Antifungal resistance in non- albicans Candida species

Collin, Berjan; Clancy, Cornelius J.; Nguyen, M. Hong

doi:10.1054/drup.1998.0059

Cited by 68 publications

(41 citation statements)

References 47 publications

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“…According to previous findings (7,15), AMB was fungicidal against all isolates tested, showing the greatest activity against C. lusitaniae isolates despite the fact that C. lusitaniae is known for rapid development of AMB resistance (4). Caspofungin displayed fungicidal activity against all isolates but C. lusitaniae 325, suggesting that its fungicidal activity is isolate and species specific.…”

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confidence: 51%

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In Vitro Pharmacodynamic Characteristics of Amphotericin B, Caspofungin, Fluconazole, and Voriconazole against Bloodstream Isolates of Infrequent Candida Species from Patients with Hematologic Malignancies

Bonaventura

Spedicato

Picciani

et al. 2004

Antimicrob Agents Chemother

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Time-kill and postantifungal effect (PAFE) of amphotericin B, caspofungin, fluconazole, and voriconazole were determined against clinical isolates of Candida guilliermondii, Candida kefyr, and Candida lusitaniae. Azoles displayed fungistatic activity and no measurable PAFE, regardless of the concentration tested. Amphotericin B and caspofungin demonstrated concentration-dependent fungicidal activity, although amphotericin B only produced a significant dose-dependent PAFE against all isolates tested.Invasive fungal infections are important causes of morbidity and mortality in immunosuppressed patients (10). Although C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis account for the majority of Candida bloodstream infections, recent epidemiologic trends indicate a shift toward infections by the less frequently isolated non-albicans Candida (NAC) species (12). Among NAC species, C. kefyr, C. guilliermondii, and C. lusitaniae are rare causes of invasive infections but are increasingly encountered among severely immunosuppressed patients occurring in nosocomial clusters and/or exhibiting innate or acquired resistance to one or more established antifungal agents, often related to intravascular catheters and breaks in infection control precautions (3-5, 11, 12, 14).Currently, knowledge of the in vitro pharmacodynamic characteristics of C. kefyr, C. guilliermondii, and C. lusitaniae is poor and limited to amphotericin B (AMB) and voriconazole (VRC) only (7,15). Therefore, we conducted time-kill and postantifungal effect (PAFE) studies with AMB, caspofungin, fluconazole (FLC), and VRC against bloodstream isolates of C. guilliermondii, C. kefyr, and C. lusitaniae from neutropenic patients.Antifungal agents. Stock solutions of AMB (Sigma-Aldrich SRL, Milan, Italy), caspofungin (Merck Sharp & Dohme Italia SpA, Rome, Italy), FLC (Pfizer Inc., New York, N.Y.), and VRC (Pfizer) were prepared in RPMI 1640 medium (Sigma) buffered to a pH of 7.0 with 0.165 M morpholinepropanesulfonic acid (MOPS) buffer (Sigma) and stored at Ϫ80°C until use. Antifungals were solubilized in sterile water, except AMB in dimethyl sulfoxide (Sigma).Test isolates. Six Candida isolates were obtained from the Clinical Microbiology Service, Department of Hematology and Oncology, "Spirito Santo" Hospital, Pescara, Italy, for use in this study: two strains each of C. guilliermondii (337 and 555), C. kefyr (240 and 270), and C. lusitaniae (325 and 447) were selected for testing.Antifungal susceptibility testing. The MIC for each isolate was determined, in triplicate, by broth microdilution techniques as outlined by the National Committee for Clinical Laboratory Standards (17). The endpoint was defined as 50% inhibition of visible growth for azoles and complete inhibition of visible growth for AMB and caspofungin.Time-kill. Before the time-kill studies were initiated, antifungal carryover effects were examined. Briefly, 100 l of a standardized suspension (1 ϫ 10 3 CFU/ml) of each isolate were added to either 900 l of sterile water with (sample) or w...

