Lucina Fossati

Mortality in patients with early- or late-onset candidaemia

Objectives Although candidaemia is a well-known complication of hospital stay and has a crude mortality of ∼40%, few data are available for episodes diagnosed within 10 days after hospital admission. In this paper, we compared the risk factors for mortality according to the onset of candidaemia. Methods This was a retrospective study of hospitalized patients with early-onset candidaemia (EOC; ≤10 days) or late-onset candidaemia (LOC; >10 days) to identify any distinct clinical characteristics and risk factors for 30 day mortality in two Italian academic centres. Results A total of 779 patients were included in the study: 183 EOC and 596 LOC. Mortality was significantly lower in EOC (71/183, 38.8% versus 283/596, 47.5%, P = 0.03). In EOC, multivariate analysis showed that inadequate initial antifungal therapy (IIAT) (P = 0.005, OR 3.02, 95% CI 1.40–6.51), Candida albicans aetiology (P = 0.02, OR 2.17, 95% CI 1.11–4.26) and older age (P < 0.001, OR 1.05, 95% CI 1.02–1.07) were independent risk factors for mortality. In LOC, liver disease (P = 0.003, OR 2.46, 95% CI 1.36–4.43), IIAT (P = 0.002, OR 2.01, 95% CI 1.28–3.15) and older age (P < 0.001, OR 1.03, 95% CI 1.02–1.04) were independently associated with a fatal outcome, while treatment with caspofungin was associated with survival (P < 0.001, OR 0.42, 95% CI 0.26–0.67). Conclusions EOC has different clinical characteristics and risk factors for mortality compared with LOC. Although EOC mortality is significantly lower, the rate of inappropriate antifungal treatment is higher. Treatment with caspofungin is significantly associated with survival in patients with LOC. Efforts are needed to improve the diagnosis and treatment of EOC.

Infections caused by carbapenem-resistant Klebsiella pneumoniae with hypermucoviscous phenotype: A case report and literature review

Fabio Arena, Lucia Henrici De Angelis, Marco Maria D’Andrea, Antonio Cannatelli, Lucina Fossati, Vincenzo Di Pilato, Tommaso Giani, Rossana Cavallo, and Gian Maria Rossolini Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Public Health and Pediatric Sciences, AOU, City of Health and Sciences, University of Turin, Turin, Italy; Department of Surgery and Translational Medicine, University of Florence, Florence, Italy; Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy; Don Carlo Gnocchi Foundation, Florence, Italy

Candidemia after cardiac surgery in the intensive care unit: an observational study

Candidemia is a well-recognized complication of hospital stay, especially in critically ill patients. There is not a general consensus that predictors for candidemia in cardiosurgical intensive care unit (cICU) are different from a general ICU and it has been reported that cardiopulmonary bypass time is a specific risk factor in the cICU. We performed a prospective study to evaluate the main predictors for candidemia in patients admitted to the cICU. Included patients were adults admitted between July 2005 and December 2007 with an ICU-length of stay (ICU-LOS) ≥48 hours after cardiac surgery. Exclusion criteria were solid organ or bone marrow transplants, previous diagnosis of candidemia or other invasive infections and ICU stay before surgery. A multiple regression analysis was performed to identify the risk factors. Among 1955 patients admitted to the cICU, 345 were enrolled. Only 26 patients (1.3%) had candidemia after an ICU-LOS of 20 days (inter-quartile range, IQR 8-49 days). Total parenteral nutrition [odds ratio (OR)=9.56; confidence interval (CI)=1.741-52.534], severe sepsis (OR=4.20; CI=1.292-13.667), simplified acute physiology score II (OR=1.16; CI=1.052-1.278) and ICU-LOS >20 days (OR=6.38; CI=1.971-20.660) were independent predictors of candidemia. Patients undergoing cardiac surgery developed candidemia late after cICU admission and the independent predictors were similar to the general ICU.

