11
INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal www.ijarke.com 38 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018 Prevalence, Distribution, Risk Factors and Antifungal Susceptibility Profiles of Candida Isolates from Patients Attending Mombasa Hospital Abdulrahman Subira, Jomo Kenyatta University of Agriculture & Technology, Kenya Dr. Rahma Udu, Technical University of Mombasa, Kenya Prof. Simon Karanja, Jomo Kenyatta University of Agriculture & Technology, Kenya 1. Introduction Candida commonly occurs as commensal organisms on the mucosal surfaces of gastrointestinal, genitourinary tracts and skin of humans but can cause mucocutaneous or invasive infections [(Pappas et al., 2004), (Kabir & Ahmad, 2013), (Mayer, Wilson, & Hube, 2013)]. Candida are emerging as a potentially pathogenic fungus in patients with broncho-pulmonary diseases (Kali et al., 2013). 2. Problem Statement Most laboratories in Mombasa do not undertake Candida identification and antifungal susceptibility tests although the Vitek (BioMérieux) system enables clinical laboratories to perform routine identification of Candida and antifungal susceptibility easier and more accurately (Melhem et al., 2013). Various Candida species (Mainly mucocutaneous but also few cases of systemic Candida infections) are isolated from clinical specimens in the Microbiology laboratory at Mombasa Hospital with few cases of resistance to some antifungal agents identified (Mombasa hospital health management information system). 3. Research Objective The study was guided by the following specific objectives: i. To determine the prevalence and distribution of Candida species among patients attending Mombasa Hospital. ii. To determine the antifungal susceptibility profiles of the Candida isolated from clinical specimens in Mombasa Hospital. iii. To determine the risk factors associated with isolation of Candida among patients attending Mombasa Hospital Abstract Candida causes mucocutaneous or invasive infections. Most laboratories in Mombasa do not undertake Candida species identification and antifungal susceptibility routinely. Objectives: This study sought to determine the prevalence, distribution, risk factors and antifungal susceptibilities of Candida isolated in Mombasa Hospital. Materials and Methods: In a cross- sectional study, 384 patient samples selected by systematic random sampling were cultured. Identification and antifungal susceptibilities for yeast isolates were done on Vitek 2 compact. Chi-square and logistic regression analysis were done using SPSS version 20. Differences in parameter estimates were deemed statistically significant at P < 0.05. Results: The prevalence of Candida was 8.6%. Candida albicans (7.8%) and Candida tropicalis (0.8%). Candida isolates were susceptible to Flucytosine (100%), Micafungin and Caspofungin (96.97%), Voriconazole (93.94%) and Fluconazole (81.82%). 9.09% isolates were resistant and intermediate to Fluconazole while 15.15% were resistant to Amphotericin B. Pregnant women (P = 0.000), diabetics (P = 0.008), chronically ill patients (P = 0.026) and catheterized patients (P = 0.023) were at most risk of Candida infections. Conclusion: Candida is a common cause of infections among patients in Mombasa Hospital. Flucytosine is an effective antifungal agent. Resistance to azoles and Amphotericin B should be considered when starting empirical treatment. Key words: Candida species, Prevalence, Antifungal sensitivity, Risk Factors INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE (IJARKE Science & Technology Journal)

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH …...becoming more useful now to provide such information to facilitate a more informed and evidence based treatment decision. 5. Literature

  • Upload
    others

  • View
    3

  • Download
    0

Embed Size (px)

Citation preview

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

38 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

Prevalence, Distribution, Risk Factors and Antifungal Susceptibility

Profiles of Candida Isolates from Patients Attending Mombasa Hospital

Abdulrahman Subira, Jomo Kenyatta University of Agriculture & Technology, Kenya

Dr. Rahma Udu, Technical University of Mombasa, Kenya

Prof. Simon Karanja, Jomo Kenyatta University of Agriculture & Technology, Kenya

1. Introduction

Candida commonly occurs as commensal organisms on the mucosal surfaces of gastrointestinal, genitourinary tracts and skin

of humans but can cause mucocutaneous or invasive infections [(Pappas et al., 2004), (Kabir & Ahmad, 2013), (Mayer, Wilson,

& Hube, 2013)]. Candida are emerging as a potentially pathogenic fungus in patients with broncho-pulmonary diseases (Kali et

al., 2013).

2. Problem Statement

Most laboratories in Mombasa do not undertake Candida identification and antifungal susceptibility tests although the Vitek

(BioMérieux) system enables clinical laboratories to perform routine identification of Candida and antifungal susceptibility easier

and more accurately (Melhem et al., 2013). Various Candida species (Mainly mucocutaneous but also few cases of systemic

Candida infections) are isolated from clinical specimens in the Microbiology laboratory at Mombasa Hospital with few cases of

resistance to some antifungal agents identified (Mombasa hospital health management information system).

3. Research Objective

The study was guided by the following specific objectives:

i. To determine the prevalence and distribution of Candida species among patients attending Mombasa Hospital.

ii. To determine the antifungal susceptibility profiles of the Candida isolated from clinical specimens in Mombasa

Hospital.

iii. To determine the risk factors associated with isolation of Candida among patients attending Mombasa Hospital

Abstract

Candida causes mucocutaneous or invasive infections. Most laboratories in Mombasa do not undertake Candida species

identification and antifungal susceptibility routinely. Objectives: This study sought to determine the prevalence, distribution,

risk factors and antifungal susceptibilities of Candida isolated in Mombasa Hospital. Materials and Methods: In a cross-

sectional study, 384 patient samples selected by systematic random sampling were cultured. Identification and antifungal

susceptibilities for yeast isolates were done on Vitek 2 compact. Chi-square and logistic regression analysis were done using

SPSS version 20. Differences in parameter estimates were deemed statistically significant at P < 0.05. Results: The prevalence

of Candida was 8.6%. Candida albicans (7.8%) and Candida tropicalis (0.8%). Candida isolates were susceptible to

Flucytosine (100%), Micafungin and Caspofungin (96.97%), Voriconazole (93.94%) and Fluconazole (81.82%). 9.09%

isolates were resistant and intermediate to Fluconazole while 15.15% were resistant to Amphotericin B. Pregnant women (P =

0.000), diabetics (P = 0.008), chronically ill patients (P = 0.026) and catheterized patients (P = 0.023) were at most risk of

Candida infections. Conclusion: Candida is a common cause of infections among patients in Mombasa Hospital. Flucytosine

is an effective antifungal agent. Resistance to azoles and Amphotericin B should be considered when starting empirical

treatment.

