TREATMENT OF CANDIDIASIS USING CONVENTIONAL ANTIFUNGAL DRUGS

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ABSTRACT

Candidiasis is an opportunistic mycoses caused by the yeast genus Candida. The genus comprises of many species of which Candidaalbicansis the most common. Candidiasis can cause a wide spectrum of clinical syndromes which include cutaneous candidiasis, gastrointestinal tract candidiasis, respiratory tract candidiasis, genitourinary tract candidiasis, hepatosplenic candidiasis and systemic candidiasis. Conventional antifungal drugs are drugs widely accepted for the treatment of fungal infections. Conventional antifungal drugs used in the treatment of candidiasis belong to three (3) principal classes: the Echinocandins (caspofungin, anidulafungin and micafungin) used for the treatment of systemic candidiasis, the Azoles (fluconazole, voriconazole, posaconazole) and the Polyenes (amphotericin B) for the treatment of cutaneous and chronic mucocutaneous candidiasis. The treatments of these Candida infections with the conventional antifungal drugs vary substantially and are based on the anatomic location of the infection, the patients’ underlying disease and immune status, the patients’ risk factors for infection, and the specific species of Candida responsible for infection, though these speciesare either susceptible or resistant to the drugs, for instance, Candida krusei is susceptible to voriconazole but resistant to fluconazole. Conventional antifungal drugs are an essential key towards the treatment of candidiasis, but require monitoring and modification to ensure adequate treatment of the disease.

 

 

 

INTRODUCTION

Candidiasis is an opportunistic mycoses. It is a fungal infection caused by the yeast genus Candida.Several species of the yeast Candida are capable of causing candidiasis (Brookset al., 2013). Thegenusis composedof organisms such as Candidaalbicans(common cause of candidiasis), Candidaglabrata, Candidaparapsilosis,Candida balanitis, Candida guilliermondii,andCandidakrusei (Pfalleretal.,2007). Candidaspecies belong to the normalmicrobiotaofanindividual’s mucosal oralcavity, gastrointestinal tract andvagina (Shaoetal.,2007),andare manifested by mucocutaneous lesions, fungemia, and sometimes focal infection of multiple sites.Symptoms depend on the site of infection and include dysphagia, skin and mucosal lesions, blindness, vaginal symptoms (itching, burning, discharge), fever, shock, oliguria, renal shutdown, and disseminated intravascular coagulation. Diagnosis is done by histopathology and cultures from normally sterile sites.

Conventional antifungal drugs are drugs widely accepted to fight fungal organisms causing infection and diseases in humans. In the United States, only ten (10) antifungal drugs are currently approved by the Food and Drug Administration (FDA) for the therapy of systemic fungal infections (William, 2000). Conventional antifungal drugs used in the treatment of candidiasis belongto three (3) principal classes: polyenes (amphotericin B), echinocandins(caspofungin, anidulafungin and micafungin) and azoles (fluconazole, voriconazole, posaconazole).Candida species are susceptible, less susceptible or resistant to these antifungal drugs. For instance, some C. glabrataisolates are resistant to fluconazole and allC. krusei isolates are resistant to fluconazole.

The purpose of this presentation is to educate on the widely accepted antifungal drugs for the treatment of candididiasis in different locations of the human body, the Candida species’ susceptibility and resistance to the drugs, and administration of the drugs.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CANDIDIASIS

Candidiasis is an opportunistic infection. It’s a yeast infection caused by Candida species (most often C. albicans), C. kruseiCandidaglabrata, Candidaparapsilosis, Candida balanitis, Candida guilliermondii, andCandidatropicalis, Candida cystitis, Candida kefyr, and Candida lusitaniae. Candida species are commensal organisms that inhabit the gastrointestinal tract and sometimes the skin. Candidiasis results from endogenous organisms unlike other systemic mycoses. Candidal infections are one of the most common hospital-acquired infections. It occurs both in men, female and children. It can be transmitted through various means such as oral sex, sex, breast feeding etc. Symptoms depend on the site of infection and include dysphagia, skin and mucosal lesions, blindness, vaginal symptoms (itching, burning, discharge), fever, shock, oliguria, renal shutdown, and disseminated intravascular coagulation. Diagnosis is confirmed by histopathology and cultures from normally sterile sites.