Healthcare-Associated Klebsiella pneumoniae carbapenemase Producing K. pneumoniae Bloodstream Infection: The Time Has Come

TO THE EDITOR—Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae (KPC-Kp) has reached a worldwide diffusion, and the associated mortality rate of infected patients is ranging from 45% to 56% [1]. Several risk factors for mortality were identified in patients with KPC-Kp bloodstream infection (KPC-Kp BSI), such as the severity of the underlying disease or the delay in administration of appropriate therapy [2, 3]. Usually KPC-Kp infections arise in patients with prolonged hospital stay and have been previously treated with antibiotics [3]. We report on patients with KPC-Kp BSI diagnosed within 5 days after hospital admission [4]. The mortality was evaluated at 21 days after the first positive blood cultures, and appropriate treatment has been considered as the administration for ≥48 hours of an antibiotic with in vitro activity [5]. Eighteen patients with healthcareassociated KPC-Kp BSI were studied (Table 1). The majority of patients were men (11 [61%]), had a mean age of 63 years (standard deviation [SD], 14), had a previous admission in the 6 months before BSI onset (13 [72%]), or underwent surgery during the hospital stay (13 [72%]). Ten patients (56%) were in a medical ward at the time of diagnosis. The median time between hospital admission and KPC-Kp BSI was 3 days (SD, 1 day), and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 16 (range, 3–36). Five patients were colonized by KPC-Kp before KPC-Kp BSI. The comorbidities more frequently reported were malignancy (5 [36%]), chronic renal failure (4 [29%]), hepatopathy (3 [17%]), and cardiovascular disease (3 [17%]). After a median of 2 days (SD, 1 day), the empiric antibiotic treatment was changed and all patients were appropriately treated, mostly with combination therapy, according to the in vitro sensitivity. The overall mortality was 22% (4 patients). At univariate analysis the mortality was significantly associated with liver disease (P = .031), chronic renal failure (P = .047), and high APACHE II score (P = .01). The survival was associated with appropriate treatment administered for ≥48 hours. Usually, KPC-Kp BSI infections are diagnosed a median of 28–37 days after hospital admission [6–8]. In this study we report for the first time 18 patients with KPC-Kp BSI within 5 days after hospital admission, which had a very low crude mortality rate (22%) compared with 45% in the above-mentioned patients with nosocomial KPC-Kp BSI infections [6–8]. The pathogenesis of KPC-Kp BSI infection seems to be consistent with a multistep process where comorbidities, host factors, and prolonged antibiotic pressure contribute to the invasion of Table 1. Main Clinical Characteristics of Patients With Healthcare-Associated Klebsiella pneumoniae Carbapenemase Bloodstream Infection

The Effect on Mortality of Fluconazole or Echinocandins Treatment in Candidemia in Internal Medicine Wards

The incidence of candidemia has increased over the past two decades, with an increased number of cases in Internal Medicine and a prevalence ranging from 24% to 57%. This single-center retrospective study was performed to evaluate the epidemiology and the risk factors associated with mortality of candidemia in patients admitted to Internal Medicine wards (IMWs) of the City of Health and Sciences, Molinette Hospital, Turin, from January 2004 to December 2012. For each patient, demographic, clinical and microbiological data were collected. A case of candidemia was defined as a patient with at least one blood culture positive for Candida spp. Amongst 670 episodes of candidemia, 274 (41%) episodes occurred in IMWs. The mortality was 39% and was associated at multivariate analysis with sepsis, cirrhosis and neurologic diseases, whilst removal of central venous catheter ≤48h was significantly associated with survival. In the 77 patients treated with early antifungal therapy the mortality was 29% and was not significantly different with caspofungin or fluconazole, whilst in patients with definitive therapy the mortality was significantly lower with echinocandins compared to fluconazole (11.7% Vs. 39%; p=0.0289), a finding confirmed by multivariate analysis. The mortality was significantly associated with sepsis, cirrhosis and neurologic diseases, whilst CVC removal ≤48h was associated with survival. In patients with early therapy, fluconazole or caspofungin were equally effective. However, echinocandins were significantly more effective as definitive treatment, a finding not explained by differences in treatment delays. Further studies are needed to understand the full potential of these different therapeutic strategies in IMWs.

