|Year : 2016 | Volume
| Issue : 4 | Page : 139-142
Candiduria: Managing a therapeutic challenge diagnostically
Trupti Bajpai1, Meena Varma2, Ganesh S Bhatambare3, Maneesha Pandey4, Hariom Sharan3
1 Department of Microbiology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh; Department of Biochemistry, SOS, Indira Gandhi National Open University, New Delhi, India
2 Department of Biochemistry, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India
3 Department of Microbiology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India
4 Department of Biochemistry, SOS, Indira Gandhi National Open University, New Delhi, India
|Date of Web Publication||27-Dec-2016|
Department of Microbiology, Sri Aurobindo Institute of Medical Sciences Medical College and PG Institute, MR-10 Crossing, Indore-Ujjain Highway, Indore, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Candida species are among the most common fungal pathogens that are capable of initiating infections in both immunocompetent and immunocompromised individuals. Candidiasis is rightly called as the "disease of diseased." Candiduria is regarded as "red flag" or "surrogate marker" for associated high mortality among patients. Aim: The aim of this study was to determine the prevalence of Candida species among women patients suffering from urinary tract infection. Materials and Methods: The present prospective study was conducted in the Department of Microbiology of a teaching tertiary care hospital located in Indore. A total of 96 Candida species isolated during June 2014 to November 2015 from female urine samples were subjected to species identification by microscopic, biochemical, enzymatic, and automated methods. Results: Among the 96 Candida species, 25% isolates were Candida albicans, 70.8% were non-albicans Candida, and 4.1% were identified as Geotrichum candidum. Candida glabrata (37.5%) predominated among all the species, followed by C. albicans (25%), Candida tropicalis (16.6%) and Candida krusei (16.6%). Conclusions: The finding of candiduria in a patient should neither be dismissed nor empirically treated but requires a careful and logical evaluation. The non-albicans Candida terror should be highlighted to manage the therapeutic challenge successfully.
Keywords: Candida species, candiduria, immunocompromised, Vitek-2 compact
|How to cite this article:|
Bajpai T, Varma M, Bhatambare GS, Pandey M, Sharan H. Candiduria: Managing a therapeutic challenge diagnostically. Int J Health Syst Disaster Manage 2016;4:139-42
|How to cite this URL:|
Bajpai T, Varma M, Bhatambare GS, Pandey M, Sharan H. Candiduria: Managing a therapeutic challenge diagnostically. Int J Health Syst Disaster Manage [serial online] 2016 [cited 2021 Mar 2];4:139-42. Available from: https://www.ijhsdm.org/text.asp?2016/4/4/139/196795
| Introduction|| |
Candida species are among the most common fungal pathogens that are capable of initiating infections in both immunocompetent and immunocompromised hosts; however, the incidence of infections is much more in immunocompromised individuals. Candidiasis, hence, is rightly called as the "disease of diseased."  The presence of Candida albicans and non-albicans Candida species in urine is known as candiduria. , The finding of candiduria in a patient with or without symptoms should be neither dismissed nor empirically treated but requires a careful evaluation in a logical fashion. However, contamination can be differentiated from colonization or infection by obtaining a new urine sample to verify funguria. 
The non-albicans species are often associated with diseases rather than colonization as exhibited by commensals such as C. albicans.  The clinical manifestations of infections caused by different members of non-albicans Candida species are usually indistinguishable; however, several of these species are inherently resistant or acquire resistance or exhibit both the features with respect to commonly used antifungal drugs. With the advent and increasing use of fluconazole, non-albicans Candida have emerged as dominant flora. , Candiduria is regarded as a "red flag" or surrogate marker for associated high mortality. 
Through this study, we would like to introduce the diagnostic plan that could easily help in deciding the species causing candiduria, thereby managing the therapeutic challenges faced by the clinicians while choosing the antimycotic drugs for urinary tract infection (UTI) therapy.
| Materials and Methods|| |
The present study was conducted from June 2014 to November 2015 in the Department of Microbiology of a teaching tertiary care hospital located at Indore (Madhya Pradesh), India. A total of 96 Candida spp. isolated from the clean-catch midstream urine samples of 96 admitted female patients (>11 years of age), clinically suspected of UTI were considered for the study. Urine samples from male patients, female patients <11 years of age, those suspected of leptospirosis, renal tuberculosis, and vaginal infections were excluded from the study. The study was approved by the Institutional Ethical Committee.
The samples were inoculated on the blood agar, MacConkey agar, and UTI chromogenic media. The blood agar media and UTI chromogenic media showing tiny white, dry, translucent to opaque colonies after 24-48 h of incubation were suspected as Candida species. MacConkey media either showed no growth or very poor growth after 48 h of incubation.
Preliminary identification of the isolate was done by Gram staining and urease test. All the urease-negative isolates that microscopically demonstrated Gram-positive budding yeast cells (4-8 μm) with or without pseudohyphae were cultured on Sabouraud's dextrose (SD) agar (HiMedia, Mumbai, Maharashtra, India) with chloramphenicol and incubated at 37°C for 24-48 h. Colonies appearing pasty, opaque, slightly dome-shaped or flat, smooth, and pale-colored (white, off-white, or beige) with sweet smell reminiscent of ripe apples were suspected to be those of Candida. Candida identification on SD agar was again done by Gram stain and India ink preparation.
