions: rigorous infection control, empiric echinocandin therapy where C. auris is prevalent, and early risk stratification for patients with long hospital stays and indwelling devices. Although limited to a single center, the consistent case definitions, uniform microbiological methods, and standardized management across seven years render these findings a practical reference for institutions managing the emergence of C. auris, ultimately guiding local screening, infection control, and empirical antifungal protocols.

Best regards,

Simona Tetradov,

Corresponding author,

On behalf of all co-authors.

Round 2

Reviewer 2 Report

I believe it is not taxonomically consistent to use the term “non-auris Candida spp.”, since Candidozyma auris no longer belongs to the genus Candida. In other words, according to the current taxonomy, Candida auris is no longer a valid species name and has been reclassified as Candidozyma auris. Therefore, it is not strictly correct to refer to the remaining species as “non-auris Candida spp.”, as this terminology implies that auris is still part of the genus Candida, which is no longer the case.

Author Response

Dear Reviewer,

We would like to express our gratitude for your time and effort in reviewing our manuscript.

As noted in the previous round, we have fully addressed the major methodological concerns, including the expansion of the multivariable Cox model, the explicit inclusion of study limitations regarding retrospective clinical data, and the contextualization of transmission dynamics.

In this current revision, we have focused entirely on resolving the remaining taxonomic issue you highlighted. We completely agree that following the reclassification of Candida auris into the genus Candidozyma (Candidozyma auris), the term “non-auris Candida spp.” is taxonomically inconsistent and incorrect. To ensure compliance with current mycological nomenclature, we have performed a global, line-by-line revision of the entire manuscript. The term “non-auris Candida spp.” has been removed and replaced with taxonomically accurate denominations across all sections to "Candida spp."

Thank you once again for your rigorous guidance, which has elevated the quality of our paper.

We hope the manuscript is now fully ready for publication.