COVID-19 after 2 Years from Hospital Discharge: A Pulmonary Function and Chest Computed Tomography Follow-Up Study.

INTRODUCTION: Serial follow-up with pulmonary function testing (PFT) and chest computed tomography (CT) after severe COVID-19 are recommended. As a result, many longitudinal studies have been published on COVID-19 of different grade of severity up to 1-year follow-up. Therefore, we aimed at a long-term observational study throughout 2 years after severe COVID-19. METHODS: Severe COVID-19 patients were consecutively recruited after hospital discharge between March and June 2020 and prospectively followed up for 24 months, with mMRC dyspnea scale and PFT at 6, 12, and 24 months. Chest CT was performed when clinically indicated. RESULTS: One hundred one patients enrolled completed the observational study. At 24 months, those with reduced total lung capacity (TLC) were 16%, associated with fibrotic ground glass opacity (GGO) and mMRC score >1, respectively, in 75% and 69% of them. At 24 months, those with a reduced diffusing capacity of the lung for CO were 41%, associated with fibrotic GGO and mMRC score >1, respectively, in 53% and 22% of them. CONCLUSION: Two years after hospitalization for severe COVID-19, a non-negligible number of patients still suffer from "long COVID" due to respiratory damage.

Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study.

INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.

The Impact of Carbapenem Resistance on Mortality in Patients With Klebsiella Pneumoniae Bloodstream Infection: An Individual Patient Data Meta-Analysis of 1952 Patients.

INTRODUCTION: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. METHODS: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). RESULTS: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56-3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24-2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70-4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36-3.59; I2 = 58%). CONCLUSION: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.

Outcome of elderly patients undergoing intracranial meningioma resection: a single-center experience.

BACKGROUND: Higher life expectancy and higher mean age in general population created growing interest in medical and surgical management of meningiomas in elderly. It is well known that, due to possible complications, preoperative status and comorbidities, especially in aged people, should be carefully considered in the decision-making process. We described our experience with this kind of patients and analyzed the influence of complications on the outcome. METHODS: We conducted a monocentric retrospective study to evaluate outcome and complications in elderly patients that underwent intracranial meningioma surgery in our center in a ten-year period. Between January 2005 and December 2014, 107 patients - older than 70 years old - were operated for an intracranial meningioma. We excluded patients operated for a recurrent meningioma. We used the modified Dindo classification to describe complications and the Karnofsky Performance Status Scale and Glasgow Outcome Scale to evaluate the outcome at discharge and after a 6-month period. RESULTS: Eighty-four patients did not have postoperative complications, 10 patients had mild postoperative complications, while 13 patients suffered severe postoperative complications. As a group, patients with mild complications presented, six months after surgery, an average Karnofsky Performance Status better than preoperative one. CONCLUSIONS: Even though the fragility is considered an important risk factor, surgery for symptomatic intracranial meningiomas should be considered also in elderly patients. The presence of early postoperative mild complications does not seem to worsen the average 6-month-KSP score.

Volatile Anesthetics versus Propofol for Cardiac Surgery with Cardiopulmonary Bypass: Meta-analysis of Randomized Trials.

BACKGROUND: The aim of this systematic review and meta-analysis was to assess the effect of anesthesia maintenance with volatile agents compared with propofol on both short- and long-term mortality (primary outcomes) and major clinical events in adults undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Randomized clinical trials on the effects of current volatile anesthetics versus propofol in adults undergoing cardiac surgery with cardiopulmonary bypass were searched (1965 to September 30, 2019) in PubMed, the Cochrane Library, and article reference lists. A random effect model on standardized mean difference for continuous outcomes and odds ratio for dichotomous outcomes were used to meta-analyze data. RESULTS: In total, 37 full-text articles (42 studies, 8,197 participants) were included. The class of volatile anesthetics compared with propofol was associated with lower 1-yr mortality (5.5 vs. 6.8%; odds ratio, 0.76 [95% CI, 0.60 to 0.96]; P = 0.023), myocardial infarction (odds ratio, 0.60 [95% CI, 0.39 to 0.92]; P = 0.023), cardiac troponin release (standardized mean difference, -0.39 [95% CI, -0.59 to -0.18], P = 0.0002), need for inotropic medications (odds ratio, 0.40 [95% CI, 0.24 to 0.67]; P = 0.0004), extubation time (standardized mean difference, -0.35 [95% CI, -0.68 to -0.02]; P = 0.038), and with higher cardiac index/output (standardized mean difference, 0.70 [95% CI, 0.37 to 1.04]; P < 0.0001). The class of volatile anesthetics was not associated with changes in short-term mortality (1.63 vs. 1.65%; odds ratio, 1.04 [95% CI, 0.73 to 1.49]; P = 0.820) and acute kidney injury (odds ratio, 1.25 [95% CI, 0.77 to 2.03]; P = 0.358). CONCLUSIONS: In adults undergoing cardiac surgery with cardiopulmonary bypass, the class of volatile anesthetics was superior to propofol with regard to long-term mortality, as well as to many secondary outcomes indicating myocardial protection.

Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Active surveillance for safety monitoring of seasonal influenza vaccines in Italy, 2015/2016 season.

BACKGROUND: Surveillance for adverse events following immunization is an important component of any national immunization programme because it is critical to assessing the safety of vaccines and to detecting potentially rare and severe adverse events and responding in a timely manner. We conducted an enhanced active surveillance aimed at assessing the safety of flu vaccines in the 2015-2016 season in Italy. The study was targeted to the population groups for which the seasonal vaccine is recommended in Italy. METHODS: During the study period, a total of 3213 individuals receiving seasonal influenza vaccination were registered on the web-based platform. Any adverse events experienced after 7 days from vaccination by individuals aged six months or more were collected through a telephone interview or by a web-based self-administered questionnaire. All individuals experiencing at least one event during the 7 days of follow-up were contacted for follow-up to 60 days. RESULTS: Overall, 854 events were reported: 845 events (26%) after administration of the first dose and 9 (12%) after the second dose. The majority of adverse events reported after 7 days from the first dose were of little clinical importance, and most involved local symptoms. CONCLUSION: Our data, even though the number of vaccinated individuals was smaller than expected, is consistent with the safety of influenza vaccines in Italy during the 2015-2016 season regarding the most common adverse events. Further efforts are needed to obtain sufficient power to study rarer adverse events. Active monitoring and systematic studies to test generated signals and hypotheses are crucial to intensify awareness among the public and professionals with regard to the safety of vaccines.

Predictors of Mortality with Staphylococcus aureus Bacteremia in Elderly Adults.

OBJECTIVES: To analyze risk factors for early and late mortality in individuals aged 75 and older with Staphylococcus aureus bacteremia (SAB) in Italy. DESIGN: Four-year retrospective observational study (January 2011-December 2014). SETTING: Two tertiary care university hospitals in Italy (Santa Maria Misericordia Hospital in Udine, Policlinico Universitario Agostino Gemelli in Rome). PARTICIPANTS: All adults consecutively admitted with SAB. MEASUREMENTS: Clinical presentation, infection characteristics, and clinical outcomes of individuals aged 75 and older were compared with those of individuals younger than 75. RESULTS: Three hundred thirty-seven cases of SAB were diagnosed during the study period, 118 of which (35%) occurred in those aged 75 and older. Seven- (20.3% vs 9.2%) and 30-day (35.7% vs 20.7%) mortality were significantly higher in elderly than younger adults. Clinical presentation with septic shock, adequacy of empiric antibiotic treatment, and liver cirrhosis were found to be predictors of 7-day mortality in elderly adults with SAB. Risk factors independently associated with 30-day mortality included isolation of methicillin-resistant Staphylococcus aureus (MRSA) and not receiving an infectious disease consultation. CONCLUSION: Mortality is significantly higher in elderly than in younger adults with SAB, particularly in those presenting with septic shock, liver cirrhosis, or SAB due to MRSA. Additional risk factors for mortality included inappropriate empiric antibiotic treatment and not receiving an infectious disease consultation.

Usefulness of corset adoption after single-level lumbar discectomy: a randomized controlled trial.

