Prevalence of Fungal Urinary Tract Infections in Madinah Region

doi:10.21203/rs.3.rs-4920744/v1

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Prevalence of Fungal Urinary Tract Infections in Madinah Region

https://doi.org/10.21203/rs.3.rs-4920744/v1

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Background

Urinary tract infections (UTIs) are prevalent illnesses, affecting more than 404.6 million people globally, representing around 5.23% of the total global population. Forty percent of UTIs are caused by fungi. Candida albicans, which is naturally found on the human body, commonly causes candiduria in predisposed individuals.

Aim

This study aims to enhance understanding of the risk factors, clinical manifestations, and appropriate management of fungal UTIs. We hypothesized an increase in the prevalence of fungal disease in UTIs (FUTIs) in Madinah region, Saudi Arabia.

Materials and Methods

The study uses an observational-retrospective approach and includes all hospitalized patients with positive fungal urine cultures across all departments from June 2016 to October 2019. The prevalence, incidence, and comorbidity of FUTIs are investigated through data collection from King Fahd Hospital in Madinah, Saudi Arabia.

Results

The study, based on 87,447 admissions over 7 years, found a prevalence of FUTIs of 0.052% in the patients. The incidence rate began at 5.4 per 1000 individuals in 2016 and dramatically increased to 206 per 1000 individuals by 2019. This represents an approximately 40-fold increase over the initial rate. C. albicans was the most identified organism, accounting for 86.9% of the cases. The most prevalent comorbidity observed was renal system diseases.

Conclusion

The study highlights the increase of FUTIs, and the importance of understanding the risk factors to apply preventative measures and ensure prompt and effective intervention. It also underscores the need for continuous monitoring of FUTI in other Madinah hospitals and in Saudi Arabia

Urinary tract infections (UTIs) are common illnesses that occur when microbes enter the urethra and infect the urinary tract. These germs often originate from the skin or rectum. While UTIs can affect different parts of the urinary tract, bladder infections (cystitis) are the most common type[1]. Women experience 50–80 cases of cystitis per 100,000 people, compared to 5–7 cases per 100,000 men of the same age. Symptoms of a UTI include painful or burning urination, frequent urges to urinate with minimal output, pressure in the lower abdomen, and cloudy or foul-smelling urine. Blood in the urine is more typical among younger females, while older women may feel weak, disoriented, tired, or unsteady. The presence of a fever may indicate that the infection has spread to the kidneys [2]

Fungi species are rare but important causes of UTI [3]. The most common fungi species causing UTI is Candida albicans (30%), while Nakaseomyces glabratus was the most frequently isolated non-Candida species at 28.8%. Candida kefyr was the least common species, making up 2.5% of cases [4]. Candida albicans, which naturally exists in the human body, is essential for maintaining a healthy microbiome. It typically coexists harmlessly with healthy skin and organs, including the mouth, throat, gut, and vagina [5]. However, when the balance between normal flora and yeast is disrupted, Candida can overgrow and cause infections, known as candiduria. Candiduria is commonly seen in hospitalized patients and is associated with conditions such as diabetes mellitus, broad-spectrum antibiotic therapy, indwelling urinary devices, and structural abnormalities of the genitourinary tract [6].

The pathogenesis of Candida albicans is aided by a variety of virulence factors, including adhesion molecules, morphogenesis (the reversible transition from unicellular yeast cells to filamentous forms), and secreted aspartyl proteases. These proteases can incite macrophage chemotaxis, modify the host complement cascade, and damage epithelial cells. Phospholipases are also involved, aiding in host identification, nutrient uptake, and tissue penetration. Additionally, "phenotypic switching" in Candida albicans and other species is associated with changes in tissue affinities, colony morphology, and antigen production. This switching may provide the flexibility needed for the organism to adapt to the harsh conditions imposed by the host. According to data, the most common diagnosis among affected patients was chronic kidney disease (CKD), with 46 observations. CKD involves prolonged inflammation, which diminishes the body's ability to fight infections, thereby increasing the risk of infection for individuals with CKD [7].

