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The value of blood cultures for confirming the clinical diagnosis of sepsis is suboptimal. There is growing interest in the potential of real-time PCR technology by detection of minute amounts of pathogen DNA in patient blood samples with results available within 4–6 h. Adopting a two-step approach, we evaluated the compliance of two versions of the MicrobScan assay on a total of 748 patients with suspected bloodstream infections. The results obtained with a second version of the MicrobScan assay are characterized by increased specificity (from 95.1 to 98.2%) and sensitivity (from 76.7 to 85.1), increased throughput and the possibility of simultaneously testing different kinds of samples collected from the potential sites of infection and utilizing different syndromic panels.

During COVID-19 pandemic, implementing and maintaining an antimicrobial stewardship protocol obtained both low rates of MDR microorganisms and low antimicrobial use in an 800-bed hospital network in northern Italy. Infectious diseases specialist consulting was crucial to maintain this protocol active.

To reduce the overburden in the hospital, during the COVID-19 pandemic, some “COVID Committed Home Medical Teams” (CCHTs) were created in Italy. These units consist of a small pool of general practitioners who aim to evaluate all patients with COVID-19 who require a medical examination directly at home. After the first visit (which can end with patient hospitalisation or home management), CCHTs periodically monitor the patients’ clinical conditions and vital signs (usually a revaluation every 24–48 hours, except for a sudden worsening). However, this strategy - which reduces the pressure on hospitals - has never been evaluated for patient safety. Our study aims to determine whether a home-based monitoring and treatment strategy for non-severe COVID-19 patients was safe as direct hospital admission by the emergency department. We conducted a retrospective observational study about 1,182 patients admitted to the hospital for COVID-19 between September 2020 and April 2021, confronting in-hospital and 30-day mortality in both CCHT-referred (n=275) and directly admitted by emergency department (n=907). Patients assessed by the CCHT had lower in-hospital and 30-day mortality (18% vs 28%, p=0.001; and 20% vs 30%, p=0.002); but, in the propensity score matching comparison, there was no characteristic between the two groups turned out significantly different. CCHT did not correlate with in-hospital or 30-day mortality. CCHT is a safe strategy to reduce hospital overburden for COVID-19 during pandemic surges.

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed (n = 128) and validated (n = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital (n = 97). The score’s performance was compared to that of the National Early Warning Score 2 (NEWS2). The composite outcome of either death or oral intubation within 30 days from admission occurred in 101 and 28 patients in the two hospitals, respectively. The area under the receiver operating characteristic (AUROC) curve of the aPNea model was 0.86 (95% confidence interval (CI), 0.78–0.93) and 0.79 (95% CI, 0.73–0.89) for the development and validation cohorts, respectively. The aPNea score discriminated low-risk patients better than NEWS2 at a 10% outcome probability, corresponding to five cut-off points and one cut-off point, respectively. aPNea’s cut-off reduced the number of unnecessary hospitalizations without missing outcomes by 27% (95% CI, 9–41) in the validation cohort. NEWS2 was not significant. In the external cohort, aPNea’s cut-off had 93% sensitivity (95% CI, 83–102) and a 94% negative predictive value (95% CI, 87–102). In conclusion, the aPNea score appears to be appropriate for discharging low-risk SARS-CoV-2-infected patients from the ED.

The COVID pandemic has forcefully turned the spotlight on the importance of the diagnosis of respiratory virus infections. Viruses have always been a frequent and common cause of respiratory tract infections. Rapid molecular diagnostics applied to the diagnostics of respiratory virus infections has revolutionized microbiology laboratories only a few years ago. Few studies illustrate the epidemiology of respiratory viruses, and fewer still those that have compared the pre-pandemic to the pandemic period. During the first year of the pandemic (2020–2021) it was clear to everyone to witness a sudden disappearance of the circulation of all the other respiratory viruses, especially those typically isolated during the winter time, such as RSV and Influenza virus. In our study we wanted to verify this phenomenon and to study the epidemiology of our local reality, analyzing three consecutive flu seasons (2018–2019, 2019–2020, 2020–2021). The results lead us to note that the prevalence of positivity to respiratory virus infections went from 49.8% (2018–2019) and 39% (2019–2020) to 13.4% (2020–2021). This decrease is at least partly attributable to the security measures adopted (social distancing and mask), but it certainly opens up new scenarios when the restriction measures will be terminated. We believe such studies can provide real-world evidence of the effectiveness of public health interventions implemented during current and future pandemics.

