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Clinical Therapeutics

Recent Exposure to Caspofungin or Fluconazole Influences the Epidemiology of Candidemia: a Prospective Multicenter Study Involving 2,441 Patients

Olivier Lortholary, Marie Desnos-Ollivier, Karine Sitbon, Arnaud Fontanet, Stéphane Bretagne, Françoise Dromer, ; and the French Mycosis Study Group
Olivier Lortholary
1Institut Pasteur, Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Paris
2CNRS URA3012, Paris
3Université Paris Descartes, Service des Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Hôpital Necker-Enfants Malades, APHP, Paris
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Marie Desnos-Ollivier
1Institut Pasteur, Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Paris
2CNRS URA3012, Paris
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Karine Sitbon
1Institut Pasteur, Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Paris
2CNRS URA3012, Paris
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Arnaud Fontanet
4Institut Pasteur, Unité d'Epidémiologie des Maladies Emergentes, Paris
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Stéphane Bretagne
1Institut Pasteur, Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Paris
2CNRS URA3012, Paris
5Laboratoire de Parasitologie-Mycologie, Université Paris-Est, and Hôpital Henri Mondor, AP-HP, Créteil, France
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Françoise Dromer
1Institut Pasteur, Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, Paris
2CNRS URA3012, Paris
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  • For correspondence: francoise.dromer@pasteur.fr
DOI: 10.1128/AAC.01128-10
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    FIG. 1.

    Scheme showing the actual number of patients experiencing incident episodes of yeast fungemia or recurrences involving single or multiple isolates (mixed infections) and the corresponding number of isolates studied at NRCMA.

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    FIG. 2.

    Proportion of the five major Candida species responsible for fungemia in patients with (n = 159) or without (n = 2,289) prior exposure to fluconazole (P = 0.001) or with (n = 61) or without (n = 2,387) prior exposure to caspofungin (P < 0.001) (incident episodes and recurrences are included).

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  • TABLE 1.

    Antifungal susceptibility of the five most frequent Candida species responsible for bloodstream infections according to recent exposure to fluconazole or caspofungin prior to diagnosis of fungemiaa

    Exposure drug and antifungalNo preexposure recordedPreexposure recordedPb
    No. of isolatesGMIC (mg/liter)No. of isolatesGMIC (mg/liter)
    Fluconazole
        Total2,2890.77 (0.71-0.83)c1592.31 (1.65-3.23)<0.001
        C. albicans12910.24 (0.23-0.24)580.36 (0.25-0.51)0.053
        C. glabrata41313.97 (12.59-15.50)4618.05 (13.19-24.70)0.129
        C. parapsilosis2950.97 (0.86-1.08)231.62 (0.99-2.64)0.015
        C. tropicalis2260.84 (0.70-1.00)201.52 (0.76-3.01)0.040
        C. krusei6434.15 (29.88-39.02)1228.51 (10.78-75.41)0.402
    Caspofungin
        Total19200.07 (0.07-0.08)610.16 (0.12-0.22)<0.001
        C. albicans9930.05 (0.05-0.05)130.09 (0.04-0.22)0.252
        C. glabrata3650.07 (0.07-0.08)210.12 (0.08-0.19)0.418
        C. parapsilosis2990.28 (0.26-0.31)190.32 (0.23-0.45)0.893
        C. tropicalis1990.06 (0.05-0.06)0
        C. krusei640.15 (0.13-0.17)80.19 (0.11-0.33)0.571
    • ↵a Recent exposure was <30 days prior to diagnosis of fungemia, and data for incident episodes and first recurrences are included. GMIC, geometric mean MIC.

    • ↵b Mann-Whitney test.

    • ↵c Values in parentheses are 95% CIs.

  • TABLE 2.

    Characteristics of patients and Candida sp. isolates responsible for incident fungemia according to recorded or not recorded recent exposured to fluconazole or caspofungin

    Group and characteristicRecent exposure to fluconazoleRecent exposure to caspofungin
    None recorded (n = 2,305)Recorded (n = 136)PNone recorded (n = 2,391)Recorded (n = 50)P
    Patients
        Mean age (yr)56.9 (56.1-57.8)c50.7 (47.0-54.5)<0.00156.9 (56.0-57.7)42.7 (36.7-48.6)<0.001
        Male gendera1,392/2,305 (60.4)78/136 (57.4)0.5281,435/2,391 (60.0)35/50 (70.0)0.189
        Hematological malignancya411/2,305 (17.8)31/136 (22.8)0.168414/2,391 (17.3)28/50 (56.0)<0.001
        Intensive care unita1,073/2,305 (46.6)80/136 (58.8)0.0061,133/2,391 (47.4)20/50 (40.0)0.320
        Central venous cathetera1,723/2,305 (74.8)115/136 (84.6)0.0101,793/2,391 (75.0)45/50 (90.0)0.012
        After diagnosis of fungemia, prescription ofa:
            Fluconazole1,233/1,938 (63.6)43/129 (33.3)<0.0011,269/2,022 (62.8)7/45 (15.6)<0.001
            Caspofungin393/1,938 (20.3)52/129 (40.3)<0.001424/2,022 (21.0)21/45 (46.7)<0.001
        Death before day 30a859/2,185 (39.3)54/134 (40.3)0.856892/2,271 (39.3)21/48 (43.8)0.552
        Early death (<day 8)a481/846 (56.9)26/53 (49.1)0.318497/878 (56.6)10/21 (47.6)0.506
    Isolatesb
        Mixed infectiona75/2,305 (3.3)3/136 (2.2)0.80077/2,391 (3.2)1/50 (2.0)1.000
        Non-C. albicans speciesa1,107/2,377 (46.6)89/139 (64.0)<0.0011,157/2,465 (46.9)39/51 (76.5)<0.001
        C. glabrata isolatesa393/2,377 (16.5)35/139 (25.2)0.011413/2,465 (16.8)15/51 (29.4)0.023
        Geometric mean MIC (mg/liter) for the isolate causing fungemia
            Fluconazole0.77 (0.71-0.83)c2.14 (1.51-3.04)<0.0010.80 (0.74-0.86)2.17 (1.23-3.82)<0.001
            Caspofungin0.07 (0.07-0.08)c0.08 (0.07-0.09)0.1990.07 (0.07-0.07)0.17 (0.13-0.23)<0.001
        Episodes due to at least one isolate with decreased susceptibility toa:
            Fluconazole452/2,305 (19.6)47/136 (34.6)<0.001480/2,391 (20.1)19/50 (38.0)0.004
            Caspofungin121/1,854 (6.5)10/106 (9.4)0.231119/1,910 (6.2)12/51 (24.0)<0.001
    • ↵a The data indicate the number of individuals or isolates for whom the corresponding information was available/total number in the group (%).

    • ↵b The total number of isolates studied during incident candidemia was 2,516.

    • ↵c Values in parentheses in this row are 95% CIs.

    • ↵d Recent exposure was <30 days prior to diagnosis of fungemia.

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Recent Exposure to Caspofungin or Fluconazole Influences the Epidemiology of Candidemia: a Prospective Multicenter Study Involving 2,441 Patients
Olivier Lortholary, Marie Desnos-Ollivier, Karine Sitbon, Arnaud Fontanet, Stéphane Bretagne, Françoise Dromer and the French Mycosis Study Group
Antimicrobial Agents and Chemotherapy Jan 2011, 55 (2) 532-538; DOI: 10.1128/AAC.01128-10

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Recent Exposure to Caspofungin or Fluconazole Influences the Epidemiology of Candidemia: a Prospective Multicenter Study Involving 2,441 Patients
Olivier Lortholary, Marie Desnos-Ollivier, Karine Sitbon, Arnaud Fontanet, Stéphane Bretagne, Françoise Dromer and the French Mycosis Study Group
Antimicrobial Agents and Chemotherapy Jan 2011, 55 (2) 532-538; DOI: 10.1128/AAC.01128-10
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