Purpose of this study is to enhance the understanding of the risk factors, clinical manifestations, and appropriate management of fungal urinary tract infections (FUTIs) to ensure prompt and effective intervention. The study hypothesizes an increased prevalence of fungal disease in urinary tract infections in the Madinah region of Saudi Arabia. The prevalence and incidence of candiduria will be investigated through data collection from King Fahd Hospital (KFH) in Madinah, Saudi Arabia. There is currently no report from the Ministry of Health (MOH) regarding a significant increase in cases of fungal diseases in the Madinah region.

Study Type

This study is an observational cross-sectional retrospective approach.

Population

This data was extracted from June 2016 to October 2019. All the hospitalized patients with positive fungal urine cultures across all departments were covered. The hospital database's data for patients with positive urine cultures for FUTIs were analysed. The data comprised all occurrences of FUTIs, as well as their initial diagnosis, age, gender, comorbidities, detected species, and resistance profile. A patient was counted as a new episode in the research when admitted more than once. The urine cultures colony count of10⁴-10⁵ CFU/mL or more were determined to be significant for existing FUTIs.

Urine samples were collected when indications of infection were observed. For high-risk instances, Myco/Flytic culture vials were utilized for fungal cultures. Cultures are grown on specific media optimized for fungal growth, allowing for observation of colony morphology and identification. Staining techniques were utilized to highlight fungal elements. Positive urine cultures were processed for further identification using potassium hydroxide (KOH). Yeasts were identified conventionally and subjected to sensitivity testing using the VITEK 2 system (bioMérieux, Marcy-L'Étoile, France) following the manufacturer's instructions. In addition, the new clinical and laboratory standards institute (CLSI) recommendations served as the basis for the interpretation of the antifungal susceptibility reporting criterion.

Statistical analysis

SPSS for Windows Version 20.0. Armonk, NY: IBM Corp. was used to analyse the data. The static assets were applied as follows: they examined the precise relationship between the variables and basic descriptors such as frequencies, medians, and incidence rates per 1000 individuals were also calculated for each year, and prevalence analysis according to the total hospital admissions was 87447 over the 7 years. While Mann-Whitney U test was used to know the distribution against gender, the significant threshold of p ~ < 0.05 was used. Also, regression analysis was applied using Microsoft® Excel® for Microsoft 365 MSO (Version 2403 Build 16.0.17425.20124) 64-bit.

The total hospital admissions were 87447 over the 7-year period, the prevalence of FUTIs in the study’s 46 patients was 0.052%. There was a notable increase in the prevalence over the years: 2.1% (n = 1) in 2016, 6.5% (n = 3) in 2017, 8.6% (n = 4) in 2018, and remarkably reaching 82.6% (n = 38) in 2019. The incidence rates per 1000 individuals were also calculated for each year: 5.4 in 2016, 16.3 in 2017, 21 in 2018, and 206 in 2019, indicating a significant increase, approximately 40 folds from 2016 to 2019 (Table 1).

Table 1

Incidence rate and prevalence of fungal UTIs per year.
Year	Incidence Rate	Prevalence
2016	5.4	2.1% (n = 1)
2017	16.3	6.5% (n = 3)
2018	21	8.6% (n = 4)
2019	206	82.6% (n = 38)

Demographic character

The study involved participants ranging in age from 17 to 87 years, with an average age of 58.43 years. The most common age was 60 years, and the median age was 61.50 years. The participants were divided into three age groups. The teens group had 2.17% (n = 1) of the total patients. The adults group comprised 39.1% (n = 18) of the total. The largest group was the seniors, representing 58.69% (n = 27) of the patients. In terms of gender distribution, the study included 52.17% (n = 24) females and 47.83% (n = 22) males, making the gender ratio slightly different (Fig. 1) (Table 2).

