Review
Candidaemia in Europe: epidemiology and resistance

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Abstract

Despite the widespread use of antifungals for prophylaxis, Candida bloodstream infection (BSI) remains the most frequent life-threatening fungal disease. From an analysis of multi-institutional surveys of Candida BSIs performed in Europe, including the large prospective survey by the European Confederation of Medical Mycology (2089 episodes from seven countries), a limited role of species with decreased susceptibility to azoles in causing BSIs and a low proportion of antifungal resistance was evident. Large prospective epidemiological surveys using common databases are needed to monitor trends in incidence and changes in species distribution, to identify new at-risk patients and to evaluate the impact of the introduction into the market of new antifungal agents.

Introduction

Despite the widespread use of antifungals for prophylaxis and treatment of invasive fungal infections in immunocompromised patients, candidaemia remains the most frequent life-threatening fungal disease and is associated with a prolonged hospital stay and a resulting rise in costs [1], [2].

Most of our knowledge of the epidemiology of candidaemia comes from studies done in North America [3]. Up to 1996, only one survey involving more than one hospital in a European country had been published [4]. Therefore, in 1997 the European Confederation of Medical Mycology (ECMM) launched, among other epidemiological working group initiatives, a survey of candidaemia [5]. Six national societies participated in this prospective sequential study conducted from September 1997 to December 1999: the British, French, German-speaking, Italian, Spanish and Swedish mycology societies. A total of 2089 reports were submitted from 106 participant centres selected by the national coordinator in each country [6]. Different approaches were adopted for selection: in Italy all of the institutions present in one region and equipped with a microbiology laboratory were included in the survey, whilst in other countries only teaching or large general hospitals were selected [7], [8], [9], [10], [11], [12]. For each episode of candidaemia, a questionnaire regarding risk factors or predisposing diseases, diagnosis of candidaemia, intravascular catheter management, initial treatment and outcome (30 days after diagnosis) was completed [5].

Section snippets

Epidemiology of candidaemia

Table 1 summarises the multi-institutional surveys of Candida bloodstream infections (BSIs) performed in Europe. Few studies designed to estimate the incidence based on appropriate denominator data, such as admissions, patient-days or inhabitants, have been performed. In addition, in some series, data regarding candidaemia and invasive candidiasis are reported together.

Some surveys have focused on selected patient populations such as intensive care, neonate or cancer patients [1], [13], [14],

The ECMM survey

The countries participating in the ECMM survey reported rates of candidaemia (0.20–0.38 per 1000 admissions and 0.31–0.44 per 10 000 patient-days) comparable with those reported in other European surveys but lower than rates reported in the USA (1.5 per 10 000 patient-days) [6], [29]. A similar particularly high rate (1.64 per 10 000 patient-days) was observed in a hospital in Italy that experienced a large outbreak of Candida BSIs during the study period [12].

In general, the rate of candidaemia

Species distribution in candidaemia

Candida albicans was responsible for more than one-half of the cases in all the patient populations, except in patients with haematological malignancies (Fig. 1). In these patients, C. albicans was isolated in 35% of the cases, Candida tropicalis in 17% and other Candida species in 24%, with Candida krusei involved in one-half of these cases (12%). The same pattern of species distribution was observed in the surveillance study performed by the European Organization for Research and Treatment of

Portal of entry of Candida

Mucous membrane colonisation by Candida has been demonstrated as the leading risk factor for candidaemia in several series and biomolecular data have been published supporting colonisation as a prerequisite for subsequent deep-seated infection [30], [31], [32]. In the ECMM study, mucous membrane colonisation was shown to precede fungaemia: more than 80% of patients with BSI due to C. albicans and C. glabrata and 68% of patients with BSI due to C. tropicalis experienced colonisation of the

Outcome of candidaemia

The severity of candidaemia is confirmed by the high crude mortality rate found in the ECMM survey (38%) [6] as well as in Finland (35%) [18] and in the Barcelona area (44%) [26]. Candida krusei, C. glabrata and C. tropicalis BSIs appeared particularly severe, with an unfavourable outcome in more than 40% of patients (Table 4). This high crude mortality rate of BSIs caused by these species may be due to their occurrence in patients with underlying life-threatening conditions.

Mortality rate at

Management of candidaemia

With regard to the management of candidaemia, 84.5% of patients in the ECMM survey received antifungal treatment [6]. The others did not receive antifungals, mainly because candidaemia was associated with the terminal stage of the underlying disease. However, in some cases the potential morbidity and mortality of Candida BSI was not taken into account by the clinicians.

Fluconazole was used as the initial antifungal agent in the majority of cases (59%) reported in the ECMM series. The approach

Epidemiology of antifungal resistance

In vitro antifungal resistance is rarely detected in European multi-institutional surveys (Table 5). Less than 2% of C. albicans isolates were resistant both to flucytosine and fluconazole, and all were inhibited by <2 mg/L of amphotericin B. Among non-albicans Candida isolates, 5.32% and 10.29% were resistant to flucytosine and fluconazole, respectively.

Old and new azoles appeared to be active against the majority of bloodstream isolates (Table 6) [9], [11], [16], [25], [36], [38], [39], [40].

Conclusions

The low proportion of antifungal resistance detected in European surveys, consistent with the data reported in US surveillance programmes [3], [29], [41], [42], is reassuring and supports the consensus that antifungal susceptibility testing need only be performed in cases of breakthrough candidaemia or failure of initial therapy.

Although the incidence of candidaemia appears unchanged in surveys investigating secular trends [20], large prospective epidemiological surveys using a common database

References (42)

  • R.K. Pelz et al.

    Candida infections: outcome and attributable ICU costs in critically ill patients

    J Intensive Care Med

    (2000)
  • M.A. Pfaller et al.

    Role of sentinel surveillance of candidemia: trends in species distribution and antifungal susceptibility

    J Clin Microbiol

    (2002)
  • A. Voss et al.

    Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

    Eur J Clin Microbiol Infect Dis

    (1996)
  • ECMM Mycology Newsletter...
  • A.M. Tortorano et al.

    Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study

    Eur J Clin Microbiol Infect Dis

    (2004)
  • H. Bernhardt et al.

    Epidemiological survey on candidemia in Europe: results of Germany and Austria

    Rev Iberoam Micol

    (2000)
  • R. Grillot et al.

    ECMM prospective epidemiological survey of candidemia in Europe: report from France

    Rev Iberoam Micol

    (2000)
  • C.C. Kibbler et al.

    Management and outcome of bloodstream infections due to Candida species in England and Wales

    J Hosp Infect

    (2002)
  • L. Klingspor et al.

    A prospective epidemiological survey of candidaemia in Sweden

    Scand J Infect Dis

    (2004)
  • J. Peman et al.

    Epidemiology and antifungal susceptibility of Candida species isolated from blood: results of a 2-year multicentre study in Spain

    Eur J Clin Microbiol Infect Dis

    (2005)
  • J. Nolla Salas et al.

    Candidemia in non-neutropenic critically ill patients: analysis of prognostic factors and assessment of systemic antifungal therapy

    Intensive Care Med

    (1997)
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