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Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B ( p  = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B ( p  = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.

Introduction: Therapy of coronavirus disease 2019 (COVID-19) involves evolving algorithms that include drugs aimed at reducing disease progression by counteracting two different, but intertwined processes: ( i ) the damage caused by the virus (with antivirals); ( ii ) the damage caused by a dysregulated host response (with immunomodulatory agents)., Areas Covered: Herein, we discuss the available evidence on the efficacy and safety of antiviral agents employed over the past months for the treatment of COVID-19, and the reasons to be considered for antiviral selection., Expert Opinion: The available evidence from randomized controlled trials (RCT) currently discourages the use of lopinavir/ritonavir, hydroxychloroquine, and interferons, which did not show improved efficacy compared to standard care or placebo. Regarding remdesivir, the current body of evidence may conditionally support its use in COVID-19 patients requiring oxygen supplementation but still not requiring invasive mechanical ventilation. Finally, neutralizing monoclonal antibodies have been proven efficacious in reducing the risk of severe disease development if administered early in the course of the disease to patients at risk of progression. The results of the ongoing RCT will certainly be crucial to further improve our understanding of the optimal place in therapy of antiviral agents for COVID-19.

Burn patients are at high risk of infections due to severe impairment of immunity and loss of skin barrier function. We aimed to describe the epidemiology, incidence and risk factors for infection in a cohort of burns patients. Two hundred patients were retrospectively enrolled and subdivided into infected (N = 81) and uninfected groups (N = 119). The cumulative prevalence of infections was 27% on day 7 and 43.8% on day 28. Skin and soft tissue infections (32%) were the most frequent. Carbapenem-resistant Acinetobacter baumannii (28%), Pseudomonas aeruginosa (26%) and methicillin-resistant Staphylococcus aureus (25%) infections were most prevalent. An indwelling central venous catheter (CVC; sub-hazard ratio [SHR] 7.41, 95% confidence interval [CI] 3.78-14.62) and revised Baux score (RBS; SHR 2.08, 95% CI 0.98-4.42) were associated with higher incremental infection rate while surgical treatment resulted in a protective factor (SHR 0.45, 95% CI 0.29-0.75). RBS may be useful to stratify the infection risk: a strict collaboration between surgeons and infectious disease specialists is needed to implement source control and antimicrobial surveillance.

Introduction : The management of acute wounds may be affected by malpractices leading to poor outcome, prolonged hospital stay and inappropriate use of antibiotic therapy. Areas covered : Acute wound infections are represented by surgical site and post-traumatic infections. The aim of this expert opinion is to identify a list of inadvisable actions and to provide a guide for an optimal management of acute wound infections. A literature search using Pubmed/MEDLINE database was performed. Articles pertaining to areas covered published until December 2019 were selected. We identified the most common malpractices in this setting and, using the Choosing Wisely methodology, we proposed a list of "Don'ts" for an easy use in clinical practice. Expert opinion : Malpractices may occur from the surgical prophylaxis to the discharge of patient. A prolonged surgical prophylaxis, the underestimation of signs and symptoms, the omission of source control, the inappropriate collection of wound swab, the improper use of clinical microbiology and pharmacology, the lack of hygiene measures and the delay of discharge are all factors that may lead to unfavorable outcome. A multidisciplinary approach is needed to optimally manage these patients. The "Don'ts" refer to all professional figures involved in the management of patients with acute wound infections.

Nosocomial infections caused by Clostridium difficile , CP-Kp, ESBL-E or Candida spp. are usually associated with a high mortality rate. In this retrospective study, we evaluated the association between the patient characteristics and the risk of development of nosocomial BSI due to Candida or CP-Kp or ESBL-E. Moreover, we described the cumulative incidence of recurrent infections according to each group of nosocomial BSI. Enteral or parenteral nutrition and indwelling CVC at time of diagnosis were associated with an increased risk of candidemia or CP-Kp over ESBL-E and CDI. ESBL-E BSI was higher in patients undergoing hemodialysis, hematological stem cell transplant and neutropenic patients. The cumulative incidence for recurrent infections was higher for CP-Kp BSI and lower for candidemia. Our data highlight a different role of single patient comorbidities in the development of infections and the higher incidence of recurrent infections in CP-Kp BSI.

Introduction: Pseudomonas aeruginosa (PA) is one of the most important causes of healthcare-related infections among Gram-negative bacteria. The best therapeutic approach is controversial, especially for multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains as well as in the setting of most severe patients, such as in the intensive care unit (ICU). Areas covered: This article addresses several points. First, the main microbiological aspects of PA, focusing on its wide array of resistance mechanisms. Second, risk factors and the worse outcome linked to MDR-PA infection. Third, the pharmacological peculiarity of ICU patients, that makes the choice of a proper antimicrobial therapy difficult. Eventually, the current therapeutic options against MDR-PA are reviewed, taking into account the main variables that drive antimicrobial optimization in critically ill patients. Literature search was carried out using Pubmed and Web of Science. Expert commentary: Methodologically rigorous studies are urgently needed to clarify crucial aspects of the treatment against MDR-PA, namely monotherapy versus combination therapy in empiric and targeted settings. In the meanwhile, useful options are represented by newly approved drugs, such as ceftolozane/tazobactam and ceftazidime/avibactam. In critically ill patients, at least as empirical approach, a combination therapy is a prudent choice when a MDR-PA strain is suspected.

Introduction: Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. Its etiology is most often due to infections even though FN of other origins, such as tumor-related fever and non-infectious inflammation, should rapidly be ruled out. Initially, C-reactive protein and, more recently, procalcitonin (PCT) have been proposed as useful biomarkers for differential diagnosis. PCT was shown to be a good biomarker of bacterial infections and their clinical outcomes. Definition of standard cut-offs and design of PCT-guided treatment protocols remain however to be defined. Areas covered: In this review, highlights on the current clinical use of PCT and its potential role as a diagnostic tool have been discussed by a panel of physicians from different areas of expertise. We provide current clinical evidence that PCT has been shown to be a reliable biomarker to differentiate fever of bacterial origin from other causes. Moreover, the Authors convened to a round-table to discuss their 'real-life experience' and offer their recommendations by a Delphi survey. Expert commentary: PCT has an important clinical role in FN. Issues such as the validation of a specific decision algorithm that includes PCT to monitor antibiotic choice and treatment duration will be addressed in prospective studies.

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.

Candidemia is associated with high mortality rate especially in critically ill (ICU) patients with septic shock and echinocandins such as anidulafungin are recommended as first-line treatment. Available pharmacokinetic studies of anidulafungin in healthy volunteers and in patients with renal or hepatic impairment showed that no dose adjustment is needed even in patients receiving standard intermittent haemodialysis. However, few data are available with continuous veno-venous haemofiltration (CVVH). In this study, the pharmacokinetic of anidulafungin was studied in two ICU patients with candidemia and septic shock undergoing CVVH. Both patients had satisfactory parameters of C(max) (9.04 and 5.68 mg/l, respectively), area under the curve (AUC) (95.18 and 67.48 mg/l h) and C(min) (2.61 and 1.43 mg/l). AUC/MIC ratio and C(max)/MIC values were: 11887 and 8435; 1130.25 and 710, for patients 1 and 2, respectively. Our data confirm that in patients with septic shock anidulafungin presents only mild pharmacokinetic changes compared to data reported during CVVH alone.