Table 2

Number of FUTIs episodes per age and gender.
Age group	No. of cases	Males (22)	Females (24)
Teens (12–17)	1	0	1
Adults (18–59)	18	7	11
Seniors (+ 60)	27	15	12
Total	46	22	24

Organism frequency was slightly higher in females at 52% (n = 24) compared to males at 47% (n = 22), although this difference was not statistically significant based on a Mann Whitney U test (p-value = 0.159, confidence level of 95%). C. albicans was the predominant organism detected in both genders, accounting for 86.9% (n = 40) of cases. In addition to C. albicans, other yeasts were detected in 6.52% (n = 3) of patients, two of whom were males and one female. Candida glabrata was only detected in 2.17% (n = 1) of male patients. C. parapsilosis was found in 2.17% (n = 1) of male patients. Trichosporon mucoides was also detected in 2.17% (n = 1) of male patients (Fig. 2).

The regression analysis revealed valuable insights into the relationship between risk factors and the outcomes. The R Square value of (0.370053088) suggests that about 37% of the outcome's variance is explained by the factors in our model. Age and gender were significant predictors in our analysis, with respective P-values of (0.001575345) and (0.016753518), indicating their roles in influencing outcomes to varying degrees. Among comorbidities, urinary and gastrointestinal disorders showed non-significant impacts with P-values of (0.483104036) and (0.856041121), while respiratory and cardiac disorders also lacked significant association with P-values of (0.433342271) and (0.449263974). Cancer and stroke displayed potential associations with lower P-values of (0.908228437) and (0.37315544), although not statistically significant. In addition, others didn't show significant association with the outcome, as reflected by the overall P-value of (0.432947254) (Table 3).

Table 3

Regression analysis of risk factors in FUTIs and different comorbidities.
Risk factors and Comorbidities in FUTIs
Multiple R	0.60831989
R Square	0.370053088
Adjusted R Square	0.190068256
Standard Error	0.60549259
	P-value
Intercept	2.18559E-05
Age	0.001575345
Gender	0.016753518
GIT	0.856041121
Renal	0.483104036
CVS	0.599508028
Respiratory	0.433342271
CNS	0.449263974
Cancer	0.908228437
Stroke	0.37315544
Others	0.432947254

This observational-retrospective study aimed to determine the prevalence of fungal infections in the urinary tract. The study analysed the result of 46 patients with confirmed FUTIs at King Fahad General Hospital in Madinah, Saudi Arabia, between June 2016 and October 2019. Notably, Candida albicans was identified in 85% of the fungal-positive samples, along previous findings where C. albicanswere typically the most isolated fungal species. However, non-Candida albicans spp. were reported to be a new emerging dominant isolated group (C. tropicalis and C. glabrata) [8]. These results support our theory that Madinah has high frequency of fungal conditions in urinary tract infections.

As expected, female patients had a slightly higher percentage of positive FUTIs (52%) compared to male patients (48%). This observation is consistent with other studies due to the female short urethra and proximity to the rectum. Notably, a slightly greater number of positive fungal samples were detected in female patients (53%) compared to male patients (47%) [9].

In our study, all 46 patients showed different co-morbidities with FUTIs, which included cardiovascular diseases (e.g., acute endocarditis), renal diseases (e.g., acute kidney failure), GIT diseases (e.g., chronic gastritis), sepsis, shock, etc. This highlights the importance of understanding how they are related and their effects to provide comprehensive management and minimize the risks associated if possible. Renal system diseases were the most common (24.53%) among FUTIs patients.

