Antifungal agents resistance

Rifampin is effective against Staph, aureus, Haemophilus spp., R. equi and a variety of mycobacteria. At very high concentrations, it has activity against poxviruses and adenoviruses. Rifampin also has antifungal activity when combined with other antifungal agents. Resistance develops rapidly therefore, it is usually administered concurrently with another antimicrobial agent. In equine practice, is most commonly used in combination with erythromycin for the treatment of R. equi infections in foals. It may also be used in the treatment of refractory osteomyelitis and endocarditis caused by Staph, aureus. 

When amphotericin B is combined with flucytosine, a smaller dose of amphotericin B can be employed because of the in vitro and in vivo synergy between the two antifungal agents. Resistance develops to flucytosine in up to 30% of patients treated with flucytosine alone, limiting its usefulness as monotherapy. Combination therapy with amphotericin B and flucytosine will sterilize the CSF within... 

This is not discussed in detail since mechanisms of resistance have been carefully reviewed (Ghannoum and Rice 1999). It was pointed out that resistance has not been associated with modification of the structure. For the 1,2,4-triazoles that have been widely used, their effect is due to inhibition of the synthesis of ergosterol that is the dominant component of fungal cell membranes. Resistance is generally associated with modification of the target enzymes, for example, the epoxidation of squalene (Terbinafine) or 14a-demethylase (Fluconazole). Resistance of Candida albicans to the azole antifungal agent fluconazole demonstrated, however, the simultaneous occurrence of several types of mechanism for resistance (Perea et al. 2001) ... 

Ghannoum MA, LB Rice (1999) Antifungal agents mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 12 501-517. 

Perea S, JL Lopez-Ribot, WR Kirkpatrick, RK McAtee, RA Santillan, M Martinez, D Calabrese, D Sanglard, TP Patterson (2001) Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antibicrob Agents Chemother 45 2676-2684. 

Nonprescription topical antifungal agent not effective in the treatment of deeper fungal infections of the skin, nor is it reliable in the treatment of fungal infections involving the scalp or nail beds Candida is resistant useful for patients desiring self-medication of mild tinea infections patients must be advised of limitations... 

Transmission of resistant clones of bacteria from patient-to-patient and via environmental reservoirs Organisms with mutation for resistance in patient s flora selected for by antibacterial therapy absorbable, oral antibacterials and, often, an antifungal agent. 

This important antifungal drug (see Chapter 48 Antifungal Agents) is an alternative therapy for visceral leishmaniasis, especially in parts of India with high-level resistance to sodium stibogluconate, but its use is limited in developing countries by difficulty of administration, cost, and toxicity. 

One compound that has been associated with distal tubular injury is amphotericin B, a polyene antifungal agent used in the treatment of systemic mycoses caused by opportunistic fungi. Clinical utility of amphotericin B is limited by its nephrotoxicity, characterized functionally by polyuria resistant to antidiuretic hormone administration, hyposthenuria, hypokalemia, and mild renal tubular acidosis. 

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