EPIDEMIOLOGIA DELLE INFEZIONI DA CANDIDA

Candida is reported as an important cause of bloodstream infections (BSI) in critical patients such as cancer patients, surgical patients and premature neonates. Neonates are frequently infected or colonised during the stay in the nursery or during the delivery from Candida vaginitis that is a frequent event in pregnant women, particularly during the third trimester. Candidemia is an important challenge for public health as it is associated with severe complications, high mortality, increased length of hospital stay and great economical cost. Most of Candida BSIs develop from an endogenous source such as the colonised gut. One of the aims of this study was to assess the epidemiology of candidemia and antifungal susceptibility profiles of Candida isolates in Lombardy hospitals through a prospective survey and to evaluate the changes compared to results of a previous survey performed 10 years before in the same region. A prospective laboratory–based surveillance of candidemia was performed in 2009. The compared data reveal a threefold increase in incidence ( from 0.38 to 1,19 per 1000 admissions), aging of infected patients, an increase in surgical patients (63.8% vs.56%) and decline in crude mortality (from 35 to 27.1%). C. albicans was confirmed as the prevalent species causing candidemia although the rate was a little lower respect the previous survey (52.1% vs. 58.5%). C. glabrata was the second species with a statistically significant increase from 12.8% to 20.3%. Susceptibility testing confirmed the broad spectrum activity of amphotericin B and echinocandins. Decreased susceptibility or resistance to fluconazole was found in 24.9% of the tested isolates. The rate of high biofilm producers among Candida isolates was relevant (25.7%), however no correlation between this micribiological parameter and outcome could be demonstrated. In a previous study performed in collaboration with Massey University a particular cluster of C. albicans named General Purpose Genotype (GPG) was found more virulent than others in causing candidemia in neonates and was associated with higher mortality rate in this population. The number of cases was low and we wanted to better investigate this association by enlarging the population number. However the introduction of antifungal prophylaxis in the neonatal intensive care units lowered the number of candidemia in this patients population. Therefore we decided to investigate the prevalence of the cluster as cause of vaginitis in pregnant women that is the principal way of infection at birth. GPG strains were detected in 32% of the pregnant women with C. albicans vaginitis and in 34.7% of not-pregnant women. The prevalence of GPG among isolates from African and North African women was statistically significant (62.5% versus 18.2%). In addition it was investigated the presence of GPG in isolates from patients affected by alimentary tract colonization. The overall prevalence of the cluster was 32.7% without difference among men and women. A similar prevalence of the cluster among isolates causing colonization or candidemia was observed in neonates (34,8% vs. 33.3%). On the contrary in adult patients hospitalized in intensive care unites the rates were statistically different (42.9% vs. 11.9%). Patients with alimentary tract colonization in different sites were selected for the molecular identification of the strains by multilocus system typing. This was designed to verify if different body sites were colonized by the same strain as predictive tool of deep infection. This part of the study was performed at Massey University. However, due to problems regarding the growth of the strains, only the extraction and the amplification of the DNA was performed until now and the sequencing is in progress. GPG+ and GPG- isolates were also analyzed to detect differences in susceptibility to antifungal drugs. A decrease susceptibility to fluconazole (geometrical mean 1.53mg/l vs. 0.67mg/l) and a higher rate of resistance to 5-fluorocytosine (30% vs. 0%), were detected in GPG+ isolates. A boric acid-5-fluorocytosine based cream was suggested by guidelines for the treatment of vaginal candidosis, especially in pregnant women. Our results suggest to looking for GPG strains among vaginal isolates to avoid clinical failures with possible evolution to a chronic infection, more difficult to eradicate, and the possible vertical contamination of the newborns by a strains associated with high crude mortality rate.