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confidence: 51%

“…The culture was then incubated at 37°C with shaking. At predetermined time points (0,1,2,4,8,24, and 48 h), 100 l samples were removed and serially diluted in cold sterile distilled water, and 100 l was plated onto SDA for colony counting.PAFE. Growth control and test vials were prepared as for time-kill experiments.…”

mentioning

confidence: 99%

In Vitro Pharmacodynamic Characteristics of Amphotericin B, Caspofungin, Fluconazole, and Voriconazole against Bloodstream Isolates of Infrequent Candida Species from Patients with Hematologic Malignancies

Bonaventura

Spedicato

Picciani

et al. 2004

Antimicrob Agents Chemother

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“…Candida albicans is the most common cause of candidemia, and in general has remained susceptible in vitro to both amphotericin B and fluconazole (11,12). As the use of fluconazole increases (1), however, it is important to monitor for any increase in azole resistance among bloodstream isolates of C. albicans or any increase in frequency of bloodstream infection due to Candida species other than C. albicans, which have a higher incidence of in vitro azole resistance (e.g., C. glabrata and Candida krusei) (3).…”

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confidence: 99%

Epidemiology of Candidemia: 3-Year Results from the Emerging Infections and the Epidemiology of Iowa Organisms Study

Messer²,

et al. 2002

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Bloodstream infections due to Candida species cause significant morbidity and mortality. Surveillance for candidemia is necessary to detect trends in species distribution and antifungal resistance. We performed prospective surveillance for candidemia at 16 hospitals in the State of Iowa from 1 July 1998 through 30 June 2001. Using U.S. Census Bureau and Iowa Hospital Association data to estimate a population denominator, we calculated the annual incidence of candidemia in Iowa to be 6.0 per 100,000 of population. Candida albicans was the most common species detected, but 43% of candidemias were due to species other than C. albicans. Overall, only 3% of Candida species were resistant to fluconazole. However, Candida glabrata was the most commonly isolated species other than C. albicans and demonstrated some resistance to azoles (fluconazole MIC at which 90% of the isolates tested are inhibited, 32 g/ml; 10% resistant, 10% susceptible dose dependent). C. glabrata was more commonly isolated from older patients (P ‫؍‬ 0.02) and caused over 25% of candidemias among persons 65 years of age or older. The investigational triazoles posaconazole, ravuconazole, and voriconazole had excellent in vitro activity overall against Candida species. C. albicans is the most important cause of candidemia and remains highly susceptible to available antifungal agents. However, C. glabrata has emerged as an important and potentially antifungal resistant cause of candidemia, particularly among the elderly.

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“…Furthermore, development of resistance to conventional antifungal therapies has created concern regarding the future ability to treat infections caused by Candida spp. (9,23,38,63). Clearly, new strategies to prevent Candida infections are needed.…”

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confidence: 99%

Vaccination with Recombinant N-Terminal Domain of Als1p Improves Survival during Murine Disseminated Candidiasis by Enhancing Cell-Mediated, Not Humoral, Immunity

et al. 2005

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Candida spp. are opportunistic fungal pathogens that are among the most common causes of nosocomial bloodstream infections. The mortality attributable to disseminated candidiasis is 40 to 50% despite antifungal therapy. Clearly, new strategies are needed to prevent this life-threatening infection. Because risk factors for disseminated candidiasis are well defined and frequently of limited duration, vaccination is an appealing prophylactic strategy. We have identified a cell surface protein, Als1p, that mediates adherence of Candida albicans to a variety of human substrates and plastic. Here we report that immunizing BALB/c mice with the recombinant N-terminal domain of Als1p (rAls1p-N) improved survival during a subsequent challenge with a lethal inoculum of C. albicans. The protective 20-g dose of rAls1p-N significantly increased Candida stimulation of Th1 splenocytes and increased in vivo delayed-type hypersensitivity. In contrast, antibody titers did not correlate with protection. Finally, the vaccine was not protective in T-cell-deficient mice but was protective in B-cell-deficient mice. These data indicate that the mechanism of action of the rAls1p-N vaccine is stimulation of cell-mediated, rather than humoral, immunity against C. albicans. The majority of efforts to date have focused on the development of passive immunization strategies to prevent or treat disseminated candidiasis. In contrast, our results provide proof of principle for vaccination with an adhesin of C. albicans and emphasize the potential for cell-mediated immune modulation as a prophylactic or therapeutic strategy against disseminated candidiasis.

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Antifungal resistance in non- albicans Candida species

Cited by 68 publications

References 47 publications

In Vitro Pharmacodynamic Characteristics of Amphotericin B, Caspofungin, Fluconazole, and Voriconazole against Bloodstream Isolates of Infrequent Candida Species from Patients with Hematologic Malignancies

In Vitro Pharmacodynamic Characteristics of Amphotericin B, Caspofungin, Fluconazole, and Voriconazole against Bloodstream Isolates of Infrequent Candida Species from Patients with Hematologic Malignancies

Epidemiology of Candidemia: 3-Year Results from the Emerging Infections and the Epidemiology of Iowa Organisms Study

Vaccination with Recombinant N-Terminal Domain of Als1p Improves Survival during Murine Disseminated Candidiasis by Enhancing Cell-Mediated, Not Humoral, Immunity

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