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1.
Am J Health Syst Pharm ; 79(24): 2208-2221, 2022 12 05.
Article in English | MEDLINE | ID: mdl-36083109

ABSTRACT

PURPOSE: The pharmacology, microbiology, pharmacokinetics, pharmacodynamics, efficacy, safety, and role of ibrexafungerp in the treatment of fungal infections are reviewed. SUMMARY: Ibrexafungerp is the first triterpenoid antifungal. Similarly to echinocandins, it inhibits the synthesis of 1,3-ß-d-glucan. However, it binds to a different site on the enzyme than echinocandins, resulting in limited cross-resistance. Ibrexafungerp exerts concentration-dependent fungicidal activity against Candida species and retains in vitro activity against most fluconazole-resistant strains. It is also active against Aspergillus species. Ibrexafungerp has been shown to be safe and effective in the treatment of vulvovaginal candidiasis caused by Candida albicans in phase 2 and phase 3 clinical trials. It is approved for vulvovaginal candidiasis in adult and postmenarchal pediatric females and is given as two 150-mg tablets orally, administered 12 hours apart. Ibrexafungerp is contraindicated in pregnancy. The most commonly reported adverse reactions were diarrhea, nausea, abdominal pain, dizziness, and vomiting. Ibrexafungerp should be avoided with strong or moderate CYP3A inducers, and the dose should be reduced with strong CYP3A inhibitors. Ibrexafungerp may be useful for patients who are not able to receive fluconazole or prefer oral therapy for the treatment of vulvovaginal candidiasis. However, it is more expensive than the 150-mg tablet of generic fluconazole, which is the current standard of care for vulvovaginal candidiasis. Clinical trials are ongoing for recurrent and complicated vulvovaginal candidiasis as well as invasive candidiasis and pulmonary aspergillosis. CONCLUSION: Ibrexafungerp is an alternative to fluconazole for the treatment of vulvovaginal candidiasis in nonpregnant females. It has the potential to be useful for recurrent and complicated vulvovaginal candidiasis as well as certain invasive fungal infections.


Subject(s)
Candidiasis, Vulvovaginal , Triterpenes , Adult , Pregnancy , Female , Humans , Child , Antifungal Agents/adverse effects , Fluconazole/adverse effects , Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/drug therapy , Candidiasis, Vulvovaginal/microbiology , Triterpenes/adverse effects , Echinocandins/pharmacokinetics , Echinocandins/therapeutic use
2.
Am J Obstet Gynecol ; 227(6): 880.e1-880.e11, 2022 12.
Article in English | MEDLINE | ID: mdl-35863457

ABSTRACT

BACKGROUND: Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: This study was conducted to evaluate the efficacy and safety of oral oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode. STUDY DESIGN: Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks. RESULTS: In the induction phase, oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the OTESECONAZOLE/oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group. CONCLUSION: In participants with recurrent vulvovaginal candidiasis, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.


Subject(s)
Candidiasis, Vulvovaginal , Infections , Female , Humans , Candidiasis, Vulvovaginal/drug therapy , Candidiasis, Vulvovaginal/chemically induced , Fluconazole/therapeutic use , Fluconazole/adverse effects , Administration, Oral , Antifungal Agents/adverse effects
3.
J Obstet Gynaecol ; 42(6): 2190-2196, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35253598