This increase might be due to chronic renal conditions or kidney transplantation that affect the immune system, thus making the patient more susceptible to Candida species, particularly C. albicans can colonize the GIT of immunocompromised patients due to their disturbed immune system with a reported proportion of (13.21%).Both cardiovascular and respiratory system disorders showed a proportion of (11.32%), this might indicate a shared risk factors such as diabetes mellitus, immune diseases, chronic inflammations, and hospitalization. Central nervous system (CNS) disorders along with cancer both showed a rate of (5.66%) in patients infected with Candida. This association might indicate the progression of fungus into the bloodstream leading to fungal dissemination, therefore affecting the CNS. Patients with cancer are at increased risk of FUTIs due to immunosuppression induced by chemotherapy. A Brazilian observational retrospective study showed consistent results, as renal system diseases were the most observed (47%) among FUTIs patients, followed by immunosuppressant patients (which could be due chemotherapy and transplant) (34%) [10].

Another study from Turkey [11] showed (37.8%) of patients with FUTIs had co-morbidities with different proportions and results than our study. Diabetes mellitus had the highest co-morbidity rate of (7.81%), followed by respiratory system disorder (7.30%), cancer (4.41%), cardiovascular system disorders(4.16%),and lastly urinary tract diseases (3.99%). Comparing to our study, the causes for this difference in results are due to various factors such as genetic predisposition, behavioural habits, structural abnormalities in the urinary system, diabetic state, weak or compromised immune system, pregnancy, high blood pressure, kidney stone formation, other infections, and medical procedures like catheterization [12].

Upon analysing the positive sample distribution, it was seen that a considerable number of episodes were isolated between June 2016 and October 2019. After calculating the prevalence, we found it rose from 2.1% (n = 1) in 2016, to 82.6% (n = 38) in 2019. This indicates a gradual elevation over the years, specifically in 2019, considers that the increasing incidence of FUTIs, which is mostly associated with the renal system diseases in the data, might be due to the invasion of Candida spp., particularly in patients who could be hospitalized. In a previous study, which is different from our findings, the prevalence ranged from 8.1% in 2017 to 5.4% in 2021, showing a decrease in the prevalence. This difference could be linked to the sample size, in which ours was smaller than in their study. Also, it could be impacted by geographic areas [13]. Antifungal drugs should be prescribed appropriately for people with FUTIs and underlying medical conditions. Importantly, the patient's clinical state determines how best to treat FUTIs. The treatment for a FUTI depends on various factors, such as the symptoms, the type of fungus causing the infection, and effective patient management. To ensure the right course of treatment and effective patient management, it is still imperative to identify the specific species of Candida that is causing the disease and any underlying conditions or risk factors. Some fungal species may be more resistant to treatment or cause more severe complications. The severity of the infection is also taken into consideration while determining the treatment plan [14].

In our study, the risk factors and comorbidities were analysed using regression analysis of all the factors that could contribute to the FUTIs. The only two factors which showed statistically significant results were gender (0.016) and age (0.0015). The ages were distributed into groups as follows: teens group 2.17% (n = 1), adults group 39.1% (n = 18), and the largest group was the seniors, representing 58.69% (n = 27) of all patients' total. In addition, to explain the reasons for the gender significance in which females are more than males, this could be due to the anatomical structure of the female urinary system and its vulnerability to vaginal infections due to its proximity to the anus. In a previous study in which it is different from our findings identified significant risk factors for FUTIs this factor included urinary catheterization (43.5%), diabetes mellitus (33.6%), surgical procedures (22.7%), use of broad-spectrum antibiotics (22.7%), pregnancy (21.7%), use of systemic corticosteroids (6.9%), and cancer (0.9%). Our study regression analysis results differ from their study according to some factors like their sample size, in which ours was smaller to compare, the studied risk factors, and it depends on the geographic area as well [15].