Key words: Candida species, Prevalence, Antifungal sensitivity, Risk Factors

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE (IJARKE Science & Technology Journal)

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

39 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

4. Justification of the Study

The isolation of non albicans Candida from clinical samples, growing resistance trends to some common antifungal agents,

and the existence of some intrinsic and secondary resistance by some Candida and other yeasts to antifungal agents demonstrates

the need to provide clinicians with information regarding the local epidemiological patterns. Whereas traditionally laboratories

and clinicians have not put much emphasis on the identification of Candida and their antifungal susceptibility profiles, it is

becoming more useful now to provide such information to facilitate a more informed and evidence based treatment decision.

5. Literature Review

Risk factors for Candida infections include immune compromised states, diabetes mellitus, antibiotic use, indwelling devices,

intravenous drug use among others (Kojic, Darouiche, & Biofilms, 2004). Improved management of high-risk patients with novel

treatment methods has partly contributed to the increase in Candidiasis (Diaz & Fell, 2004),(Pappas et al., 2016). Significant

geographic variation is evident among cases of candidemia in different parts of the world hence local epidemiological data and

antifungal susceptibility profiles are of major significance (Falagas, Roussos, & Vardakas, 2010), (Colombo et al., 2006)].

Candida is the primary cause of fungal infections, particularly in immunosuppressed patients with Candida albicans being the

most common etiologic agent (Haddadi et al., 1970). A prevalence of 42.7% vaginal Candida infections was reported among

pregnant women in Thika District Hospital, Kenya with Candida albicans being the most commonly isolated species (Menza

Nelson, Wanyoike Wanjiru2, 2013). An increasing prevalence of vulvo vaginitis (Kumari et al., 2013) and pulmonary candidiasis

(Kali et al., 2013) due to non-albicans Candida species has been reported. Some Candida exhibit primary resistance due to

intrinsic resistance mechanisms and others develop secondary resistance to certain antifungal agents due to prior exposure of the

patient to the antifungal agents (Fothergill, 2012) hence empirical antifungal agents may not be efficient in treating high risk and

systemic candidiasis patients [(Aguilar et al., 2015), (Collins, Eschenauer, Salo, & Newton, 2007), (Falagas et al., 2010)].

Detection of Candida and determination of their susceptibility to antifungal agents can help improve the clinical management

of systemic mycosis (Haddadi et al., 1970). Overuse of antifungals has promoted a shift to Candida with reduced susceptibility to

antifungal agents (Lortholary, Desnos-ollivier, Sitbon, & Fontanet, 2011). Fluconazole should probably not be considered as a

first-line treatment of Candida glabrata infections and empirical treatment with echinocandins may be withheld due to decreased

susceptibility of Candida parapsilosis to echinocandins, especially Caspofungin (Falagas et al., 2010). However, susceptibility

testing of Candida glabrata isolates resulted in lower overall treatment costs, based on de-escalation in therapy from an expensive

echinocandin to Fluconazole for patients with Candida glabrata fungemia (Collins et al., 2007). Echinocandin drugs are

recommended as the first line for invasive Candida infections (Alexander et al., 2013), (Haddadi et al., 1970). Flucytosine is

administered in combination with Amphotericin B in the treatment of life threatening Candida infections or in circumstances

where drug penetration may be problematic (Hope, Tabernero, Denning, & Anderson, 2004) since yeasts develop resistance to

Flucytosine monotherapy very quickly (Kanafani & Perfect, 2008). Though its prevalence remained low (1% – 2%) among

Candida (Kanafani & Perfect, 2008) there has been reports of increasing Echinocandin resistance from 4.9% to 12.3% between

2001 and 2010 (Alexander et al., 2013).

6. Research Design

This was a cross-sectional study that was done in Mombasa Hospital, a level 5 private referral hospital in Mombasa, Kenya.

384 patient specimens that met the sample acceptance criteria for culture and sensitivity testing submitted between January and

June 2016 were selected by systematic random sampling and analyzed. Samples from non-consenting patients were not included.

6.1 Sample Collection and Laboratory Analysis

Urine (66.9%), pus swabs (11.7%), catheter tips (6.5%), sputum (5.7%), High vaginal swabs (5.2%), wound swabs (2.1%) and

tracheal aspirates (1.8%) specimens were collected and analyzed. Urine and catheter tips specimens were inoculated on blood agar

(BA), Cystine Lactose Electrolyte Deficiency (CLED) and Sabouraud Dextrose Agar (SDA) media. High vaginal swabs, Sputum,

tracheal aspirates, pus and wound swabs were cultured onto BA, Chocolate agar and SDA media and incubated aerobically for 18

to 48 hours. Gram stain was done and slides examined microscopically for Candida. McFarland adjusted turbidity level 1.8 – 2.20

suspensions were prepared. Identification and antifungal susceptibility tests were done using the Vitek 2 compact (BioMérieux).

Amphotericin B, Caspofungin, Fluconazole, Flucytosine, Micafungin and Voriconazole were selected for study. Isolates were

determined as susceptible, intermediate or resistant according to the EUCAST resistance breakpoints for antifungal agents.

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

40 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

6.2 Data Analysis

Demographic information, patient diagnosis, treatment, surgery, catheterization and culture and sensitivity data were collected

from consenting patients using standard forms. Data were analyzed using SPSS software version 20. Descriptive statistics was

used to describe the trends. Chi-square statistics and multivariate logistic regressions analysis were done test the relationship

between the risk factors and the isolation of Candida Spp.

