Candida Bloodstream Infections in Italy: Changing Epidemiology during 16 Years of Surveillance.

Although considerable progress has been made in the management of patients with invasive fungal infections, Candida bloodstream infections are still widespread in hospital settings. Incidence rates vary geographically, often because of different patient populations. The aim of the present study was to describe the epidemiology of candidemia, to analyze the trend of species distribution, and to measure the in vitro susceptibility to antifungal drugs in a university Italian hospital from 1998 to 2013. The antifungal susceptibility for all Candida isolates was evaluated by broth microdilution assay (CLSI M27-A3 document). Of 394 episodes of candidemia, the average incidence was 3.06/10,000 admissions. C. albicans and non-albicans Candida species caused 44.2% and 55.8% of the episodes, respectively. C. parapsilosis (62.2%) was the most common non-albicans. C. albicans predominated in almost all departments whereas C. parapsilosis was found in adult and paediatric oncohaematology units (34.8% and 77.6%, resp.). Overall, mortality occurred in 111 (28.2%) patients. Death occurred most often in intensive care units (47.1%) and specialist surgeries (43.7%). Most of the isolates were susceptible to antifungal drugs, but there was an upward trend for azole (P < 0.05). In conclusion, this study emphasizes the importance of monitoring local epidemiologic data and the diversity of patient groups affected.

Susceptibility to echinocandins of Candida spp. strains isolated in Italy assessed by European Committee for Antimicrobial Susceptibility Testing and Clinical Laboratory Standards Institute broth microdilution methods.

BACKGROUND: The echinocandins are recommended as first-line therapy for Candida species infections, but drug resistance, especially among Candida glabrata, is becoming more frequent. We investigated the antifungal susceptibility of anidulafungin, caspofungin, and micafungin against 584 isolates of Candida spp. (bloodstream, other sterile sites) collected from patients admitted to an Italian university hospital between 2000 and 2013. The susceptibility was evaluated using the broth microdilution method according to both the European Committee for Antimicrobial Susceptibility Testing (EUCAST EDef 7.2) and the Clinical Laboratory Standards Institute (CLSI M27-A3). The echinocandin susceptibilities were assessed on the basis of the species-specific clinical breakpoints proposed by the EUCAST version 6.1 and CLSI M27-S4 documents. The two methods were comparable by assessing essential agreement (EA), categorical agreement (CA), and Spearman's correlation analysis (rho, r). RESULTS: The modal minimum inhibitory concentrations (MICs; µg ⋅ mL (-1)) values by both methods (EUCAST/CLSI) for anidulafungin, caspofungin, and micafungin for each species were, respectively, as follows: C. albicans, 0.03/0.12, 0.016/0.5, and 0.016/0.008; C. parapsilosis complex, 2/1, 2/2, and 2/1; C. tropicalis, 0.06/0.12, 0.06/0.12, and 0.06/0.12; C. glabrata complex, 0.03/0.25, 0.06/0.12, and 0.03/0.06; C. guilliermondii, 2/1, 2/2, and 2/2; and C. krusei, 0.06/0.12, 0.12/0.5, and 0.06/0.12. The overall resistance rates for EUCAST/CLSI were as follows: anidulafungin, 2.5/0.9%; caspofungin, breakpoint not available/3.8%; micafungin, 2.7/1.5%. Candida glabrata complex was the least susceptible to all three echinocandins, and the percentages of resistant isolates by EUCAST/CLSI were as follows: anidulafungin, 13.5/2.7%; caspofungin, breakpoint not available/16.2%; micafungin, 18.9/13.5%. The overall EA was 93 % for micafungin, 92% for anidulafungin, and 90% for caspofungin. The CA was >90% for all organism-drug combinations with the exception of C. glabrata and anidulafungin (89%). Spearman's rho for EUCAST/CLSI was 0.89 (p < 0.001) for caspofungin, 0.85 (p < 0.001) for anidulafungin, and 0.83 for micafungin (p < 0.001). CONCLUSIONS: Independent of the procedure applied, no alarming resistance to the tested agents was found, although a reduced susceptibility was detected for C. glabrata complex. The EUCAST and CLSI methods produce similar MICs, indicating that using one method or the other should not result in susceptibilities different enough to affect treatment decisions.

Mold contamination in a controlled hospital environment: a 3-year surveillance in southern Italy.

BACKGROUND: Environmental monitoring of airborne filamentous fungi is necessary to reduce fungal concentrations in operating theaters and in controlled environments, and to prevent infections. The present study reports results of a surveillance of filamentous fungi carried out on samples from air and surfaces in operating theaters and controlled environments in an Italian university hospital. METHODS: Sampling was performed between January 2010 and December 2012 in 32 operating theaters and five departments with high-risk patients. Indoor air specimens were sampled using a microbiological air sampler; Rodac contact plates were used for surface sampling. Fungal isolates were identified at the level of genera and species. RESULTS: Sixty-one samples (61/465; 13.1%) were positive for molds, with 18 from controlled environments (18/81; 22.2%) and 43 (43/384; 11.2%) from operating theaters. The highest air fungal load (AFL, colony-forming units per cubic meter [CFU/m(3)]) was recorded in the ophthalmology operating theater, while the pediatric onco-hematology ward had the highest AFL among the wards (47 CFU/m(3)). The most common fungi identified from culture of air specimens were Aspergillus spp. (91.8%), Penicillium spp., (6%) and Paecilomyces spp. (1.5%). During the study period, a statistically significant increase in CFU over time was recorded in air-controlled environments (p = 0.043), while the increase in AFL in operating theaters was not statistically significant (p = 0.145). Molds were found in 29.1% of samples obtained from surfaces. Aspergillus fumigatus was the most commonly isolated (68.5%). CONCLUSIONS: Our findings will form the basis for action aimed at improving the air and surface quality of these special wards. The lack of any genetic analysis prevented any correlation of fungal environmental contamination with onset of fungal infection, an analysis that will be undertaken in a prospective study in patients admitted to the same hospital.

