Fluconazole Amphotericin

Candidiasis of the alimentary tract mucosa responds to amphotericin, fluconazole, ketoconazole, miconazole or nystatin as lozenges (to suck, for oral infection), gel (held in the mouth before swallowing), suspension or tablets. 

Treatment fluconazole, itraconazole, ketoconazole, Amphotericin B Consider liposomal products decrease or stop CSA or TAC to minimize nephrotoxicity Remember to adjust doses of renally eliminated drugs (e.g., acyclovir, ganciclovir, TMP-SMX)... 

Treatment of fungal IE is exceptionally difficult. There is a significant lack of studies to identify and recommend the most appropriate therapy. Currently, amphotericin B is the most common treatment. However, valve replacement surgery is often considered an adjunct therapy. Intravenous antifungal therapy requires high doses for a minimum of 8 weeks of treatment. Oral azoles (e.g., fluconazole) are used as long-term suppressive therapy to prevent relapse. The exact role of some... 

Two to three weeks of fluconazole or itraconazole solution are highly effective and demonstrate similar clinical response rates.32 Doses of 100 to 200 mg are effective in immunocompetent patients but doses up to 400 mg are recommended for immunocompromised patients. Due to variable absorption, ketoconazole and itraconazole capsules should be considered second-line therapy. In severe cases, oral azoles may prove ineffective, warranting the use of amphotericin B for 10 days. Although echinocandins and voriconazole are effective in treatment of esophageal candidiasis, experience remains limited. 

Twenty percent of HIV-infected patients develop fluconazole-resistant Candida albicans isolates after repeated exposure to fluconazole.33 To treat fluconazole-resistant oropharyngeal candidiasis, daily itraconazole for 2 to 4 weeks may be used. Oral itraconazole solution exhibits a mycological cure rate of 88% and a clinical cure rate of 97% in immunocompromised patients.34 Fluconazole-resistant esophageal candidiasis should be treated with intravenous amphotericin B or caspofungin. 

If a patient is non-neutropenic and has never received prior azole therapy, fluconazole 800 mg/day is an appropriate first-line therapy for invasive candidiasis until identification of the Candida isolate. Amphotericin B deoxycholate 0.7 mg/kg per day or caspofungin 70 mg on day 1, then 50 mg/day, voriconazole, or a lipid amphotericin B formulation are recommended as empiric therapy in patients with neutropenic fever. 

Urinary candidiasis Fluconazole 200 mg IV or PO for 7-14 days OR Amphotericin B 0.3 mg/kg per day IV for 1-7 days Asymptomatic candiduria does not required therapy However, treatment is recommended in neutropenic, low-birth-weight infants, and patients undergoing urologic manipulations or those with renal allografts Amphotericin B bladder irrigation no longer recommended... 

Mucocutaneous candidiasis is generally not life-threatening nor invasive and can be treated with topical azoles (clotrimazole troches), oral azoles (fluconazole, ketoconazole, or itraconazole), or oral polyenes (such as nystatin or oral amphotericin B). Orally administered and absorbed azoles (ketoconazole, fluconazole, or itraconazole solution), amphotericin B suspension, intravenous caspofungin, or intravenous amphotericin B are recommended for refractory or recurrent infections.20... 

Although more invasive, esophageal candidiasis does not typically evolve into a life-threatening infection. However, topical therapy is ineffective. Azoles (fluconazole, itraconazole solution, or voriconazole), echinocandins, or intravenous amphotericin B (in cases of unresponsive infections) are effective treatment options. Parenteral therapy should be used in patients who are unable to take oral medications.20... 

Response to antifungal therapy in invasive candidiasis is often more rapid than for endemic fungal infections. Resolution of fever and sterilization of blood cultures are indications of response to antifungal therapy. Toxicity associated with antifungal therapy is similar in these patients as described earlier with the caveat that some toxicities maybe more pronounced in crit-ically-ill patients with invasive candidiasis. Nephrotoxicity and electrolyte disturbances, with amphotericin B in particular, are problematic and may not be avoidable even with lipid amphotericin B formulations. Fluconazole and echinocandins are generally safer options, and are generally well tolerated. Decisions to use one class of agents over the other is principally driven by concerns of non-albicans species, patient tolerability, or history of prior fluconazole exposure (risk factor for non-albicans species.). 

Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients a randomised non-inferiority trial. Lancet 2005 366 1435-1442. 

The answer is d. (Hardman, pp 1183-1184.) Mucocutaneous infections, most commonly Candida albicans, involve the moist skin and mucous membranes. Agents used topically include amphotericin B, nystatin, miconazole, and clotrimazole. Ketoconazole and fluconazole are administered orally in pill form for treatment of chronic infections... 

Due to the high relapse rate following acute therapy for C. neoformans, AIDS patients require lifelong maintenance or suppressive therapy. The standard of care for AIDS-associated cryptococcal meningitis is primary therapy, generally using amphotericin B with or without flucytosine followed by maintenance therapy with fluconazole for the fife of the patient. 

Itraconazole and ketoconazole (200-800 mg/day orally for 1 year) are effective in 74% to 86% of cases, but relapses are common fluconazole 200-400 mg daily is less effective (64%) than ketoconazole or itraconazole, and relapses are seen in 29% of responders Severe disease Amphotericin B 0.7 mg/kg/day for a minimum total dose of 35 mj kg is effective in 59% to 100% of cases and should be used in patients who require hospitalization or are unable to take itraconazole because of drug interactions, allergies, failure to absorb drug or failure to improve clinically after a minimum of 12 weeks of itiaconazole therapy... 

Disseminated histoplasmosis Acute (Infantile) Subacute Progressive histoplasmosis (immunocompetent patients and immunosuppressed patients without AIDS) 0.02-0.05 Disseminated histoplasmosis Untreated mortality 83% to 93% relapse 5% to 23% in non-AIDS patients therapy is recommended tor all patients Nonimmunosuppressedpatients Ketoconazole 400 mj day orally x 6-12 months or amphotericin B 35 mg/kg IV Immunosuppressed patients (non-AIDS) or endocarditis or CNS disease Amphotericin B >35 mg/kg x 3 months followed by fluconazole or itraconazole 200 mg orally twice daily x 12 months Life-threatening disease Amphotericin B 0.7-1 mg/kg/day IV for a total dosage of 35 mj kg over 2-4 months once the patient is afebrile, able to take oral medications, and no longer requires blood pressure or ventilatory support therapy can be changed to itraconazole 200 mg orally twice daily for 6-18 months Non-life-threatening disease Itraconazole 200-400 mg orally daily for 6-18 months fluconazole therapy 400-800 mg daily should be reserved for patients intolerant to itraconazole, and the development of resistance can lead to relapses... 

For patients unable to tolerate a full course of amphotericin B, consider lipid formulations of amphotericin B or fluconazole >800 mg orally daily. 

Specific antifungals (and their usual dosages) for the treatment of coccidioidomycosis include amphotericin B IV (0.5 to 1.5 mg/kg/day), ketocona-zole (400 mg orally daily), IV or oral fluconazole (usually 400 to 800 mg daily, although dosages as high as 1,200 mg/day have been utilized without complications), and itraconazole (200 to 300 mg orally twice daily as either capsules or solution). If itraconazole is used, measurement of serum concentrations may be helpful to ascertain whether oral bioavailability is adequate. 

Treatment of cryptococcosis is detailed in Table 38-3. For asymptomatic, immunocompetent persons with isolated pulmonary disease and no evidence of CNS disease, careful observation may be warranted. With symptomatic infection, fluconazole or amphotericin B is warranted. 

The combination of amphotericin B with flucytosine for 6 weeks is often used for treatment of cryptococcal meningitis. An alternative is amphotericin B for 2 weeks followed by fluconazole for an additional 8 to 10 weeks. Suppressive therapy with fluconazole 200 mg/day for 6 to 12 months is optional. 

