Pharmacokinetic parameters of CAZ-AVI in the normal lung and in models of pneumonia: lessons for treatment optimization in critical care.

The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to ß-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-ß-lactam ß-lactamase inhibitor avibactam, which exhibits broad-spectrum ß-lactamase inhibition in vitro, are combined to form ceftazidime-avibactam (CAZ-AVI). In this narrative review, we summarize data on pharmacokinetic (PK) parameters for CAZ-AVI in both animal and human models of pneumonia, as well as in healthy individuals. We assessed current literature performing an extensive search of the literature, using as search words 'CAZ-AVI', 'pharmacokinetics', 'pneumonia', 'lung', and 'epithelial lining fluid'. Overall, lung exposure studies of CAZ-AVI revealed that the epithelial lining fluid penetration ranges between 30% and 35% of plasma concentration. Despite the fair lung penetration of CAZ-AVI, this antimicrobial agent has a pivotal role in managing patients with multi-drug resistant Gram-negative pneumonia, however further studies are needed to better assess its PK profile.

Clinical correlates of circulating small dense low-density lipoproteins in acute infective endocarditis.

BACKGROUND AND AIM: Infective endocarditis (IE) is a complex thrombo-inflammatory disorder, the pathogenesis of which involves a multifaceted interplay between vascular damage and bacterial virulence factors. This study aimed to assess the prognostic role of small dense low-density lipoprotein (sdLDL) cholesterol in patients with IE and its correlation with various disease-related features. METHODS: A cohort of 198 patients with definite IE was included in this study. Clinical, laboratory, and echocardiographic parameters were meticulously analyzed, with a specific focus on comorbidities. sdLDL levels were measured using stored plasma samples obtained upon admission during the acute phase of the disease. RESULTS: The median level of sdLDL was 24 mg/dL [with an interquartile range of 17.9-35.2 mg/dL], and this value showed a statistically significant positive correlation with LDL/HDL cholesterol and triglycerides (p < 0.01 for all). Furthermore, a remarkable inverse correlation between C-reactive protein and D-dimer levels was observed (p < 0.0001). Univariate analysis revealed that patients with sdLDL levels ≤ 24 mg/dL had 2.75 times higher odds of in-hospital mortality (95% Confidence Interval:1.08-6.98, p = 0.031). In addition, nonsurvivors had significantly lower median sdLDL levels (19.7 vs. 26.0 mg/dL, p = 0.041). Lower sdLDL levels were also associated with embolic complications, larger vegetation size, and positive blood cultures for Staphylococci (p = 0.019, p = 0.022, and p < 0.001, respectively). CONCLUSIONS: Low circulating sdLDL levels in the acute phase of IE were significantly correlated with unfavorable clinical outcomes. These results suggest that the sdLDL level may serve as an important marker of disease severity in IE and may represent a link between vascular damage, embolic complications, and disease progression.

Features of infective endocarditis in a contemporary cohort of persons who inject drugs: a matched comparison analysis of long-term prognostic factors.

The objective of the study was to assess the short- and long-term mortality of infective endocarditis (IE) among people who inject drugs (PWID). Using prospectively collected data on hospitalized patients (years 2000 through 2021) with IE, PWID were identified and included in this study. Survival analysis was performed to analyze short- and long-term mortality and study their risk factors among PWID and a matched group of non-intravenous drug users (N-IDU). In a study of 485 patients admitted for IE, 55 (11%) of them were PWID. These PWID patients were 1:1 age- and sex- matched to an N-IDU group (N = 55 per group). Both groups had similar baseline comorbid conditions, including congestive heart failure, type 2 diabetes, and neoplastic diseases. However, PWID were more likely to have HCV co-infection (62% vs 16%, respectively, p < 0.001) and advanced liver disease/cirrhosis (52% vs 7.9%, respectively, p < 0.001). IE in PWID more often affected the tricuspid valve (42% vs 22%, respectively, p = 0.024) and presented with more embolic events (66% vs 35%, respectively, p < 0.01). S. aureus was the primary cause of IE in PWID (44% vs 21%, respectively, p = 0.01). After adjusting for other variables, PWID (HR = 2.99, 95% CI [1.06, 8.43], p = 0.038) and valve bioprosthetic replacement (HR = 5.37, 95% CI [1.3, 22.1], p = 0.02) were independently associated with increased mortality risk, whereas IE caused by tricuspid valve infection was associated with reduced mortality risk (HR = 0.25, 95% CI [0.06, 0.97], p = 0.046). In this cohort, PWID had increased risk of long-term mortality after hospital discharge for IE, when compared to matched N-IDU with similar baseline characteristics. The reasons behind the significant increase in mortality warrant further investigation.

