Angeles
07-21-2007, 12:30 PM
Please see below abstract a friend sent me via email regarding Amphoterecin B. I've never heard of it before and it is supposed to be an excellent treatment for resistant yeast. Itis very toxic though when taken orally but in the report below it was applied locally in teh vagina. I have forwarded this same report to my doctor who is an infectious deseases gyne. I still need to talk to him about it. Check it out!********************************************************
AMPHOTERICIN B Article:
Sue Ellen Baum, MD, Joseph T. Morris, MD, Madigan Army Medical Center, Ft Lewis, Wash.
Infect Med 18(2):114,117, 2001. © 2001 Cliggott Publishing, Division of SCP Communications
Abstract and Introduction
Abstract
A persistent vaginal infection with Candida glabrata failed to respond to multiple courses of oral and topical antifungals. Intravaginal treatment with a 0.3% solution of amphotericin B achieved a microbiologic cure.
Introduction
Candida (Torulopsis) glabrata is the second leading cause of yeast vaginitis, accounting for 15% to 20% of yeast vaginitis cases.[1] Azole resistance occurs more frequently in vitro in isolates of C glabrata than in Candida albicans. Reports of C glabrata vaginitis demonstrate higher failure rates of standard therapies and higher incidence of recurrence of vaginitis when this organism is isolated from patients.[2] In resistant cases, boric acid has been used with some success.[3] Fothergill et al[4] demonstrated in vitro that synergy could be achieved against C glabrata by using combinations of terbinafine with the triazoles fluconazole and itraconazole. A case of C glabrata vaginitis is presented that was refractory to the above combination therapy. Clinical and microbiologic cure was achieved with amphotericin B vaginal instillations.
Case Report
A 49-year-old menopausal, nondiabetic, HIV-negative, multiparous woman was referred to the infectious disease clinic for persistent vaginitis, apparently resulting from a perioperative course of antibiotics, that was unresponsive to standard therapies. The patient's vaginitis symptoms included vulvar erythema, pruritus, and a white discharge.
The patient had used over-the-counter preparations of clotrimazole and miconazole for relief without improvement. Her primary care provider had attempted treatment with the following antifungal therapies: single 150-mg oral doses of fluconazole on 4 occasions, and 2 7-day courses of terconazole. Concurrently with oral fluconazole, combination topical nystatin, triamcinolone, and clobetasol for secondary inflammation had also been prescribed. The patient had also received oral and intravaginal estrogen therapy. When cultures of her vaginal discharge grew C glabrata, she was given boric acid vaginal suppositories, 600 mg/d for 7 days, but this treatment was unsuccessful both clinically and microbiologically. At the time of her referral, the patient complained of persistent vaginal discharge and pruritus despite these therapies.
The patient's past medical history was remarkable for a unilateral nephrectomy for a congenital malformation and a hysterectomy for cervical dysplasia. Vaginal examination was remarkable for a thick white discharge. Laboratory evaluation before her referral to the infectious disease clinic revealed a serologic test negative for HIV, a normal serum glucose level, and tests negative for herpes simplex virus and human papilloma virus DNA. Cultures again revealed C glabrata. Because of the higher incidence of both refractory vaginitis and C glabrata isolation in HIV-positive patients, HIV serology was repeated, with negative results.
The patient was initially treated with combination oral terbinafine, 250 mg/d and itraconazole, 200 mg/d for 7 days. She continued to have symptoms and repeated culture again showed C glabrata. Treatment was then changed to combination terbinafine, 250 mg/d, and fluconazole, 400 mg/d, for 7 days. Symptoms and positive cultures persisted, and the fluconazole dosage was increased to 600 mg/d and terbinafine was continued at the same dosage as before. The patient remained symptomatic and culture-positive for C glabrata. Following failure of these therapies, the patient's yeast isolate was sent to the Audie L. Murphy Memorial Veterans Hospital in Texas for sensitivity testing by macrobroth dilution and was found to be resistant in vitro to terbinafine (minimum inhibitory concentration [MIC] greater than 4), fluconazole (MIC greater than 32), and the combination of these agents (MIC greater than 2 and 8 at 24 hours, and 2 and 16 at 48 hours). Because topical amphotericin B preparations and topical flucytosine were unavailable on our formulary, the patient was then treated with a 0.3% solution of amphotericin B in 60-mL vials given intravaginally daily for 7 days, after which microbiologic cure was achieved. A follow-up culture at 3 months was again negative for C glabrata.
Discussion
The increasing incidence of resistant yeast infections, including infection with C glabrata, will necessitate new treatment strategies for localized as well as systemic infection. Despite failure of combination therapy with terbinafine and fluconazole or itraconazole in this particular patient, these regimens may prove effective in less resistant isolates. Treatment failure was predictable in this patient based on her in vitro sensitivities. The use of intravaginal amphotericin B douches provides a possible effective form of therapy without the toxicity of systemic amphotericin B and at this time has reliable activity against this resistant pathogen. These therapies may become increasingly useful in an era of increasing fungal resistance to the azole drugs.
References
Sobel JD. Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann N Y Acad Sci. 1988;544:547-557.
Redondo-Lopez V, Lynch M, Schmitt C, et al. Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. Obstet Gynecol. 1990;76:651-655.
Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis. 1997;24:649-652.
Fothergill AW, Leitner I, Meingassner JG, et al. Combination antifungal susceptibility testing of terbinafine and the triazoles fluconazole and itraconazole. In: Program and abstracts of the 36th Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy; August 15-18, 1996; New Orleans. Abstract 91.
