ceftobiprole for the treatment of infective endocarditis a case series

Abstract Objectives Ceftobiprole is a relatively new cephalosporin with broad-spectrum activity and good tolerability. Despite its promising characteristics, to our knowledge, only two case reports, previously published also by some of us, is available concerning its administration for the treatment of infective endocarditis. Hereby we report our experience in this field. Methods All the patients with infective endocarditis treated with ceftobiprole were enrolled. Results 12 cases of endocarditis were treated with ceftobiprole, 11/12 in combination with daptomycin and 1/12 as monotherapy. Gram-positive bacteria were isolated in 12/12 patients; 3 cases were polymicrobial. Cure rate was 83% (10/12 patients). In 9/12 (75%) cases, patients were switched to ceftobiprole following failure of previous antimicrobial regimen. In 3/3 patients in which ceftobiprole was administered because of persistently positive blood culture, bacteraemia clearance was rapidly achieved. Conclusions Ceftobiprole, especially in combination, could be a promising alternative treatment for infective endocarditis

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Nelfinavir: An Old Ally in the COVID-19 Fight?

After almost three years of the pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still spreading around the world, causing notable sanitary and social issues. New antiviral therapies are constantly under investigation. However, few options have been approved for the treatment of COVID-19. Clinical trials are currently ongoing to evaluate the efficacy of nelfinavir on mild–moderate COVID-19. This study aims to investigate the activity of this compound on SARS-CoV-2 “Variants of Concern” (VOCs), comparing its effectiveness with the approved drugs remdesivir and molnupiravir. The experiments were conducted in a biosafety level 3 facility. In this study, we used a Vero-E6-cell-based infection assay to investigate the in vitro activity of nelfinavir, molnupiravir, and remdesivir. Four strains of SARS-CoV-2 were tested: 20A.EU1, B.1.1.7, P.1, and B.1.617.2. All compounds reached micromolar/submicromolar EC50, EC90, and EC99. Furthermore, the Cmax/EC50 and Cmax/EC90 ratios were >1 for all compounds and all variants tested. Our study demonstrated that nelfinavir, as molnupiravir, and remdesivir are effective in vitro on SARS-CoV-2 variants

KPC-producing Klebsiella pneumoniae gut decolonisation following ceftazidime/avibactam-based combination therapy: A retrospective observational study

KPC-producing Klebsiella pneumoniae (KPC-Kp) gut colonization is a major risk factor for developing systemic infections. Ceftazidime/avibactam could have a role as decolonization therapy in special situations PATIENTS AND METHODS: retrospective, observational, multicenter study. We compared KPC-Kp gut decolonization rate of ceftazidime/avibactam-based therapy (Group A) and other antimicrobial regimens (Group B) in patients with a KPC-Kp infection

Personalized machine learning approach to predict candidemia in medical wards

Purpose Candidemia is a highly lethal infection; several scores have been developed to assist the diagnosis process and recently different models have been proposed. Aim of this work was to assess predictive performance of a Random Forest (RF) algorithm for early detection of candidemia in the internal medical wards (IMWs). Methods A set of 42 potential predictors was acquired in a sample of 295 patients (male: 142, age: 72 +/- 15 years; candidemia: 157/295; bacteremia: 138/295). Using tenfold cross-validation, a RF algorithm was compared with a classic stepwise multivariable logistic regression model; discriminative performance was assessed by C-statistics, sensitivity and specificity, while calibration was evaluated by Hosmer-Lemeshow test. Results The best tuned RF algorithm demonstrated excellent discrimination (C-statistics = 0.874 +/- 0.003, sensitivity = 84.24% +/- 0.67%, specificity = 91% +/- 2.63%) and calibration (Hosmer-Lemeshow statistics = 12.779 +/- 1.369,p = 0.120), markedly greater than the ones guaranteed by the classic stepwise logistic regression (C-statistics = 0.829 +/- 0.011, sensitivity = 80.21% +/- 1.67%, specificity = 84.81% +/- 2.68%; Hosmer-Lemeshow statistics = 38.182 +/- 15.983,p < 0.001). In addition, RF suggests a major role of in-hospital antibiotic treatment with microbioma highly impacting antimicrobials (MHIA) that are found as a fundamental risk of candidemia, further enhanced by TPN. When in-hospital MHIA therapy is not performed, PICC is the dominant risk factor for candidemia, again enhanced by TPN. When PICC is not used and MHIA therapy is not performed, the risk of candidemia is minimum, slightly increased by in-hospital antibiotic therapy. Conclusion RF accurately estimates the risk of candidemia in patients admitted to IMWs. Machine learning technique might help to identify patients at high risk of candidemia, reduce the delay in empirical treatment and improve appropriateness in antifungal prescription

Beta Lactams Plus Daptomycin Combination Therapy for Infective Endocarditis: An Italian National Survey (BADAS)

Background: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. Methods: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. Results: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. Conclusions: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin