You are here

  • Home
  • Archive
  • Volume 14, Issue 10
  • Clinical outcomes of antifungal therapy on Candida pulmonary colonisation in immunocompetent patients with invasive ventilation: a systematic review and meta-analysis

Article Text

Article menu
Intensive care
Original research
Clinical outcomes of antifungal therapy on Candida pulmonary colonisation in immunocompetent patients with invasive ventilation: a systematic review and meta-analysis
  1. Linqi Li1,2,
  2. Shan Su3,
  3. Hongzhong Yang4,
  4. He-Bin Xie1,2
  1. 1The Affiliated Changsha Central Hospital, University of South China, Changsha, Hunan, China
  2. 2School of Public Health, University of South China, Hengyang, Hunan, China
  3. 3Department of Respiratory and Critical Care Medicine, Zhaoqing First People's Hospital, Zhaoqing, Guangdong, China
  4. 4Department of Respiratory and Critical Care Medicine, The Affiliated Changsha Central Hospital, University of South China, Changsha, Hunan, China
  1. Correspondence to He-Bin Xie; 2018050642{at}usc.edu.cn; Hongzhong Yang; hzhy82{at}sina.cn

Abstract

Objective This study aimed to use systematic review and meta-analysis to establish the influence of antifungal therapy on pulmonary Candida colonisation of patients with mechanical ventilation (MV).

Design Systematic review and meta-analysis.

Data sources An extensive search was undertaken on publications from inception to 25 July 2023, through PubMed, Web of Science, Medline, Embase, China National Knowledge Infrastructure, Wanfang Data and VIP Databases.

Eligibility criteria for selecting studies Randomised trials, cohort studies and case-control studies comparing the efficacy of antifungal treatment in immunocompetent patients with pulmonary Candida colonisation after invasive ventilation.

Data extraction and synthesis Two reviewers independently extracted the data and assessed the quality of studies. Dichotomous outcomes were expressed as ORs with 95% CIs. Continuous outcomes were expressed as standardised mean differences (SMD) with 95% CIs.

Primary and secondary outcome measures The primary outcomes included intensive care unit (ICU), hospital, 28-day, and 90-day mortality. The secondary outcomes included ICU length of stay, MV duration and ventilator-associated pneumonia (VAP).

Results Nine high-quality studies were included. According to the data collected from these nine studies, there is no significant evidence showing a difference between the therapy group treated with antifungal drugs and the control group without antifungal drugs in clinical outcomes, including ICU mortality (OR: 1.37; 95% CI 0.84 to 2.22), hospital mortality (OR: 1.17; 95% CI 0.57 to 2.38), 28-day mortality (OR: 0.71; 95% CI 0.45 to 1.14), 90-day mortality (OR: 0.76; 95% CI 0.35 to 1.63), ICU length of stay (SMD: −0.15; 95% CI −0.88 to 0.59), MV duration (SMD: 0.11; 95% CI −0.88 to 1.10) and VAP (OR: 1.54; 95% CI 0.56 to 4.20). Subgroup analysis of different treatment types indicates that the combined effect size is stable and unaffected by different treatment types including inhalation (OR: 2.32; 95% CI 0.30 to 18.09) and intravenous (OR: 0.65; 95% CI 0.13 to 3.34).

Conclusion The application of antifungal treatment did not improve clinical outcomes in patients with MV. We do not suggest initiating antifungal treatment in patients with Candida pulmonary colonisation after invasive ventilation.

Trial registration number International Prospective Register of Systematic Reviews, CRD42020161138.

  • Meta-Analysis
  • Adult intensive & critical care
  • Pulmonary Disease

Data availability statement

Data are available upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi-org.ezproxy.u-pec.fr/10.1136/bmjopen-2024-083918

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Strengths and limitations of this study

    • This study included a number of outcome indicators to assess the effectiveness of antifungal treatment, with subgroup analyses performed based on the type of treatment administered.

    • Most studies included are retrospective studies, raising potential concerns regarding their external validity.

    • Some studies described the precise style, name, dose and administration method of antifungal drugs, while others did not.