ABSTRACT

The study aims to evaluate the additive effect of intra-vaginal gentian violet (GV) on a single dose oral 200 mg fluconazole for acute vaginal candidiasis (VC). Women aged ≥18 years who had VC were randomly allocated to receive either fluconazole 200 mg (group 1, FLU, N = 90); or the fluconazole with GV (group 2, FLU + GV, N = 93). Outcome measures were 2-week clinical cure rate, conversion of positive fungal culture, time-to-cure, side effects, satisfaction and symptomatic recurrence within 2 months. No significant difference of participants' characteristics was observed. They were 32.4 ± 8.7 year-old and non-obese. Participants receiving FLU + GV had higher clinical cure rates (81.7% vs. 74.4%, p=.236); lower recurrence rate (19.4% vs. 30.0%, p=.097); shorter time-to-cure (3.1 vs. 4.0 days, p=.013); but lower culture conversion rate (74.2% vs. 80.0%, p=.351). Participants in both groups reported high satisfaction and none had severe adverse events. In conclusion, the addition of GV results in a shorter time-to-cure but not cure rate. Clinical trial registration: TCTR20180917003 (http://thaiclinicaltrials.org/show/TCTR20180917003).Impact StatementWhat is already known on this subject? The efficacy of fluconazole for acute vaginal candidiasis is limited to 75-90% due to drug resistance and non-albicans Candida. Gentian violet (GV) has long been used for mucosal candidiasis; and is recommended as the second line treatment for women with recurrent vulvovaginal candidiasis (RVVC).What do the results of this study add? Adding GV to a single oral 200 mg fluconazole results in a quicker resolution of symptoms of acute VC but not cure rate. The participants' satisfaction and acceptance are high. Lifestyle modification, particularly reduction of sugar-rich diet, associates with the higher culture-based cure rate.What are the implications of these findings for clinical practice and/or further research? As GV is widely and easily accessible, and speculum examination with or without microscopy is the main diagnostic tool of VC; the single application of GV seems doable in real-life practice. This simple anti-septic solution can accelerate symptom resolution. However, the proper frequency of GV application should be further explored. As importantly, lifestyle modification should always be included in counselling session to optimise treatment outcome.


Subject(s)
Candidiasis, Vulvovaginal , Candidiasis , Adolescent , Adult , Antifungal Agents , Candidiasis, Vulvovaginal/chemically induced , Female , Fluconazole , Gentian Violet/therapeutic use , Humans , Sugars/therapeutic use , Young Adult
4.
Ann Pharmacother ; 55(4): 543-548, 2021 04.
Article in English | MEDLINE | ID: mdl-32808541

ABSTRACT

OBJECTIVE: To review the incidence, risk factors, prevention, and management of genital mycotic infections (GMIs) associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. DATA SOURCES: A literature search of PubMed and Reactions Weekly was performed in February 2020 with updated searches monthly through July 2020 to identify relevant data regarding SGLT2 inhibitors and GMIs. Manufacturers of each agent were contacted, and clinical practice guidelines were consulted. STUDY SELECTION AND DATA EXTRACTION: All available literature was evaluated for inclusion based on relevance to the research question, timeliness of the publication, validity, and impact on current practice. A date limit was not set; however, publications from 2010 to July 2020 were prioritized. DATA SYNTHESIS: The 3- to 4-fold increased incidence of GMIs is considered a classwide effect of SGLT2 inhibitors. Female sex and a prior history of GMIs are factors associated with the highest risk, whereas circumcised males are at the lowest risk of SGLT2 inhibitor-induced GMI. Personal hygiene advice can reduce the infection risk. When candidiasis occurs, it is often mild and responsive to treatment and often does not require discontinuation of the medication. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This narrative review can assist in shared decision-making discussions with patients who may benefit from SGLT2 inhibitors and provides guidance for health care professionals managing SGLT2 inhibitor-associated GMIs. CONCLUSIONS: SGLT2 inhibitors predispose patients to developing mild GMIs. Strong consideration should be given to avoid SGLT2 inhibitors in female patients with a history of severe, recurrent infections. Preventive strategies are optimized diabetes management and personal hygiene advice.


