Treatment of Refractory Trichomoniasis

Transcription

1 Treatment of Refractory Trichomoniasis Christina Muzny, MD, MSPH Associate Professor of Medicine, Division of Infectious Diseases University of Alabama at Birmingham Last Updated: 3/19/2018 uwptc.org

2 Disclosures K23AI (NIH/NIAID) BV pathogenesis study R01AI (NIH/NIAID) Trichomonas vaginalis treatment trial in HIV-negative women

3 Treatment of T. vaginalis: 5-Nitroimidazoles Preferred Regimens: - Metronidazole (MTZ) 2 grams po X 1 dose - Tinidazole (TIN) 2 grams po X 1 dose Alternative Regimen: - MTZ 500 mg po bid X 7 days 2015 CDC STD Treatment Guidelines

4 Refractory Trichomoniasis: Drug Resistance uwptc.org

5 Poll #1: What is the Prevalence of Metronidazole Resistance among T. vaginalis-infected Women in the U.S.? A) 0% B) 1% C) 2-5% D) 5-10% E) Unknown

6 Prevalence of T. vaginalis Isolates with Resistance to Metronidazole (9.6%) and Tinidazole (0.6%) in Birmingham, AL In vitro resistance was poorly correlated with clinical response to therapy; 5-nitroimidazole resistance may be relative and not absolute Antimicrob Agents Chemother 2006;50:

7 Resistance to 5-Nitroimidazoles: Distribution of Minimum Lethal Concentrations (MLCs) of Tinidazole and Metronidazole, STD Surveillance Network, (n=538) MLC <25 μg/ml= susceptible MLC μg/ml = low level resistance n=23 (4.3%) MLC 200 μg/ml = moderate level resistance MLC >400 μg/ml = high level resistance *Low-level MTZ resistance is more common than high-level resistance and can be overcome with high-dose TIN* Emerg Infect Dis 2012;18:939-43

8 Poll #2: If your T. vaginalis-infected patient fails both single dose AND multi-dose MTZ (and re-infection is excluded) what should you do next? A) Give another course of MTZ 500 mg po BID X 7 days B) Give a dose of TIN 2g po X 1 C) Perform susceptibility testing on the T. vaginalis isolate D) Prescribe intravaginal boric acid 600 BID X 14 days E) Prescribe intravaginal betadine douches, 20 ml of a 10% solution twice daily for 2 days per week X 14 days

9 Dosing for Drug Resistance 1 (avoid single-dose therapy) If patient fails single dose MTZ and re-infection is excluded: - MTZ 500 mg po bid for 7 days (15% of T. vaginalis-infected women treated with single dose MTZ have persistent infection 2 ) If this does not work, consider: MTZ or TIN 2 grams po daily for 5-7 days Perform susceptibility testing on the T. vaginalis isolate -> CDC Intravaginal paromomycin in combination with high-dose TIN, intravaginal boric acid, or nitazoxanide High dose TIN at 2 3g po daily in combination with intravaginal TIN 500 mg twice daily for 14 days NOT Recommended: intravaginal betadine douches, clotrimazole, acetic acid, furazolidone, gentian violet, nonoxynol-9, potassium permanganate, topic microbicides CDC STD Treatment Guidelines; 2 Sex Trans Dis 2013;40:

10 Successful Treatment of Refractory T. vaginalis Using IV Metronidazole 1 1 Int J STD AIDS 2015; 26: ; 2 Int J STD AIDS 2016; 27:

11 T. vaginalis Treatment in the Setting of Allergy, Intolerance, or Adverse Reactions to 5- Nitroimidazoles uwptc.org

12 Vaginally Administered Medications for T. vaginalis Treatment in the Setting of Intolerance or Adverse Reactions to 5-Nitroimidazoles Oral MTZ and TIN can be associated with significant GI side effects The major limitation of vaginally administered medications is the non-accessibility of other infected organs (cervix, bladder, and Bartholin s, Skene s, and periurethral glands) However, intravaginal medications can be considered in certain circumstances: - Cases of 5-nitroimidazole allergy - When desensitization to 5-nitroimidazoles is not possible - When severe side effects due to systemic administration of 5- nitroimidazoles are observed - When other systemic treatment options are limited Clin Micro Rev 2017;30:

13 Intravaginal MTZ/Miconazole Pilot study of Neo-Penotran Forte (intravaginal product of 750 mg MTZ/200 mg miconazole) to determine efficacy for T. vaginalis treatment Randomized dose-ranging pilot study conducted in 2 phases consisting of 20 participants in each phase Phase 1: intravaginal product BID X 7 days vs. MTZ 2 gram dose Phase 2: intravaginal product QD X 7 days vs. MTZ 2 gram dose No significant difference noted in cure rates in either phase Well tolerated May represent a viable alternative for treatment in cases of GI intolerance to systemic 5-nitroimidazoles however can be costly and only available at a compounding pharmacy Sex Transm Dis 2013;40:710-4

14 Poll #3: What is your next step for a T. vaginalis-infected patient reporting an immediate type hypersensitivity reaction to MTZ? A) TIN 2g po X 1 B) TIN 2g po daily X 5 days C) Refer to an allergist to consider desensitization D) Give intravaginal MTZ 37.5 mg BID X 14 days E) Hope that the trichomonas goes away on its own!

15 Immediate Type Hypersensitivity Reaction to 5- Nitroimidazoles Patients with an immediate-type hypersensitivity reaction to 5-nitroimidazoles can potentially be managed by desensitization in consultation with an allergist - If desensitization is not an option, intravaginal therapy with drugs other than 5-nitroimidazoles can be attempted, but cure rates may be low (<50%) 2015 CDC STD Treatment Guidelines; Sexual Health 2012;9: ; Sex Transm Dis 2017;44:120

16 Alternative Treatment Options for T. vaginalis in the Setting of Severe Allergy or Drug Resistance Sex Transm Infect 2013;89:

17 Cost of T. vaginalis Medications Without Insurance (Birmingham, AL pharmacy data; *=has to be made in a compounding pharmacy) Metronidazole 2 grams po X 1 - $8-11 Metronidazole 500 mg po BID X 7 days - $13-18 Tinidazole 2 grams po X 1 - $24-50 Tinidazole 2 grams po daily X 7 days - $79-94 Intravaginal metronidazole BID X 14 days - $ Intravaginal tinidazole BID X 14 days - $ Intravaginal boric acid 600 mg BID X 60 days - $60* Intravaginal paramomycin (5 g of a 5% cream qhs) X 14 days - $85* Intravaginal Neo-Penotran Forte (750 mg MTZ/200 mg miconazole) BID X 7 days - $105* Intravaginal betadine douches, 20 ml of a 10% solution twice daily for 2 days per week X 14 days - $100.00* Intravaginal furazolidone (100 mg per 5-g applicator of 3% nonoxynol-9) BID X 14 days unknown, not carried in our local pharmacies*

18 THANK YOU! Questions/Comments?