6.3 Ethical Issues

Approval to conduct this study was given by the ethical review committee at Pwani University, Kilifi, Kenya. Participation in

the study was voluntarily. There were no health risks to the study subjects. Confidentiality to participants’ information was

maintained by means of codes and unauthorized access to the data was not allowed.

7. Research Findings

The Overall prevalence of Candida isolates in Mombasa Hospital was 8.6%. Urine had the highest proportion (54.4%) of

Candida isolates followed by High Vaginal Swabs (18.2 %) and sputum (15.2%) specimens. The proportion of Candida in

tracheal aspirates (3%) and in pus swabs (3%) were relatively low among all samples whereas no Candida was isolated from

wound swabs (Table 1). Chi-square (𝑥2 ,0.05, 6 = 21.466) test showed that the types of specimens investigated had significant

association with the isolation of Candida.

Table 1: Proportion of Candida Isolates in Sample Types

Patient type n (%) Candida

positive samples

Frequency (%)

Candida

negative samples

Frequency

(%)

d

f 𝑥2

(Fis

her’s

Exact)

p-

value

Sample

types

Urine 257

(66.9)

18 (54.5) 239 (68.1) 6 21.

466

0.0

02

Catheter Tip 25

(6.5)

2 (6.1) 23 (6.6)

HVS 20

(5.2)

6 (18.2) 14 (4.0)

Pus swabs 45

(11.7)

1 (3.0) 44 (12.5)

Tracheal

aspirates

7 (1.8) 1 (3.0) 6 (1.7)

Wound swabs 8 (2.1) 0 (0) 8 (2.3)

Sputum 22

(5.7)

5 (15.2) 17 (4.8)

Total 384 33 351

7.1 Risk Factors for Candida isolation

The proportion of patients with Candida in non-diabetic [21 (63.6%)] patients was much higher than that in patients with

history of diabetes 12 (36.4%). Chi-square result (𝑥2, 0.05, 1= 7.0612) showed that there is a significant association between

patients with history of diabetes and the isolation of Candida (Table 2). The proportion of non-operated [25 (75.8%)] patients

samples with Candida was much higher than the proportion of operated [8 (24.2%)] patients samples with Candida. Chi square

(𝑥2, 0.05, 1= 0.12) test indicated that there was no association between the isolation of Candida and surgical intervention (Table

2). 42 (10.9%) patients’ samples were collected from pregnant women. Non-pregnant patients 20 (60.6%) samples had much

higher proportion of Candida isolates compared to lower proportion in pregnant women’s 13 (39.4%) samples. Chi-square result

(𝑥2, 0.05, 1= 30.011) showed that there is a significant association between pregnancy and the isolation of Candida among the

patients’ samples investigated (Table 2). The proportion of catheterized (45.5%) Candida positive patients’ samples was slightly

less than the non-catheterized patients (54.5%) samples. Chi-square (𝑥2, 0.05, 1= 5.174) showed that there is a significant

association between catheterization and the isolation of Candida among the patients’ specimens investigated (Table 2). Among

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

41 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

the patients with chronic illnesses, (18.2%) had Candida. Chi-squares statistics (𝑥2, 0.05, 1= 4.971) indicated a significant

association between chronic illness and isolation of Candida (Table 2).

Table 2: Prevalence of Isolation of Candida with regards to various Risk Factors

Patients’ characteristics n (%) Candida

positive

samples

Frequency (%)

Candida

negative

samples

Frequency (%)

𝑥2 df p-

value

OR

Diabetes Diabetic 73 (19) 12 (36.4) 61 (17.4) 7.0612 1 0.008 0.37

Non diabetic 311 (81) 21 (63.6) 290 (82.6)

Total 384 33 351

Surgery Done 103

(26.8)

8 (24.2) 95 (27.1) 0.123 1 0.726 1.16

Not done 281

(73.2)

25 (75.8) 256 (72.9)

Total 384 33 351

Pregnancy pregnant 42 (10.9) 13 (39.4) 29 (8.3) 30.011 1 0.000 0.14

Non Pregnant 342

(89.1)

20 (60.6) 322 (91.7)

Total 384 33 351

Catheterization Catheterized 109

(28.4)

15 (45.5) 94 (26.8) 5.174 1 0.023 0.44

Non

Catheterized

275

(71.6)

18 (54.5) 257 (73.2)

Total 384 33 351

Chronic

illnesses

Chronically ill 31 (8.1) 6 (18.2) 25 (7.1) 4.971 1 0.026 0.35

Not chronically

ill

353

(91.9)

27 (81.8) 326 (92.9)

Total 384 33 351

7.2 Distribution of Candida Species among Patients Attending Mombasa Hospital

Two types of Candida were isolated from all samples investigated. Candida albicans 30 (90.9%) was the predominant species

while 3(9.1%) Candida tropicalis were isolated.

7.3 Antifungal Susceptibility Profiles of the Candida Isolates

All [33 (100%)] Candida isolates were sensitive to Flucytosine. [32 (97%)] Candida were sensitive to Micafungin and

Caspofungin and 1 (3.0%) isolate showed resistance to the two drugs. 31 (93.9%) Candida isolates were sensitive to Voriconazole

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

42 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

with two isolates showing resistance. 27 (81.8%) of the isolates were sensitive to Fluconazole while [3 (9.1%)] isolates showed

resistance and [3 (9.1%)] intermediate responses. 5 (15.2%) Candida isolates showed resistance to Amphotericin B. Chi square

(𝑥2, 0.05, 1 = 20.165) results indicated that there is an association between the antifungal drug used and susceptibility of the

Candida species isolated. (Table 3)

Table 3: Response of Candida to the Six Anti-fungal Drugs Investigated

Antifungal Susceptibility: Frequency (%) n = 198

Antifungal Sensitive Intermediate Resistant 𝑥2

(Fisher’s Exact)

p-value

Voriconazole 31 (93.9) 0 (0) 2 (6.1) 20.165 0.028

Fluconazole 27 (81.8) 3 (9.1) 3 (9.1)