Subject(s)
Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/prevention & control , Disease Management , Genitalia/drug effects , Hygiene , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Canagliflozin/adverse effects , Canagliflozin/therapeutic use , Candidiasis, Vulvovaginal/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Female , Genitalia/microbiology , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Male , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
5.
Obstet Gynecol ; 134(3): 573-580, 2019 09.
Article in English | MEDLINE | ID: mdl-31403592

ABSTRACT

OBJECTIVE: To examine the relationship between hormonal contraception and vaginal infections with bacterial vaginosis, vaginal candidiasis, or trichomoniasis. METHODS: Couples who were human immunodeficiency virus (HIV) serodiscordant in Zambia were enrolled in a longitudinal cohort study. From 1994 to 2002, both partners were seen quarterly and received physical exams including genital examinations. Separate rates for three outcome infections of interest (bacterial vaginosis, vaginal candidiasis, and trichomoniasis) were calculated. Bivariate associations between baseline and time-varying covariates and outcome infections of interest were evaluated using unadjusted Anderson-Gill survival models. Adjusted hazard ratios (aHRs) were generated using multivariable Anderson-Gill survival models that included demographic and clinical factors associated with both hormonal contraceptive use and each infection of interest. RESULTS: There were 1,558 cases of bacterial vaginosis, 1,529 cases of vaginal candidiasis, and 574 cases of trichomoniasis over 2,143 person-years of observation. Depot medroxyprogesterone acetate (DMPA) users had significantly lower rates of trichomoniasis and bacterial vaginosis. In adjusted models, DMPA was protective for bacterial vaginosis (aHR=0.72; 95% CI 0.54-0.95), candidiasis (aHR 0.75, 95% CI 0.57-1.00) and trichomoniasis (aHR=0.43, 95% CI 0.25-0.74). Oral contraceptive pills were protective for candidiasis (aHR=0.79, 95% CI 0.65-0.97). CONCLUSION: We confirm that DMPA use was associated with reduced rates of the three most common causes of vaginitis, and oral contraceptive pill use was associated with reduced rates of candidiasis among women in couples who were HIV discordant.


Subject(s)
Contraceptives, Oral, Hormonal/adverse effects , HIV Seropositivity/microbiology , Hormonal Contraception/adverse effects , Vaginitis/chemically induced , Adult , Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/epidemiology , Candidiasis, Vulvovaginal/virology , Female , HIV Seronegativity , Humans , Male , Medroxyprogesterone Acetate/adverse effects , Sexual Partners , Trichomonas Vaginitis/chemically induced , Trichomonas Vaginitis/epidemiology , Trichomonas Vaginitis/virology , Vaginitis/epidemiology , Vaginitis/virology , Vaginosis, Bacterial/chemically induced , Vaginosis, Bacterial/epidemiology , Vaginosis, Bacterial/virology , Zambia/epidemiology
6.
Menopause ; 25(2): 133-138, 2018 02.
Article in English | MEDLINE | ID: mdl-28926514

ABSTRACT

OBJECTIVE: Vulvovaginal atrophy (VVA) is characterized by vaginal changes, dyspareunia, and itching/irritation. Efficacy and safety of a lower-dose estradiol vaginal cream (0.003%) were evaluated in postmenopausal women with VVA-related dyspareunia. METHODS: This was a phase 3, randomized, double-blind, placebo-controlled study. Sexually active postmenopausal women with moderate-severe dyspareunia as the most bothersome symptom, ≤5% vaginal superficial cells, and vaginal pH >5.0 were randomized (1:1) to 0.003% estradiol vaginal cream (15 µg estradiol; 0.5 g cream) or placebo (0.5 g cream) applied daily for 2 weeks followed by three applications/week for 10 weeks. Coprimary outcomes were changes in dyspareunia severity, vaginal cytology, and vaginal pH from baseline to final assessment. Additional efficacy outcomes and safety were assessed. RESULTS: A total of 550 participants (average age, 58 y) were randomized. Compared with placebo, estradiol reduced dyspareunia severity (mean change from baseline ±â€ŠSD: -1.5 ±â€Š1.0 estradiol vs -1.2 ±â€Š0.9 placebo), decreased vaginal pH (-1.36 ±â€Š0.89 vs -0.53 ±â€Š0.92), and improved vaginal cytology (percentage superficial and parabasal cells 10.1 ±â€Š16.7 vs 1.4 ±â€Š6.1 and -48.5 ±â€Š45.1 vs -14.6 ±â€Š39.6; P < 0.001, all) at the final assessment. In addition, estradiol decreased dyspareunia severity at weeks 8 and 12, vaginal/vulvar irritation/itching at weeks 4 and 12, and dryness at week 12 versus placebo (P < 0.01, all). VVA severity, pH, and cytology improved at week 12 with estradiol versus placebo (P < 0.001, all). Vulvovaginal mycotic infections were more frequent with estradiol. One serious event leading to discontinuation occurred with estradiol. No deaths occurred. CONCLUSIONS: Lower-dose estradiol vaginal cream (0.003%) dosed three applications/week is an effective and well-tolerated treatment for VVA-related dyspareunia.


Subject(s)
Dyspareunia/drug therapy , Estradiol/therapeutic use , Estrogens/therapeutic use , Vagina/pathology , Vaginal Creams, Foams, and Jellies/therapeutic use , Vulva/pathology , Administration, Topical , Aged , Atrophy/drug therapy , Candidiasis, Vulvovaginal/chemically induced , Double-Blind Method , Estradiol/adverse effects , Estrogens/adverse effects , Female , Humans , Hydrogen-Ion Concentration , Middle Aged , Postmenopause , Pruritus Vulvae/drug therapy , Severity of Illness Index , Vagina/chemistry , Vaginal Creams, Foams, and Jellies/adverse effects
7.
Am J Obstet Gynecol ; 217(6): 678.e1-678.e9, 2017 12.
Article in English | MEDLINE | ID: mdl-28867602

ABSTRACT

BACKGROUND: A novel single oral dose granule formulation of secnidazole 2 g, a 5-nitroimidazole with a longer half-life (∼17 hours) than metronidazole (∼8 hours), is being developed to treat bacterial vaginosis. OBJECTIVE: We sought to evaluate the effectiveness and safety of single-dose secnidazole 2 g compared to placebo for the treatment of women with bacterial vaginosis. STUDY DESIGN: In all, 189 women with bacterial vaginosis were randomized 2:1 to receive a single oral dose of secnidazole 2 g (N = 125) or matched placebo (N = 64) at 21 centers in the United States. The primary endpoint was the proportion of clinical outcome responders, defined as those with: (1) normal vaginal discharge; (2) negative 10% potassium hydroxide whiff test; and (3) <20% clue cells of total epithelial cell count on microscopic examination of the vaginal wet mount, using saline at the test of cure/end of study visit (study days 21-30). Secondary efficacy analyses included clinical cure rates, defined as: (1) responders with normal vaginal discharge; (2) negative potassium hydroxide whiff tests; and (3) clue cells <20% assessed at the interim visit (study days 7-14), and test of cure/end of study (study days 21-30). In addition, based on the 2016 US Food and Drug Administration draft guidance, patients with baseline Nugent scores 7-10 were evaluated for clinical cure using the following clinical assessments on study days 7-14: (1) resolution of the abnormal vaginal discharge; (2) a negative potassium hydroxide whiff test; and (3) clue cells <20%. The study was designed and powered to demonstrate the efficacy of single-dose secnidazole 2 g compared to placebo; safety and tolerability were also assessed. Due to a prespecified institutional review board-approved protocol calling for withdrawal of randomized, treated patients with a Nugent score <4 or with a separate sexually transmitted infection, this modified intent-to-treat population was the primary analysis population. Statistical comparisons used a stratified Cochran-Mantel-Haenszel test with a .05 level of significance (2-sided). RESULTS: Single-dose secnidazole 2 g was superior to placebo for the primary and all secondary efficacy measures in the modified intent-to-treat population, with clinical outcome responder rates of 53.3% (57/107) vs 19.3% (11/57; P < .001). Clinical cure rates, based on an alternate definition of responder, which accounted for resolution of abnormal discharge consistent with bacterial vaginosis, were consistent with the clinical outcome responder rate analysis (58.9% vs 24.6%; P < .001) for single-dose secnidazole 2 g vs placebo. Clinical cure rates based on the 2016 US Food and Drug Administration guidance were 64.0% vs 26.4% for single-dose secnidazole 2 g vs placebo. Based on the investigator's clinical assessment at the test of cure/end of study visit, significantly more patients receiving single-dose secnidazole 2 g vs placebo required no additional bacterial vaginosis treatment (68.0% [68/100] vs 29.6% [16/54]; P < .001). Adverse events considered by the investigator to be related to study drug occurred in only 20.0% of single-dose secnidazole 2 g-treated patients vs 10.9% of placebo patients, and they included diarrhea (4.0% vs 1.6%), headache (4.0% vs 3.1%), nausea (4.8% vs 1.6%), and vulvovaginal candidiasis (4.0% vs 3.1%). CONCLUSION: Single-dose secnidazole 2 g was superior to placebo on all primary and secondary outcomes and was well tolerated; these results support its role for the treatment of women with bacterial vaginosis.