Leadless Pacemaker Infection Risk in Patients with Cardiac Implantable Electronic Device Infections: A Case Series and Literature Review.

(1) Background: Leadless pacemakers (LPs) have been proposed as a reimplantation strategy in pacing-dependent patients undergoing cardiac implantable electronic device (CIED) extraction for infection. In this study, we analysed the risk of LP infection when this device is implanted before lead extraction. (2) Methods: This was a retrospective study including patients who underwent LP implantation between 2017 and 2022. Patients were divided in two groups according to whether LP was implanted following CIED extraction for infection (Group 1) or other indications (Group 2). The primary aim was to describe the risk of LP infection. (3) Results: We included in this study 49 patients with a median age of 81 [20-94] years, mostly males (36, 73%). In Group 1 patients, 17 cases (85%) showed systemic CIED infections, and 11 (55%) had positive lead cultures. Most Group 1 cases (n = 14, 70%) underwent one stage of LP implantation and CIED extraction. Mortality rate during follow-up was 20% (nine patients). Patients were followed up for a median of 927 [41-1925], days and no cases of definite or suspected LP infections were identified. (4) Conclusions: The risk of LP infection was extremely low. LP appears as a potential option for reimplantation in this setting and should be considered in pacing-dependent patients at a high risk of CIED infection recurrence.

Decoding Sepsis-Induced Disseminated Intravascular Coagulation: A Comprehensive Review of Existing and Emerging Therapies.

Disseminated intravascular coagulation (DIC) is a recurrent complication of sepsis. Since DIC not only promotes organ dysfunction but also represents a strong prognostic factor, it is important to diagnose DIC as early as possible. When coagulation is activated, fibrinolysis is inhibited, blood thinners are consumed, and a condition is created that promotes blood clotting, making it more difficult for the body to remove fibrin or prevent it from being deposited in the blood vessels. This leads to microvascular thrombosis, which plays a role in organ dysfunction. Despite efforts to understand the underlying mechanisms of sepsis-induced DIC, healthcare providers worldwide still face challenges in effectively treating this condition. In this review, we provide an in-depth analysis of the available strategies for sepsis-induced DIC, considering their effectiveness, limitations, and potential for future advances. Corticosteroids (CS), recombinant thrombomodulin (rTM), vitamin C, fibrinolytic therapy, and platelet transfusion are among the treatments discussed in the review. In addition, we are specifically addressing immunomodulatory therapy (IMT) by investigating treatments such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), and mesenchymal stem cell therapy (MSC). Finally, we also examined how these therapies might affect COVID-19 cases, which often present with sepsis-induced DIC. The review suggests that targeted experiments with randomization are needed to verify the effectiveness of these treatments and to discover novel approaches to treat sepsis-induced DIC. By increasing our knowledge of sepsis-induced DIC, we can develop targeted treatments that have the potential to save lives and improve outcomes.

Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview.

Sepsis is a major global health problem that results from a dysregulated and uncontrolled host response to infection, causing organ failure. Despite effective anti-infective therapy and supportive treatments, the mortality rate of sepsis remains high. Approximately 30-80% of patients with sepsis may develop disseminated intravascular coagulation (DIC), which can double the mortality rate. There is currently no definitive treatment approach for sepsis, with etiologic treatment being the cornerstone of therapy for sepsis-associated DIC. Early detection, diagnosis, and treatment are critical factors that impact the prognosis of sepsis-related DIC. Over the past several decades, researchers have made continuous efforts to better understand the mechanisms of DIC in sepsis, as well as improve its quantitative diagnosis and treatment. This article aims to provide a comprehensive overview of the current understanding of sepsis-related DIC, focusing on common causes and diagnoses, with the goal of guiding healthcare providers in the care of patients with sepsis.

