Fungal infections, explicitly Candida species have been the major cause of mortality and morbidity in hospitalized patients and predominantly in the Critical Care Units [1] [2]. Candida species reside inside the host as normal flora and dwell in the oral cavity of healthy human beings, however, in immunocompromised patients, these commensal microorganisms are capable of causing disease [3]. Prominently causing nosocomial infections, Candida spp. rates the fourth in causing all bloodstream infections and third of bloodstream infections in critically ill patients [4]. Worldwide in tertiary care hospitals, those results attribute to mortality rates of 15% ± 35% in adults and 10% ± 15% in neonates [5]. Based on studies done in several hospitalized patients, including intensive care unit patients, candidemia causes mortality of 47% among the patients [6].

In the USA, Candida species are considered as the third or fourth most causative agent of healthcare-acquired infections [5] and lead to a 30% - 60% mortality rate of hospitalized patients [6]. These are associated with changes in the individuals’ physiology and immunocompromised state which results in severe infections [3]. Several risk factors of the origin of the Candida infections in hospitalized patients could be endogenously brought by the patients themselves or could be from instruments in the hospital. It might also be contributed to contaminations of hospital surroundings or cross-infection from health workers which would attribute to the exogenous cause [5] [7] [8]. Candidemia is frequently seen among those infections, especially with patients in Critical Care Units [5]. Moreover, as a result of these infections, expanded costs in healthcare are incurred, ranging from $35,000 to $68,000 for a single candidemia case in the United States [8].

Patterns of anti-fungal drug resistance by Candida species have been causing stern public health challenges and were encompassed in CDC’s 2013 Antibiotic Resistance Threat Report [9] [10]. Critically ill patients undergo invasive treatments and consume several anti-fungal drugs, however, results of anti-fungal resistance have been causing epidemiological unsustainability [11] [12]. Certain Candida strains are progressively resistant to commonly used antifungal drugs. Based on recent data from CDC, a discernable shift is observed in candidemia occurrences with augmented drug resistance to first-line and second-line antifungal drugs such as Azoles and Echinocandins [10]. In the United States, 46,000 hospitalized patients face Candida infections each year, and approximately 30% of those who harbor drug-resistant Candida species are estimated to die during hospitalization [10]. Several reports state that the increase of anti-fungal resistance has been resulting in high mortality and morbidity in critical care patients [2] [13]. This has contributed to many deaths due to Candida infections in the past years [11] [12].

According to literature from Kenya, the significant agent for hospital infections is considered to be Candida albicans [14] [15]. However, Candida auris has recently been observed frequently in a tertiary care hospital in Nairobi, Kenya grounded on several lab reports from ICU and HDU patients. Swift dissemination of this multi-drug resistant species is discerned in different parts of the world [2]. It was first reported in 2009 and since then it has been detected in five continents causing serious hospital-acquired infections [2]. A study conducted in Kenya recorded a drug resistance pattern of Candida albicans andCandida parapsilosis isolates towards fluconazole [14] [16], however, drug susceptibility patterns of the novel species, Candida auris remains unreported up-to-date in Kenya. Therefore, the aim of this study was to determine the prevalence and antifungal susceptibility profile of Candida species among critical care unit patients of the hospital.

This study documents the prevalence of candidemia among patients admitted to the critical care unit of a tertiary care hospital in Nairobi, Kenya. The results showed a higher prevalence of 8.2% compared to a study previously conducted in Kenya showing a rate of 5 cases of candidemia per 100,000 patients [15]. The increased candidemia could be attributed to the number of invasive measures taken in hospitalized patients when handling their medical care and the immunocompromised state of the patients also plays a role in the severity of the infection. This ascent in prevalence demonstrates a public health challenge, especially to those who are hospitalized in ICU and HDU and have relatively severe illnesses.

Existing publications of Candida infections in Kenya states that the most frequently isolated Candida species was Candida albicans [14] [16], however, this study highlights the onset of the new species, Candida auris in high prevalence. Candida auris was first isolated in 2009 and recorded cases are portrayed by elevated levels of total mortality [2] [24] [25] and high antifungal resistance rates [26]. Of note, the vast majority of the infections reported involved patients that are critically ill [24] [27]. Furthermore, identification has been difficult by microbiological techniques [2] [28] [29] notwithstanding Candida auris being one of the most prevalent species which increases the risk of misidentification and hence improper treatment. Candida auris’s high virulence [30] [31], a profile of multi-drug resistance [32], and rapid outbreak and global propagation marks it as a worldwide threat [2].

The antifungal susceptibility tests performed showed a susceptible profile of all isolates towards Echinocandins and Amphotericin B and Voriconazole. A study conducted in a tertiary care hospital in Italy, however, showed a resistance pattern of Candida albicans towards Voriconazole [33]. Besides, as evidenced in certain reports Candida species are usually susceptible to Amphotericin-B as an antifungal drug [33], and the resistance to Echinocandins is in very low percentages

Classification of sensitive and resistant according to the rules of the Clinical and Laboratory Standards Institute M27-A3 [23]: Fluconazole (S: 8 µg/mL; R: 64 µg/ml); Voriconazole (S: 1 µg/mL; R: 4 µg/mL); Flucytosine (S: 4 µg/mL; R: 32 µg/mL); Amphotericin B (S < 1 µg/mL; R > 2 µg/mL); Echinocandins (S < 2 µg/ml, sensitive breakpoint only). S, sensitive; R, resistant.

to Candida albicans and non-albicans except for Candida glabrata [34] .Moreover, a study conducted in Kenya showed a resistance pattern of Candida albicans towards Fluconazole at a rate of 26% [16]. Interestingly, there was no isolate of Candida albicans showing resistance to any of the drug classes used in this study. Aware of the latter assertion, the increased susceptibility of Candida albicans might indicate the enhancement of drug regime towards this species as research was done massively targeting it in Kenya [14] [15] [35].