    • This study is limited by the number of studies included, especially when it comes to single outcomes such as intensive care unit mortality.

    • Most studies included were cohort studies instead of random control trials, which provide stronger evidence.

    Introduction

    Candida frequently exists in the normal oral cavity, upper respiratory tract, lower intestinal tract and vagina.1 In tracheal aspirates from patients with mechanical ventilation (MV), 30% have Candida isolation, and nearly 50% from patients suspected to have ventilator-associated pneumonia (VAP).2 3 When respiratory Candida colonisation is detected, it is difficult to differentiate between relatively harmless colonisation and invasive infection, and leads to a therapeutic dilemma.4 Although few studies reported limited attributable intensive care unit (ICU) mortality of VAP, the death rate related to VAP cannot be denied according to the majority of previous studies.5–8 The incidence of VAP frequently extends hospital stay, elevates the economic burden and raises the mortality rate.9 The presence of Candida in respiratory samples is defined as Candida colonisation instead of infection because the appearance of Candida pneumonia is rare.10–13 For several years, arguments have arisen about whether Candida colonisation negatively affects or simply indicates disease severity or immunosuppression in critically ill patients.13–15 We found that the outcomes of antifungal treatment for Candida colonisation in pulmonary tract among different studies were controversial, as some studies found that antifungal treatment was associated with lower mortality, some found that treatment made no difference in mortality, while others found that it prolonged MV duration, ICU length of stay and hospital length of stay.10 11 16 17 Therefore, we performed a systematic review and meta-analysis to establish the influence of antifungal treatment on pulmonary Candida colonisation.

    Method

    Information sources and search strategy

    This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria for systematic reviews and meta-analyses.18 An extensive search was undertaken on publications from inception to 25 July 2023, through PubMed, Web of Science, Medline, Embase, China National Knowledge Infrastructure, Wanfang Data and VIP Databases. The searching syntax included the following Medical Subject Headings and text words, which are varied individually according to different databases: VAP, Candida. We used the following search strategies in all of the databases above: (ventilator-associated pneumonia OR VAP OR pneumonia, ventilator-associated OR ventilator-associated pneumonia OR ventilator-acquired pneumonia OR mechanical ventilation) AND (Candida OR Candida spp OR Candida colonization OR Candida airway colonization). There were no language restrictions on studies searching. The listed references of relevant studies were also evaluated to enlarge the search scope and ensure a complete search. Full search strategy of PubMed database is provided in the online supplemental material. Selection process of the article was performed by two researchers (LL and SS) independently. The titles and abstracts of the entries identified in the search were screened. Full-text version of all articles that potentially met the eligibility criteria was reviewed to make a decision. Disagreements, if any, were resolved through discussion with a third researcher (H-BX).

    Inclusion criteria

    Randomised trials, cohort studies and case-control studies were included while selecting. In the included studies, the patients were adults (≥18 years old) who were diagnosed with pulmonary Candida colonisation after invasive ventilation. Pulmonary Candida colonisation was defined as the presence of Candida in bronchoalveolar lavage samples, endotracheal aspiration samples, protected brush specimens or any positive airway secretion specimens.

    Exclusion criteria

    We excluded case reports and studies on pregnant, immunocompromised patients or those who received antifungal treatment for reasons other than Candida colonisation. Patients with candidemia or invasive candidiasis were also excluded, and the diagnostic criteria were positive results of direct detection, in which blood or tissue specimens were cultured, or indirect detection, in which surrogate markers and PCR assays were used.19

    Data collection

    We screened titles and abstracts, reviewed the full text and extracted data using an Excel sheet (Microsoft Corporation). We primarily collected the characteristics of title, author, journal, year, type, participants, inclusion or exclusion criteria, interventions and clinical outcomes. Clinical outcomes included 28-day mortality, 90-day mortality, ICU mortality, hospital mortality, ICU length of stay, MV duration and VAP. Disagreements were resolved by discussion with a third reviewer if necessary.

