Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Pharmaceutical industry wikipedia , lookup
Neuropharmacology wikipedia , lookup
Polysubstance dependence wikipedia , lookup
Drug interaction wikipedia , lookup
Prescription costs wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Psychedelic therapy wikipedia , lookup
Esophageal Candidiasis in Patients with AIDS Case • 32-year-old male with AIDS • CD4 50 cells/mm3 • Reports severe pain and difficulty swallowing • “It feels like food gets stuck below my throat” • Denies other symptoms • Reports history of oral candidiasis What is the most likely diagnosis? Esophageal Candidiasis Objectives • Upon completion of this activity, participants should be able to: – Recognize symptoms of esophageal candidiasis – Review methods for diagnosing esophageal candidiasis – Discuss treatments for esophageal candidiasis Overview • Candida ssp is an opportunistic fungus (yeast) • Candida albicans is the most common etiology of esophagitis in patients with AIDS • Candida tropicalis, Candida Krusei, Candida glabrata, and Candida parapsilosis can also cause esophagitis Overview • Occurs in 20–40% of patients with AIDS • Patients usually have CD4 <100 cells/mm3 Esophagitis – Other Causes • Less common causes: HSV, CMV and aphthous ulcerations • Rare causes: lymphoma, KS, PCP, Cryptosporidia, TB, histoplasmosis, M. avium • Consider non-HIV-related causes if CD4 >200 cells/mm3 (e.g., gastro esophageal reflux disease—GERD, medication- and food-induced) Clinical Presentation • Odynophagia (painful swallowing) • Dysphagia (difficulty swallowing) • Diffuse retrosternal pain • Occasional nausea and vomiting • Oral candidiasis often present but not required Diagnosis • Usually made clinically based on symptoms • Endoscopy only if empirical azole therapy fails • Response to empiric treatment precludes need for endoscopic esophageal candidiasis diagnosis • When needed, diagnosis by endoscopy is made based on visual appearance of white pseudomembranous plaques in the esophagus Diagnosis • Brushings or biopsy can be taken during endoscopy for microscopy or culture • Fungal culture of esophageal pseudomembranous plaques is useful for identification of Candida species and resistance testing (when available) Treatment – Basic Principles • No place for topical treatment • Treat empirically with systemic drugs • Azoles are first-line of therapy – Fluconazole included in class • HAART reduces relapses First Line Therapy • Fluconazole 200 mg po daily (preferred) x 14–21 days • Itraconazole solution 200 mg po daily x 14–21 days – Itraconazole also available in capsule but better absorption with liquid formulation – Ketoconazole rarely used due to erratic absorption Second Line Therapy • Amphotericin B 0.3-0.7 mg/kg IV daily – Or lipid formulations of amphotericin • If available, can also use – Echinocandins • Caspofungin, micafungin – Alternative azoles with increased activity against fluconazole-resistant Candida • Voriconazole, posaconazole, itraconazole Treatment • Assess response to therapy within 5–7 days • Continue therapy for 14–21 days after clinical improvement • Use intravenous drugs for patients unable to swallow If no Response to Fluconazole • Check medication adherence • Reconsider diagnosis • Refer for endoscopy • Consider resistance to azole therapy – especially if repeated courses of azole treatment or if maintenance therapy used Other Treatment Considerations • Azoles prone to drug interactions through the cytochrome P450 (CYP450) pathway • The CYP450 enzymes are involved in the metabolism of most commonly prescribed drugs • Check package insert for drug interactions when prescribing azoles Other Treatment Considerations • Absorption of itraconazole capsules is pH dependent. Absorption affected by: 1. Antipeptic Ulcer Drugs • H2 blockers • Proton pump inhibitors • Antacids 2. Antiretroviral Drugs • Buffered didanosine • Liquid formulation better absorbed but must be taken on an empty stomach (preferred) Other Treatment Considerations • Fluconazole absorption is not affected by food or gastric pH • Hepatotoxicity and gastrointestinal intolerance can occur with azole therapy Other Treatment Considerations • Amphotericin B is renally eliminated • Amphotericin B is not a substrate, inhibitor or inducer of the CYP450 enzymes • Thus, amphotericin B is not prone to drug interactions through the CYP450 enzymes Other Treatment Considerations • Common side effects of amphotericin B – – – – – Nephrotoxicty Electrolyte abnormalities Infusion-related chills Injection site pain and irritation Phlebitis • Increased risk for amphotericin B-induced nephrotoxicity when given concurrently with other nephrotoxic drugs Prophylaxis • Prophylaxis/maintenance not generally recommended, but consider if frequent recurrences • Fluconazole 100–200 mg po daily Itraconazole liquid 200 mg po daily can be used as an alternative Additional Considerations • Use analgesic therapy for pain relief • Reinforce importance of maintaining adequate nutrition • Avoid foods that are hot/cold/spicy to avoid exacerbating discomfort caused by dysphagia and odynophagia • Favor pureed/mashed foods and liquids served at room temperature Summary • Candida albicans is the most common etiology of esophagitis in patients with AIDS • Treat empirically with fluconazole • If no response to treatment, consider alternative etiology, inadequate adherence, drug resistance • Azoles are prone to drug interactions through the CYP450 pathway • Azoles can cause gastrointestinal and hepatic toxicity Summary • Amphoterycin B for second line therapy • Amphoterycin B is not prone to drug interactions through the CP450 pathway • Common side effects include nephrotoxicity, infusion-related chills and fever, phlebitis and electrolyte abnormalities Summary • Prophylaxis usually not recommended • Reinforce the importance of adequate nutrition • Pain management is crucial • HAART reduces relapses References • Ally R, Schurmann D, Kreisel W, et al. 2001. A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis. 33:1447-1454. • Arathoon EG, Gotuzzo E, Noriega LM, et al. 2002. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiasis. Antimicrob Agents Chemother. 46:451-457. • Bonacini M, Young T, Laine L. 1991. The causes of esophageal symptoms in human immunodeficiency virus infection. A prospective study of 110 patients. Arch Intern Med. 151:1567-1572. References • Clinical Infectious Diseases 2004; 38:165-89. • Connoly GM, Hawkins D, Harcourt-Webster JN et al. Oesophageal symptoms, their causes, treatment, and prognosis in patients with the acquired immunodeficiency syndrome. Gut. 1989;30:1033-1039. • de Wet N, Llanos-Cuentas A, Suleiman J, et al. 2006. A multicenter randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS. Clin Infect Dis. 42:1179-1186. • de Wet N, Llanos-Cuentas A, Suleiman J, et al. 2004. A randomized, double-blind, parallel-group, doseresponse study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients. Clin Infect Dis. 39:842-849. References • Maenza JR, Keruly JC, Moore RD, et al. 1996. Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients. J Infect Dis. 174:219-221. • Vazquez JA. 2000. Therapeutic options for the management of oropharyngeal and esophageal candidiasis in HIV/AIDS patients. HIV Clin Trials. 1:47-59. • Villanueva A, Arathon EG, Gotuzzo, et al. 2001. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 33:15291535.