Micafungin 32 (97) 0 (0) 1 (3.0)

Caspofungin 32 (97) 0 (0) 1 (3.0)

Amphotericin B 27 (81.8) 1 (3.0) 5 (15.2)

Flucytosine 33 (100) 0 (0) 0 (0)

Total 182 (91.9) 4 (2.0) 12 (6.1)

7.4 Analysis

Bivariate correlation analysis to determine the correlation between the dependent variable (isolation of Candida) and the risk

factors; diabetes, pregnancy, surgical interventions, catheterization and chronic illnesses showed a strong positive correlation

between pregnancy and the isolation of Candida. Hence, Pregnant women (p = 0.000) stand a relatively higher risk of isolation of

Candida followed by diabetics (p = 0.008), catheterization (p = 0.023) and those patients with chronic illnesses (p = 0.026). No

correlation was found between surgery and isolation of Candida in this study (Table 4).

Table 4 Correlation of Risk Factors and Isolation of Candida

Risk factors associated with isolation of Candida

Correlations Diabetes Pregnant Operated On Catheterization Chronic illnesses

Pearson Correlation 0.136** 0.280** -0.018 0.116* 0.114*

Sig. (2-tailed) /p-value 0.008 0.000 0.727 0.023 0.026

N 384 384 384 384 384

* Correlation is significant at the 0.05 level(2-tailed).

** Correlation is significant at the 0.01 level (2-tailed).

The logistic regression model affirmed that at 5% level of significance, pregnancy (p = 0.000), chronic illness (p = 0.049),

diabetes (p = 0.024) and age (p = 0.024) were statistically significant. The probability of patient acquiring Candida infection and

hence isolation of Candida keeping other factors constant is given by the following equation;

4321

4321

028.0176.196.21.1621

028.0176.12.96x1.162

xxxxe

xxxei

Where 421 ,...;, xxx represents diabetes, pregnancy, chronic illness, age respectively.

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

43 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

On the other hand, the logistic regression model showed that, surgery (p = 0.398) and catheterization (p = 0.27) were not

statistically significant risk factors associated with the isolation of Candida in Mombasa hospital (Table 5).

Table 5 Logistic Regression Analysis for the Risk Factors

Variables in the Equation B S.E. Wald df Sig.

(p - value)

Exp (B)

(Odds Ratio)

Step 1a

Diabetes 1.162 0.515 5.090 1 0.024 3.196

Pregnant 2.967 0.642 21.384 1 0.000 19.439

Operated On -0.467 0.553 0.715 1 0.398 0.627

Catheterisation 0.595 0.539 1.218 1 0.270 1.813

Chronic Illnesses 1.176 0.599 3.860 1 0.049 3.241

Constant -4.260 2.282 3.487 1 0.062 0.014

a. Variable(s) entered on step 1: Diabetes, Pregnant, Operated On, Catheterization, Chronic Illnesses.

7.5 Risk Estimates

The likelihood of a pregnant woman acquiring Candida is seven times that of non-pregnant women and catheterized patients

are twice as likely to acquire Candida infections as non-catheterized patients. Moreover, patients with chronic illness are three

times riskier of acquiring Candida infections compared to those without chronic illness. Finally, diabetic patients are almost three

times as likely as non-diabetic patients to acquire Candida Infections (Table 6).

Table 6 Risk Estimate for Various Risk Factors

8. Discussion

8.1 Prevalence of Candida

The prevalence of superficial (19.68%) and invasive (12.42%) Candida infections is relatively high in Africa and Middle East

region and a decreasing proportion of Candida albicans in more recent years (Omrani, Pecen, Hajek, Raghubir, & Zigmond,

2014) is seen.

Findings of the current study incriminated Candida 33 (8.6%) as the most prevalent pathogen in urogenital and broncho-

pulmonary infections. Geographic differences could be a contributing factor for the variation in prevalence of Candida (Li et al.,

2013). The prevalence of Candida was high in urine (54.5%) and High vaginal swabs (HVS) (18.2%) samples compared to other

sample types investigated in this study. These findings resonate with those of a North India study which reported that (30.6%) of

patients with complaints of vulvovaginitis grew Candida (Kumari et al., 2013). Candida was isolated from 13 (39.4%) pregnant

women’s samples in this study concurring with the Thika District Hospital study which reported a prevalence of 42.7% of

candidiasis in pregnant women (Menza Nelson, Wanyoike Wanjiru, 2013).

Pregnancy Catheterization chronic illness Diabetes

(pregnant / Non pregnant) (Catheterization / Non

Catheterization)

(chronic illness / no

chronic illness)

(Diabetic/Non diabetic)

Risk estimate value 95% Confidence

Interval

value 95% Confidence

Interval

value 95% Confidence

Interval

value 95% Confidence

Interval

Lower Upper Lower Upper Lower Upper Lower Upper

Odds Ratio 7.217 3.259 15.982 2.278 1.104 4.703 2.898 1.095 7.672 2.717 1.269 5.815

For Cohort

Candida positive

5.293 2.846 9.843 2.102 1.099 4.021 2.530 1.132 5.659 2.434 1.256 4.719

For Cohort

Candida negative

0.733 0.598 0.900 0.851 1.001 0.851 0.873 0.733 1.040 0.896 0.806 0.996

N of valid cases 384 384 384 384

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

44 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

Further, the results are in congruence with previous studies that identified Candida as an emerging potential pathogen in

patients with broncho-pulmonary diseases (Kali et al., 2013) since it rated sputum (15.2%) samples as the third most prevalent

source of Candida.