Infective endocarditis involving MitraClip© devices: a systematic literature review.

PURPOSE: Progress of interventional cardiology has boosted the use of newer cardiac devices. These devices are perceived to be less prone to infections compared to traditional surgical prostheses, but little data are currently available. In this systematic review (SR), we summarize current literature regarding the clinical characteristics, management, and outcomes of patients with MitraClip-related infective endocarditis (IE). METHODS: We conducted a SR of PubMed, Google Scholar, Embase, and Scopus between January 2003 and March 2022. MitraClip-related IE was defined according to 2015 ESC criteria whereas MitraClip involvement as vegetation on the device or on the mitral valve. Risk of bias was assessed through standardized checklist and potential bias of underestimation cannot be excluded. Data regarding clinical presentation, echocardiography, management, and outcome were collected. RESULTS: Twenty-six cases of MitraClip-related IE were retrieved. The median age of patients was 76 [61-83] years with a median EuroScore of 41%. Fever was present in 65.8% of patients followed by signs and symptoms of heart failure (42.3%). IE occurred early in 20 (76.9%) cases with a median time between MitraClip implantation and IE symptom onset of 5 [2-16] months. Staphylococcus aureus was the major causative microorganism (46%). Surgical mitral valve replacement was needed in 50% of patients. A conservative medical approach was considered in the remainder. The overall in-hospital mortality rate was 50% (surgical group: 38.4%; medical group: 58.3%; p = 0.433). CONCLUSION: Our results suggest that MitraClip-related IE affects elderly, comorbid patients, is mostly due to Staphylococcus aureus, and has a poor prognosis irrespective of the therapeutic approach. Clinicians must be aware of the features of this new entity among cardiovascular infections.

Long-Term Outcome of Infective Endocarditis Involving Cardiac Implantable Electronic Devices: Impact of Comorbidities and Lead Extraction.

(1) Background: Management of cardiac implantable electronic device-related infective endocarditis (CIED-IE) hinges on complete hardware removal. We assessed whether long-term prognosis is affected by device removal, considering baseline patient comorbid conditions; (2) Methods: A total of 125 consecutive patients hospitalized for CIED-IE were included in this retrospective analysis. Outcomes were in-hospital, one-year, and long-term mortality. There were 109 patients who underwent device removal, 91 by transvenous lead extraction (TLE) and 18 by open heart surgery (OHS); (3) Results: TLE translated into lower hospital mortality (4.4% vs. 22.5% with OHS; p = 0.03). Septic pulmonary embolism was the only independent predictor of in-hospital mortality (OR:7.38 [1.49-36.6], p = 0.013). One-year mortality was in contrast independently associated to tricuspid valve involvement (p = 0.01) and Charlson comorbidity index (CCI, p = 0.039), but not the hardware removal modality. After a median follow-up of 41 months, mortality rose to 24%, and was significantly influenced only by CCI. Specifically, patients with a higher CCI who were also treated with TLE showed a survival rate not significantly different from those managed with medical therapy only; (4) Conclusions: In CIED-IE, TLE is the strategy of choice for hardware removal, improving early outcomes. Long-term benefits of TLE are lessened by comorbidities. In cases of CIED-IE with high CCI, a more conservative approach might be an option.

Clinical Characteristics and Outcome of MDR/XDR Bacterial Infections in a Neuromuscular Semi-Intensive/Sub-Intensive Care Unit.

(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population.

Dissecting the correlates of N-terminal prohormone brain natriuretic peptide in acute infective endocarditis.