Risk factors for mortality in patients with Staphylococcus aureus bloodstream infection

In this two year retrospective analysis, we evaluated the epidemiology and risk factors for mortality of Staphylococcus aureus bloodstream infection (SaBSI). Methicillin-susceptible S. aureus (MSSA) was isolated in 84 (44.2%) and methicillin-resistant S. aureus (MRSA) in 106 episodes (55.8%). The mortality rate after 21 days was 16.4%. At univariate analysis older age, no removal of central venous catheter (CVC), prosthetic heart valves, severe sepsis, septic shock and high APACHE II score were significantly associated with mortality, whereas treatment duration > 48 hours, appropriate targeted therapy and prolonged treatment duration were significantly associated with survival. At multivariate analysis, prosthetic valves, septic shock and fever 48 hours after the diagnosis were significantly related to mortality. In this study, the mortality was associated with clinical rather than microbiological factors.

The effect on mortality of fluconazole or echinocandins treatment in internal medicine wards

The incidence of candidemia has increased over the past two decades, with an increased number of cases in Internal Medicine and a prevalence ranging from 24% to 57%. This single-center retrospective study was performed to evaluate the epidemiology and the risk factors associated with mortality of candidemia in patients admitted to Internal Medicine wards (IMWs) of the City of Health and Sciences, Molinette Hospital, Turin, from January 2004 to December 2012. For each patient, demographic, clinical and microbiological data were collected. A case of candidemia was defined as a patient with at least one blood culture positive for Candida spp. Amongst 670 episodes of candidemia, 274 (41%) episodes occurred in IMWs. The mortality was 39% and was associated at multivariate analysis with sepsis, cirrhosis and neurologic diseases, whilst removal of central venous catheter ≤48h was significantly associated with survival. In the 77 patients treated with early antifungal therapy the mortality was 29% and was not significantly different with caspofungin or fluconazole, whilst in patients with definitive therapy the mortality was significantly lower with echinocandins compared to fluconazole (11.7% Vs. 39%; p=0.0289), a finding confirmed by multivariate analysis. The mortality was significantly associated with sepsis, cirrhosis and neurologic diseases, whilst CVC removal ≤48h was associated with survival. In patients with early therapy, fluconazole or caspofungin were equally effective. However, echinocandins were significantly more effective as definitive treatment, a finding not explained by differences in treatment delays. Further studies are needed to understand the full potential of these different therapeutic strategies in IMWs.

Molecular epidemiology of methicillin-resistant S. aureus in the ICU setting

There were 62 MRSA strains from respiratory samples (57; 92 %) or blood (5; 8 %): overall 54 (87 %) HA-MRSA and 8 (13 %) CA-MRSA; respiratory samples accounted for 50 (93 %) and 7 (87.5 %) of HA-MRSA and CA-MRSA strains, respectively. The molecular characterization and spa typing analysis are reported in Table 1: most MRSA had SCCmec II (35 cases, 56.4 %), of which 31 were HA-MRSA. The most common clone was t242 (50 %) and it was associated with SCCmec type II (87 %) and HAMRSA (89 %). All isolates were susceptible to linezolid, whilst 13 and 6 isolates had a minimum inhibitory concentration (MIC) for vancomycin or daptomycin, respectively, above the EUCAST breakpoints for sensitivity. Ten of the t242 strains (32 %) had a vancomycin MIC greater than 2 mg/L, including one with a daptomycin MIC greater than 1 mg/L. The t242 strain represented 77 % (10 out of 13) of MRSA non-sensitive to vancomycin. These strains were further analyzed in order to confirm the high MIC value for vancomycin in a referral microbiology laboratory

Epidemiology and risk factors for mortality in bloodstream infection by CP-Kp, ESBL-E, Candida and CDI: A single center retrospective study