SARS-CoV-2 infection is associated with an increased risk of thrombotic events, especially during severe forms of disease. Here we describe the clinical history of a patient with a mild form of Covid-19 infection presenting with multiple cerebral ischemic lesions that evolved in an atypical way.

Background Recently many serological assays for detection of antibodies to SARS-COV-2 virus were introduced on the market. Aim of this study was to assess the diagnostic performance of an automated CLIA for quantitative detection of anti-SARS-CoV-2 IgM and IgG antibodies. Methods A total of 354 sera, 89 from consecutive patients diagnosed with COVID-19 (43 mild, 32 severe and 13 critical) and 265 from asymptomatic and negative on rRT-PCR testing healthcare workers, were evaluated for IgM and IgG anti-SARS-CoV-2 antibodies with MAGLUMI immunoassay. Results The overall sensitivity and specificity were 86.5% (95%CI: 77.6–92.8) and 98.5% (95%CI:96.2–99.6), respectively. PPV, PPN, LR+, LR- and OR were 95.1 (95%CI: 87.8–98.6), 95.6 (95%CI: 92.4–97.7), 57.3 (95%CI: 21.6–152.1), 7.3 (95%CI: 4.31–12.4) and 418.6 (95%CI: 131.2–1335.2), respectively. The levels of SARS-CoV-2 IgM and IgG antibodies were 1.22 ​± ​1.2 AU/mL and 15.86 ​± ​24.83 AU/mL, 2.86 ​± ​2.4 AU/mL and 69.3 ​± ​55.5 AU/mL, 2.47 ​± ​1.33 AU/mL and 83.9 ​± ​83.9 AU/mL in mild, severe and critical COVID-19 groups, respectively. A significant difference in antibody levels between mild and severe/critical subjects has been shown. Conclusions The CLIA assay showed good diagnostic performance and a significant association between antibody levels and severity of the disease was found.

Background Early detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected patients who could develop a severe form of COVID‐19 must be considered of great importance to carry out adequate care and optimise the use of limited resources. Aims To use several machine learning classification models to analyse a series of non‐critically ill COVID‐19 patients admitted to a general medicine ward to verify if any clinical variables recorded could predict the clinical outcome. Methods We retrospectively analysed non‐critically ill patients with COVID‐19 admitted to the general ward of the hospital in Pordenone from 1 March 2020 to 30 April 2020. Patients' characteristics were compared based on clinical outcomes. Through several machine learning classification models, some predictors for clinical outcome were detected. Results In the considered period, we analysed 176 consecutive patients admitted: 119 (67.6%) were discharged, 35 (19.9%) dead and 22 (12.5%) were transferred to intensive care unit. The most accurate models were a random forest model (M2) and a conditional inference tree model (M5) (accuracy = 0.79; 95% confidence interval 0.64–0.90, for both). For M2, glomerular filtration rate and creatinine were the most accurate predictors for the outcome, followed by age and fraction‐inspired oxygen. For M5, serum sodium, body temperature and arterial pressure of oxygen and inspiratory fraction of oxygen ratio were the most reliable predictors. Conclusions In non‐critically ill COVID‐19 patients admitted to a medical ward, glomerular filtration rate, creatinine and serum sodium were promising predictors for the clinical outcome. Some factors not determined by COVID‐19, such as age or dementia, influence clinical outcomes.