    Quality assessment

    We used the Cochrane risk assessment tool to measure the risk of randomised-controlled trials, and the Newcastle–Ottawa scale to measure the quality of cohort and case-control studies.20 Studies that scored at least six points were regarded as high quality and included in the analysis.

    Patient and public involvement

    Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

    Statistical analysis

    Statistical analysis was performed by Stata software (V.16.0). Dichotomous outcomes, such as VAP, ICU mortality, hospital mortality, 28-day mortality and 90-day mortality, were expressed as ORs with 95% CIs. Continuous outcomes (ICU length of stay and MV duration) were expressed as standardised mean differences (SMD) with 95% CIs. We analysed the data using the inverse-variance method with the fixed-effect model if there was no obvious heterogeneity (p>0.1), or else random-effect model if the heterogeneity was significant (p<0.1). Moreover, heterogeneity was quantified using the I2 test. The interpretation of I2 was guided by the Cochrane Handbook for Systematic Reviews of Interventions (V.5.2.0, updated June 2017). Sensitivity analyses were conducted by excluding one study at a time from the analysis to assess the stability of the results. Subgroup analyses were performed on the effect of antifungal therapy. Publication bias was not assessed since there were fewer than 10 studies in this meta-analysis.

    Results

    Study selection

    In total, 2947 records were identified. With 1246 duplicates removed and 1670 irrelevant records excluded, we assessed 31 studies for eligibility, of which 9 were included. 22 studies were excluded because of the lack of antifungal treatment, lack of supporting experimental data, lack of detection of pulmonary secretion and occurrence in a special population (figure 1). All patients received MV, had at least one positive culture of Candida in the pulmonary tract and received different antifungal treatments.

    Figure 1
    Figure 1

    Flowchart of studies identified, excluded and included.

    Study characteristics and quality assessment

    Of the nine articles included in the study, seven were retrospective cohort studies, one case-control study and one randomised clinical trial. Two studies were conducted in North America, five in Europe and two in Asia, giving the studies a wide geographical coverage. Other characteristics of the included studies are summarised in online supplemental table 1, including years of accuracy, location, study design, population, number of patients, outcomes, Candida colonisation and antifungal treatment. The columns of the quality assessment list and their corresponding points are listed in online supplemental table 2. All included studies were assessed to be of high quality.

    Effect of antifungal therapy on pulmonary Candida colonisation patients’ mortality

    Three studies, including Ioannou,2 Ong21 and Nseir,22 reported ICU mortality. We found no significant difference between the therapy and control groups (OR: 1.37; 95% CI 0.84 to 2.22). Six studies, including Du,4 Ioannou, Zhang,23 Griffin,24 Lindau25 and Albert,26 reported hospital mortality. The pooled results showed no significant difference between the therapy and control groups (OR: 1.17; 95% CI 0.57 to 2.38). Four studies, including Du, Zhang, van der Geest27 and Albert, reported 28-day mortality. The results showed no significant difference between the therapy and control groups (OR: 0.71; 95% CI 0.45 to 1.14). Three studies, Du, van der Geest and Albert, reported 90-day mortality. The results showed no significant difference between the therapy and control groups (OR: 0.76; 95% CI 0.35 to 1.63). No indicator showed statistical significance with respect to mortality (figure 2).

    Figure 2
    Figure 2

    (A) Forest plot for intensive care unit mortality. (B) Forest plot for hospital mortality. (C) Forest plot for 28-day mortality. (D) Forest plot for 90-day mortality.

    Effect of antifungal therapy on pulmonary Candida colonisation patients’ ICU length of stay

    Four studies, including Zhang, Griffin, Ong and Nseir, reported ICU length of stay. The results indicated non-significant differences for ICU length of stay among patients receiving antifungal treatment (SMD: −0.15; 95% CI −0.88 to 0.59), as shown in figure 3.

    Figure 3
    Figure 3

    Forest plot for intensive care unit length of stay. SMD, standardised mean difference.

    Effect of antifungal therapy on pulmonary Candida colonisation patients’ MV duration

    Three studies, including Zhang, Griffin and Nseir, reported the duration of MV. We did not identify a significant difference between the therapy and control groups regarding MV duration (SMD: 0.11; 95% CI −0.88 to 1.10), as shown in figure 4.

