Maintenance Fluconazole Therapy for Recurrent Vulvovaginal Candidiasis

[Dr.Vad]

Уважаемые коллеги!

В последнем NEJM 2004:Volume 351:876-883 противорецидивная терапия кандидиаза флюконазолом:

Maintenance Fluconazole Therapy for Recurrent Vulvovaginal Candidiasis

Jack D. Sobel et al.

Background No safe and convenient regimen has proved to be effective for the management of recurrent vulvovaginal candidiasis.

Methods After inducing clinical remission with open-label fluconazole given in three 150-mg doses at 72-hour intervals, we randomly assigned 387 women with recurrent vulvovaginal candidiasis to receive treatment with fluconazole (150 mg) or placebo weekly for six months, followed by six months of observation without therapy. The primary outcome measure was the proportion of women in clinical remission at the end of the first six-month period. Secondary efficacy measures were the clinical outcome at 12 months, vaginal mycologic status, and time to recurrence on the basis of Kaplan–Meier analysis.

Results Weekly treatment with fluconazole was effective in preventing symptomatic vulvovaginal candidiasis. The proportions of women who remained disease-free at 6, 9, and 12 months in the fluconazole group were 90.8 percent, 73.2 percent, and 42.9 percent, as compared with 35.9 percent, 27.8 percent, and 21.9 percent, respectively, in the placebo group (P< 0.001). The median time to clinical recurrence in the fluconazole group was 10.2 months, as compared with 4.0 months in the placebo group (P<0.001). There was no evidence of fluconazole resistance in isolates of Candida albicans or of superinfection with C. glabrata. Fluconazole was discontinued in one patient because of headache.

Conclusions Long-term weekly treatment with fluconazole can reduce the rate of recurrence of symptomatic vulvovaginal candidiasis. However, a long-term cure remains difficult to achieve.

[Chebotnikova T.]

Д-р Вадим,

флуконазол - препарат первой линии для терапии кандидоза слизистых, в т.ч. рецидивирующего. Нет здесь ничего сверхнеожиданного, на мой взгляд. Дозировки, правда, и эффективность, по моему мнению могут быть несколько иными.

[Alexei]

Мне попадалась информация, что достаточно 150 мг однократно для нерецидивирующего?

[Dr.Vad]

Фрагмент редкомментария:

Complicated candidiasis is much less common than uncomplicated disease. Severe symptoms usually require 7 to 14 days of therapy instead of the short course used for uncomplicated candidiasis. Candida species other than Candida albicans account for only about 10 percent of all infections, but only about half of these infections respond to either oral or vaginal azole therapy. Patients with chronic, recurrent candidiasis account for the remainder of cases of complicated candidiasis. Most cases of recurrent candidiasis are caused by C. albicans. The problem for both patients and physicians is that although complicated candida vulvovaginitis affects only a small proportion of cases of candidiasis, it leads to a substantial percentage of the total physician visits, because the symptoms and the disease usually clear only with very specific therapy or repeated treatment.

In this issue of the Journal, Sobel et al. report on the treatment of an important subgroup of women with candida infections, the 5 to 8 percent with chronic, recurrent vulvovaginal candidiasis, defined as four or more episodes per year. This is a manageable form of complicated candidiasis (see Table), and the report, confirming the findings of smaller studies, shows that three doses of fluconazole given at three-day intervals, followed by a single weekly dose, interrupts recurrent candidiasis for six months (the duration of treatment in this study) in more than 90 percent of study participants, as compared with only 36 percent of those given three doses of fluconazole followed by weekly placebo. Local intravaginal azole therapy given once or twice a week is also effective for recurrent candidiasis, but it is more cumbersome to use and is less popular with patients than the oral regimen. Fluconazole was well tolerated and safe, unlike long-term ketoconazole therapy, which has potential liver toxicity. Unlike antibiotics that are given to suppress chronic urinary tract infections, six months of fluconazole treatment did not cause resistance to fluconazole in these women with normal immune function. Such resistance has been a problem when fluconazole has been given on a long-term basis to patients with depressed immune function from human immunodeficiency virus infection. Prolonged suppressive therapy is now the standard of care for chronic, recurrent candida vulvovaginitis, and managed care groups need to start authorizing payment for prolonged suppressive therapy with fluconazole or intravaginal azoles.

Among the patients in the fluconazole group in the study by Sobel et al., about 9 percent had recurrent candida infection despite weekly fluconazole suppression, and within six months after suppression ceased, recurrent infection had developed in 57 percent. The failure to eradicate candida accounted for some recurrent symptoms, and in a separate report, this research group found a few behavioral factors to be loosely associated with recurrence. However, in large part, recurrence after stopping suppressive therapy with fluconazole remains unstudied and unexplained.

Thus, a number of questions remain. The optimal duration of suppressive therapy is unknown, and the pathophysiology of chronic, recurrent vulvovaginal candidiasis remains unclear. Some patients with persistent candida infection did not have recurrent symptomatic disease, whereas other patients in whom cultures showed no candida had recurrent symptoms. The role of mucosal immunity in protecting against recurrence, on the one hand, or in generating an excessive response resulting in symptoms despite a low concentration of candida, on the other hand, requires exploration, as do virulence factors on the microbe itself. Further work is required to eradicate this troublesome condition, but the current report describes an effective treatment strategy for the time being.