In vitro activities of amphotericin B deoxycholate and liposomal amphotericin B against 604 clinical yeast isolates.

We determined the in vitro antifungal activity of liposomal amphotericin B (L-AmB) against 604 clinical yeast isolates. Amphotericin B deoxycholate (D-AmB) was tested in parallel against all the isolates. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 method. Overall, L-AmB was highly active against the isolates (mean MIC, 0.42 µg ml(-1); MIC90, 1 µg ml(-1); 97.2 % of MICs were ≤1 µg ml(-1)) and comparable to D-AmB (mean MIC, 0.48 µg ml(-1); MIC90, 1 µg ml(-1); 97.3 % of MICs were ≤1 µg ml(-1)). The in vitro activity of D-AmB and L-AmB was correlated (R(2) = 0.61; exp(b), 2.3; 95 % CI, 2.19-2.44, P<0.001). Candida albicans (mean MICs of D-AmB and L-AmB, 0.39 µg ml(-1) and 0.31 µg ml(-1), respectively) and Candida parapsilosis (mean MICs of D-AmB and L-AmB, 0.38 µg ml(-1) and 0.35 µg ml(-1), respectively) were the species most susceptible to the agents tested, while Candida krusei (currently named Issatchenkia orientalis) (mean MICs of D-AmB and L-AmB, 1.27 µg ml(-1) and 1.13 µg ml(-1), respectively) was the least susceptible. The excellent in vitro activity of L-AmB may have important implications for empirical treatment approaches and support its role in treatment of a wide range of invasive infections due to yeasts.

The role of procalcitonin in neonatal intensive care unit patients with candidemia.

Candidemia is a major infectious complication in neonatal patients. The isolation of yeasts from blood is still the "gold standard" for its diagnosis, but other laboratory markers (i.e., circulating antigens) have been studied with varying specificities and sensitivities. The aim of this study was to evaluate the role of procalcitonin for the diagnosis of candidemia in neonatal patients at high risk. To verify if the use of different commercial methods can highlight dissimilar results of sensitivity and/or specificity, the determination of procalcitonin serum levels was estimated by two systems. Overall, 90 patients from a Neonatal Intensive Care Units were enrolled, of whom six developed Candida bloodstream infection. Four of six infants with candidemia had slight increase of procalcitonin values (0.5-1 ng/mL). Only one baby showed very high levels but he had fungal and bacterial sepsis at the same time, while no elevation was observed in the sixth patient. No statistically significant difference was observed between two different methods at the time of monitoring (p>0.643). Both methods showed a sensitivity of 83.3 % at diagnosis, while the specificity was 73.8 and 63.1 % by methods A and B, respectively. In the light of the low sensibility and specificity of this assay, we can assume that the determination of procalcitonin would not seem to play a significant role in the diagnosis of fungal infection in neonatal patients.

Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial.

INTRODUCTION: Candida prophylaxis in ICU is still a matter of debate. Oral chemoprophylaxis has been advocated to reduce the incidence of Candida colonisation and infection. METHODS: We performed a randomised trial studying a single drug (nystatin) versus control in surgical/trauma ICU patients. Multiple-site testing for fungi was performed in each patient on ICU admission (T0) and subsequently every 3 days (T3, T6, T9, and so forth). The primary evaluation criterion was the time course of the corrected colonisation index. RESULTS: Ninety-nine patients were enrolled. At admission, 69 patients exhibited Candida colonisation: the most frequently colonised body sites were the stomach and the pharynx. The most frequent isolated species was Candida albicans. The corrected colonisation index was similar in the two groups at T0 (P = 0.36), while a significant statistical difference was observed between the treatment and control groups at T6 (median 0.14 and 0.33, respectively; P = 0.0016), at T9 (median 0.00 and 0.28, respectively; P = 0.0001), at T12 (median 0.00 and 0.41, respectively; P = 0.0008), and at T15 (median 0.00 and 0.42, respectively; P < 0.0003). The same results were obtained in the subgroup of patients already colonised at ICU admission. CONCLUSION: This trial shows that nystatin prophylaxis significantly reduces fungal colonisation in surgical/trauma ICU patients, even if already colonised. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01495039.

Candida colonization index in patients admitted to an ICU.

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.

Diagnostic performance of 1→3-ß-d-glucan in neonatal and pediatric patients with Candidemia.

Fungal sepsis is one of the major problems in neonatal and pediatric care unit settings. The availability of new diagnostic techniques could allow medical practitioners to rapidly identify septic patients and to improve their outcome. The aim of this study was to evaluate the performance of the 1→3-ß-d-glucan (BDG), individually and in comparison with the Candida mannan (CM) antigen, in ten preterm infants and five onco-haematological pediatric patients with Candida bloodstream infections already proven by positive culture. The serum levels of BDG were >80 pg/mL on the same day as a positive blood culture in all examined patients, while CM antigen was negative in the patients with C. parapsilosis fungemia and in one further case due to C. albicans. These results suggest that a regular monitoring of serum circulating antigens (i.e., 1→3-ß-d-glucan) combined with other microbiological and clinical information, may allow earlier and accurate diagnosis. However, further studies are necessary to confirm its usefulness in routine clinical practice.