Candida overgrowth can cause multiple medical conditions such as oral thrush, diaper rash in newborns, and vaginal yeast infections [15]. It emphasizes how important it is to maintain a healthy microbial flora to prevent this kind of overgrowth and the health issues that go along with it. With a proportion of 87%(n = 40), C. albicans is the most causative fungus because of its pathogenicity, propensity to produce biofilms, and presence in the human microbiome. Although other species of Candida may have similar virulence characteristics, C.albicans is more capable of infecting host tissues and colonizing them. Its importance in UTIs is attributed to its interactions with the host immune system, biofilm formation, and possible antibiotic resistance [16]. Nevertheless, other research revealed the opposite of our findings, with non-Candida being most of the isolated fungus (297; 86.3%), and C. albicans accounting for (47; 13.7%) of the total episodes [10]. Numerous factors, including local epidemiology, patient characteristics, patterns of antibiotic usage, diagnostic techniques, and possible sampling bias, may be accountable for this.

In our study, yeast (6.5%, n = 3), Trichopteran mucoidal(2.2%, n = 1), Candida glabrata (2.2%, n = 1), and Candida parapsilosis (2.2%, n = 1) follow Candida albicans. There are numerous reasons why the non-albican species are less common than Candida albicans, including the status of host’s immune system, ability of adhering and colonizing of different Candida species, ecological habitat, and antifungal susceptibility. The most common site of C. parapsilosis isolation from human hands is the subungual region [17]. Despite being a common oral, skin, and nail flora, Trichosporon is the cause of both superficial and profound infections in people [18]. C. glabrata, on the other hand, is a commensal of human mucosa, specifically the vaginal, gastrointestinal, and oral epithelia. However, it lacks the harsh characteristics of other species of Candida, namely the ability to create filaments that cause tissue damage and immune cell lysis [19]

In conclusion, the analysis of urine samples collected over a four-year period from 46 patients revealed a significant rise in FUTIs, particularly candiduria in Madinah region of Saudi Arabia. Our findings revealed Candida albicans as the most common species responsible for the majority of FUTI cases, consistent with previous researches highlighting its pathogenicity. Non-Candida albicans species, such as Candida glabrata and Candida parapsilosis, also emerged as significant contributors to FUTIs. Our study identified various comorbidities associated with FUTIs, highlighting the causes and association between underlying health conditions and susceptibility to FUTIs. Furthermore, our analysis highlighted the importance of gender and age as risk factors for FUTIs, with females and seniors being more susceptible to the infection.

The retrospective nature of the study and the reliance on KFH records may introduce bias, and there may be limitations to the finding's applicability to other populations or regions. Considering the current findings, future directions in FUTIs research should focus on delineating optimal management strategies while effectively addressing existing limitations. This entails further investigation into novel therapeutic approaches, refining diagnostic methods for early detection, exploring antimicrobial stewardship programs, and enhancing our understanding of host-pathogen interactions to develop targeted interventions. Additionally, efforts should be directed towards overcoming challenges such as limited antifungal options, increasing rates of drug resistance, and the need for standardized guidelines to streamline clinical decision-making. By prioritizing these avenues, future research endeavors aim to significantly advance our ability to manage candiduria effectively, ultimately improving patient outcomes and reducing healthcare burden.

UTIs: Urinary Tract Infections

FUTs: Fungal Disease in UTIs

IRB: Institutional Review Board

CKD : Chronic Kidney Disease

KFH: King Fahd Hospital

MOH: Ministry of Health

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding

Authors declare no funding resource

Authors Contributions

LA , YA , RA, WA collected the data. AK performed statistical analysis. OS a senior author who revised the manuscript. All authors Wrote the manuscript and discussed the results

Ethical Declarations

Ethics approval and consent to participate

It was approved by the local Institutional Review Board (IRB 590) Taibah University and the Ethics Committee of the General Directorate of Health Affairs in Medina, Ministry of Health, Saudi Arabia (Approval #: H-03-M-084). Informed consent requirements were waived by the committee given the nature of the study application form.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

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You are reading this latest preprint version

Prevalence of Fungal Urinary Tract Infections in Madinah Region

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Version 1

Abstract

Background

Aim

Materials and Methods

Results

Conclusion

Figures

Background

Methods

Study Type

Population

Statistical analysis

Results

Demographic character

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1