Isolation Itraconazole

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. 

Cryptococcal meningitis is fatal if left untreated. Because pneumonia frequently precedes dissemination of disease and subsequent meningitis, all patients with culture-, histopathology-, or serology-proven disease should receive antifungal therapy. In patients with isolated pulmonary cryptococcosis, fluconazole is generally considered to be the therapy of choice (see Table 81-2).37 Alternatively, itraconazole or combination therapy (fluconazole plus flucytosine) has also been used with some success in patients. 

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... 

Cross-resistance - Fungal isolates exhibiting reduced susceptibility to fluconazole or itraconazole also may show reduced susceptibility to voriconazole, suggesting that cross-resistance can occur among these azoles. 

When itraconazole therapy may be indicated, isolate and identify the type of organism responsible for the infection however, therapy may be initiated prior to obtaining these results when clinically warranted. 

Diekema D3 et al Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin against 448 recent clinical isolates of filamentous fungi. 3 Clin Microbiol 2003 41 3623. [PMID 12904365]... 

Pharmaceutical cocrystals are a relatively new area of research and have been widely pursued only since around 2000. To date, the most notable example of a drug that has been isolated as a useful cocrystal is itraconazole, which is the subject of the Case Study below. 

Among the imidazole derivatives, numerous case reports or studies have shown that ketoconazole, fluconazole, and itraconazole can inhibit ciclosporin metabolism and increase blood ciclosporin concentrations (267). Ketoconazole, which is undoubtedly the most potent inhibitor, has been used to reduce the dose, and therefore the cost or adverse effects, of ciclosporin (268-270). There was also a beneficial effect on the rate of rejection or infection. In contrast, interactions with metronidazole and miconazole have only been described in isolated case histories (SEDA-19, 351) (5). 

Flucytosine has been successfully used in combination with ketoconazole, fluconazole, and itraconazole. Flucytosine and ketoconazole were synergistic in about 40% of yeast isolates resistant to flucytosine alone. The synergistic action of flucytosine with the triazoles against Candida species was seen both in vitro and in vivo (3-6). 

Hypokalemia, occurring either in isolation or with hypertension, has been reported regularly in a small fraction of patients (23). Marked ankle edema with weight gain was seen in a patient taking itraconazole 400 mg/day, in whom there was no explanation other than the use of the drug after withdrawal of the itraconazole the symptoms disappeared. Hypokalemia and edema have also been... 

Fig. 11.5 E-test on an isolate of Candida albicans. Inhibition zone edges are distinct and the MICs for itraconazole (IT) and fluconazole (FL) (0.064 mg/L and 1.5 mg/L, respectively) are easily decipherable.

Fernandez-Torres, B., Vazquez-Veiga, H., Llovo, X., Pereiro, M., Jr., and Guarro, J. (2000) In vitro susceptibility to itraconazole, clotrimazole, ketoconazole and terbinafine of 100 isolates of Trichophyton rubrum. Chemotherapy, 46, 390-394. 

Approximately 46% of C. glabrata Isolates and 31 % of C. krusei Isolates are resistant to Itraconazole. 

In an isolated case hepatic and pulmonary toxicity occurred when nitrofurantoin was given with fluconazole, but not with itraconazole. 

An isolated report describes a very marked increase in the anticoagulant effects of warfarin, accompanied by bruising and bleeding, in a patient given itraconazole. Limited evidence su ests that itraconazole may increase the risk of over-anticoagulation with acenocoumarol or phenprocoumon. 

Qu Y, Fang M, Gao B, Amouzadeh HR, Li N, Narayanan P, Acton P, Lawrence J, Vargas HM (2013). Itraconazole decreases left ventricular contractility in isolated rahhit heart mechanism of action. Toxicol Appl Pharmacol 268(2) 113-122. 

The threat of serious complications and the availability of effective, nontoxic drugs has led the majority of centers to undertake preventive therapy for Candida or Aspergillus infection (Dummer et al. 2004). The protocols are typically based on fluconazole for Candida and itraconazole for Aspergillus. Such strategies undoubtedly result in over treatment but have been justified by the reduction in serious fungal infections (Hamacher et al. 1999 Paradis and Williams 1993). The treatment of all respiratory isolates of Candida and Aspergillus infection with fluconazole or itraconazole reduced the lifetime incidence of fungal infections from 14% to 5% (Paradis and Williams 1993). 

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