Susceptibility Patterns of Candida spp. Collected from Intensive Care Units: A Prospective Study in 2020–2022 ^†

Abstract

The frequency of Candida spp. isolates as a cause of hospital infections has risen, and in vitro antifungal susceptibility testing (AST) plays an increasingly important role in guiding therapeutic decisions. This multicenter study aimed to determine AST pattern of Candida spp. isolates from Intensive Care Unit (ICU) patients. In total, 674 patients were enrolled, and axillar/inguinal swabs were collected at admission and during the ICU stay (5th and 8th day). In vitro AST was performed on 355 Candida spp. isolates, according to the concentration gradient Etest^® strip technique. The overall susceptibility rates were 100%, 99.7%, 98.3%, and 97.7% for amphotericin B, voriconazole, anidulafungin, and fluconazole, respectively. The current study demonstrates that antifungal resistance remains infrequent among Candida spp. isolates in Portugal’s ICUs.

1. Introduction

The frequency of Candida spp. isolates as a cause of hospital infections has risen in recent years, leading to high morbidity and mortality rates [1]. Studies have shown that Candida species are the second or the third most common cause of septicemia in Intensive Care Unit (ICU) patients [2], and Candida spp. colonization can be a predictor of candidemia among this cohort of patients [3]. Most often empirical antifungals are prescribed for candidemia, mainly based on locally and country-wide antifungal surveillance data, which differ for every geographic region [4]. Therefore, this study aimed to evaluate antifungal susceptibility pattern of Candida spp. colonization isolates from ICU patients.

2. Materials and Methods

In this multicenter prospective observational study, 675 patients in ICU were recruited from January 2020 through December 2022. Collection of axillar/inguinal swabs was made at admission and during the ICU stay (5th and 8th day). Patient data were obtained through a form containing epidemiological and clinical information. This investigation has been approved by the Institutional Ethical Board of all institutions enrolled. Isolates were identified by cultural, Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS), and molecular methods. In vitro antifungals susceptibility tests (AST) were performed for fluconazole, voriconazole, amphotericin B, and anidulafungin, according to the concentration gradient Etest^® strip technique, following the manufacturer’s instructions. C. parapsilosis ATCC 22019 and C. krusei ATCC 6258 standard strains were used as quality controls. Results were interpreted based on the clinical breakpoints recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST).

3. Results

In total, 355 Candida species isolates were recovered from 988 samples. E-test determination was performed for the isolates, namely, C. albicans (n = 185), the C. parapsilosis complex (n = 112) (C. parapsilosis sensu stricto (n = 109), C. orthopsilosis (n = 2), and C. metapsilosis (n = 1)), C. glabrata (n = 36), C. tropicalis (n = 15), C. lusitaniae (n = 4), and C. guilliermondii (n = 3).

Most Candida species exhibited susceptibility to antifungals. Amphotericin B, voriconazole, and anidulafungin were the drugs for which all Candida species showed more susceptibility, which were, respectively, 100%, 99.7%, and 97.5%. The overall rate of resistance to fluconazole was 2.3%. For fluconazole, NAC isolates were more resistant (1.4%) than C. albicans (0.8%). The rates of susceptibility to fluconazole were 96.8, 95.5, and 100% in C. albicans, C. parapsilosis, and C. tropicalis, respectively. For the other triazole tested, voriconazole, resistance was only observed for C. albicans (1.6%) isolates, but 3.2% (6/185) and 2.7% (3/112) of C. albicans and C. parapsilosis, respectively, presented MICs within the intermediate category. Resistance to drugs within the same class was detected, with two strains of C. albicans and one strain of C. parapsilosis showing resistance to the two azoles tested. Resistance to anidulafungin was observed for three species: C. tropicalis (6.7%), C. albicans (3.8%), and C. parapsilosis (2.7%).

4. Discussion

The current study demonstrates the prevalence and antifungal susceptibility pattern of Candida species in Portugal’s ICUs. Within this cohort, antifungal resistance is infrequent among Candida isolates. Similarly to published data, in our isolates, azole resistance was noted in C. albicans, C. parapsilosis, and C. glabrata, whereas echinocandin resistance was noted in C. albicans, C. parapsilosis, and C. tropicalis [5,6,7,8].

The overall rates of resistance were 2.3 and 0.3% for fluconazole and voriconazole, respectively, which were in line with previous reports, particularly from other European countries [2]. Studies on antifungal susceptibility profiles in Portugal are not recent and used small samples, making it impossible to draw conclusions about antifungal resistance [9,10]. Still, despite the differences in practical details and origin of the isolates, Faria-Ramos et al. [10] reported higher resistance rates: 5 and 12% for fluconazole and voriconazole, respectively.

In this study, three Candida spp. exhibited resistance to anidulafungin, namely, C. tropicalis (6.7%, 1/15), C. albicans (1.6%, 3/185), and C. parapsilosis (0.9%, 1/112). C. glabrata and other Candida spp. did not show any resistance to anidulafungin. These results were in line with the resistance values reported in the literature [6,11,12].

In conclusion, these observations emphasized the importance of knowing the local epidemiology and resistance patterns for Candida spp. within institutions to guide therapeutic decisions.