The mycological workup for speciation of Candida isolates was simultaneously initiated with Germ tube test. The isolates producing germ tubes within 2 h of incubation were further subjected to temperature studies, chlamydospore formation, and biochemical tests. Germ tube negative isolates were classified on the basis of colony color on chromogenic media (HiCrome Candida Differential Agar - M1297A) and sugar assimilation test using sugar discs (xylose, glucose, sucrose, lactose, trehalose, cellobiose, raffinose, melibiose, inositol, dulcitol, galactose and maltose) (HiMedia, Mumbai, Maharashtra, India) (Deorukhkar et al., 2013). ,,,,,,,, The identity of yeasts that could not be confirmed by the auxanographic carbohydrate assimilation test was determined by the Vitek-2 compact automated system. Candida was confirmed as a pathogen based on the patient's gender, age, underlying diseases, and hospitalization status of the patients during the entire study period.
| Results|| |
A total of 96 Candida spp. isolated during our study period (from July 2014 to November 2015) were identified to the species level. All the isolates were from female patients (>11 years of age) clinically suspected of UTI. Among these 96 isolates, 24 (25%) were identified as C. albicans, 68 (70.8%) were identified as non-albicans Candida species, while 4 (4.1%) were identified as Geotrichum candidum [Figure 1]a and b. Among the 68 non-albicans Candida, 36 (37.5% of total Candida) were identified as Candida glabrata, 16 (16.6% of total Candida) as Candida krusei, and also rest of the 16 (16.6% of total Candida) isolates were identified as Candida tropicalis [Table 1].
|Figure 1: (a) Growth of Geotrichum candidum on chromogenic media (b) Gram-stained cells of Geotrichum candidum|
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|Table 1: Prevalence of various species of Candida in culture-positive urine samples |
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| Discussion|| |
UTI has increased in the last two decades probably due to many predisposing factors associated with the occurrence of candiduria. Several predisposing factors responsible for candiduria include broad-spectrum antibiotic therapy, self-medication, surgeries, administration of corticosteroids or immune-suppressive therapy, diabetes, hypertension, stone-formation, urologic structural abnormalities, malnutrition, extremes of age, indwelling urinary devices or prosthesis, low-level individual hygiene, social behaviors, unsuitable air conditioning, extended hospitalization, drug addiction, immunological deficiencies, empirical use of antimycotic drugs, and the personnel's hands. ,,,,,,,,, Besides, systemic conditions such as Vitamin B deficiency, hypothyroidism, and lymphoblastoma favor Candida infection. Traumatic ulceration, postoperative situations, malignancy, and anemia also predispose candidiasis. In addition, yeasts are also isolated from patients suffering from kidney diseases, epididymitis, neoplastic diseases, urogenital anomalies, obstructive uropathy, cystitis, prostatitis, and hemolytic-uremic syndrome. ,
Our study exclusively included women patients because this group is known to be highly susceptible to candiduria even confirmed through studies by Passos et al.  (66.2% women as compared to 33.8% men), Behzadi et al.  (56.5% women as compared to 43.5% men), and Tomczak et al.  (70.2% women as compared to 29.7% men). The most frequent risk factors of UTIs with fungal etiology in women are gender (women), genetic inheritance, pregnancy, and frequent intercourse. Yeasts may ascend from the genital tract to the urinary tract explaining a higher incidence of candiduria in women. As the girl matures, hormonal changes make them more vulnerable to Candida infection. Hormonal changes during pregnancy may also be responsible for the growth of fungi. Although Candida infection is not a classical sexually transmitted disease, it is known to be transmitted, in some cases through sexual intercourse, especially among sexually active women and sex workers, especially in case of unprotected sex and in those with multiple sex partners.  By suppressing susceptible endogenous bacterial flora in the gastrointestinal and lower genital tracts, antibiotic favors epithelial surface fungal colonization, with ready access to the urinary tract, especially in the presence of indwelling bladder catheter. Actually, antibiotic treatment reduces the number of susceptible bacteria species that may be antagonistic to the fungi, thereby enhancing their growth. , The proliferation of Candida in diabetic patients may be attributed to high level of blood sugar, which acts as an energy source to the yeasts.