8.2 Candida species distribution

The most frequently isolated Candida was Candida albicans (San Miguel et al., 2005), (Celebi, Hacimustafaoglu, Ozdemir,

& Ozkaya, 2008). In congruence with previous studies, which identified Candida albicans as the most common etiologic agent of

fungal infections (Haddadi et al., 1970), (Menza Nelson, Wanyoike Wanjiru2, 2013), (Mutua, Revathi, & Machoki, 2010), the

proportion of Candida albicans (90.9%) was significantly higher than Candida tropicalis (1.9%) in this study. No other Candida

was isolated. The findings of Candida albicans as the most predominant Candida in all sample types corresponds with a study in

India which identified Candida albicans as the most predominant in pulmonary Candidiasis (Kali et al., 2013). Contrary to a study

which reported an increasing prevalence of vulvo vaginitis due to non-albicans Candida species (Kumari et al., 2013), this study

reported a very low proportion of non albicans Candida amongst vaginal samples. This could be attributed to geographical

variation (Falagas et al., 2010), (Li et al., 2013), Candida tropicalis has been identified as the most prevalent of the non-Candida

albicans group (Kothavade, Kura, Valand, & Panthaki, 2016), (Ann et al., 2007). Furthermore, this study concurs with a study in

Brazil which reported Candidaalbicans83(92.3%) as the most predominantly isolated Candida from pregnant women (Dias,

Souza, Melhem, Szeszs, & Filho, 2011).

8.3 Antifungal susceptibility profiles

Although the and antifungal resistance of Candida differ among geographies necessitating localized surveys of the prevalence

and drug resistance of Candida in order to ensure effective antifungal therapy against invasive Candida (Li et al., 2013), routine

typing and antifungal susceptibility testing of Candida isolates prior to therapy has not been given appropriate attention to

determine the occurrence of resistant genotypes and consequently, there is no data about prevalent Candida and their antifungal

susceptibility patterns in some regions (Mukasa et al., 2015). Also culture procedures are considered to be expensive, time

consuming thus leading to a delay in the treatment and there is a risk of loss of patients on follow-up (Dias, Souza, Melhem,

Szeszs, & Filho, 2011b).

Majority of the Candida responded well to the antifungal drugs investigated in this study. However, the finding of some

resistant Candida isolates here is supported by studies that reported trends of increasing resistance to antifungal agents amongst

some Candida infections [(Cisterna, Ezpeleta, & Tellería, 2005),(Ingham et al., 2012)].

In the current study, 3 (9.1%) Candida showed resistance and 3 (9.1%) intermediate responses to Fluconazole. 2(6.1%)

Candida showed resistance to Voriconazole. Fluconazole resistance has been reported albeit at higher prevalence (13.6 % )

(Aguilar et al., 2015) compared to the current findings.

Azole resistance has been reported as a cause of recurrent vulvovaginal candidiasis and has been associated with the use and

occasional overuse of Fluconazole (White, Marr, & Bowden, 1998) and in surgical intensive care patients treated with

Fluconazole. Amphotericin B recorded the highest 5 (15.2%) Candida isolates resistance in the current study. Several strains of

Fluconazole and Amphotericin B-resistant Candida albicans have been found elsewhere in HIV infected patients who have

received prolonged courses of antifungal prophylaxis with azoles (White et al., 1998).All 33 (100%) Candida were sensitive to

Flucytosine hence it was affirmed that Flucytosine is a potent antifungal agent. This confirms that although there is primary

resistance to Flucytosine, its prevalence remains very low in certain yeasts (1%–2% among Candida isolates). However,

secondary resistance to Flucytosine is common in patients receiving Flucytosine monotherapy (Lopez-ribot et al., 1998), (Hope et

al., 2004). Caspofungin is the most effective agent against all Candida species (Haddadi et al., 1970) hence the minimal resistance

to Micafungin (3.03%) and Caspofungin (3.03%) in this study. However, although echinocandin drugs are recommended as the

first line for invasive candidiasis, reports of echinocandin resistance in patients with infections due to resistance in Candida

glabrata has increased (Alexander et al., 2013).

8.4 Risk factors associated with isolation of Candida

8.4.1 Pregnancy

Patients who presented with candiduria were younger, more commonly female and pregnant (Achkar & Fries, 2010). This

study reported a (39.4%) prevalence of Candida in pregnant women correlating with a prevalence of 36% vulvovaginal

candidiasis among pregnant women in Nigerian cities (Olowe, Makanjuola, Olowe, & Adekanle, 2014) and 45.4% prevalence of

Candida in HVS samples in Mbarara, Uganda (Mukasa et al., 2015). Chi-square test confirmed that indeed pregnancy was a

significant risk factor associated with isolation of Candida. This could be attributed mainly to the fact that pregnant women have

relatively reduced immunity [(Nnaemeka, 2010), (Mukasa et al., 2015)]that predisposes them to developing candidiasis of the

genitourinary tract. Although Candida albicans often colonises the vagina (Apalata, B, Aw, Wh, & Moodley, 2014) and Candida

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

45 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

also live commensally in the genitor-urinary tract [(S et al., 2016)]. Candida infections mainly occur as opportunistic infections

due to altered conditions of the host [(Okungbowa, Isikhuemhen, & Dede, 2003),(Apalata et al., 2014)].The change in pH of

vaginal secretions from an alkaline pH to an acid pH during pregnancy facilitates thriving of Candida organisms [(Apalata et al.,

2014), (Kamath, Pais, & Nayak, 2013), (Nnaemeka, 2010)]. Higher estrogen levels (Soong & Einarson, 2009) and higher

glycogen content in vaginal secretions during pregnancy increase a woman’s risk of developing vulvo vaginal candidiasis

(Kamath et al., 2013). Pregnancy is one among several risk factors associated with Vulvovaginal Candidiasis (Apalata et al.,

2014).

8.4.2 Diabetes

The current study in Mombasa hospital established that the prevalence of isolation of Candida in diabetic patients is 3.1%. The

chi-square and logistic regression results revealed that diabetes was a significant risk factor associated with isolation of Candida.