Subject(s)
Antiprotozoal Agents/therapeutic use , Metronidazole/analogs & derivatives , Vaginosis, Bacterial/drug therapy , Administration, Oral , Adolescent , Adult , Candidiasis, Vulvovaginal/chemically induced , Diarrhea/chemically induced , Double-Blind Method , Female , Headache/chemically induced , Humans , Metronidazole/therapeutic use , Middle Aged , Nausea/chemically induced , Treatment Outcome , Vaginal Discharge , Young Adult
8.
Womens Health (Lond) ; 12(3): 379-88, 2016 06.
Article in English | MEDLINE | ID: mdl-26928259

ABSTRACT

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as canagliflozin, are used in patients with Type 2 diabetes mellitus (T2DM). In clinical studies, canagliflozin significantly reduced A1C, bodyweight and blood pressure, and was generally well tolerated with no increased risk of hypoglycemia. Most common adverse effects observed were genital mycotic infections and urinary tract infections, and increased urination. Approximately 10% of women treated with canagliflozin experienced a genital mycotic infection compared with 3% treated with placebo; those with a prior history were at greater risk. Approximately 9% of women treated with canagliflozin reported a urinary tract infection compared with 7% treated with placebo. Most adverse events were considered mild to moderate in intensity and responded to standard therapy. Treatment with canagliflozin was effective and generally well tolerated in both women (and men) with T2DM.


Subject(s)
Canagliflozin/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Canagliflozin/administration & dosage , Candidiasis, Vulvovaginal/chemically induced , Female , Genital Diseases, Female/chemically induced , Humans , Hypoglycemic Agents/administration & dosage , Urinary Tract Infections/chemically induced
11.
Dtsch Med Wochenschr ; 138 Suppl 1: S6-15, 2013 Apr.
Article in German | MEDLINE | ID: mdl-23529570

ABSTRACT

OBJECTIVE: Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS: This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA1c, 7.7 %), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤ 10 or ≤ 20 mg/day, respectively. RESULTS: The primary end point, adjusted mean HbA1c reduction with dapagliflozin (-0.52 %) compared with glipizide (-0.52 %), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (-3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥ 5 % body weight reduction (33.3 %) versus glipizide (2.5 %; p < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5 %) versus glipizide (40.8 %; p < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. CONCLUSIONS: Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Glipizide/therapeutic use , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors , Aged , Balanitis/chemically induced , Benzhydryl Compounds , Body Weight/drug effects , Candidiasis, Vulvovaginal/chemically induced , Diabetes Mellitus, Type 2/blood , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , Germany , Glipizide/adverse effects , Glucosides/adverse effects , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/blood , Kaplan-Meier Estimate , Male , Metformin/adverse effects , Middle Aged , Sodium-Glucose Transporter 2 , Urinary Tract Infections/blood , Urinary Tract Infections/chemically induced
12.
J Low Genit Tract Dis ; 15(4): 263-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21959570