    Figure 4
    Figure 4

    Forest plot for MV duration. MV, mechanical ventilation; SMD, standardised mean difference.

    Effect of antifungal therapy on VAP

    Six studies, including Du, Zhang, Griffin, Lindau, van der Geest and Ong, reported VAP. No significant difference was found between therapy and control groups (OR: 1.54; 95% CI 0.56 to 4.20), as shown in figure 5.

    Figure 5
    Figure 5

    Forest plot for ventilator-associated pneumonia.

    Subgroup analysis

    We conducted a subgroup analysis based on the effect of antifungal therapy on VAP of the included studies. The result of the subgroup analysis indicates that the combined effect size is stable and unaffected by different treatment types, as shown in online supplemental figure 1.

    Sensitivity analysis and publication bias

    A sensitivity analysis was performed by sequentially excluding one study at a time. This exclusion did not significantly impact the results, with the pooled OR ranging from 1.00 (0.51–1.96) to 2.07 (0.74–5.78) (online supplemental figure 2). Because only nine related studies were included in this report, approaches for detecting publication bias would have exhibited limited efficacy. Consequently, the evaluation of publication bias was not conducted.

    Discussion

    In this study, we observed that antifungal therapy administered to mechanically ventilated patients with Candida colonisation did not show a significant impact on patient outcomes, which were measured by indicators, including mortality, hospital length of stay, ICU length of stay, MV duration and incidence of VAP, and the result is stable when taking different treatment types into consideration. A study by Du declared that antifungal treatment was associated with a reduced risk of VAP, while an autopsy study involving 232 samples showed that, although Candida is a common pathogen, the incidence of Candida pneumonia in ICU patients is extremely low.4 11 Inconsistent with the results of the previous studies, a meta-analysis found that Candida pulmonary colonisation probably had poorer clinical outcomes, owing to longer MV duration, higher 28-day mortality, higher ICU mortality and longer ICU length of stay.28 Furthermore, a study by Ioannou found that about half of the patients with Candida spp. isolation from their respiratory secretions were treated with antifungals. Considering the factor that patients under more critical condition could be treated with antifungals more often, a multivariate regression analysis was conducted identifying antifungal use as an independent factor associated with total hospital mortality.2 Without listing the specific articles for verification, the guideline strongly recommends that Candida colonisation rarely requires treatment with antifungal therapy.29 Our study may help to provide more information on this problem: whether Candida pulmonary colonisation simply symbolises the severity of diseases or actually has an influence on outcomes.30 31

    Candida colonisation in the respiratory tract is related to higher inflammation and may accelerate the disease process.32 33 A few studies used inhalation of antifungal drugs as therapy, which did not show a significant influence on patients’ outcomes. This may lead to direct inhibition or damage of the alveolar-capillary membrane, resulting in an influx of surfactant-inactivating plasma proteins.21 27 After Candida colonisation, current increases in antifungal drug resistance in Candida spp. and clinical treatment failures are of concern.34 Previous history of antifungal prescription influences Candida species distribution and susceptibility profile to antifungal agents.35 Inadequate dose and treatment failure may contribute to high mortality.36

    Considering the various conditions, we thought that various factors cause poor clinical outcomes: antifungal treatment may have more harm than benefit in clinically ill patients. Different antifungal drugs can have varying sensitivities or resistances as well as potential toxicity or adverse effects. Inadequate dosing of antifungal drugs may also be a contributing factor. Although the analysis of this study showed that antifungal treatment did not improve patients’ clinical outcomes, the sample size of included studies was limited and the 95% CIs were wide. Further studies should be conducted to verify their influence. Considering retrospective and current studies can only provide hypotheses to support the existence of a correlation, a prospective randomised controlled trial might be a more appropriate solution to explore the effect of antifungal treatment on patients with respiratory Candida colonisation in combination with MV.

