European Journal of Cardiovascular Medicine

Candida infections, particularly those caused by resistant strains, pose significant challenges in healthcare settings globally. Candida species are ubiquitous fungi that are typically benign commensals but can cause infections ranging from superficial mucosal to severe invasive diseases. The rise in invasive candidiasis has notably increased in hospitalized patients, largely due to growing numbers of immunocompromised individuals, including those undergoing chemotherapy, transplant recipients, and patients with HIV/AIDS.^[1][2]

The spectrum of diseases caused by Candida includes thrush, esophagitis, vulvovaginitis, and potentially life-threatening bloodstream infections or candidemia, which carry high morbidity and mortality rates. One of the main concerns in the management of candidiasis is the increasing resistance to antifungal agents, particularly to fluconazole and other azoles, which are commonly used for treatment. This resistance complicates therapeutic strategies and highlights the need for ongoing surveillance to guide clinical decision-making.^[3][4]

Hospital environments can act as reservoirs for resistant Candida species, with transmission facilitated by medical procedures and devices, healthcare worker-to-patient contact, or patient-to-patient transmission. The intensive use of broad-spectrum antibiotics, immunosuppressive therapy, and invasive devices such as catheters and ventilators further enhance susceptibility to infections.^[5][6]

Aim

To determine the prevalence and antifungal resistance patterns of Candida species isolated from hospitalized patients.

Objectives

1. To identify the prevalence of different Candida species among hospitalized patients.
2. To assess the resistance patterns of these isolates to commonly used antifungal medications.
3. To analyze the factors associated with antifungal resistance in these Candida species.

Source of Data

Data were sourced from clinical specimens of hospitalized patients suspected of fungal infections.

Study Design

This was a cross-sectional observational study.

Study Location

The study was conducted at a tertiary care hospital.

Study Duration

The study spanned from January 2023 to December 2023.

Sample Size

The study comprised 200 clinical isolates from hospitalized patients.

Inclusion Criteria

Included were samples from patients with clinical signs of fungal infection, hospitalized during the study period.

Exclusion Criteria

Excluded were samples from outpatients, patients without consent, and samples contaminated with multiple fungi.

Procedure and Methodology

Clinical samples (blood, urine, respiratory secretions, and tissue biopsies) were collected aseptically and processed for fungal culture. Isolated Candida species were identified using standard microbiological techniques.

Sample Processing

Samples were cultured on Sabouraud's dextrose agar, and isolates were identified based on colony morphology, Gram staining, and biochemical tests (CHROMagar Candida). Antifungal susceptibility testing was performed using the disk diffusion method.

Statistical Methods

Data were analyzed using SPSS version 25.0. Descriptive statistics, chi-square tests, and logistic regression were employed to describe prevalence rates and analyze resistance patterns.

Data Collection

Data collection included patient demographics, clinical data, laboratory results, and outcomes regarding infection resolution or persistence. Data were maintained in a secure, anonymized database to ensure confidentiality and compliance with ethical standards.

Table 1: Prevalence and Antifungal Resistance Patterns of Candida Species Isolated from Hospitalized Patients

Table 1 describes the overall distribution and resistance patterns of Candida species among 200 isolates. It was found that Candida albicans was the most prevalent, comprising 69% (138 isolates) of the samples, which significantly outnumbered the non-albicans Candida species at 31% (62 isolates). Both types showed statistically significant prevalence with p-values less than 0.001. Concerning antifungal resistance, 23.5% of the isolates were resistant to Fluconazole and 9% to Echinocandins, with respective p-values indicating significant resistance levels.

Table 2: Prevalence of Different Candida Species Among Hospitalized Patients

Table 2 breaks down the prevalence of different Candida species among the hospitalized patients. Again, Candida albicans was predominant at 69%, followed by Candida glabrata at 16%, Candida parapsilosis at 9%, Candida tropicalis at 4%, and Candida krusei at 2%. Each species’ presence in the cohort was statistically significant, indicating a diverse yet predominantly albicans Candida environment within the hospital setting.

Table 3: Resistance Patterns of Isolated Candida to Commonly Used Antifungal Medications

Table 3 shifts focus to the resistance patterns against commonly used antifungal medications among the isolated Candida. Here, resistance to Fluconazole was noted in 23.5% of the isolates, Itraconazole in 19.5%, Voriconazole in 13.5%, Echinocandins in 9%, and Amphotericin B in 6%. Each medication's resistance data was statistically significant, suggesting a substantial challenge in managing infections with these antifungals due to resistance.

Table 4: Factors Associated with Antifungal Resistance in Isolated Candida Species

Table 4 examines the factors associated with antifungal resistance in the isolated Candida species. Significant associations were found with previous antifungal use (37%), hospital stays longer than 7 days (41.5%), the use of central venous catheters (33.5%), ICU admissions (28%), and immunosuppressive therapy (24.5%). Each factor demonstrated a significant correlation with increased resistance, underscoring the complex interplay between patient management practices and the development of antifungal resistance.

