Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection.

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders. Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Ceftaroline for severe community-acquired pneumonia: A real-world two-centre experience in Italy and Spain.

BACKGROUND: Ceftaroline is one of latest additions to the armamentarium for treating community-acquired pneumonia (CAP). This study aimed to describe the outcome of severe CAP (SCAP) in a cohort of hospitalised patients treated with ceftaroline. METHODS: A retrospective, observational study of patients with SCAP treated with ceftaroline in two hospitals in Spain and Italy. The primary objective was to explore 30-day mortality after diagnosis of SCAP. RESULTS: During the study period the following were observed: there were 89 cases of SCAP treated with ceftaroline and 53 cases used in combination with other antibiotics (60%). Overall, 30-day mortality and clinical failure were 20% (18 of 89) and 36% (32 of 89), respectively. Independent predictors of 30-day mortality were: increasing age (OR for 1 year increase 1.0, 95% CI 1.0-1.1, P 0.043), presence of solid neoplasm (OR 4.0, 95% CI 1.0-15.1, P 0.044) and concomitant therapy with oseltamivir (OR 8.5, 95% CI 1.2°57.3, P 0.029). The only independent predictor of clinical failure was the time elapsing from SCAP diagnosis to ceftaroline therapy (OR for each passing day 1.5, 95% CI 1.1-1.9, P 0.003). The clinical success rate was 64% (57 of 89). In the subgroups of patients with proven Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) infection, clinical success was 83% (10 of 12), 75% (three of four) and 56% (five of nine), respectively. CONCLUSIONS: Considering its spectrum of activity, ceftaroline could represent an important therapeutic option for SCAP. Further studies are needed to identify the precise clinical success rate against MRSA in a larger cohort of patients with SCAP.

Management of vertebral osteomyelitis over an eight-year period: The UDIPROVE (UDIne PROtocol on VErtebral osteomyelitis).

OBJECTIVES: Vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians because of its insidious and indolent course, which makes diagnosis difficult. METHODS: All patients with a suspected diagnosis of VO were analyzed over an 8-year period (January 2009 to January 2017). The UDIPROVE protocol (UDIne PROtocol on VErtebral osteomyelitis) was applied in all cases. The primary endpoint was the performance of the UDIPROVE protocol to obtain the causal bacteria of infection. RESULTS: During the study period, 133 episodes of confirmed VO were observed. The etiology of infection was obtained in 73.6% of cases: 70.5% were gram-positive, 16.3% were gram-negative, and 13.2% were mycobacteria. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed that for tubercular VO, the median standard uptake value (SUV) was higher when compared with VO caused by other bacteria. Clinical cure at the end of therapy was reported in 85.7% of patients. Previous antimicrobial therapy and a delay of more than 5 days in performing biopsy were associated with an undiagnosed etiology of VO. Targeted antibacterial therapy and follow-up with FDG-PET/CT were associated with clinical cure at the end of therapy, while the involvement of more than two vertebrae and inadequate drainage were associated with failure. CONCLUSIONS: Rigorous application of the UDIPROVE protocol allowed the causative pathogens of VO to be obtained - at about twice the rate reported in the literature. The use of FDG-PET/CT for the follow-up of infection was more reliable when compared to magnetic resonance imaging (MRI).

Should High-dose Daptomycin be an Alternative Treatment Regimen for Enterococcal Endocarditis?

INTRODUCTION: Previous series on the use of daptomycin in enterococcal infective endocarditis (EIE) have shown various outcomes, including higher mortality rates. We analyzed the effectiveness of high-dose daptomycin for the treatment of EIE. METHODS: We performed a prospective study from 2010 to 2018 in a referral center in patients with native (NVE) and prosthetic valve endocarditis (PVE) due to Enterococcus spp. The standard high-dose daptomycin at our institution is 10-12 mg/kg/day (CLCr > 30 ml/min). We compared the efficacy of a daptomycin-based regimen (DBR) versus daptomycin-sparing regimen (DSR) and daptomycin monotherapy versus combination therapy. Primary endpoints of the study were evaluation of risk factors associated with 30-day mortality and failure at end of therapy. RESULTS: We collected 43 EIE cases; 29 were NVE (67.4%). Overall, 16 (37.2%) were treated with DBR, mainly with combination regimens (11, 68.7%), in the majority of cases in association with ß-lactam (7, 43.7%). The mean administered dose of daptomycin was 10.125 mg/kg/day (range 8-12 mg/kg/day). Overall, patients treated with DBR compared with patients treated with DSR had no higher mortality rates and/or failure at end of therapy (6.2% vs. 22. 2%; P 0.41 and MICs 0.25-2 mg/l, 6.2% vs. 3.7%; P 1.0). In the sub-group of patients with NVE and PVE treated with DBR and DSR, no difference was found regarding the primary endpoints on the single or combined use of daptomycin. CONCLUSION: Our findings suggest that high-dose daptomycin might be used as an alternative treatment regimen in EIE.

Daptomycin-containing regimens for treatment of Gram-positive endocarditis.

PURPOSE: Infective endocarditis (IE) is a severe infection, and a leading cause of mortality and morbidity. Due to its favourable microbiological and pharmacological characteristics, daptomycin is routinely used in clinical practice for treating IE. METHODS: A prospective study was conducted at a large tertiary-care hospital in Italy over an 8-year period (January 2010-January 2018) on all patients with native-valve endocarditis (NVE) or prosthetic-valve endocarditis (PVE) caused by Gram-positive bacteria. Patients with NVE and PVE treated with regimens that included daptomycin at different dosages (daptomycin-containing regimens, DCR) were compared with those treated with non-DCR. Primary endpoints of the study were 30-day mortality and clinical treatment failure. RESULTS: During the study period, 327 patients with Gram-positive NVE (n = 224, 68.8%) or PVE (n = 103, 31.2%) were analysed. Eighty-four (37.5%) NVE patients were treated with daptomycin, alone (59.9%) or with other antimicrobials. Most PVE patients (n = 61, 58%) were treated with a DCR, which always consisted of daptomycin plus other drugs. Among PVE patients, treatment with a DCR was associated with lower 30-day mortality than treatment with a non-DCR (6.5% vs. 38%, P < 0.001). Among NVE patients treated with DCRs, risk factors for 30-day mortality were streptococcal infections, persistent bacteraemia, and standard-dose (4-6 mg/kg) rather than high-dose daptomycin therapy. Overall, surgical treatment of IE and DCR were associated with clinical success and 30-day survival. CONCLUSIONS: Compared with non-DCRs, using single-drug or multiple-drug DCRs is associated with lower 30-day mortality in PVE, but with higher 30-day mortality in NVE at approved doses and in a subgroup of streptococcal IE.