    Based on the findings of this meta-analysis, the use of antifungal medication on mechanical-ventilated patients with respiratory Candida colonisation does not appear to improve patients’ clinical outcomes. No significant differences were observed in ICU mortality, hospital mortality, 28-day mortality, 90-day mortality, ICU length of stay, MV duration and VAP associated with different treatment regimens. Further analysis of subgroups based on different treatment types confirmed these conclusions. Therefore, the use of antifungal medication is not recommended for the decolonisation of mechanical-ventilated patients with respiratory Candida colonisation.

    The strength of this study is that it included a number of outcome indicators to assess the effectiveness of antifungal treatment, with subgroup analyses performed based on the type of treatment administered. However, it encountered several limitations. Most studies included are retrospective studies, raising potential concerns regarding their external validity. Additionally, some studies described the precise style, name, dose and administration method of antifungal drugs, while others did not. Furthermore, this study is limited by the number of studies included, especially when it comes to single outcomes, such as ICU mortality. Moreover, most studies included were cohort studies instead of random control trials, which provide stronger evidence.

    Data availability statement

    Data are available upon reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    Not applicable.

    References

    1. ↵
      1. Pendleton KM,
      2. Huffnagle GB,
      3. Dickson RP
      . The significance of Candida in the human respiratory tract: our evolving understanding. Pathog Dis 2017;75:ftx029. doi:10.1093/femspd/ftx029
    2. ↵
      1. Ioannou P,
      2. Vouidaski A,
      3. Spernovasilis N, et al
      . Candida spp. isolation from critically ill patients’ respiratory tract. Does antifungal treatment affect survival? Germs 2021;11:536–43. doi:10.18683/germs.2021.1288
      OpenUrlPubMed
    3. ↵
      1. Charles MP,
      2. Easow JM,
      3. Joseph NM, et al
      . Aetiological agents of ventilator-associated pneumonia and its resistance pattern - a threat for treatment. Australas Med J 2013;6:430–4. doi:10.4066/AMJ.2013.1710
      OpenUrlPubMed
    4. ↵
      1. Du H,
      2. Wei L,
      3. Li W, et al
      . Effect of Nebulized Amphotericin B in Critically ill Patients With Respiratory Candida spp. De-colonization: A Retrospective Analysis. Front Med (Lausanne) 2021;8:723904. doi:10.3389/fmed.2021.723904
    5. ↵
      1. Tehrani S,
      2. Saffarfar V,
      3. Hashemi A, et al
      . A Survey of Genotype and Resistance Patterns of Ventilator-Associated Pneumonia Organisms in ICU Patients. Tanaffos 2019;18:215–22.
      OpenUrlPubMed
    6. ↵
      1. Farag AM,
      2. Tawfick MM,
      3. Abozeed MY, et al
      . Microbiological profile of ventilator-associated pneumonia among intensive care unit patients in tertiary Egyptian hospitals. J Infect Dev Ctries 2020;14:153–61. doi:10.3855/jidc.12012
      OpenUrlPubMed
    7. ↵
      1. Babaei S,
      2. Pourabdollah M,
      3. Aslanimehr M, et al
      . Frequency of Multi-Drug Resistance and Molecular Characteristics of Resistance to Colistin in Acinetobacter baumannii Collected from Patients in Intensive Care Units with Ventilator-Associated Pneumonia. Tanaffos 2021;20:345–52.
      OpenUrlPubMed
    8. ↵
      1. Bekaert M,
      2. Timsit J-F,
      3. Vansteelandt S, et al
      . Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med 2011;184:1133–9. doi:10.1164/rccm.201105-0867OC
      OpenUrlCrossRefPubMedWeb of Science
    9. ↵
      1. Huang Y,
      2. Jiao Y,
      3. Zhang J, et al