BACKGROUND The incidence of C. difficile infection (CDI) and of bloodstream infection (BSI) caused by Candida spp., ESBL-E-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing K. pneumoniae (CP-Kp) is associated with high mortality. METHODS We conducted a single centre retrospective study on patients admitted to Molinette Hospital, Turin, Italy, from January 2013 to April 2015 with CDI or BSI caused by Candida, ESBL-E or CP-Kp. For each patient demographic, clinical and microbiological data were collected. Aims of this study were to describe epidemiology and to evaluate risk factors for in-hospital mortality in this group of patients. RESULTS Seven hundred-eighty six cases were analyzed: 398 CDI, 137 candidemia, 125 ESBL-E BSI and 126 CP-Kp BSI. CDI, candidemia and ESBL-E BSI were more frequently reported in internal medicine wards (IMW), whilst CP-Kp were more described in intensive care unit (ICU). Sixty-six percent of patients had a previous hospitalization and the majority of patients had several medical comorbidities. In-hospital death occurred in 23.4%. Independent risk factors for mortality were antibiotic therapy before hospital admission, cardiovascular diseases, neutropenia, urinary catheter, total parenteral nutrition, SIRS and higher creatinine levels at diagnosis. Previous abdominal surgery, inflammatory bowel disease, higher serum albumin levels at the admission and fever at diagnosis were significantly associated with survival. CONCLUSION Our data showed that CDI, ESBL-E BSI and candidemia are more frequent in frail patients, admitted to IMW, with chronic comorbidities and broad exposure to antibiotic therapies, with the exception for CP-Kp BSI, still more common in the ICU.

Violation of prophylactic vancomycin administration timing is a potential risk factor for rate of surgical site infections in cardiac surgery patients: a prospective cohort study

BackgroundIntensivists and cardiothoracic surgeons are commonly worried about surgical site infections (SSIs) due to increasing length of stay (LOS), costs and mortality. The antimicrobial prophylaxis is one of the most important tools in the prevention of SSIs. The objective of this study was to investigate the relationship between the timing of antimicrobial prophylaxis administration and the rate of SSIs.MethodsA prospective cohort study was carried out over 1-year period in all consecutive adult patients undergoing elective cardiac surgery. The population was stratified in patients whose antimicrobial prophylaxis administration violated or not the vancomycin timing protocol (i.e., when the first skin incision was performed before the end of vancomycin infusion). To compare SSI rates, the cohort was further stratified in patients at low and high risk of developing SSIs.ResultsOver the study period, 1020 consecutive adult patients underwent cardiac surgery and according to study inclusion criteria, 741 patients were prospectively enrolled. A total of 60 SSIs were identified for an overall infection rate of 8.1%. Vancomycin prophylaxis timing protocol was violated in 305 (41%) out of 741 enrolled patients. SSIs were observed in 3% of patients without violation of the antimicrobial prophylaxis protocol (13/436) compared with 15.4% of patients with a violation of the timing protocol (47/305) (P < 0.0001). Patients at low risk with protocol violation had a higher occurrence of SSIs (P = 0.004) and mortality (P = 0.03) versus patients at low risk without protocol violation. Similarly, patients at high risk with protocol violation had a higher occurrence of SSIs (P < 0.001) and mortality (P < 0.001) versus patients at high risk without protocol violation. The logistic regression analysis showed that internal mammary artery use (P = 0.025), surgical time (P < 0.001), intensive care unit (ICU) LOS (P = 0.002), high risk of developing SSIs (P < 0.001) and protocol violation (P < 0.001) were risk factors for SSI occurrence as well as age (P = 0.003), logistic EuroSCORE (P < 0.001), ICU LOS (P < 0.001), mechanical ventilation time (P < 0.001) and protocol violation (P < 0.001) were risk factors for mortality.ConclusionsThis study showed that violation of the timing of prophylactic vancomycin administration significantly increased the probability of SSIs and mortality from infectious cause in cardiac surgery patients.