PURPOSE: To explore the prognostic value and the correlates of NT-proBNP in patients with acute infective endocarditis, a life-threatening disease, with an often unpredictable outcome given by the lack of reliable prognostic parameters. METHODS: We retrospectively studied 337 patients admitted to our centre between January 1, 2006 and September 30, 2020 with available NT-proBNP level at admission. Our analyses were performed considering NT-proBNP as both a categorical variable, using the median value as the cut-off level, and numerical variable. Study end points were in-hospital mortality, cardiac surgery and 1 year survival. RESULTS: NT-proBNP was an independent predictor of in-hospital mortality (OR 14.9 [95%C.I. 2.46-90.9]; P = .003). Levels below 2926 pg/mL were highly predictive of a favorable in-hospital outcome (negative predictive value 96.6%). Patients with higher NT-proBNP levels showed a significantly lower survival rate at 1 year follow-up (log-rank P = .005). NT-proBNP was strongly associated with chronic kidney disease (P < .001) and significantly higher in patients with prior chronic heart failure (P = .001). NT-proBNP was tightly related to staphylococcal IE (P = .001) as well as with higher CRP and hs-troponin I (P = 0.023, P < .001, respectively). CONCLUSION: Our results confirm the remarkable prognostic role of NT-proBNP in patients with IE and provide novel evidences of its multifaceted correlates in this unique clinical setting. Our data strongly support the incorporation of NT-proBNP into the current diagnostic work-up of IE.

Prognostic Value of Decreased High-Density Lipoprotein Cholesterol Levels in Infective Endocarditis.

(1) Background: Simple parameters to be used as early predictors of prognosis in infective endocarditis (IE) are lacking. The aim of this study was to evaluate the prognostic role of high-density-lipoprotein cholesterol (HDL-C) and also of total-cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and triglycerides, in relation to clinical features and mortality, in IE. (2) Methods: Retrospective analysis of observational data from 127 consecutive patients with a definite diagnosis of IE between 2016 and 2019. Clinical, laboratory and echocardiography data, mortality, and co-morbidities were analyzed in relation to HDL-C and lipid profile. (3) Results: Lower HDL-C levels (p = 0.035) were independently associated with in-hospital mortality. HDL-C levels were also significantly lower in IE patients with embolic events (p = 0.036). Based on ROC curve analysis, a cut-off value was identified for HDL-C equal to 24.5 mg/dL for in-hospital mortality. HDL-C values below this cut-off were associated with higher triglyceride counts (p = 0.008), higher prevalence of S. aureus etiology (p = 0.046) and a higher in-hospital mortality rate (p = 0.004). Kaplan-Meier survival analysis showed higher 90-day mortality in patients with HDL-C ≤ 24.5 mg/dL (p = 0.001). (4) Conclusions: Low HDL-C levels could be used as an easy and low-cost marker of severity in IE, particularly to predict complications, in-hospital and 90-day mortality.

Dalbavancin treatment for spondylodiscitis: multi-center clinical experience and literature review.

Dalbavancin is a novel lipoglycopeptide antibiotic, characterized by a broad spectrum of activity against Gram-positive cocci. However, its efficacy in spondylodiscitis treatment is not fully established. All adult patients diagnosed with spondylodiscitis and treated with dalbavancin were included across four Italian medical centers from January 2018 to April 2021. We collected clinical and laboratory data, and presented follow-up findings along with a thorough literature review. 13 patients (mean age= 65 years) were included in this study. Dalbavancin was administered as first line treatment in six (46%) of the patients. Reasons for using Dalbavancin included treatment simplification (62%) and clinical failure of previous antibiotics (23%). In general, Dalbavancin was well tolerated with minimal adverse events, and clinical success was achieved in 11/13 (85%) of the patients during hospitalization with additional antibiotics required in the remaining two cases. Five months after discharge, no mortality was observed, however, 42% of patients required additional antibiotics for signs of infection on follow-up imaging. Our study suggests that Dalbavancin could be an effective and safe option in treating spondylodiscitis, however, the scarcity of studies on the topic is concerning. Thus, further studies with large samples and long-term follow-up are warranted to compare the efficacy of Dalbavancin with other available treatment options.

Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis.