ABSTRACT

OBJECTIVE: : This study aimed to explore the role of hormone replacement therapy (HRT) in susceptibility to vulvovaginal candidiasis (VVC) in a private vulval disease referral practice. METHODS: : Between January 2009 and December 2010, 149 healthy, nondiabetic patients with vulvar conditions were compared for significant differences in vaginal swab result, age, and diagnosis between those using and not using HRT. Detailed clinical data were collected from those with VVC. RESULTS: : The mean ages of the HRT (n = 70) and non-HRT (n = 79) groups were 62.5 and 62.5 years, respectively. Positive cultures for Candida were found in 34 (48.5%) of 70 patients on HRT and in 2 (3%) of 79 subjects not on HRT (p < .001). Culture-positive, clinical VVC was identified in 34 (49%) of 70 patients on HRT and in 1 (1%) of 79 patients not on HRT (p < .001). Candida species (32 Candida albicans and 2 Candida glabrata) were isolated from the 34 VVC patients, and of these, 23 (67%) had a history of recurrent or chronic candidiasis before menopause. All 34 had been previously treated with antifungal therapy without ceasing HRT and had been unresponsive to treatment or had relapse after treatment. In 27 (79%) of 34 patients, HRT was suspended during treatment. Of those who remained on HRT during treatment or resumed it after treatment, prophylactic antifungal treatment was initiated in 15 (44%) to prevent recurrence. All patients responded to the antifungal treatment provided HRT was suspended or prophylactic treatment was used. CONCLUSIONS: : Postmenopausal women taking HRT are significantly more prone to develop VVC than women who are not and those with VVC are likely to have been susceptible to it before menopause.


Subject(s)
Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/epidemiology , Hormone Replacement Therapy/adverse effects , Postmenopause , Aged , Aged, 80 and over , Candida albicans/classification , Candida albicans/isolation & purification , Candida glabrata/classification , Candida glabrata/isolation & purification , Female , Humans , Middle Aged
13.
Glycoconj J ; 26(9): 1125-34, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19326211

ABSTRACT

Cervical mucins are glycosylated proteins that form a protective cervical mucus. To understand the role of mucin glycans in Candida albicans infection, oligosaccharides from mouse cervical mucins were analyzed by liquid chromatography-mass spectrometry. Cervical mucins carry multiple alpha(1-2)fucosylated glycans, but alpha(1,2)fucosyltransferase Fut2-null mice are devoid of these epitopes. Epithelial cells in vaginal lavages from Fut2-null mice lacked Ulex europaeus agglutinin-1 (UEA-I) staining for alpha(1-2)fucosylated glycans. Hysterectomy to remove cervical mucus eliminated UEA-I and acid mucin staining in vaginal epithelial cells from wild type mice indicating the cervix as the source of UEA-I positive epithelial cells. To assess binding of alpha(1-2) fucosylated glycans on C. albicans infection, an in vitro adhesion assay was performed with vaginal epithelial cells from wild type and Fut2-null mice. Vaginal epithelial cells from Fut2-null mice were found to bind increased numbers of C. albicans compared to vaginal epithelial cells obtained from wild type mice. Hysterectomy lessened the difference between Fut2-null and wild type mice in binding of C. ablicans in vitro and susceptibility to experimental C. albicans vaginitis in vivo. We generated a recombinant fucosylated MUC1 glycanpolymer to test whether the relative protection of wild type mice compared to Fut2-null mice could be mimicked with exogenous mucin. While a small portion of the recombinant MUC1 epitopes displayed alpha(1-2)fucosylated glycans, the predominant epitopes were sialylated due to endogenous sialyltransferases in the cultured cells. Intravaginal instillation of recombinant MUC1 glycanpolymer partially reduced experimental yeast vaginitis suggesting that a large glycanpolymer, with different glycan epitopes, may affect fungal burden.


