Fluconazole resistance in AIDS patients

Willocks, Lorna; Leen, Clifford; Brettle, R.P.; Urquhart, Donna M.; Russell, Theresa; Milne, L. J. R.

doi:10.1093/jac/28.6.937

Cited by 90 publications

(63 citation statements)

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“…However, due to the widespread use of immunosuppressive agents and/or broadspectrum antimycotic therapy, the frequency of mucosal and systemic C. glabrata infections has increased significantly, making it the second or third most common cause of candidiasis after C. albicans (22,24,35,36,52,72,73,84). Infections caused by C. glabrata are particularly difficult to treat, as resistance to azole antifungal agents including fluconazole is common (22,31,36,69,79,82,83). Consequently, C. glabrata infections often result in high morbidity and mortality in immunocompromised hospitalized patients (22).…”

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confidence: 99%

Comparison of Pathogenesis and Host Immune Responses toCandida glabrataandCandida albicansin Systemically Infected Immunocompetent Mice

et al. 2001

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Cytokine-mediated host defense against Candida glabrata infection was compared to that against C. albicans, using immunocompetent murine models of systemic candidiasis. The pathogenesis of infection was evaluated morphologically and by culture of target organs, while the kinetics of induction of cytokine mRNAs and corresponding proteins were determined in kidneys by real-time reverse transcription-PCR and cytokinespecific murine enzyme-linked immunosorbent assays, respectively. Systemic infection with C. glabrata resulted in a chronic, nonfatal infection with recovery of organisms from kidneys, while intravenous inoculation with C. albicans resulted in rapid mortality with logarithmic growth of organisms in kidneys and recovery of C. albicans from the spleen, liver, and lungs. Survival of C. glabrata-infected mice was associated with rapid induction of mRNAs and corresponding immunoreactive proteins for the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-12 (IL-12), and gamma interferon (IFN-␥) and the lack of induction of protein for the anti-inflammatory cytokine IL-10. In contrast, mortality in C. albicans-infected mice was associated with induction of mRNA and corresponding protein for IL-10 but delayed (i.e., TNF-␣) or absent (i.e., IL-12 and IFN-␥) induction of immunoreactive proinflammatory cytokines. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to TNF-␣, IL-12, or IFN-␥, and the effect on growth of C. glabrata in kidneys was assessed. Neutralization of endogenous TNF-␣ resulted in a significant increase in C. glabrata organisms compared to similarly infected mice administered an isotype-matched control MAb, while neutralization of endogenous IL-12 or IFN-␥ had no significant effect on C. glabrata replication. These results demonstrate that in response to intravenous inoculation of C. glabrata, immunocompetent mice develop chronic nonfatal renal infections which are associated with rapid induction of the proinflammatory cytokines TNF-␣, IL-12, and IFN-␥. Furthermore, TNF-␣ plays a key role in host defense against systemic candidiasis caused by either C. glabrata or C. albicans, as the absence of endogenous TNF-␣ activity was associated with enhanced tissue burden in both infection models.

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confidence: 99%

Comparison of Pathogenesis and Host Immune Responses toCandida glabrataandCandida albicansin Systemically Infected Immunocompetent Mice

et al. 2001

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“…Although this infection is not life-threatening, the sustained immunosuppression seen in these patients facilitates recurrences of infection (9). Consequently, several courses of acuteor long-term suppressive therapy are often required and may contribute to the development of resistant strains (3,4,21).…”

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In vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus

Barchiesi

Colombo

McGough

et al. 1994

Antimicrob Agents Chemother

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A broth macrodilution technique, which was performed by following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P), was applied to study the in vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from the oral cavities of 100 patients infected with human immunodeficiency virus. The in vitro data demonstrated that itraconazole had good activity against the tested isolates; for 90%o of all strains of C. albicans, MICs were 1 ,Lg/ml, and only one isolate was highly resistant to this triazole (MIC, >16 ,ug/ml). However, the itraconazole MICs for the fluconazole-susceptible isolates were significantly lower than those for the fluconazole-resistant isolates; the MICs for 50 and 90%o of the isolates tested were .0.03 and 0.25 ,ug/ml, respectively, for the fluconazole-susceptible isolates and 0.5 and 1 ,ug/ml, respectively, for the fluconazole-resistant isolates (P = 0.00001). Our findings could be of clinical relevance because human immunodeficiency virus-infected patients who fail fluconazole therapy for oral and/or esophageal candidiasis may require itraconazole at doses higher than those used in standard therapy.Oropharyngeal candidiasis caused by Candida albicans is the most commonly diagnosed opportunistic infection in human immunodeficiency virus (HIV)-infected patients (17). Although this infection is not life-threatening, the sustained immunosuppression seen in these patients facilitates recurrences of infection (9). Consequently, several courses of acuteor long-term suppressive therapy are often required and may contribute to the development of resistant strains (3, 4, 21).Fluconazole and itraconazole are both used either in the treatment of acute oropharyngeal candidiasis or in the prophylaxis of oropharyngeal candidiasis in these patients (1). The lack of standardized methods for in vitro antifungal susceptibility testing presents difficulties in recognizing resistant strains. The Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards (NCCLS) has recently proposed a broth macrodilution reference method for susceptibility testing of yeasts (10). In the study described here, we investigated the in vitro activity of itraconazole against fluconazole-susceptible and -resistant C. albicans isolates from the oral cavities of 100 HIV-infected patients by using the proposed NCCLS method. patients, and each strain represented a unique isolate from a patient. The isolates were chosen from among all C. albicans isolates sent to the laboratory for in vitro susceptibility testing with fluconazole by a previously published broth macrodilution method (15). In order to obtain isolates of C. albicans with different patterns of in vitro susceptibility to fluconazole, we included isolates for which fluconazole MICs ranged from <1.25 to >80 ,ug/ml. All of the isolates were retested for their susceptibilities to fluconazole and tested for their susceptibilities to itra...

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“…Treatment demands the use of the antifungal agents such as griseofulvin and amphotericin B 1) . However, the high cost of this kind of treatment, especially in developing countries the long period of therapy and the emergence of the resistant strains to the antifungal agents should hinder the eradication of these diseases 2,3) . The lack of some new antifungal agents, the apparent increase of the infections by the dermatophytes and the emergence of the resistant to the antifungal therapy lead to the identification of new antifungal agents with potential interest in the treatment of serious fungal infections.…”

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confidence: 99%

The Antidermatophytic Potential of the Marine Isolate of Aspergillus sp. Collected from South Coast of Korea

Bajpai¹,

Kang²

2008

Korean Journal of Environmental Agriculture

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This study was carried out to assess the antidermatophytic potential of the ethyl acetate (EtOAc) extract of the marine isolate of Aspergillus sp.. The fungus was isolated by serial dilution, and was identified Aspergillus sp.. The EtOAc extract of the fungus was examined to evaluate the antidermatophytic efficacy against the fungal pathogens infecting human skin using the disc diffusion and MIC (minimum inhibitory concentration) determination methods. The EtOAc extract (5 l disc μ

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Fluconazole resistance in AIDS patients

Cited by 90 publications

References 0 publications

Comparison of Pathogenesis and Host Immune Responses toCandida glabrataandCandida albicansin Systemically Infected Immunocompetent Mice

Comparison of Pathogenesis and Host Immune Responses toCandida glabrataandCandida albicansin Systemically Infected Immunocompetent Mice

In vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus

The Antidermatophytic Potential of the Marine Isolate of Aspergillus sp. Collected from South Coast of Korea

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