Scientific on microscope

Drug Resistance

Research shows that a growing number of yeast species are developing resistance to fluconazole 3

Yeast species are less resistant to miconazole, the
active ingredient in MONISTAT®

4 facts about drug resistance in VVC

Pie Chart : In the past 5% of infections were caused by non-albicans Candida species
Pie Chart : In the present 29.2% of infections are caused by non-albicans Candida species

1The prevalence off VVC caused by non-albicans Candida 3

The prevalence of VVC caused by non-albicans Candida has increased greatly-and these species are less susceptible to fluconazole18

Although Candida albicans is still the most common cause, non-albicans species now account for 30% of vaginal yeast infections. Many are resistant to commonly prescribed antifungal agents, making treatment more challenging.

2Fluconazole resistance often begins in the gut

Oral fluconazole is systemic, and a significant amount of the drug remains in the GI tract. Repeated use reduces the C. albicans population in the gut, allowing resistant non-albicans species to thrive and reach the vagina.4

resistant non-albicans species
Graph chart : Starting from 2400000 Rx Units and increasing over time to reach about 4500000 Rx Units

Source: IMS 2Q2016, IPSOS Survey August, 2016 

3Fluconazole doses have increased dramatically

The number of fluconazole pills prescribed has more than doubled since 2005, and nearly 60% of patients get more than 1 fluconazole tablet initially.5 These dosing trends may be another indicator of growing resistance.

4Optimal treatment for non-albicans VVC is not yet established

CDC Guidelines suggest a non-fluconazole azole for 7-14 days first-line2

The Guidelines also include recommendations for treating VVC in certain populations, including women who are pregnant, diabetic, or immunocompromised.

In a study looking at MIC90 trends from 1986 – 2007 for 250 C. albicans vaginal isolates3:

  • Miconazole: MIC90 unchanged (0.06 μg/mL)
    • Percent isolates with MIC90 ≥ 0.5 μg/mL increased from 2% to 9% during this period but since this is a topical agent and vaginal fluid levels exceed 10 μg/mL, resistance is unlikely to be an issue
Species trough a microscope
Graph chart : Showing no changement from 1987 to 2007

Evolution and selection of vaginal-colonizing Candida 3

Evolution and selection of vaginal-colonizing Candida Candida species with reduced susceptibility could play a critical early role in the development of antifungal resistance among C. albicans isolates responsible for refractory candidiasis.3

  • Fluconazole MIC90: 0.25 μg/mL → 0.5 μg/mL
    • Percent isolates with MIC90 ≥ 1 μg/mL and ≥ 2 μg/mL both increased from 3% to 9% over this period
    • While not a clinically significant MIC90 increase, the increase in isolates with elevated MIC90 may have clinical relevance given the achievable concentrations of fluconazole in vaginal fluid (maximum 2 μg/mL)

Fluconazole use has increased dramatically over time3

Routine use of prescription oral fluconazole may create an environment where non-albicans Candida, which are less susceptible to azoles, thrive and spread in the vagina.

  • Oral fluconazole achieves low tissue concentration at the site of infection while the rest remains in systemic circulation.
  • A significant amount of the drug remains in the GI tract, reducing C. albicans but allowing less-susceptible non-albicans species to grow.
  • These non-albicans species reach the vagina and are more likely to be resistant to fluconazole treatment.

Repeat systemic antifungal therapy perpetuates drug-resistant species.

Graph : Fluconazole MICs doubled from 1986 to 2007
Graph : 2005 to 2014 Fluconazole units went from 2.3 millions to 3.1 millions