      . Microbial Etiology and Prognostic Factors of Ventilator-associated Pneumonia: A Multicenter Retrospective Study in Shanghai. Clin Infect Dis 2018;67:S146–52. doi:10.1093/cid/ciy686
      OpenUrlCrossRefPubMed
    10. ↵
      1. Hamet M,
      2. Pavon A,
      3. Dalle F, et al
      . Candida spp. airway colonization could promote antibiotic-resistant bacteria selection in patients with suspected ventilator-associated pneumonia. Intensive Care Med 2012;38:1272–9. doi:10.1007/s00134-012-2584-2
      OpenUrlCrossRefPubMed
    11. ↵
      1. Meersseman W,
      2. Lagrou K,
      3. Spriet I, et al
      . Significance of the isolation of Candida species from airway samples in critically ill patients: a prospective, autopsy study. Intensive Care Med 2009;35:1526–31. doi:10.1007/s00134-009-1482-8
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      1. La Y,
      2. Kwon DE,
      3. Jeon S, et al
      . Clinical Implication of Candida Score in Multidrug-Resistant Pneumonia with Airway Candida Colonization. Infect Chemother 2022;54:287–97. doi:10.3947/ic.2022.0024
      OpenUrlPubMed
    13. ↵
      1. Azoulay E,
      2. Timsit J-F,
      3. Tafflet M, et al
      . Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest 2006;129:110–7. doi:10.1378/chest.129.1.110
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      1. Delisle MS,
      2. Williamson DR,
      3. Perreault MM, et al
      . The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients. J Crit Care 2008;23:11–7. doi:10.1016/j.jcrc.2008.01.005
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      1. Williamson DR,
      2. Albert M,
      3. Perreault MM, et al
      . The relationship between Candida species cultured from the respiratory tract and systemic inflammation in critically ill patients with ventilator-associated pneumonia. Can J Anaesth 2011;58:275–84. doi:10.1007/s12630-010-9439-5
      OpenUrlCrossRefPubMed
    16. ↵
      1. Terraneo S,
      2. Ferrer M,
      3. Martín-Loeches I, et al
      . Impact of Candida spp. isolation in the respiratory tract in patients with intensive care unit-acquired pneumonia. Clin Microbiol Infect 2016;22:94. doi:10.1016/j.cmi.2015.09.002
      OpenUrl
    17. ↵
      1. Rouzé A,
      2. Loridant S,
      3. Poissy J, et al
      . Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med 2017;43:1668–77. doi:10.1007/s00134-017-4932-8
      OpenUrlCrossRefPubMed
    18. ↵
      1. Shamseer L,
      2. Moher D,
      3. Clarke M, et al
      . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015;350:g7647. doi:10.1136/bmj.g7647
    19. ↵
      1. Kullberg BJ,
      2. Arendrup MC
      . Invasive Candidiasis. N Engl J Med 2015;373:1445–56. doi:10.1056/NEJMra1315399
      OpenUrlCrossRefPubMed
    20. ↵
      1. Li Q,
      2. Abdalkader M,
      3. Siegler JE, et al
      . Mechanical Thrombectomy for Large Ischemic Stroke: A Systematic Review and Meta-analysis. Neurology (ECronicon) 2023;101:e922–32. doi:10.1212/WNL.0000000000207536
      OpenUrl
    21. ↵
      1. Ong DSY,
      2. Klein Klouwenberg PMC,
      3. Spitoni C, et al
      . Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study. Crit Care 2013;17:R233. doi:10.1186/cc13056
    22. ↵
      1. Nseir S,
      2. Jozefowicz E,
      3. Cavestri B, et al
      . Impact of antifungal treatment on Candida-Pseudomonas interaction: a preliminary retrospective case-control study. Intensive Care Med 2007;33:137–42. doi:10.1007/s00134-006-0422-0
      OpenUrlCrossRefPubMedWeb of Science
    23. ↵
      1. Zhang G,
      2. Feng BB,
      3. Lu ZH, et al
      . Impact of antifungal therapy in mechanically ventilated patients with Candida spp. colonization in lower respiratory tract. Zhonghua Yi Xue Za Zhi 2017;97:2198–201. doi:10.3760/cma.j.issn.0376-2491.2017.28.008
      OpenUrlPubMed
