Molecular Epidemiology of Candidemia: Evidence of Clusters of Smoldering Nosocomial Infections

Abstract

Background. Invasive fungal infections pose a serious threat to hospitalized patients worldwide. In particular, the prevalence of clusters of nosocomial infection among patients with candidemia remains unknown. The aim of this study was to investigate the molecular epidemiology of candidemia in a nationwide setting in Iceland during a 16-year period.Methods. The genotypes of all available fungal bloodstream isolates during 1991-2006 ( ) were detern p 219 mined by polymerase chain reaction fingerprinting with use of 4 separate primers. Clusters were defined as isolation of у2 strains with genotypes that had у90% relatedness in the same hospital within a period of 90 days.Results. Candida albicans represented 61.6% of isolates, followed by Candida glabrata (13.7%), Candida tropicalis (9.1%), and Candida parapsilosis (8.7%). Polymerase chain reaction fingerprinting revealed 35 clones of C. albicans, 10 clones of C. glabrata, 7 clones of C. tropicalis, 4 clones of C. parapsilosis, and 5 clones of Candida dubliniensis. Overall, 18.7%-39.9% of all infections were part of nosocomial clusters, most commonly caused by C. albicans, C. parapsilosis, and C. tropicalis. Most clusters involved 2 cases and disproportionately affected patients in adult and neonatal intensive care units ( ). The 7-day (16%) and 30-day (32%) case-fatality rates among P p .045 cluster-associated cases did not differ statistically significantly from those for sporadic nosocomial infections. None of the clusters were identified by the hospital surveillance team.Conclusions. In an unselected patient population, as many as one-third of all cases of candidemia may be attributable to nosocomial clusters. The risk is dependent on hospital wards and patient populations; it is highest in intensive care units. Small clusters are not identified by routine hospital surveillance.

Different scenarios for Candida parapsilosis fungaemia reveal high numbers of mixed C. parapsilosis and Candida orthopsilosis infections

“…The identification in this study of genetically related isolates, persistently isolated from BSI occurring in different patients in the same hospital, sometimes over several years, further reinforces the environmental acquisition of these infections. The temporal persistence of single C. parapsilosis strains over long periods of time in the same hospital or ward has been described in other studies, and was also associated with outbreaks (Á smundsdó ttir et al, 2008;Romeo et al, 2013;Viviani et al, 2006).…”

Nationwide Study of Candidemia, Antifungal Use, and Antifungal Drug Resistance in Iceland, 2000 to 2011

“…This is also two to three times higher than that reported from the other Northern European countries (6.9 to 11.3 cases/100,000 population) (10,11,13) but lower than the rates reported from Spain (38.8/100,000 population) (7) and among white neonates in two population-based U.S. studies (37 and 41/100,000 population) (6,33). By genotyping of Candida blood isolates, we have previously shown that nosocomial clustering of candidemia is particularly prevalent in the neonatal intensive care unit setting (21). Our study, therefore, confirms and emphasizes the risk of candidemia in this vulnerable population and the importance of preventive measures.…”

“…Species identification was based on colony morphology following culture on chromogenic agar (CHROMagar Co., Paris, France) and analysis of sugar assimilation profiles (API 20C AUX and API ID 32C; bioMérieux). In cases where a definite species identification could not be made by these methods, species identification was achieved by using PCR fingerprinting or ITS sequence analysis, as previously described (21,22).…”

Diagnostic Issues, Clinical Characteristics, and Outcomes for Patients with Fungemia

“…The crude 30-day mortality was 30 to 40% in most population-based studies enrolling patients until the turn of the millennium (2,4,12,14,16,29,41,42,49,52) but was lower in recent studies (16,17,36) and higher for ICU patients (7,33), patients infected with C. glabrata (54), and patients with delayed initiation of appropriate antifungal treatment (20,34). Because timing and diagnostic sensitivity are still major issues in the management of fungemia, an understanding of diagnostic features, risk groups, and epidemiology is of utmost importance for selection of patients who may benefit from early antifungal treatment and for selection of the most appropriate antifungal agent before species identification is available.…”