Subject(s)
Candidiasis, Vulvovaginal/prevention & control , Cervix Mucus/metabolism , Fucose/metabolism , Mucins/metabolism , Polysaccharides/metabolism , Animals , Candida albicans/growth & development , Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/pathology , Carbohydrate Sequence , Cell Adhesion , Cervix Mucus/microbiology , Colony Count, Microbial , Disease Susceptibility , Epithelial Cells/enzymology , Epithelial Cells/microbiology , Epithelial Cells/pathology , Epitopes/immunology , Female , Fucosyltransferases/deficiency , Fucosyltransferases/metabolism , Hysterectomy , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Mucin-1/metabolism , Recombinant Proteins/metabolism , Vaginal Smears , Galactoside 2-alpha-L-fucosyltransferase
14.
Pediatr Dermatol ; 25(2): 179-83, 2008.
Article in English | MEDLINE | ID: mdl-18429774

ABSTRACT

For patients who fail traditional acne therapy or experience side effects, other treatments are needed. Cephalexin has been noted to be efficacious in some instances. This study aimed to assess the therapeutic efficacy of cephalexin for acne. A retrospective chart review of 93 acne patients treated with cephalexin was performed. Data collection included patient demographics, other acne therapies, clinical response, and side effects. Of the 98 courses of cephalexin, 4% of patients cleared, 45% were much improved, 29% were somewhat improved, 16% experienced no change, and 6% worsened at first follow-up visit. The median treatment length was 6 months. Eighty-four percent of patients had previously used a systemic antibiotic(s) for acne. Seven percent experienced adverse effects. This is a small retrospective analysis without a comparison group and is limited by the number of patients and nonstandardized treatment lengths and charting procedures. Cephalexin is a promising alternative treatment for acne, with 78% of patients exhibiting at least some clinical improvement.


Subject(s)
Acne Vulgaris/drug therapy , Anti-Bacterial Agents/administration & dosage , Cephalexin/administration & dosage , Administration, Oral , Adolescent , Adult , Anti-Bacterial Agents/adverse effects , Candidiasis, Vulvovaginal/chemically induced , Cephalexin/adverse effects , Child , Female , Humans , Male , Retrospective Studies
16.
Infect Dis Obstet Gynecol ; 11(3): 157-60, 2003.
Article in English | MEDLINE | ID: mdl-15022876

ABSTRACT

OBJECTIVE: To address the putative association of antibiotic use and subsequent yeast vaginitis in a population of non-pregnant women. METHODS: Three hundred and sixteen women who received medical care in rural family medicine clinics enrolled in this study. Participants were pre-menopausal and non-pregnant and were followed until they used a course of antifungal therapy for vaginitis, became pregnant or moved from the catchment area. At entry subjects were free of vaginitis symptoms and had taken no antibiotics for 30 days. Patients were followed by repeated review of clinic records, hospital records and telephone or personal interviews. Data collection included documentation of episodes of antifungal treatment for vulvovaginal candidiasis and confirmed antibiotic treatment or credible history of antibiotic use prior to the use of antifungal therapy. Physician-reported uses of antibiotic and antifungal as well as patient-reported uses of these were recorded. RESULTS: There were four reported cases of antifungal therapy following within a month of antibiotic use, in contrast to 484 antibiotic uses not followed by antifungal use. If time of observation was extended to 6 months from antibiotic use, there were 13 uses of antifungal therapy after antibiotics and 475 uses of antibiotics not followed by antifungal therapy. CONCLUSION: Our results cast doubt on the association of antibiotics as a putative cause of yeast vulvovaginitis.