These findings concurred with those of other studies in recognizing diabetes as a significant risk factor associated with isolation of

Candida in various patient sub populations. Diabetes mellitus is one of the common predisposing factors for vaginal Candidiasis

[(Leon, Jacober, Sobel, & Foxman, 2002)]. In a study in Pakistan involving Candida esophagitis, it was revealed that diabetes

mellitus was one of the major risk factors for candidiasis (Yakoob et al., 2003). This is because the elevated glucose levels

characteristic of diabetes provide the carbon needed for Candida overgrowth and infection (S et al., 2016).

8.4.3 Surgical interventions

Colonization with Candida in surgical patients is common and occurs before development into invasive candidiasis (Liew et

al., 2015). An increasing number of serious Candida infections on surgical patients that may be related to improvements in

surgical technique and perioperative care (Marsh, Tally, Kellum, & Callow, 1982). 8(2.1%) patients who had undergone surgery

at the Mombasa hospital had Candida. Surgery was not a statistically significant factor associated with isolation of Candida.

These findings were lower compared to a previous study where Candida were observed in 33% of the colonized patients

confirming the vulnerability of the critically ill surgical patients to fungal infections (Rasilainen, Juhani, & Kalevi, 2015). The

observed difference could be due to the kind of patients selected. The higher prevalence may be due to the focus on critically ill

surgical patients in the former study while the current study has included non-critically ill surgical patients including those

undergoing simple surgeries like caesarean section and appendectomy.

8.4.4 Catheterization

Prolonged duration of catheterization is a common risk factor for fungal infections (Mohammad, 2012) since fungal infections

constitutes a significant proportion of all catheter associated urinary tract infection.

Both Chi-square results (P = 0.023 at 5% level of significance) and logistic regression analysis (P = 0.0026) showed that

catheterization is a significant risk factor associated with isolation of Candida at Mombasa hospital. Moreover, urinary

catheterization, among other factors has also been associated with isolation of Candida and a common predisposing factors for

invasive Candidiasis (Aguilar et al., 2015).

8.4.5 Chronic Illnesses (HIV, Cancer and Renal Transplant)

The advent of the human immunodeficiency virus (HIV) epidemic and the increased use of immunosuppressive drugs for

serious medical conditions dramatically increased the number of persons who are severely immunocompromised (Enrique &

Puebla, 2012) and in whom Candida are the most common cause of fungal infection (Enrique & Puebla, 2012). Such patients

require prolonged prophylactic antifungal treatments due to the risk of developing fungal infections including candidiasis. The

current study indicated that 31(8.1%) patients had chronic illnesses including HIV, cancer and kidney diseases. Chi-square results

revealed a correlation between chronic illnesses and isolation of Candida (P = 0.026 at 5 % level of significance) and concurred

with the logistic regression analysis (P = 0.033). Candiduria occurs typically in elderly, hospitalized, or immunocompromised

patients and in neonates (Achkar & Fries, 2010) hence the findings of high prevalence of Candida in urine (4.7%) specimens in

this study. A higher proportion of samples were collected from elderly (51%) and hospitalized (65.1%) patients. The risk of

isolation of Candida in patients suffering from chronic illnesses in this study concurs with findings of earlier studies where

Candida esophagitis was associated with chronic diseases (Yakoob et al., 2003). Candida infections in the gut occur mostly in

immunocompromised patients, in patients who are on steroid therapy, in those with diabetes mellitus and HIV infection [(Report

& Gupta, 2012),(Omrani et al., 2014)].

9. Conclusions and Recommendations

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

46 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

Candida 33(8.6%) is a major cause of genitourinary and broncho-pulmonary infections in Mombasa hospital. Candida

albicans 30 (90.9%) and Candida tropicalis 3 (1.9%) were isolated. No resistance to Flucytosine was observed but minimal

resistance in Micafungin (3%) and Caspofungin (3%) was observed. Amphotericin B, Voriconazole and Fluconazole showed

some considerable resistance hence resistance to azoles and Amphotericin B should be envisaged when considering an empirical

or de-escalation treatment strategy. This study affirmed that pregnancy, chronic illness and diabetes were statistically significant

risk factors and provided a model equation for the estimation of the probability of a patient acquiring Candida infections in

Mombasa hospital to aid in prevention approaches.

References

1. Achkar, J. M., & Fries, B. C. (2010). Candida Infections of the Genitourinary Tract, 23(2), 253–273.

https://doi.org/10.1128/CMR.00076-09

2. Aguilar, G., Delgado, C., Corrales, I., Izquierdo, A., Gracia, E., Moreno, T., … Belda, F. J. (2015). Epidemiology of

invasive candidiasis in a surgical intensive care unit : an observational study. BMC Research Notes, 4–9.

https://doi.org/10.1186/s13104-015-1458-4

3. Alexander, B. D., Johnson, M. D., Pfeiffer, C. D., Jiménez-Ortigosa, C., Catania, J., Booker, R., … Pfaller, M. a. (2013).

Increasing echinocandin resistance in candida glabrata: Clinical failure correlates with presence of FKS mutations and

elevated minimum inhibitory concentrations. Clinical Infectious Diseases, 56(12), 1724–1732.

https://doi.org/10.1093/cid/cit136

4. Ann, Y. I., Chai, L., Wang, Y. U. E., Khoo, A. I. L., Chan, F. Y. E. E., & Chow, C. (2007). Predominance of Candida

tropicalis bloodstream infections in a Singapore teaching hospital, (August), 435–439.

https://doi.org/10.1080/13693780701385868

5. Apalata, T., B, L. M., Aw, S., Wh, C., & Moodley, P. (2014). Factors Associated with Symptomatic Vulvovaginal

Candidiasis : A Study among Women Attending a Primary Healthcare Clinic in Kwazulu ‑ Natal , South Africa, 4(3).

https://doi.org/10.4103/2141-9248.133470

6. Celebi, S., Hacimustafaoglu, M., Ozdemir, O., & Ozkaya, G. (2008). Nosocomial candidaemia in children: Results of a

9-year study. Mycoses, 51(3), 248–257. https://doi.org/10.1111/j.1439-0507.2007.01464.x

7. Cisterna, R., Ezpeleta, G., & Tellería, O. (2005). Epidemiology of Bloodstream Candida spp . Infections Observed

During a Surveillance Study Conducted in Spain. Epidemiology Insights.