Table 1 presents the prevalence and antifungal resistance patterns among 200 isolates. Candida albicans remains the most prevalent species, found in 69% of the cases, which is consistent with global trends that suggest C. albicans as the dominant pathogen in candidiasis.

Non-albicans Candida species make up 31%, which is significant and aligns with studies indicating an increase in infections caused by these species, often associated with higher antifungal resistance. Notably, resistance to fluconazole and echinocandins was observed in 23.5% and 9% of isolates, respectively, which underscores concerns about growing resistance trends reported in literature: Badiee P et al. (2022)^[7], which showed a rising trend in non-albicans Candida infections, particularly those resistant to fluconazole. Jensen RH et al. (2016)^[8], where echinocandin resistance was increasingly noted, particularly in C. glabrata isolates. Aldardeer NF et al. (2020) ^[9]

Table 2 details the prevalence of specific Candida species. The dominance of C. albicans is noted along with significant presence of C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. These findings mirror those reported by Sajjan AC et al. (2014)^[10] which also noted the prevalence rates of C. glabrata and C. parapsilosis rising, particularly in nosocomial infections. These trends emphasize the need for vigilant surveillance and species-specific antifungal strategies.

Table 3 shows varied resistance patterns against major antifungals. The observed resistance to fluconazole and itraconazole reflects broader concerns about azole resistance, as reported by Badiee P et al. (2017)^[11]. Resistance to amphotericin B and voriconazole remains concerning but less frequent, which is consistent with global data suggesting limited but significant resistance to these drugs, necessitating ongoing monitoring and resistance management strategies.

Table 4 identifies factors associated with antifungal resistance, highlighting previous antifungal use, extended hospital stays, the use of central venous catheters, ICU admissions, and immunosuppressive therapy as significant contributors to resistance development. These factors are widely recognized in literature as risk factors for developing invasive candidiasis and antifungal resistance: Liu F et al. (2021)^[12]

This cross-sectional study has elucidated significant insights into the prevalence and antifungal resistance patterns of Candida species isolated from hospitalized patients, highlighting critical aspects that could guide future clinical strategies and policies for managing candidiasis in hospital settings.

The findings confirm that Candida albicans remains the predominant species among Candida isolates, accounting for 69% of cases. However, there is a considerable presence of non-albicans Candida species, which exhibit distinct resistance profiles, particularly towards commonly used antifungals such as fluconazole. Notably, 23.5% of the isolates were resistant to fluconazole, while resistance to echinocandins was observed in 9% of cases. These resistance rates are alarming, given the reliance on these antifungal agents for treatment protocols, underscoring the urgent need for enhanced surveillance and resistance management strategies.

Moreover, the study identified several risk factors associated with antifungal resistance, including prior antifungal use, prolonged hospital stays, the utilization of central venous catheters, ICU admissions, and immunosuppressive therapy. These factors are indicative of the complex interplay between hospital-based medical practices and the development of fungal resistance, suggesting that interventions aimed at optimizing antifungal use and reducing invasive procedures could substantially mitigate resistance development.

In conclusion, the growing prevalence of antifungal resistance among Candida species in hospital environments poses a significant challenge to effective clinical management. This study underscores the necessity for ongoing monitoring of antifungal susceptibility patterns and the implementation of rigorous infection control practices. There is also a pronounced need for educational programs to raise awareness about the prudent use of antifungal agents and the implementation of stewardship programs. Such measures will be crucial in curbing the spread of resistant Candida strains and ensuring the efficacy of existing and future antifungal therapies.

1. Single-Center Design: The study was conducted in a single tertiary care hospital, which may limit the generalizability of the findings to other settings. Different hospitals may have varying patient demographics, healthcare practices, and local antifungal usage patterns that could influence the prevalence and resistance patterns of Candida species.
2. Cross-Sectional Nature: Due to the cross-sectional design of the study, it is challenging to establish causality between observed antifungal resistance and specific risk factors. Longitudinal studies would be better suited to understanding the dynamics of Candida colonization and infection, including resistance development over time.
3. Sampling Limitations: The study relied on available clinical samples, which may not represent all hospital-acquired Candida infections. Certain infections might have been asymptomatic or subclinical, and therefore not sampled or cultured, potentially leading to underreporting of both prevalence and resistance.
4. Resistance Testing: Resistance was determined using standard laboratory methods, which, while reliable, may not reflect the resistance patterns seen in clinical settings where multiple antifungal agents are used simultaneously. Moreover, emerging resistance mechanisms may not be detectable with routine susceptibility testing.
5. Lack of Detailed Clinical Data: The study did not consistently capture detailed clinical data for each patient, such as the duration of antifungal treatment, specific underlying conditions, or the impact of antifungal resistance on clinical outcomes. This data could provide deeper insights into the factors driving resistance patterns and the clinical implications of antifungal resistance.
6. Exclusion of Other Fungi: The focus was solely on Candida species; however, other fungi might co-infect patients, influencing the clinical management and outcomes of fungal infections. A broader microbial examination could provide a more comprehensive understanding of the microbial ecology in hospital settings.
7. Statistical Power: Although the sample size was adequate to estimate the prevalence of Candida infections and resistance, smaller subgroups (e.g., rare Candida species or specific resistance patterns) may not have been adequately powered to detect all clinically significant associations.
8. Temporal and Seasonal Variations: The study did not account for potential temporal or seasonal variations in Candida infections and antifungal resistance, which could affect the reliability of extrapolating these results acr