    24. ↵
      1. Griffin M,
      2. Kosmisky DE,
      3. Templin MA, et al
      . Antifungal use in immunocompetent, critically ill patients with pneumonia does not improve clinical outcomes. Heart Lung 2016;45:538–43. doi:10.1016/j.hrtlng.2016.08.002
      OpenUrlPubMed
    25. ↵
      1. Lindau S,
      2. Nadermann M,
      3. Ackermann H, et al
      . Antifungal therapy in patients with pulmonary Candida spp. colonization may have no beneficial effects. J Intensive Care 2015;3:31. doi:10.1186/s40560-015-0097-0
    26. ↵
      1. Albert M,
      2. Williamson D,
      3. Muscedere J, et al
      . Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomized placebo controlled pilot trial (CANTREAT study). Intensive Care Med 2014;40:1313–22. doi:10.1007/s00134-014-3352-2
      OpenUrlCrossRefPubMed
    27. ↵
      1. van der Geest PJ,
      2. Dieters EI,
      3. Rijnders B, et al
      . Safety and efficacy of amphotericin-B deoxycholate inhalation in critically ill patients with respiratory Candida spp. colonization: a retrospective analysis. BMC Infect Dis 2014;14:575. doi:10.1186/s12879-014-0575-3
    28. ↵
      1. Huang D,
      2. Qi M,
      3. Hu Y, et al
      . The impact of Candida spp airway colonization on clinical outcomes in patients with ventilator-associated pneumonia: A systematic review and meta-analysis. Am J Infect Control 2020;48:695–701. doi:10.1016/j.ajic.2019.11.002
      OpenUrlPubMed
    29. ↵
      1. Pappas PG,
      2. Kauffman CA,
      3. Andes DR, et al
      . Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1–50. doi:10.1093/cid/civ933
      OpenUrlCrossRefPubMed
    30. ↵
      1. Cornely OA,
      2. Bassetti M,
      3. Calandra T, et al
      . ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012;18 Suppl 7:19–37. doi:10.1111/1469-0691.12039
      OpenUrlCrossRef
    31. ↵
      1. Xu WM,
      2. Shui W,
      3. Lin JC, et al
      . The serum glucan level and pathological changes of antifungal treatment for lower respiratory tract infection of Candida albicans. Med Mycol 2015;53:153–9. doi:10.1093/mmy/myu068
      OpenUrlCrossRefPubMed
    32. ↵
      1. Yeter HH,
      2. Erten Y,
      3. Sevmez H, et al
      . Oral Candida Colonization as a Risk Factor for Chronic Inflammation and Atherosclerosis in Hemodialysis Patients. Ther Apher Dial 2019;23:542–9. doi:10.1111/1744-9987.12803
      OpenUrlPubMed
    33. ↵
      1. Patel M
      . Oral Cavity and Candida albicans: Colonisation to the Development of Infection. Pathogens 2022;11:335. doi:10.3390/pathogens11030335
    34. ↵
      1. Bailly S,
      2. Maubon D,
      3. Fournier P, et al
      . Impact of antifungal prescription on relative distribution and susceptibility of Candida spp. - Trends over 10 years. J Infect 2016;72:103–11. doi:10.1016/j.jinf.2015.09.041
      OpenUrlCrossRefPubMed
    35. ↵
      1. Hrabovský V,
      2. Takáčová V,
      3. Schréterová E, et al
      . Distribution and antifungal susceptibility of yeasts isolates from intensive care unit patients. Folia Microbiol (Praha) 2017;62:525–30. doi:10.1007/s12223-017-0525-8
      OpenUrl
    36. ↵
      1. de Cássia Orlandi Sardi J,
      2. Silva DR,
      3. Soares Mendes-Giannini MJ, et al
      . Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic options. Microb Pathog 2018;125:116–21. doi:10.1016/j.micpath.2018.09.014
      OpenUrlCrossRefPubMed

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • LL and SS contributed equally.

    • Contributors H-BX and HY provided article ideas and completed a literature search. LL and SS contributed to the data analysis and manuscript writing. H-BX is the guarantor.

    • Funding This study was funded by Changsha Municipal Health Committee (No.KJ-B2023032).

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.