OBJECTIVE In this paper, the authors sought to verify whether corset adoption could improve the short-term and midterm outcome scores of patients after single-level lumbar discectomy. METHODS A monocentric, randomized controlled trial of 54 consecutive patients who underwent single-level lumbar discectomy at the authors' institution was performed from September 2014 to August 2015. Patients were randomly assigned to use or not use a lumbar corset in the upright position. Patients with previous interventions for disc herniation or with concomitant canal or foraminal stenosis were excluded. The visual analog scale, Oswestry Disability Index, and Roland Morris Disability Questionnaire were used to compare groups at the 1- and 6-month follow-up time points. RESULTS No significant differences between the 2 groups were reported at either time point for any given outcome irrespective of the scale used. CONCLUSIONS Corset adoption does not improve the short-term and midterm outcomes of patients after single-level lumbar discectomy.

Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials.

Background: The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. Methods: Randomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned. Results: Thirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74-0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics. Conclusions: RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.

Epidemiology, management, and outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections in hospitals within the same endemic metropolitan area.

In the last decade, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become endemic in several countries, including Italy. In the present study, we assessed the differences in epidemiology, management, and mortality of CR-Kp bloodstream infection (BSI) in the three main adult acute-care hospitals of the metropolitan area of Genoa, Italy. From January 2013 to December 2014, all patients with CR-Kp BSI were identified through the computerized microbiology laboratory databases of the three hospitals. The primary endpoints of the study were incidence and characteristics of CR-Kp BSI in hospitals within the same endemic metropolitan area. Secondary endpoints were characteristics of CR-Kp BSI in hospitals with and without internal infectious diseases consultants (IDCs) and 15-day mortality. During the study period, the incidence of healthcare-associated CR-Kp BSI in the entire study population was 1.35 episodes per 10,000 patient-days, with substantial differences between the three hospitals. Patients admitted to the two hospital with internal IDCs were more likely to receive post-susceptibility test combined therapy including carbapenems (77% vs. 26%, p<0.001), adequate post-susceptibility test therapies (86% vs. 52%, p<0.001), and post-susceptibility therapies prescribed by an infectious diseases specialist (84% vs. 14%, p<0.001). Overall, the crude 15-days mortality was 26%. In the final multivariable model, only septic shock at BSI presentation was unfavorably and independently associated with 15-days mortality (odds ratio [OR] 6.7, 95% confidence intervals [CI] 2.6-17.6, p<0.001), while a protective effect was observed for post-susceptibility test combined therapies including a carbapenem (OR 0.11, 95% CI 0.03-0.43, p=0.002). Mortality of CR-Kp remains high. Differences in the incidence of CR-Kp BSI were detected between acute-care centers within the same endemic metropolitan area. Efforts should be made to improve the collaboration and coordination between centers, to prevent further diffusion of CR-Kp.

Trends of influenza B during the 2010-2016 seasons in 2 regions of north and south Italy: The impact of the vaccine mismatch on influenza immunisation strategy.

Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012-2013. Most of influenza B infections were found in children aged ≤ 14 y and significant differences were observed in the age-groups infected by the different lineages. B/Victoria strains prevailed in younger population than B/Yamagata, but also were more frequently found in the community setting. Conversely, B/Yamagata viruses were prevalent among hospitalized cases suggesting their potential role in the development of more severe disease. The relative proportions of viral lineages varied from year to year, resulting in different lineage-level mismatch for the B component of trivalent influenza vaccine. Our findings confirmed the need for continuous virological surveillance of seasonal epidemics and bring attention to the adoption of universal influenza immunization program in the childhood. The use of tetravalent vaccine formulations may be useful to improve the prevention and control of the influenza burden in general population.

Correction to: Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy.

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Daniele Roberto Giacobbe1, Valerio Del Bono1, Malgorzata Mikulska1, Giulia Gustinetti1, Anna Marchese2, Federica Mina3, Alessio Signori4, Andrea Orsi5, Fulvio Rudello6, Cristiano Alicino5, Beatrice Bonalumi3, Alessandra Morando7, Giancarlo Icardi5, Sabrina Beltramini3, Claudio Viscoli1; On behalf of the San Martino Antimicrobial Stewardship Group.

Global reaction to the recent outbreaks of Zika virus: Insights from a Big Data analysis.

OBJECTIVE: The recent spreading of Zika virus represents an emerging global health threat. As such, it is attracting public interest worldwide, generating a great amount of related Internet searches and social media interactions. The aim of this research was to understand Zika-related digital behavior throughout the epidemic spreading and to assess its consistence with real-world epidemiological data, using a behavioral informatics and analytics approach. METHODS: In this study, the global web-interest and reaction to the recently occurred outbreaks of the Zika Virus were analyzed in terms of tweets and Google Trends (GT), Google News, YouTube, and Wikipedia search queries. These data streams were mined from 1st January 2004 to 31st October 2016, with a focus on the period November 2015-October 2016. This analysis was complemented with the use of epidemiological data. Spearman's correlation was performed to correlate all Zika-related data. Moreover, a multivariate regression was performed using Zika-related search queries as a dependent variable, and epidemiological data, number of inhabitants in 2015 and Human Development Index as predictor variables. RESULTS: Overall 3,864,395 tweets, 284,903 accesses to Wikipedia pages dedicated to the Zika virus were analyzed during the study period. All web-data sources showed that the main spike of researches and interactions occurred in February 2016 with a second peak in August 2016. All novel data streams-related activities increased markedly during the epidemic period with respect to pre-epidemic period when no web activity was detected. Correlations between data from all these web platforms resulted very high and statistically significant. The countries in which web searches were particularly concentrated are mainly from Central and South Americas. The majority of queries concerned the symptoms of the Zika virus, its vector of transmission, and its possible effect to babies, including microcephaly. No statistically significant correlation was found between novel data streams and global real-world epidemiological data. At country level, a correlation between the digital interest towards the Zika virus and Zika incidence rate or microcephaly cases has been detected. CONCLUSIONS: An increasing public interest and reaction to the current Zika virus outbreak was documented by all web-data sources and a similar pattern of web reactions has been detected. The public opinion seems to be particularly worried by the alert of teratogenicity of the Zika virus. Stakeholders and health authorities could usefully exploited these internet tools for collecting the concerns of public opinion and reply to them, disseminating key information.

The impact of 10-valent and 13-valent pneumococcal conjugate vaccines on hospitalization for pneumonia in children: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed at summarizing available data on the impact of PCV10 and PCV13 in reducing the incidence of CAP hospitalizations in children aged <5years. METHODS: A systematic search of the literature was conducted. We included time-series analyses and before-after studies, reporting the incidence of hospitalization for pneumonia in the periods before and after the introduction of PCV10 or PCV13 into the immunization program. Pooled estimates of Incidence Rate Ratio (IRR) were calculated by using a random-effects meta-analytic model. Results were stratified according to age-groups (<24months and 24-59months) and case definitions of pneumonia (clinically and radiologically confirmed pneumonia). RESULTS: A total of 1533 potentially relevant articles were identified. Of these, 12 articles were included in the analysis. In children aged <24months, the meta-analysis showed a reduction of 17% (95%CI: 11-22%, p-value<0.001) an of 31% (95%CI: 26-35%, p-value<0.001) in the hospitalization rates respectively for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs. In children aged 24-59months, the meta-analysis showed a reduction of 9% (95%CI: 5-14%, p-value<0.001) and of 24% (95%CI: 12-33%, p-value<0.001) in the hospitalization rates for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs. High heterogeneity was detected among studies evaluating the hospitalization rate for clinically and radiologically confirmed pneumonia. CONCLUSIONS: The results of this study revealed a significant impact of PCV10 and PCV13 in reducing the hospitalizations for pneumonia, particularly in children aged <24months and for radiologically confirmed disease. Further appropriately designed studies, comparing the impact of PCV10 and PCV13, are needed in order to obtain solid data on which to establish future immunization strategies.

Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy.

