Advertisement

Amphotericin B-resistant yeast infection in severely immunocompromised patients

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Systemic yeast infections are a major cause of morbidity and mortality in severely immunocompromised patients. The in vitro susceptibility to amphotericin B of 29 yeasts causing fungemia was examined in 26 patients undergoing allogeneic or autologous bone marrow transplantation and/or myelosuppressive chemotherapy. The minimal inhibitory concentrations (MICs) of amphotericin B observed with blood isolates from these patients were significantly higher than those observed with blood, sputum, or skin isolates from non-immunocompromised patients (p <0.01). All episodes (10 of 10) of bloodstream infection in immunocompromised patients caused by isolates with MICs greater than 0.8 μg/ml were fatal, versus eight of 17 episodes of bloodstream infection caused by yeasts with MICs of 0.8 μg/ml or less (p = 0.04). Although 15 of 26 patients received empiric treatment with amphotericin B before laboratory evidence of fungemia developed, the amphotericin B susceptibilities of their isolates were not significantly different from those of patients who had not received empiric amphotericin B treatment. It is concluded that yeast fungemia in severely immunocompromised patients is often caused by organisms resistant to the usual concentrations of amphotericin B obtainable in vivo, and that this finding is clinically significant.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Young RC
        • Bennett JE
        • Geelhoed GW
        • Levine AS
        Fungemia with compromised host resistance: a study of 70 cases.
        Ann Intern Med. 1974; 80: 605-612
        • Singer C
        • Kaplan MH
        • Armstrong D
        Bacteremia and fungemia complicating neoplastic disease; a study of 364 cases.
        Am J Med. 1977; 62: 731-742
        • Meunier-Carpentier F
        • Kiehn TE
        • Armstrong D
        Fungemia in the immunocompromised host: changing patterns, antigenemia, high mortality.
        Am J Med. 1981; 71: 363-370
        • Horn R
        • Wong B
        • Kiehn TE
        • Armstrong D
        Fungemia in a cancer hospital: changing frequency, earlier onset, and results of therapy.
        Rev Infect Dis. 1985; 7: 646-655
        • Edwards Jr, JE
        • Lehrer RI
        • Stiehm ER
        • Fischer TJ
        • Young LS
        Severe candidal infections.
        in: Clinical perspective, immune defense mechanisms, and current concepts of therapy. 4th ed. Ann Intern Med. 89. 1978: 91-106
        • Pizzo PA
        • Robichaud KJ
        • Gill FA
        • Witebsky FG
        Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia.
        Am J Med. 1982; 72: 101-111
        • Holleran WM
        • Wilbur JR
        • Degregorio MW
        Empiric amphotericin B therapy in patients with acute leukemia.
        Rev Infect Dis. 1985; 7: 619-624
        • Pizzo PA
        • Commers J
        • Cotton D
        • et al.
        Approaching the controversies in antibacterial management of cancer patients.
        Am J Med. 1984; 76: 436-449
        • Shadomy S
        • Espinel-Ingroff A
        • Cartwright RY
        Laboratory studies with antifungal agents: susceptibility tests and bioassays.
        in: 4th ed. Manual of clinical microbiology. American Society of Microbiology, Washington1985: 991-999
        • Powderly WG
        • Granich GG
        • Herzig GP
        • Krogstad DJ
        HPLC measurement of amphotericin B serum levels in cancer patients.
        (abstr)in: Program and abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society of Microbiology, New York1987: 233
        • Drutz DJ
        • Lehrer RI
        Development of amphotericin B-resistant Candida tropicalis in a patient with defective leukocyte function.
        Am J Med Sci. 1978; 276: 77-92
        • Pappagianis D
        • Collins MS
        • Hector R
        • Remington J
        Development of resistance to amphotericin B in Candida lusitaniae infecting a human.
        Antimicrob Agents Chemother. 1979; 16: 123-126
        • Merz WG
        • Sandford GR
        Isolation and characterization of a polyene-resistant variant of Candida tropicalis.
        J Clin Microbiol. 1979; 9: 677-680
        • Dick JD
        • Merz WG
        • Saral R
        Incidence of polyene-resistant yeasts recovered from clinical specimens.
        Antimicrob Agents Chemother. 1980; 18: 158-163
        • Dick JD
        • Rosengard BR
        • Merz WG
        • Stuart RK
        • Hutchins GM
        • Seral R
        Fatal disseminated candidiasis due to amphotericin B resistant Candida guillermondii.
        Ann Intern Med. 1985; 102: 68-69
        • Sud IJ
        • Feingold DS
        Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans.
        Antimicrob Agents Chemother. 1983; 23: 185-187
        • Sokol-Anderson ML
        • Brajtburg J
        • Medoff G
        Amphotericin B-induced oxidative damage and killing of Candida albicans.
        J Infect Dis. 1986; 154: 76-83
        • Andrews JR
        The radiobiology of human cancer radiotherapy.
        University Park Press, Baltimore1978
        • Bachur NR
        • Gordon SL
        • Gee MV
        A general mechanism for microsomal activation of quinone anticancer agents to free radicals.
        Cancer Res. 1978; 38: 1745-1750
        • Medoff G
        • Comfort M
        • Kobayashi GS
        Synergistic action of amphotericin B and 5-fluorocytosine for Candida species.
        in: 2nd ed. Proc Soc Exp Biol Med. 138. 1971: 571-574
        • Bennett JE
        • Dismukes WE
        • Duma RJ
        • et al.
        A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis.
        N Engl J Med. 1979; 301: 126-131
        • Chesny PJ
        • Tests KC
        • Mulvihill JJ
        • Salit IE
        • Marks MI
        Successful treatment of Candida meningitis with amphotericin B and 5-fluorocytosine in combination.
        J Pediatr. 1976; 89: 1017-1019
        • Eilard T
        • Beskow D
        • Norrby R
        • Wahlen P
        • Alestig K
        Combined treatment with amphotericin B and flucytosine in severe fungal infections.
        J Antimicrob Chemother. 1976; 2: 239-246
        • Kauffman CA
        • Frame PT
        Bone marrow toxicity associated with 5-fluorocytosine therapy.
        Antimicrob Agents Chemother. 1977; 11: 244-247