Chronic Vulvovaginal Candidiasis

David A. Eschenbach, M.D.

[Rodionov]

Эффективно, да. А как насчет безопасности? ОДна головная боль на 400 женщин за 6 месяцев. Сомнительно. И ни у кого ферменты не выросли?

Если уж заговорили о флюконазоле. В дружественной нам ЛОР-клинике появилась новая тема докторской. Background: Полипы в носу растут от грибов, надо лечить грибы. Материалы и методы: Оперируем полипы, затем на 3 месяца назначаем дифлюкан в приличной дозе (точно не помню), смотрим частоту рецидивов.

Но вот вопрос, кто будет анализировать безопасность?

[Dr.Vad]

Уважаемый Антон Владимирович!

"Гепатотоксичность" флюконазола может проиллюстрировать следующий пример:

Ann Intern Med. 1999 Nov 16;131(10):729-37.

Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial.

Winston DJ, Pakrasi A, Busuttil RW.

Department of Medicine, University of California, Los Angeles, Medical Center, 90095, USA.

212 liver transplant recipients who received fluconazole (400 mg/d) or placebo until 10 weeks after transplantation.
Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01).

Несмотря на б0льшую дозу в течение 2,5 мес. и наличие не своей печени никакой реакции.

[Rodionov]

Спасибо, уважаемый Вадим Валерьевич, за Вашу как всегда меткую ссылку. Просто как-то мы привыкли относиться к противогрибковым препаратам с большой осторожностью в плане их возможной токсичности. Будем посмотреть...

[Chebotnikova T.]

Я бы сказала, что то, что написано в аннотации производит сильное впечатление , однако постоянно назначая азолы в промышленных масштабах, не то что с гепатотоксичным действием, даже с головной болью Вам вряд ли придется иметь дело.

Вадим,
в общем- то обсуждаются вполне актуальные проблемы рецидивирующего кандидоза, - те же, что задаются в Москве или Воронеже, например, и так же мы, авторы - все в процессе поиска их решения.

[Dr.Vad]

Metronidazole/nystatin Effective for Vaginosis

NEW YORK (Reuters Health) - For the treatment of vaginal bacterial infections, ovules containing the combination of metronidazole plus nystatin are significantly more effective than metronidazole gel, according to results of a trial conducted in Lima, Peru.

Bacterial vaginosis (BV) is a common condition caused by organisms with exotic names such as Gardnerella and Trichomonas. Symptoms include vaginal discharge and odor.

In Latin America, metronidazole plus the anti-fungal agent nystatin in intravaginal ovules, administered nightly for five to seven nights, is often prescribed for vaginal discharge -- but the effectiveness of this treatment is unproven. This prompted Dr. Sixto Sanchez and colleagues to compare it to metronidazole once nightly for five nights, which is approved by the U.S. FDA.

Of 151 women with BV randomly assigned to one of the two treatments, 138 (91 percent) returned at least once for follow-up, the team notes in the American Journal of Obstetrics and Gynecology.

Rates of persistent or recurrent vaginosis at 14, 42, and 104 days were 20 percent, 38 percent, and 52 percent, respectively, after gel treatment; after ovule treatment the corresponding rates were significantly lower -- 4 percent, 17 percent, and 33 percent.

The investigators think that the higher content of metronidazole in the ovules (500 milligrams) compared with the gel (37.5 mg per dose) might explain the better efficacy of this treatment, although additional studies are needed.

They also think the findings suggest that unprotected sex increases the risk of recurrence of vaginosis after initial improvement.

SOURCE: American Journal of Obstetrics and Gynecology, December 2004.

[basic]

Доброго времени суток, коллеги.
Наше отношение к нарушениям соотношения влагалищной флоры, которые проявялются в виде рецидивирующего бактериального вагиноза, вагинального кандидоза, дисбиоза и т.д., конечно обусловленно изучением трихомонадоносительства и хронического трихомониаза и давно публиковалось на страницах форума. Я не буду на этом останавливаться, к тому же ( по моему) на форуме осталась страничка по Ассоциатам в диагностике и лечении хронических воспалительных процессов. Отношение к применению местной теапии нитроинидазолами и + сочетании с антимикотиками( а ведь есть еще и дополнительные препараты, включающие нитроинидазол+ антимикотик+ гидрокортизон и т.д.)

Мы считаем, что местная терапия только ухудшает результаты Вашего лечения. 1- Врач не может оценить динамику терапии. хорошо когда Вы лечите острый процесс, а если хронический вялотекущий , да к тому же и так без четких клинических признаков , колпит.- Вы никогда адекватно не оцените состояние пациенты при использовании местных препаратов.
2- Использование местных препаратов способствуют хронизации инфекции. трихомонада уходит в субэпителиальный слой, переходит в н изкометаболическую форму, приобретает атипическую форму. Именно поэтому в дальнейщшем Вы получите и рецидивирующий бактериальный вагиноз и отрицательный батериальный скрининг, ну и как следствие хронический трихомониаз.
Ну и последенее: 151 женщина с бактериальным вагинозом без адеватного обследования на атипические урогенитальные инфекции - это не повод для серьезной научной публикации.
С уважением и приветом из Киева d-r Basic
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