In our study, 70.8% of non-albicans Candida predominated C. albians (25%). Such results were found to be consistent with the results of Tomczak et al.,  Behzadi et al.,  and Ng et al.  that detected higher, i.e., 53.5%, 51.9%, and 52.5% non-albicans Candida as compared to 46.5%, 49.1%, and 47.4% C. albicans, respectively. However, C. albicans predominated non-albicans Candida in the studies performed by Passos et al.  (69.1%) and Ashour et al.  (56.5%). Candida species are considered important parts of microbial normal flora in healthy humans. Furthermore, they colonize on the external side of the urethral opening in premenopausal and healthy females. Various predisposing factors may lead to an imbalance between C. albicans, non-albicans Candida species, and other host normal flora. Under such conditions, the commensal species of Candida may convert into opportunistic microorganisms creating Candida UTIs in the host.  Among the various treatment options for patients with Candida UTI, fluconazole is known to be the most suitable antifungal agent of choice achieving high urine concentrations with the oral formulations. Rarely, amphotericin B or flucytosine is used. Newer azole agents and echinocandin are not recommended for treatment of UTIs since they fail to achieve adequate concentrations.  The widespread prophylactic use of azoles and reduced threshold for empiric initiation of antifungal treatments among critically ill patients have led to a notable shift from infections with C. albicans to infections with non-albicans Candida species.  These non-albicans Candida should not be overlooked as mere commensals or nonpathogenic commensals as most of them are known to show reduced susceptibility to commonly used antifungal drugs.  These non-albicans are not only adapted well to kidneys and collecting system but also more difficult to eradicate than C. albicans.  Among these, C. glabrata is the main species exhibiting multidrug resistance (resistance to at least two classes of antifungal drugs). 
One of the very interesting and alarming findings in our study was the prevalence of C. glabrata (37.5%) that predominated C. albicans (25%) significantly (P < 0.001). Such results were against the studies done by Passos et al.,  Tomczak et al.,  Behzadi et al.,  Ashour et al.,  and Ng et al.  In all these studies, C. albicans predominated C. glabrata. However, C. glabrata was the most predominant non-albicans Candida among all the other non-albicans Candida species except the results of Ng et al.  that detected C. tropicalis (59%) as the most predominant species, followed by C. albicans (47.4%), C. parapsolis (24.9%), and C. glabrata (12.3%). C. albicans (46.5%, 49.1%) predominated C. glabrata (30.5%, 21.2%) followed by C. tropicalis (5.7%, 14.4%) in the studies of Tomczak et al.  and Behzadi et al.,  respectively, while Ashour et al.  detected the higher prevalence of C. albicans (56.5%), followed by C. glabrata (41.9%) and C. krusei (1.6%).
Although C. albicans is frequently reported as the most prevalent species infecting the urinary tract, non-albicans Candida species appear better adapted to the urinary tract environment, which are increasing especially due to varying predisposing factors. ,, Until the last decade, C. glabrata was considered a relatively nonpathogenic commensal fungal organism of human mucosal tissues. However, the use of immunosuppressive therapy has significantly increased the infections due to C. glabrata. Treating C. glabrata infections is difficult because the organism exhibits innate resistance to azole antimycotic therapy. 
C. albicans and C. glabrata are the two most common pathogenic yeasts of humans; yet, they are phylogenetically, genetically, and phenotypically very different. While C. albicans follow an aggressive strategy to subvert the host response and to obtain nutrients for its survival, C. glabrata seems to have evolved a strategy which is based on stealth, evasion, and persistence. C. albicans is a diploid, polymorphic fungus that ranks first in causing systemic candidiasis and nosocomial UTIs worldwide. The morphological flexibility, such as switching between yeast and hyphal (pseudohyphal) forms and back, is one of the most well-known pathogenic factors in C. albicans.  In addition, there are several attributes such as adhesion, invasion, stereotropism (thigmotropism), discharging hydrolytic enzymes, and biofilm formation which are considered as absolute pathogenic mechanisms pertaining to C. albicans.  In contrast, C. glabrata is strictly haploid and normally grows only in the yeast form. The morphological flexibility of C. albicans seems to play fundamental roles in several aspects of infection. In contrast, the pathogenicity of C. glabrata seems to be independent of morphology. Yet, both these species are closely associated with humans and similarly successful as commensals and as pathogens.  The transition of Candida species from commensal to a potent pathogen is facilitated by number of virulence factors such as adherence to host tissues and medical devices, secretion of extracellular hydrolytic enzymes, and biofilm formation.  C. glabrata apparently adapts well to selected urine properties such as substrate availability, osmolality, and urine pH.  C. glabrata has been reported commonly inpatients with prolonged duration of hospitalization (Ng et al., 2015). 
G. candidum was found to be the causative agent of UTI (urinary geotrichosis) in 4 (4.1%) out of 96 urine samples in our study. This seems to be an exceptional finding because this saprophytic and commensal fungus is an occasional opportunistic pathogen. Most of the times, it is underreported since it is misidentified as Candida species. 
| Conclusions|| |
Our study highlights the logical evaluation and processing of samples with candiduria so as to avoid unnecessary implications of antibiotic therapy. The excessive use of antifungals must be responsible for the spread of non-albicans Candida in our case. Identification of Candida species would further help in deciding the drugs of choice during empirical therapy. However, our study could not differentiate the prevalence of Candida among married and unmarried female patients.
The authors wish to thank the technical staff for their timely help. They are also grateful to the dean and the chairperson of the institute for providing the favorable atmosphere for conducting the research.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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