Amphotericin B with flucytosine is the initial treatment of choice for acute therapy of cryptococcal meningitis in AIDS patients. Many clinicians will initiate therapy with amphotericin B, 0.7 mg/kg/day IV (with flucytosine, 100 mg/kg/day). After 2 weeks, consolidation therapy with either itraconazole 400 mg/day orally or fluconazole 400 mg/day orally can be administered for 8 weeks or until CSF cultures are negative. Lifelong therapy with fluconazole is then recommended. 

Isolated pulmonary disease (without evidence of CNS infection) Asymptomatic disease Drug therapy generally not required observe carefully or fluconazole 400 mg orally daily x 3-6 months Mild to moderate symptoms Fluconazole 200-400 mg orally daily x 3-6 months severe disease or inability to take azoles amphotericin B 0.4-0.7 mg/kg/day (total dose of 1-2 g)... 

Cryptococcemia wilh positive serum antigen titer (>1 8), cutaneous infection, a positive urine culture, or prostatic disease Recurrent or progressive disease not responsive to amphotericin B Isolated pulmonary disease (without evidence of CNS infection) Clinician must decide whether to follow the pulmonary therapeutic regimen or the CNS (disseminated) regimen Amphotericin Brf IV 0.5-0.75 mj kj day intrathecal amphotericin B 0.5 mg 2-3 times weekly Mild to moderate symptoms or asymptomatic with a positive pulmonary specimen Fluconazole 200-400 mg orally daily x lifelong or Itraconazole 200-400 mg orally daily x lifelong or... 

CNS disease acute (induction/con-solidation therapy) (follow all regimens with suppressive therapy) Fluconazole 400 mg orally daily + flucytosine 100-150 mg/kg/ day orally x l o weeks Severe disease Amphotericin B until symptoms are controlled, followed by fluconazole Amphotericin Brf IV 0.7-1 mg/kj day orally x >2 weeks, then fluconazole 400 mg orally daily x >8 weekse or Amphotericin Brf IV 0.7-1 mg/kg/day + flucytosine 100 mg/kg/ day orally x 6-I0weekse or Amphotericin Brf IV 0.7-1 mg/kg/day x 6-10 weekse or Fluconazole 400-800 mg orally daily x 10-12 weeks or Itraconazole 400-800 mg orally daily x 10-12 weeks or Fluconazole 400-800 mg orally daily + flucytosine 100-150 mg/ kg/day orally x 6 weekse or... 

Amphotericin IV 0.7-1 mg/kg/day x 2 weeks, followed by fluconazole 400-800 mg orally daily 8-10 weeks, followed by fluconazole 200 mg orally daily x 6-12 months (in patients intolerant to fluconazole, substitute itraconazole 200-400 mg orally daily)... 

Treatment of candidiasis is presented in Table 38-4. Amphotericin B may be switched to fluconazole (IV or oral) for completion of therapy. Azoles and deoxycholate amphotericin B are similarly effective however, fewer adverse effects are observed with azoles. Echinocandins are at least as effective as amphotericin B or fluconazole in nonneutropenic adult patients with candidemia. 

Candida albicans, C. tropicalis, C parapsilosis and resolution of signs and symptoms of infection Remove existing central venous catheters when feasible, plus Amphotericin B IV 0.6 mg/k day or Fluconazole IV/po 6 mg/kg/day or An echinocandin or Amphotericin B IV 0.7 mg/kg/day plus fluconazole IV/po 800 mg/day Patients intolerant or refractory to other therapf Amphotericin B lipid complex IV 5 m k day Liposomal amphotericin B IV 3-5 mg/kg/day Amphotericin B colloid dispersion IV 2-6 mg/k day (continued)... 

Lipid formulation of amphotericin B IV 3-5 m kg/day Chronic disseminated candidiasis Treatment duration Until calcification or resolution of lesions (hepatosplenic candidiasis) stable patients Fluconazole IV/po 6 mg/kg/day... 

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