Dr Baum is a resident in internal medicine and Dr Morris is chief, department of infectious diseases, Madigan Army Medical Center, Ft Lewis, Wash.
AMPHOTERICIN B Article:
Sue Ellen Baum, MD, Joseph T. Morris, MD, Madigan Army Medical Center, Ft Lewis, Wash.
Infect Med 18(2):114,117, 2001. © 2001 Cliggott Publishing, Division of SCP Communications
Abstract and Introduction
Abstract
A persistent vaginal infection with Candida glabrata failed to respond to multiple courses of oral and topical antifungals. Intravaginal treatment with a 0.3% solution of amphotericin B achieved a microbiologic cure.
Introduction
Candida (Torulopsis) glabrata is the second leading cause of yeast vaginitis, accounting for 15% to 20% of yeast vaginitis cases.[1] Azole resistance occurs more frequently in vitro in isolates of C glabrata than in Candida albicans. Reports of C glabrata vaginitis demonstrate higher failure rates of standard therapies and higher incidence of recurrence of vaginitis when this organism is isolated from patients.[2] In resistant cases, boric acid has been used with some success.[3] Fothergill et al[4] demonstrated in vitro that synergy could be achieved against C glabrata by using combinations of terbinafine with the triazoles fluconazole and itraconazole. A case of C glabrata vaginitis is presented that was refractory to the above combination therapy. Clinical and microbiologic cure was achieved with amphotericin B vaginal instillations.
Case Report
A 49-year-old menopausal, nondiabetic, HIV-negative, multiparous woman was referred to the infectious disease clinic for persistent vaginitis, apparently resulting from a perioperative course of antibiotics, that was unresponsive to standard therapies. The patient's vaginitis symptoms included vulvar erythema, pruritus, and a white discharge.
The patient had used over-the-counter preparations of clotrimazole and miconazole for relief without improvement. Her primary care provider had attempted treatment with the following antifungal therapies: single 150-mg oral doses of fluconazole on 4 occasions, and 2 7-day courses of terconazole. Concurrently with oral fluconazole, combination topical nystatin, triamcinolone, and clobetasol for secondary inflammation had also been prescribed. The patient had also received oral and intravaginal estrogen therapy. When cultures of her vaginal discharge grew C glabrata, she was given boric acid vaginal suppositories, 600 mg/d for 7 days, but this treatment was unsuccessful both clinically and microbiologically. At the time of her referral, the patient complained of persistent vaginal discharge and pruritus despite these therapies.
The patient's past medical history was remarkable for a unilateral nephrectomy for a congenital malformation and a hysterectomy for cervical dysplasia. Vaginal examination was remarkable for a thick white discharge. Laboratory evaluation before her referral to the infectious disease clinic revealed a serologic test negative for HIV, a normal serum glucose level, and tests negative for herpes simplex virus and human papilloma virus DNA. Cultures again revealed C glabrata. Because of the higher incidence of both refractory vaginitis and C glabrata isolation in HIV-positive patients, HIV serology was repeated, with negative results.
The patient was initially treated with combination oral terbinafine, 250 mg/d and itraconazole, 200 mg/d for 7 days. She continued to have symptoms and repeated culture again showed C glabrata. Treatment was then changed to combination terbinafine, 250 mg/d, and fluconazole, 400 mg/d, for 7 days. Symptoms and positive cultures persisted, and the fluconazole dosage was increased to 600 mg/d and terbinafine was continued at the same dosage as before. The patient remained symptomatic and culture-positive for C glabrata. Following failure of these therapies, the patient's yeast isolate was sent to the Audie L. Murphy Memorial Veterans Hospital in Texas for sensitivity testing by macrobroth dilution and was found to be resistant in vitro to terbinafine (minimum inhibitory concentration [MIC] greater than 4), fluconazole (MIC greater than 32), and the combination of these agents (MIC greater than 2 and 8 at 24 hours, and 2 and 16 at 48 hours). Because topical amphotericin B preparations and topical flucytosine were unavailable on our formulary, the patient was then treated with a 0.3% solution of amphotericin B in 60-mL vials given intravaginally daily for 7 days, after which microbiologic cure was achieved. A follow-up culture at 3 months was again negative for C glabrata.
Discussion
The increasing incidence of resistant yeast infections, including infection with C glabrata, will necessitate new treatment strategies for localized as well as systemic infection. Despite failure of combination therapy with terbinafine and fluconazole or itraconazole in this particular patient, these regimens may prove effective in less resistant isolates. Treatment failure was predictable in this patient based on her in vitro sensitivities. The use of intravaginal amphotericin B douches provides a possible effective form of therapy without the toxicity of systemic amphotericin B and at this time has reliable activity against this resistant pathogen. These therapies may become increasingly useful in an era of increasing fungal resistance to the azole drugs.
References
Sobel JD. Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann N Y Acad Sci. 1988;544:547-557.
Redondo-Lopez V, Lynch M, Schmitt C, et al. Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. Obstet Gynecol. 1990;76:651-655.
Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis. 1997;24:649-652.
Fothergill AW, Leitner I, Meingassner JG, et al. Combination antifungal susceptibility testing of terbinafine and the triazoles fluconazole and itraconazole. In: Program and abstracts of the 36th Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy; August 15-18, 1996; New Orleans. Abstract 91.
Dr Baum is a resident in internal medicine and Dr Morris is chief, department of infectious diseases, Madigan Army Medical Center, Ft Lewis, Wash.