CONVENTIONAL ANTIFUNGAL DRUGS

Conventional antifungal drugs are drugs widely or generally accepted for the treatment of fungal infections and diseases. In the United States, only ten (10) antifungal drugs are currently approved by the Food and Drug Administration (FDA) for the therapy of systemic fungal infections (William, 2000). These drugs belong to four principal classes: polyenes, pyrimidines, azoles and echinocandins.

TREATMENT USING CONVENTIONAL ANTIFUNGAL DRUGS.

Conventional antifungal drugs used in the treatment of candidiasis belong to three (3) principal classes: polyenes (amphotericin B), echinocandins (caspofungin, anidulafungin and micafungin) and azoles (fluconazole, voriconazole, posaconazole).

The treatments used to manageCandida infections vary substantially and are based on the anatomic location of the infection, the patients’ underlying disease and immune status, the patients’ risk factors for infection, the specific species of Candida responsible for infection, and, in some cases, the susceptibility of the Candida species to specific antifungal drugs.

TREATMENT BASE ON SITE/LOCATION OF THE INFECTION IN THE BODY.

CUTANEOUS CANDIDIASIS

Cutaneous candidiasis is a candida infection of the skin (Edwards et al., 2014). If the infection is a paronychia, oral antifungal therapy with fluconazole is efficient. In cases of extensive cutaneous infections, infections in immunocompromised patients, folliculitis, or onychomycosis, systemic antifungal therapy is used.

Oral Candidiasis: Also known as oral thrush, occurs when your immune system is weakened by disease or by drugs or when antibiotics disturb the natural balance of microorganisms in your body, HIV, cancer, uncontrolled diabetes and more (Knapp and Flynn et al., 2009). Candidiasis is a common opportunistic fungal infection of the oral cavity (Yuvrajet al., 2010). The infection is caused by Candida albicans. Oral candidiasis can be a frequent and significant source of oral discomfort, pain, loss of taste, and aversion to food. Symptoms in children and adults are creamy white lesions on the tongue, inner cheeks and sometimes the gums, redness or soreness in the mouth and more. Oral fluconazole, 100 mg once daily for 2 weeekscan be used for its treatment.Voriconazole and posaconazole are also used because they stop the growth of the yeast that cause this disease (Dominguez and Levin et al., 2012).

 

 

Source: (Knapp and Flynn, 2009)

Figure 1: Images of oral thrush in the mouth

CHRONIC MUCOCUTANEOUS CANDIDIASIS

This condition is generally treated with oral azoles, such as fluconazole at a dose of 100-400 mg/d or itraconazole at a dose of 200-600 mg/d until the patient improves. The initial therapy for acute infection is always followed by maintenance therapy with the same azole for life.

Gastrointestinal Candidiasis

  • Oropharyngeal candidiasis
  • Oropharyngeal candidiasis (OPC): Systemic oral azoles (fluconazole,itraconazole, or posaconazole) are used to treat OPC.
  • Infections in HIV-positive patients respond slowly and recur within 6 months of the initial infection. Patients with advanced HIV infection (CD4 cell counts < 50/µL) may develop refractory OPC. High doses of fluconazole (up to 800 mg/d), Posaconazole suspension at 400 mg orally twice per day are used in treatment of these patients.Echinocandins such as caspofungin(50 mg/d IV) andanidulafungin (100 mg/d IV) is also used in such patients. Amphotericin B is also used though in low doses (0.3-0.7 mg/kg).
  • Candida esophagitis: This specie causes esophageal candidiasis. Systemic therapy with fluconazole for 14-21 days is used against this organism. Parenteral therapy with fluconazole may be required initially if the patient is unable to take oral medications. Daily therapy with fluconazole 100-200 mg/d is effective to prevent recurrences.