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed. Coagulation parameters were measured on admission. (3) Results: D-dimers levels (p = 0.012) and a prolonged PT-INR (p = 0.013) were associated with higher in-hospital mortality, while prolonged aPTT (p = 0.021) was associated with increased 1-year mortality. Staphylococcus aureus (S. aureus) infection (p = 0.003), prosthetic valve endocarditis (PVE) (p = 0.001), surgical indication (p = 0.002) and higher D-dimer levels (p = 0.005) were independent predictors of in-hospital mortality. PVE (p = 0.001), a higher Charlson Comorbidity Index (p = 0.049), surgical indication (p = 0.001) and prolonged aPTT (p = 0.012) were independent predictors of 1-year mortality. Higher levels of D-dimers (p < 0.001) and a shorter aPTT (p < 0.001) were associated with embolic complications of IE. S. aureus etiology was bound to higher D-dimers levels (p < 0.001) and a shorter aPTT (p = 0.006). (4) Conclusions: Elevated D-dimers are associated with a higher risk for in-hospital mortality in IE patients. High D-dimers and a short aPTT are associated with a higher risk for embolic events in IE. A longer aPTT is associated with 1-year mortality.

Predictors of long-term mortality in left-sided infective endocarditis: an historical cohort study in 414 patients.

INTRODUCTION: Very limited data are available on the long-term outcome of infective endocarditis (IE) and its determinants. The aim of this study was to identify the predictors of long-term mortality in patients affected by left sided IE (LSIE). METHODS: This was an historical retrospective observational study on prospectively collected data from patients with LSIE hospitalized in our Unit (January 2000-December 2017). Multiple variables relevant to history, physical examination, laboratory tests, echocardiography, comorbidities, complications and outcome were analysed by Cox regression to identify predictors of long-term mortality. RESULTS: 414 patients were included, and followed up for a median of 39 months [IQR 11-74]. Median age was 59 years [range 3-89], and most patients were male. Over 50% showed at least one comorbidity. Hyperglycaemia, increased creatinine and an indication for surgery predicted in-hospital mortality, while a prior myocardial infarction, chronic kidney disease (CKD) on hemodialysis and a larger vegetation were independent predictors of 1-year mortality. At multivariate analysis, peripheral arterial disease (p= 0.017), hyperglycemia on admission (p=0.013) and a higher BMI (p=0.009) were independent predictors of long-term mortality in 1-year survivors. At multivariable Cox proportional hazard regression, peripheral arterial disease (p=0.002), hyperglycemia (p=0.041) and CKD on hemodialysis (p=0.025) confirmed to be independently associated with an increased risk of long-term mortality in the overall 414 patient cohort. CONCLUSIONS: Cardiovascular and metabolic risk signals, specifically peripheral arterial disease and hyperglicemia, affect long-term mortality of LSIE. An active and long-term follow up seems warranted in IE survivors showing these conditions at outset.

Cardiac sequelae after coronavirus disease 2019 recovery: a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease. OBJECTIVES: To assess the range of cardiac sequelae after COVID-19 recovery. DATA SOURCES: PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021). STUDY ELIGIBILITY CRITERIA: Prospective and retrospective studies, case reports and case series. PARTICIPANTS: Adult patients assessed for cardiac manifestations after COVID-19 recovery. EXPOSURE: Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR. METHODS: Systematic review. RESULTS: Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1-180 days). Common short-term cardiac abnormalities (<3 months) included increased T1 (proportion: 30%), T2 (16%), pericardial effusion (15%) and late gadolinium enhancement (11%) on CMR, with symptoms such as chest pain (25%) and dyspnoea (36%). In the medium term (3-6 months), common changes included reduced left ventricular global longitudinal strain (30%) and late gadolinium enhancement (10%) on CMR, diastolic dysfunction (40%) on echocardiography and elevated N-terminal proB-type natriuretic peptide (18%). In addition, COVID-19 survivors had higher risk (risk ratio 3; 95% CI 2.7-3.2) of developing heart failure, arrythmias and myocardial infarction. CONCLUSIONS: COVID-19 appears to be associated with persistent/de novo cardiac injury after recovery, particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later. Larger well-designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact.

Cardiac complications during the active phase of COVID-19: review of the current evidence.