8. Collins, C. D., Eschenauer, G. a., Salo, S. L., & Newton, D. W. (2007). To test or not to test: A cost minimization

analysis of susceptibility testing for patients with documented Candida glabrata fungemias. Journal of Clinical

Microbiology, 45(6), 1884–1888. https://doi.org/10.1128/JCM.00192-07

9. Colombo, A. L., Nucci, M., Park, B. J., Nouér, S. a., Arthington-Skaggs, B., Da Matta, D. a., … Morgan, J. (2006).

Epidemiology of candidemia in Brazil: A nationwide sentinel surveillance of candidemia in eleven medical centers.

Journal of Clinical Microbiology, 44(8), 2816–2823. https://doi.org/10.1128/JCM.00773-06

10. Dias, L. B., Souza, M. De, Melhem, C., Szeszs, M. W., & Filho, J. M. (2011a). No Title, 1300–1307.

11. Dias, L. B., Souza, M. De, Melhem, C., Szeszs, M. W., & Filho, J. M. (2011b). No Title, 1300–1307.

12. Diaz, M. R., & Fell, J. W. (2004). High-Throughput Detection of Pathogenic Yeasts of the Genus Trichosporon, 42(8),

3696–3706. https://doi.org/10.1128/JCM.42.8.3696

13. Enrique, L., & Puebla, J. (2012). Fungal Infections in Immunosuppressed Patients.

14. Falagas, M. E., Roussos, N., & Vardakas, K. Z. (2010). Relative frequency of albicans and the various non-albicans

Candida spp among candidemia isolates from inpatients in various parts of the world: A systematic review. International

Journal of Infectious Diseases, 14(11), e954–e966. https://doi.org/10.1016/j.ijid.2010.04.006

15. Fothergill, A. W. (2012). Interactions of Yeasts, Moulds, and Antifungal Agents. Interactions of Yeast, Moulds, and

Antifungal Agents: How to Detect Resistance, 65–75. https://doi.org/10.1007/978-1-59745-134-5

16. Haddadi, P., Zareifar, S., Badiee, P., Alborzi, A., Mokhtari, M., Zomorodian, K., … Jafarian, H. (1970). Yeast

Colonization and Drug Susceptibility Pattern in the Pediatric Patients With Neutropenia. Jundishapur Journal of

Microbiology, 7(8), 1–6. https://doi.org/10.5812/jjm.11858

17. Hope, W. W., Tabernero, L., Denning, D. W., & Anderson, M. J. (2004). Molecular Mechanisms of Primary Resistance

to Flucytosine in Candida albicans Molecular Mechanisms of Primary Resistance to Flucytosine in Candida albicans,

48(11), 4377–4386. https://doi.org/10.1128/AAC.48.11.4377

18. Ingham, C. J., Boonstra, S., Levels, S., Lange, M. De, Meis, J. F., & Peter, M. (2012). Rapid Susceptibility Testing and

Microcolony Analysis of Candida spp . Cultured and Imaged on Porous Aluminum Oxide, 7(3), 1–8.

https://doi.org/10.1371/journal.pone.0033818

19. Kabir, M. A., & Ahmad, Z. (2013). Candida infections and their prevention. ISRN Preventive Medicine, 2013(Vvc),

763628. https://doi.org/10.5402/2013/763628

20. Kali, A., Charles, M. P., Joseph, N. M., Umadevi, S., Kumar, S., & Easow, J. M. (2013). Prevalence of Candida co-

infection in patients with pulmonary tuberculosis. Australasian Medical Journal, 6(8), 387–391.

https://doi.org/10.4066/AMJ.2013.1709

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

47 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

21. Kamath, P., Pais, M., & Nayak, M. G. (2013). Original Research Article Risk of vaginal candidiasis among pregnant

women, 2(9), 141–146.

22. Kanafani, Z. A., & Perfect, J. R. (2008). Resistance to Antifungal Agents : Mechanisms and Clinical Impact, 46.

https://doi.org/10.1086/524071

23. Kojic, E. M., Darouiche, R. O., & Biofilms, C. (2004). Candida Infections of Medical Devices, 17(2), 255–267.

https://doi.org/10.1128/CMR.17.2.255

24. Kothavade, R. J., Kura, M. M., Valand, A. G., & Panthaki, M. H. (2016). Candida tropicalis : its prevalence ,

pathogenicity and increasing resistance to fluconazole, (2010), 873–880. https://doi.org/10.1099/jmm.0.013227-0

25. Kumari, V., Banerjee, T., Kumar, P., Pandey, S., Tilak, R., & Pradesh, U. (2013). Emergence of non-albicans Candida

among candidal vulvovaginitis cases and study of their potential virulence factors , from a tertiary care center , North,

144–147.

26. Leon, E. M. De, Jacober, S. J., Sobel, J. D., & Foxman, B. (2002). women with type 1 and type 2 diabetes, 6, 1–6.

27. Li, F., Wu, L., Cao, B., Zhang, Y., Li, X., & Liu, Y. (2013). Surveillance of the prevalence, antibiotic susceptibility, and

genotypic characterization of invasive candidiasis in a teaching hospital in China between 2006 to 2011. BMC Infectious

Diseases, 13(1), 353. https://doi.org/10.1186/1471-2334-13-353

28. Liew, Y. X., Teo, J., Too, I. A., Ngan, C. C., Tan, A. L., Chlebicki, M. P., … Lee, W. (2015). Candida Surveillance in

Surgical Intensive Care Unit ( SICU ) in a Tertiary Institution. BMC Infectious Diseases, 1–8.

https://doi.org/10.1186/s12879-015-0997-6

29. Lopez-ribot, J. L., Atee, R. K. M. C., Lee, L. N., Kirkpatrick, W. R., White, T. C., Sanglard, D., & Patterson, T. F.

(1998). Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial Candida

albicans Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis, 42(11), 2932–

2937.