Subject(s)
Anti-Bacterial Agents/adverse effects , Antifungal Agents/therapeutic use , Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/drug therapy , Administration, Oral , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Candidiasis, Vulvovaginal/physiopathology , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Middle Aged , Risk Assessment , Severity of Illness Index , Treatment Outcome , Vaginitis/chemically induced , Vaginitis/microbiology
18.
Pediatrics ; 104(6): e72, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10586006

ABSTRACT

OBJECTIVE: This study examined the prevalence of gonorrhea in girls <12 years of age who presented with vaginitis and in whom sexual abuse was not suspected. DESIGN: A prospective, consecutive patient series was performed in a pediatric emergency department with 90 000 visits per year and in 2 affiliated pediatric continuity clinics. All girls (Tanner I or II) between the ages of 12 months and 12 years, presenting with a chief complaint of vaginal discharge, burning, pain, or itching, were enrolled (n = 93). Patients were excluded (n = 6) if there was a history of sexual abuse. The presence or absence of vaginal discharge, vaginal erythema, or trauma was recorded. Physicians were instructed to collect cultures for Neisseria gonorrhea (GC), Chlamydia trachomatis, and bacteria/yeast. Wet prep, urinalysis, urine culture, serum rapid plasma reagin, and fungal culture were obtained at the physician's discretion. RESULTS: Of the girls, 43 had a vaginal discharge on examination. Of these girls, 4 (9%) had GC, 9 (26%) had group A, B, or F streptococcus and 1 had Staphylococcus aureus. Of the girls, 44 had no discharge on examination. In this group, 3 had streptococcus infection and 2 had Candida albicans. Both children with C albicans had been treated recently with systemic antibiotics. Those girls with a vaginal discharge on examination had a microbial etiology significantly more often than did those without discharge. All of the girls with infection were Tanner I on genital examination. CONCLUSIONS: The prevalence of unsuspected GC infection was high and emphasizes the importance of culturing Tanner I girls for GC when they have a vaginal discharge along with routine bacterial cultures. Testing and/or treating for C albicans should be considered when there has been recent antibiotic use. Girls with vaginal complaints but without vaginal discharge may have a bacterial infection, but such diagnoses occur less frequently than with girls who have a discharge.


Subject(s)
Gonorrhea/complications , Vaginal Discharge/etiology , Vaginitis/microbiology , Anti-Bacterial Agents/adverse effects , Candidiasis, Vulvovaginal/chemically induced , Candidiasis, Vulvovaginal/complications , Candidiasis, Vulvovaginal/diagnosis , Child , Child, Preschool , Female , Gonorrhea/diagnosis , Humans , Infant , Prospective Studies , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Vaginal Discharge/microbiology
20.
Zentralbl Gynakol ; 119(11): 545-9, 1997.
Article in German | MEDLINE | ID: mdl-9480609

ABSTRACT

Fungal vaginal infections/colonisations can be divided into a symptomatic vaginal candidiasis and an asymptomatic vaginal Candida-carriage. The latter seems to be a predisposing factor for the development of a symptomatic vaginal candidiasis. The fungal organism isolated most frequently is Candida albicans, followed by Candida glabrata, which was previously also known as Torulopsis glabrata. To a lower extend, other Candida species such as Candida tropicalis and Candida krusei can be prevalent in the vulvovaginal region. Predisposing factors for vaginal candidiasis are gravidity, diabetes mellitus or a therapy with immunosuppressive agents. Also gestagenes showed to be a pre-disposing factor for vaginal candidiasis. Divergent results concerning the predisposition to vaginal candidiasis or colonisation due to oral contraception have so far been reported. Therefore we performed a study with two healthy collectives of female volunteers (n = 2 x 60) which were different concerning the taking of oral contraceptives. Overall, in 17% of the subjects (20/120) yeast could be cultured out of the vaginal secretions. There was no evidence for a higher rate of Candida-colonisation in subjects taking oral contraceptives. Further, there was no evidence for a relationship between the length of the taking of oral contraceptives and the rate of vaginal yeast-carriage. Also the type of oral contraceptive (combination or sequential contraceptive) had no influence on the frequency of Candida-carriage. Candida albicans was the most prevalent yeast (16/20), followed by Candida glabrata (4/20).


Subject(s)
Candidiasis, Vulvovaginal/chemically induced , Contraceptives, Oral/adverse effects , Adult , Carrier State/microbiology , Contraceptives, Oral/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Risk Factors , Vagina/microbiology
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