Growing reports since the beginning of the pandemic and till date describe increased rates of cardiac complications (CC) in the active phase of coronavirus disease 2019 (COVID-19). CC commonly observed include myocarditis/myocardial injury, arrhythmias and heart failure, with an incidence reaching about a quarter of hospitalized patients in some reports. The increased incidence of CC raise questions about the possible heightened susceptibility of patients with cardiac disease to develop severe COVID-19, and whether the virus itself is involved in the pathogenesis of CC. The wide array of CC seems to stem from multiple mechanisms, including the ability of the virus to directly enter cardiomyocytes, and to indirectly damage the heart through systemic hyperinflammatory and hypercoagulable states, endothelial injury of the coronary arteries and hypoxemia. The induced CC seem to dramatically impact the prognosis of COVID-19, with some studies suggesting over 50% mortality rates with myocardial damage, up from ~ 5% overall mortality of COVID-19 alone. Thus, it is particularly important to investigate the relation between COVID-19 and heart disease, given the major effect on morbidity and mortality, aiming at early detection and improving patient care and outcomes. In this article, we review the growing body of published data on the topic to provide the reader with a comprehensive and robust description of the available evidence and its implication for clinical practice.

Diagnostic and infection control strategies for Clostridioides difficile infections in a setting of high antimicrobial resistance prevalence.

Clostridioides difficile (CD) is a major nosocomial pathogen and the leading cause of antibiotic-associated diarrhoea. In light of the strong association between antimicrobial use and CD infections (CDI), it may be hypothesised that areas at higher prevalence of antimicrobial resistance, like the region of Campania in southern Italy, could also have a higher rate of CDI. In this multicentre, region-based, prospective study, we analysed such issues, exploiting CDI incidence data collected from local hospitals. In 2016, the Italian National Centre for Disease Control supported a project involving three Italian regions: Friuli Venezia Giulia, Lazio and Campania. In Campania, a network of 49 hospitals willing to participate in the project was created. The project consisted of two phases: a survey on practice patterns concerning CDI and an epidemiological surveillance study. We identified a stringent need to improve awareness about CDI among the regional health-care community, as a widespread lack of surveillance programmes for CDI control was observed (existing in only 40% of participating facilities). Moreover, almost half of the participating hospitals (n=16, 43%) had no standardised procedures or protocols to control and prevent CDI. In the second phase of the study, we collected data of CDI cases during a six-month surveillance programme. In all, 87 CDI cases were observed, for a total of 903,334 patient bed-days and 122,988 admissions. According to the above data, CDI incidence was 0.96 cases/10000 patient bed-days, much lower than expected based on prior studies conducted elsewhere. The results of our study suggest CDI remains a rather neglected clinical issue in Campania. Despite a high burden of antimicrobial resistance and antimicrobial use in our geographic setting, we observed a very low incidence of CDI. Such a low incidence could be explained by underdiagnosis, but could also be related to actual diet, the lower patient age or the specific genetic background. However, further studies are warranted to either confirm or rebut the above hypotheses.

Prognostic value of pro-adrenomedullin and copeptin in acute infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP). METHODS: We studied 196 patients with definite IE. Clinical, laboratory and echocardiography parameters were analyzed, with a focus on co-morbidities. PCT, pro-ADM and copeptin were measured on stored plasma samples obtained on admission during the acute phase of the disease. RESULTS: Pro-ADM and copeptin were significantly higher in older patients and associated with prior chronic kidney disease. Pro-ADM was an independent predictor of hospital mortality (OR 3.29 [95%C.I. 1.04-11.5]; p = 0.042) whilst copeptin independently predicted 1-year mortality (OR 2.55 [95%C.I. 1.18-5.54]; p = 0.017). A high PCT value was strictly tied with S. aureus etiology (p = 0.001). CRP was the only biomarker associated with embolic events (p = 0.003). CONCLUSIONS: Different biomarkers correlate with distinct IE outcomes. Pro-ADM and copeptin may signal a worse prognosis of IE on admission to the hospital and could be used to identify patients who need more aggressive treatment. CRP remains a low-cost marker of embolic risk. A high PCT value should suggest S. aureus etiology.