BACKGROUND: The overuse of antimicrobials favors the dissemination of antimicrobial resistance, as well as invasive fungal diseases and Clostridium difficile infections (CDI). In this study, we assessed the impact of a mixed educational and semi-restrictive antimicrobial stewardship (AMS) project in a large teaching hospital in Italy. METHODS: The AMS project was conducted from May 2014 to April 2016. It consisted of two initiatives in two consecutive periods: (1) educational activities; (2) semi-restrictive control of antimicrobial prescribing through a computerized software. The primary endpoint was consumption of antibacterials and antifungals. Secondary endpoints were incidence of CDI, methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI, and Candida BSI. RESULTS: During the study period, a statistically significant reduction in consumption was observed for antibacterials (-1.45 defined daily doses (DDD)/1000 patient-days monthly, 95% confidence intervals [CI] -2.38 to -0.52, p 0.004), mainly driven by reductions in the use of fluoroquinolones, third/fourth generation cephalosporins, and carbapenems. No decrease in consumption of antifungals was observed (-0.04 DDD/1000 patient-days monthly, 95% CI -0.34 to +0.25, p 0.750). A statistically significant trend towards reduction was observed for incidence of CRKP BSI (incidence rate ratio 0.96, 95% CI 0.92-0.99, p 0.013). No statistically significant variations in trends were observed for CDI, MRSA BSI, and Candida BSI. CONCLUSIONS: The mixed AMS project was effective in reducing the use of major antibacterials and the incidence of CRKP BSI. Further research is needed to assess the extent of long-term benefits of semi-restrictive approaches.

Invasive Candida Infections in Liver Transplant Recipients: Clinical Features and Risk Factors for Mortality.

BACKGROUND: Invasive fungal infections remain a leading cause of morbidity and mortality among liver transplant recipients (LTRs). In this patient population, invasive Candida infections (ICIs) account for the large majority of cases. To date, only small studies and case-series analysing clinical presentation and risk factors for mortality in LTRs with ICIs are available. METHODS: We performed a retrospective multicenter multinational study in 10 centers in Europe and Brazil. All consecutive LTRs developing ICIs during the period January 2011 to December 2013 were included in the study. RESULTS: A total of 42 LTRs were included. Median age was 52.5 years, and 78.6% of patients were men. Viral hepatitis was the most common cause for liver transplantation (42.9%). Candidemia represented the majority of cases (24, 57.1%), followed by intra-abdominal candidiasis (18, 42.9%). Overall 30-day mortality was 23.8%, with higher mortality in patients with candidemia compared with intra-abdominal candidiasis (37.5% vs 5.6%, P = 0.02). Multivariate analysis showed candidemia to be a risk factor associated with mortality among LTRs presenting ICIs (odds ratio, 11.86; 95% confidence interval, 1.5-280; P = 0.01). Candida albicans represented the most common isolate (59.5%). High rates of antifungal resistances were found, with 16.7% and 4.8% of isolates displaying resistance to azoles and caspofungin, respectively. CONCLUSIONS: Our study confirms the occurrence of high mortality rates in LTRs developing ICIs. Mortality rates varied according to the type of infection, with candidemia representing a risk factor for mortality. The high rates of antifungal resistance should be considered in the choice of the empiric antifungal regimen.

Effectiveness of pneumococcal vaccines in preventing pneumonia in adults, a systematic review and meta-analyses of observational studies.

INTRODUCTION: S. pneumoniae can cause a wide spectrum of diseases, including invasive pneumococcal disease and pneumonia. Two types of pneumococcal vaccines are indicated for use in adults: 23-valent pneumococcal polysaccharide vaccines (PPV23) and a 13-valent pneumococcal conjugate vaccine (PCV13). OBJECTIVE: To systematically review the literature assessing pneumococcal vaccine effectiveness (VE) against community-acquired pneumonia (CAP) in adults among the general population, the immunocompromised and subjects with underlying risk factors in real-world settings. METHODS: We searched for peer-reviewed observational studies published between 1980 and 2015 in Pubmed, SciELO or LILACS, with pneumococcal VE estimates against CAP, pneumococcal CAP or nonbacteremic pneumococcal CAP. Meta-analyses and meta-regression for VE against CAP requiring hospitalization in the general population was performed. RESULTS: 1159 unique articles were retrieved of which 33 were included. No studies evaluating PCV13 effectiveness were found. Wide ranges in PPV23 effectiveness estimates for any-CAP were observed among adults ≥65 years (-143% to 60%). The meta-analyzed VE estimate for any-CAP requiring hospitalization in the general population was 10.2% (95%CI: -12.6; 33.0). The meta-regression indicates that VE against any-CAP requiring hospitalization is significantly lower in studies with a maximum time since vaccination ≥60 months vs. <60 months and in countries with the pediatric PCV vaccine available on the private market. However, these results should be interpreted cautiously due to the high influence of two studies. The VE estimates for pneumococcal CAP hospitalization ranged from 32% (95%CI: -18; 61) to 51% (95%CI: 16; 71) in the general population. CONCLUSIONS: Wide ranges in PPV23 effectiveness estimates for any-CAP were observed, likely due to a great diversity of study populations, circulation of S. pneumoniae serotypes, coverage of pediatric pneumococcal vaccination, case definition and time since vaccination. Despite some evidence for short-term protection, effectiveness of PPV23 against CAP was not consistent in the general population, the immunocompromised and subjects with underlying risk factors.

Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study.

PURPOSE: The aim of the study was to describe the characteristics of cirrhotic patients with candidemia and intra-abdominal candidiasis (IAC) and to evaluate the risk factors associated with 30-day mortality. METHODS: A multicenter multinational retrospective study including all consecutive episodes of candidemia and IAC in adult patients with liver cirrhosis in 14 European hospitals during the period 2011-2013 was performed. RESULTS: A total of 241 episodes (169 candidemia, 72 IAC) were included. Most Candida infections were acquired in hospital (208, 86.3%), mainly in the intensive care unit (ICU) (121, 50.2%). At clinical presentation, fever was seen in 60.6% of episodes (146/241) and septic shock in 34.9% (84/241). C. albicans was the most common species (found in 131 episodes, 54.4%), followed by C. glabrata (35, 14.5%) and C. parapsilosis (34, 14.1%). Overall, the 30-day mortality was 35.3%. Multivariable analysis identified candidemia (OR 2.2, 95% CI 1.2-4.5) and septic shock (OR 3.2, 95% CI 1.7-6) as independent factors associated with 30-day mortality. Adequate antifungal treatment (OR 0.4, 95% CI 0.3-0.9) was associated with survival benefit. CONCLUSIONS: A shift towards increasing prevalence of C. glabrata and C. parapsilosis species in patients with liver disease was documented. Candidemia and IAC were associated with significant mortality in cirrhotic patients. Thirty-day mortality was associated with candidemia and severe clinical presentation, whereas adequate antifungal treatment improved the prognosis.

Characteristics of Staphylococcus aureus Bacteraemia and Predictors of Early and Late Mortality.

We aimed to describe the characteristics of patients with Staphylococcus aureus bacteremia and to evaluate the risk factors associated with early (7-day) and late (30-day) mortality. We performed an observational study including all consecutive episodes of Staphylococcus aureus bacteremia diagnosed at two Italian university hospitals during 2010-2014. A total of 337 patients were included. Mean age was 69 years (range, 57-78) and 65% were males. Methicillin-resistant S. aureus (MRSA) was identified in 132/337 (39%)cases. Overall 7- and 30-day mortality were 13% and 26%, respectively. Early mortality was associated with increased Charlson scores (OR 1.3, 95% CI 1.1-1.5), MRSA bacteremia (OR 3.2, 95% CI 1.4-8.1), presentation with septic shock (OR 13.5, 95% CI 5.4-36.4), and occurrence of endocarditis (OR 4.5, 95%CI 1.4-14.6). Similar risk factors were identified for late mortality, including increased Charlson scores (OR 1.2, 95% CI 1.1-1.4), MRSA bacteremia (OR 2.1, 95% CI 1.2-3.9), presentation with septic shock (OR 4, 95%CI 1.7-9.7), occurrence of endocarditis (OR 3.8, 95% CI 1.4-10.2) as well as Child C cirrhosis (OR 3.9, 95% CI 1.1-14.4) and primary bacteremia (OR 2.5, 95%CI 1.3-5). Infectious disease consultation resulted in better outcomes both at 7 (OR 0.1, 95% CI 0.05-0.4) and at 30 days (OR 0.4, 95% CI 0.2-0.7). In conclusion, our study highlighted high rates of MRSA infection in nosocomial Staphylococcus aureus bacteremia. Multiple comorbidities, disease severity and methicillin-resistance are key factors for early and late mortality in this group. In patients with Staphylococcus aureus bacteremia, infectious disease consultation remains a valuable tool to improve clinical outcome.