30. Lortholary, O., Desnos-ollivier, M., Sitbon, K., & Fontanet, A. (2011). Recent Exposure to Caspofungin or Fluconazole

Influences the Epidemiology of Candidemia : a Prospective Multicenter Study Involving 2 , 441 Patients ᰔ, 55(2), 532–

538. https://doi.org/10.1128/AAC.01128-10

31. Marsh, P. K., Tally, F. P., Kellum, J., & Callow, A. (1982). Candida Infections in Surgical Patients Risk Factors for

Candida Infection, (January 1977), 42–47.

32. Mayer, F. L., Wilson, D., & Hube, B. (2013). Candida albicans pathogenicity mechanisms. Virulence, 4(2), 119–128.

https://doi.org/10.4161/viru.22913

33. Melhem, M. S. C., Bertoletti, a., Lucca, H. R. L., Silva, R. B. O., Meneghin, F. a., & Szeszs, M. W. (2013). Use of the

VITEK 2 system to identify and test the antifungal susceptibility of clinically relevant yeast species. Brazilian Journal of

Microbiology, 44(4), 1257–1266. https://doi.org/10.1590/S1517-83822014005000018

34. Menza Nelson, Wanyoike Wanjiru2, M. W. M. (2013). Prevalence of Vaginal Candidiasis and Determination of the

Occurrence of Candida Species in Pregnant Women Attending the Antenatal Clinic of Thika. Open Journal of Medical

Microbiology, 2013(December), 264–272. http://dx.doi.org/10.4236/ojmm.2013.34040

35. Mohammad, E. J. (2012). Catheter Associated Fungal Urinary Tract Infection, 11(3), 326–329.

36. Mukasa, K. J., Herbert, I., Daniel, A., Livingstone, K., Joel, B., & Frederick, B. (2015). HHS Public Access, 5(4), 322–

331. https://doi.org/10.9734/BMRJ/2015/13804.Antifungal

37. Mutua, F., Revathi, G., & Machoki, J. M. (2010). SPECIES DISTRIBUTION AND ANTIFUNGAL SENSITIVITY

PATTERNS OF VAGINAL YEASTS SPECIES DISTRIBUTION AND ANTIFUNGAL SENSITIVITY PATTERNS

OF VAGINAL YEASTS, 87(4), 156–162.

38. Nnaemeka, O. (2010). Prevalence of Vaginal Candidiasis among Pregnant Women in Nnewi Town of Anambra State ,

Nigeria ( Pp . 539-548 ), 4(17), 539–548.

39. Okungbowa, F. I., Isikhuemhen, O. S., & Dede, A. P. O. (2003). The distribution frequency of Candida species in the

genitourinary tract among symptomatic individuals in Nigerian cities, 60–63.

40. Olowe, O. A., Makanjuola, O. B., Olowe, R., & Adekanle, D. A. (2014). Original paper Prevalence of vulvovaginal

candidiasis , trichomoniasis and bacterial vaginosis among pregnant women receiving antenatal care in southwestern

nigeria, 4, 193–197. https://doi.org/10.1556/EUJMI-D-14-00027

41. Omrani, A. S., Pecen, L., Hajek, P., Raghubir, N., & Zigmond, J. (2014). Prevalence of invasive and superficial candida

infections in africa and middle east ; a systematic review and meta-analysis, 48(5), 2019.

42. Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-zeichner, L., … Sobel, J. D. (2016).

Clinical Practice Guideline for the Management of Candidiasis : 2016 Update by the Infectious Diseases Society of

America, 62, 1–50. https://doi.org/10.1093/cid/civ933

43. Pappas, P. G., Rex, J. H., Sobel, J. D., Filler, S. G., Dismukes, W. E., Walsh, T. J., & Edwards, J. E. (2004). Guidelines

for treatment of candidiasis. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of

America, 38(2), 161–189. https://doi.org/10.1097/01.idc.0000130888.27859.52

44. Rasilainen, S. K., Juhani, M. P., & Kalevi, L. A. (2015). Microbial colonization of open abdomen in critically ill surgical

patients. World Journal of Emergency Surgery, 1–8. https://doi.org/10.1186/s13017-015-0018-5

45. Report, C., & Gupta, N. (2012). A Rare Cause of Gastric Perforation- Candida Infection : A Case Report and Review of

the Literature, 6(9), 1564–1565. https://doi.org/10.7860/JCDR/2012/4632.2563

INTERNATIONAL JOURNAL OF ACADEMICS & RESEARCH - IJARKE ISSN IJARKE Science & Technology Journal

www.ijarke.com

48 IJARKE PEER REVIEWED JOURNAL Vol. 1, Issue 1 August, 2018

46. S, I. L., Sa, S., Adam, M., Than, L., Thian, L., & Doblin, S. (2016). Yeast Infection and Diabetes Mellitus among

Pregnant Mother in Malaysia, 23(6), 27–34.

47. San Miguel, L. G., Cobo, J., Otheo, E., Sánchez-Sousa, A., Abraira, V., & Moreno, S. (2005). Secular trends of

candidemia in a large tertiary-care hospital from 1988 to 2000: emergence of Candida parapsilosis. Infection Control and

Hospital Epidemiology : The Official Journal of the Society of Hospital Epidemiologists of America, 26(6), 548–552.

https://doi.org/10.1086/502582

48. Soong, D., & Einarson, A. (2009). Motherisk Update Vaginal yeast infections during pregnancy, 55, 255–256.

https://doi.org/10.1002/14651858.CD000225.9.

49. White, T. C., Marr, K. a, & Bowden, R. a. (1998). Clinical, cellular, and molecular factors that contribute to antifungal

drug resistance. Clinical Microbiology Reviews, 11(2), 382–402.

50. Yakoob, J., Jafri, W., Abid, S., Jafri, N., Islam, M., Hamid, S., Jafri, N. (2003). Candida esophagitis : Risk factors in non-

HIV population in Pakistan, 9(10), 2328–2331.