Genital Mycotic Infections in Patients With Diabetes

Drexel University College of Medicine, Philadelphia, PA. .
Postgraduate Medicine (Impact Factor: 1.7). 05/2013; 125(3):33-46. DOI: 10.3810/pgm.2013.05.2650
Source: PubMed


Patients with diabetes, especially those with poorly controlled glycemia, are prone to developing genital mycotic infections-vulvovaginal candidiasis in women and Candida balanitis in men-the latter almost exclusively in uncircumcised men. Candida albicans is the most common pathogen causing balanitis and is also the dominant cause of vulvovaginal candidiasis in women with diabetes, although Candida glabrata is a prominent pathogen in women with type 2 diabetes mellitus. Candida glabrata is less virulent but also less susceptible to conventional antifungal treatment. High blood glucose levels promote yeast attachment and growth, and also interfere with immune responses in the host. In uncircumcised men, the moist, warm space underneath the foreskin is thought to promote yeast growth, especially when hygiene is poor. Several other risk factors have been identified that predispose to genital mycotic infections, including antibiotic use, corticosteroid use, immunosuppression, atopy, and, in women only, genetics, pregnancy, estrogen/oral contraceptive use, and select sexual behaviors (eg, orogenital sex). In patients with hyperglycemia, risk is increased for not only incident infection but also for recurrence, underscoring the key role of establishing and maintaining euglycemia in the management of genital mycotic infections in patients with diabetes. In addition to blood glucose control, first-line treatment involves either an antifungal cream/ointment (or suppository for women only) that is applied intravaginally by women and directly to the affected area(s) by men, or oral treatment, which infrequently causes systemic side effects. Antifungal treatment should also be offered to sexual partners of patients with diabetes with a genital mycotic infection if the partner is similarly infected. Given high efficacy rates, follow-up test-of-cure after the completion of treatment is generally unnecessary.

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    • "Most of these patients were diabetics (43.6%) admitted for complications of diabetes mellitus (DM), followed by pregnant females admitted for antenatal care (20.5%). This was consistent with Nyirjesy and Sobel (2013) who identified DM and pregnancy as important risk factors of Candida spp. genital infections and determining C.albicans as the predominant isolated pathogen in their study. "
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    ABSTRACT: Biofilm formation is often associated with increased Candida resistance towards antifungal agents. Therefore, the current study aimed to assess the incidence of biofilm formation among Candida isolates and to investigate the effect of high doses of fluconazole {FLC}, voriconazole {VOC} and amphotericin B {AMB}, singly and in combination on mature biofilms. Moreover, it aimed to assess the expression of selected genes (CDR 1, KRE1 and SKN 1) responsible for Candida biofilms resistance. The study included 49 patients; samples were collected from King Khalid Hospital, Riyadh, Saudi Arabia. Isolates were prepared for biofilm formation and quantification using 0.4% (w/v) crystal violet. Minimum Inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) were conducted by broth microdilution method. Biofilm eradication was evaluated using counting, XTT stain intensity and observed under the inverted microscope. Selected genes were evaluated in Candida biofilms under the effect of antifungal exposure using QPCR. The major isolates were C. albicans (65.3%) followed by C. tropicalis and C. glabrata. 77.6% of the strains were biofilm formers. AMB showed susceptibility in 87.8% of isolates, followed by VOC (77.6%) and FLC (67.3%). MIC50 and MIC90 was (0.03, 0.125), (0.5, 8), (2, > 128) μg/ml for AMB, VOC and FLC, respectively. 34.7% and 18.4% of the isolates were antagonistic to AMB/ FLC and AMB/VOC respectively. Mature biofilms of ten selected isolates were found resistant to FLC (1000 μg/ml). VOR and AMB concentration required to inhibit biofilm formation was 16-250 fold higher than the MIC for planktonic cells. Isolates showed significant reduction with antifungal combination when compared with the untreated controls (p value ⩽0.01), or using fluconazole alone (p value ⩽0.05). High doses of the antifungals were employed to assess the effect on the persisters’ selected gene expression. Marked over expression of SKN1 and to a lesser extent KRE 1 were noticed among the mature biofilms treated with AMB alone or in combination after 1h of exposure, and SKN 1 expression was even more sharply induced after 24h. No statistically significant over expression of CDR 1 was observed in biofilms after exposure to high doses of FLC, VOC or any of the combinations used.
    Saudi Pharmaceutical Journal 12/2013; 23(1). DOI:10.1016/j.jsps.2013.12.007 · 1.28 Impact Factor
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    ABSTRACT: Abstract Objective: To characterise genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) using pooled data from Phase 3 studies. Research design and methods: Genital mycotic infections with canagliflozin 100 and 300 mg were evaluated in Population 1 (N=2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.8), including patients from 4 placebo-controlled studies, and Population 2 (N=9439; mean exposure [weeks]: canagliflozin, 68.1; control, 64.4), including patients from 8 placebo/active-controlled studies (including older patients and those with renal impairment or high cardiovascular disease risk). Clinical trial registration:, NCT01081834; NCT01106625; NCT01106677; NCT01106690; NCT01032629; NCT01064414; NCT01106651; NCT00968812 Main outcome measures: Adverse events suggestive of genital mycotic infections were recorded, with additional information collected using supplemental electronic case report forms. Results: In Population 1, genital mycotic infection incidence was higher with canagliflozin 100 and 300 mg than placebo (95% confidence intervals excluded zero) in females (10.4%, 11.4%, 3.2%) and males (4.2%, 3.7%, 0.6%). These were generally mild to moderate in intensity, none were serious, and few led to discontinuation. Most events with canagliflozin were treated with antifungal therapies, and median symptom duration following treatment initiation was similar across groups; few patients had >1 event (females, 2.3%; males, 0.9%). Findings with canagliflozin 100 and 300 mg versus control were similar in Population 2 (females: 14.7%, 13.9%, 3.1%; males: 7.3%, 9.3%, 1.6%); a low proportion of males underwent circumcision across groups. Most events with canagliflozin occurred within the first 4 months in females and first year in males; no consistent evidence of dose-dependence was observed. Key limitations included lack of laboratory confirmation for most events and variable treatment methods. Conclusions: Genital mycotic infection incidences were higher with canagliflozin than control in patients with T2DM; events were generally mild to moderate in intensity and responded to standard treatments.
    Current Medical Research and Opinion 02/2014; 30(6). DOI:10.1185/03007995.2014.890925 · 2.65 Impact Factor
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    ABSTRACT: Canagliflozin is the first available oral inhibitor of sodium/glucose cotransporter 2 (SGLT2) in the market. At the outset it sounds excellent for the use in the elderly diabetic population, because of its minimal tendency to cause hypoglycemia. However, the clinician needs to exercise caution as it needs to be dosed renally. The clinician needs to be circumspect about potential drug interactions, especially when there is an underlying chronic kidney disease (CKD) and congestive heart failure (CHF). Also its use is best avoided in people who are predisposed to genital mycotic and urinary tract infections (UTI).
    Journal of Pharmacology and Pharmacotherapeutics 04/2014; 5(4):227-231. DOI:10.4103/0976-500X.142428
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