1. Magalhães YC, Bomfim MR, Melônio LC, Ribeiro PC, Cosme LM, Rhoden CR, Marques SG. Clinical significance of the isolation of Candida species from hospitalized patients. Brazilian Journal of Microbiology. 2015 Mar 31;46(1):117-23.
2. Kaur R, Dhakad MS, Goyal R, Kumar R. Emergence of non-albicans Candida species and antifungal resistance in intensive care unit patients. Asian Pacific Journal of Tropical Biomedicine. 2016 May 1;6(5):455-60.
3. Tadec L, Talarmin JP, Gastinne T, Bretonnière C, Miegeville M, Le Pape P, Morio F. Epidemiology, risk factor, species distribution, antifungal resistance and outcome of Candidemia at a single French hospital: a 7‐year study. Mycoses. 2016 May;59(5):296-303.
4. Solomon DA, Nyerere AK, Kanyua A, Ngugi CW. Prevalence, species distribution and antifungal susceptibility profile of candida species isolated from bloodstream of critical care unit patients in a tertiary care hospital in Kenya. Open Journal of Medical Microbiology. 2021 Feb 2;11(1):32-46.
5. El-Ganiny AM, Yossef NE, Kamel HA. Prevalence and antifungal drug resistance of nosocomial Candida species isolated from two university hospitals in Egypt. Current medical mycology. 2021 Mar;7(1):31.
6. Zeng ZR, Tian G, Ding YH, Yang K, Liu JB, Deng J. Surveillance study of the prevalence, species distribution, antifungal susceptibility, risk factors and mortality of invasive candidiasis in a tertiary teaching hospital in Southwest China. BMC infectious diseases. 2019 Dec;19:1-2.
7. Badiee P, Boekhout T, Haddadi P, Mohammadi R, Ghadimi-Moghadam A, Soltani J, Zarei Mahmoudabadi A, Ayatollahi Mousavi SA, Najafzadeh MJ, Diba K, Salimi-Khorashad AR. Epidemiology and antifungal susceptibility of Candida species isolated from 10 tertiary care hospitals in Iran. Microbiology spectrum. 2022 Dec 21;10(6):e02453-22.
8. Jensen RH, Johansen HK, Søes LM, Lemming LE, Rosenvinge FS, Nielsen L, Olesen B, Kristensen L, Dzajic E, Astvad KM, Arendrup MC. Posttreatment antifungal resistance among colonizing Candida isolates in candidemia patients: results from a systematic multicenter study. Antimicrobial agents and chemotherapy. 2016 Mar;60(3):1500-8.
9. Aldardeer NF, Albar H, Al-Attas M, Eldali A, Qutub M, Hassanien A, Alraddadi B. Antifungal resistance in patients with Candidaemia: a retrospective cohort study. BMC infectious diseases. 2020 Dec;20:1-7.
10. Sajjan AC, Mahalakshmi VV, Hajare D. Prevalence and antifungal susceptibility of Candida species isolated from patients attending tertiary care hospital. IOSR J Dent Med Sci. 2014;13(05):44-9.
11. Badiee P, Badali H, Boekhout T, Diba K, Moghadam AG, Hossaini Nasab A, Jafarian H, Mohammadi R, Mirhendi H, Najafzadeh MJ, Shamsizadeh A. Antifungal susceptibility testing of Candida species isolated from the immunocompromised patients admitted to ten university hospitals in Iran: comparison of colonizing and infecting isolates. BMC infectious diseases. 2017 Dec;17:1-8.
12. Liu F, Zhong L, Zhou F, Zheng C, Zhang K, Cai J, Zhou H, Tang K, Dong Z, Cui W, Zhang G. Clinical features, strain distribution, antifungal resistance and prognosis of patients with non-albicans candidemia: A retrospective observational study. Infection and Drug Resistance. 2021 Aug 17:3233-46.