Furthermore, an increased resistance pattern in three species was observed in this study. Candida auris was seen to have a high resistance pattern up to 256 µg/ml for fluconazole indicating no susceptible isolate from all the 9 isolates tested against fluconazole. The power of Candida auris to establish uniform resistance to fluconazole might increase the mortality rates of immunocompromised patients [2] [36]. This study additionally acquired a drug resistance pattern towards Flucytosine by Candida tropicalis with 3 (100%) isolates showing increased MIC values as was classified resistant by CLSI breakpoints. A study conducted in Paris indicates the increased resistant activity of Candida tropicalis towards Flucytosine [37], however, this has not been documented in Kenya previously. In spite of certain reports expressing Candida parapsilosis as frequently susceptible to azoles [38] [39], several pieces of research have indicated its increased resistance towards Fluconazole [23] [40] [41]. In this study, all isolated Candida parapsilosis were discovered resistant to Fluconazole.

The drug susceptibility results exhibited a resistance pattern in the entirety of the isolated species of Candida parapsilosis, Candida auris, and Candida tropicalis. Critically ill patients face the threat of morbidity and mortality as a result of the wide use of broad-spectrum anti-fungal drugs where there is a development of resistance by Candida species [2]. Inherent causes of resistance are also noted on top of the usual acquired pattern of drug resistance after antifungal drugs are administered to patients [2] [42]. This intrinsic nature of resistance is usually seen in non-albicans, as is documented in this study. Despite the fact that the onset of drug resistance happens in several cases the pattern of complete resistance in all three species might show transmission of the Candida species among the patients. Infection control in patients with Candida has never been a challenge previously since it was comprehended that Candida infections derive essentially from the translocation of host flora to usually sterile locations, such as the bloodstream. Similar patterns of resistance, however, may suggest that the same strain circulates across the patients attributed to hospitalized patients’ transmission as is confirmed by numerous studies [43] [44] [45]. The increased resistance of the Candida species inclines a high risk to hospitalized patients and might attribute to increased death rate particularly in critically ill patients.

There are increased candidemia cases in the critical care units of the health facility and dependent on the outcomes acquired, the study determined an exceptionally pervasive occurrence of new Candida species: Candida auris, and its drug-resistant property as a high threat to the public. Thus, measures ought to be taken to control the infection and transmission to diminish the mortality and morbidity of critically ill patients. Additionally, Echinocandins showed high potency as antifungal drugs against albicans and non-albicans whereas Fluconazole and Flucytosine were proved to be less effective drugs in the conspicuously seen species of Candida auris,Candida parapsilosis,and Candida tropicalis. Consequently, for an appropriate drug regime, physicians should be alert of the drug susceptibility patterns of Candida species in the locality before prescribing any of the anti-fungal drugs. All in all, the onset of new species and increased drug resistance patterns warrant constant drug monitoring. As this study was limited to Nairobi, researches of Candida blood stream infections in critical care units should be done in hospitals in other parts of Kenya for a comprehensive and updated prevalence study and to monitor the spread of Candida auris in the country. Moreover, the molecular basis of resistance should also be established in future studies for enhanced treatment.

We would like to acknowledge AFRICA-ai-JAPAN Project for funding this research. We would also like to convey our gratitude to Nairobi Hospital, especially the Microbiology Department and Mrs. Felister Musyoki, and One health, HORN for their material and physical support. Our appreciation goes to Mr. Pawlos Semere Tsegay for his continuous support throughout the research and Mr. James Gachugia for his assistance in editing the manuscript.

This project is funded by AFRICA-ai-JAPAN Project for materials and reagents used in the research.

DAS, AKN, AK, CWN conceived and designed the study. DAS performed laboratory analysis and data analysis. DAS drafted the manuscript. All authors read, reviewed, and approved the final manuscript.

Ethical approval was obtained from Jomo Kenyatta University of Agriculture and Technology’s Ethics Review Committee and the study site hospital’s Ethics Review Committee. No patient was recruited solely for the study, but rather the study was part of the normal patient care process. Access to the data was strictly prohibited to maintain the confidential information of the patient. Patient Identification was done in a way that doesn’t disclose the real information of the patient to avoid the leak of patient history.

The data can be provided upon request from the corresponding author.

The authors declare that there is no conflict of interest regarding the publication of this paper.

Solomon, D.A., Nyerere, A.K., Kanyua, A. and Ngugi, C.W. (2021) 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, 11, 32-46. https://doi.org/10.4236/ojmm.2021.111003

CCU: Critical Care Units;

ICU: Intensive Care Unit;

HDU: Highly Dependent Unit;

SDA: Saboraud Dextrose Agar;

JKUAT: Jomo Kenyatta University of Agriculture and Technology.