Ceftobiprole is an advance generation cephalosporin which has broad-spectrum bacterial activity (both against Gram-positive and negative pathogens) and was approved for the treatment of community-acquired pneumonia (CAP) and non-ventilated hospital-acquired pneumonia (HAP) in most European countries. We aimed to evaluate the efficacy and safety of ceftobiprole in the treatment of pneumonia in a cohort of severely ill patients admitted to the emergency department (ED).1-year observational retrospective mono-centric study. Were defined two primary endpoints: first, to evaluate the clinical cure at the test-of-cure (TOC); the second, to evaluate the early improvement, defined as a reduction of symptoms and inflammatory parameters 72 hours after the start of treatment. The secondary endpoint is to evaluate the reduction of antibiotic "burden" using ceftobiprole despite standard of care in severe hospital-acquired pneumonia.During the study period, a total of 48 patients with severe pneumonia received ceftobiprole: twenty-two patients (45.8%) as empiric therapy, 9 (18.5%) as a de-escalation option from previous combination therapies, 13 patients (27.1%) as an escalation therapy from ceftriaxone or amoxicillin/clavulanate and four patients (8.3%) as a targeted therapy based on microbiological results. Ceftobiprole mean duration therapy was 10.2 days. Forty-six patients with severe pneumonia had an early clinical improvement 72 hours after the start of treatment (95.8%). In general, ceftobiprole was well tolerated; only one patient suspended the drug because of poor tolerability. The clinical cure at TOC was 85.4% and 30-days crude mortality was 10.4%.This study confirms that ceftobiprole is effective in severely ill patients with pneumonia at risk of poor outcomes.

Carbapenem-resistant Klebsiella pneumoniae strains, New Delhi metallo-β-lactamase-1 producers, are still rare in Italy, being endemic in Southeast Asiatic region. In October 2016, a multidrug-resistant K. pneumoniae was isolated from blood and urine of an Italian long-hospitalized patient with urosepsis without travel history abroad. To the best of our knowledge, this is the first report of bacteremia caused by an ST16 K. pneuomoniae New Delhi metallo-β-lactamase-1 and OXA-232 co-producing carbapenemase, in Italy.

The objective of this study was to determine risk factors and outcomes of infections by multidrug-resistant gram-negative (MDR GN) bacteria in 241 recipients of hematopoietic stem cell transplantation (HSCT). The cumulative incidence of infections was 10.5% (95% CI, 12.0% to 25.8%), with 57% of infections occurring during the period of severe neutropenia (neutrophil count

The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved. Optimal PK/PD exposure was considered a steady-state concentration to minimum inhibitory concentration ratio ( C ss /MIC) of 1–4. Univariate binary logistic regression analysis was performed to identify independent predictors of clinical outcome. Among the 30 eligible patients, 53.3% had infections caused by meropenem-resistant KPC-Kp (MIC ≥ 16 mg/L). Tigecycline and colistin were the two antimicrobials most frequently combined with meropenem. Mean doses of continuous-infusion meropenem ranged from 1.7 to 13.2 g/daily. The C ss /MIC ratio was ≥1 in 73.3% of cases and ≥4 in 50.0%. Clinical outcome was successful in 73.3% of cases after a median treatment length of 14.0 days. In univariate analysis, a significant correlation with successful clinical outcome was found for a C ss /MIC ratio ≥1 (OR = 10.556, 95% CI 1.612–69.122; P = 0.014), a C ss /MIC ratio ≥4 (OR = 12.250, 95% CI 1.268–118.361; P = 0.030) and a Charlson co-morbidity index of ≥4 (OR = 0.158, 95% CI 0.025–0.999; P = 0.05). High-dose continuous-infusion meropenem optimised by means of real-time TDM may represent a valuable tool in improving clinical outcome when dealing with the treatment of infections caused by KPC-Kp with a meropenem MIC ≤ 64 mg/L.

A 57-year-old man presented with triple valve infective endocarditis. There were vegetations on the tricuspid, mitral, and aortic valve. He had multiple complications such as pulmonary abscess, severe anaemia, and congestive heart failure. His general condition was extremely poor. Intensive medical therapy, such as blood transfusion, mechanical ventilation, and inotropic support, allowed him to tolerate surgery. Triple valve replacement was successfully performed without major complication. Vegetation cultures grew Streptococcus bovis and Enterecoccus faecalis. At 1 year follow-up, the patient is alive in NYHA functional class I.

a

we report a prospective study to define the epidemiological, clinical, microbiological, echocardiographic characteristics and the out-come of IE in different age groups in order to evaluate age-related differences.

Enterococcal endocarditis represents the third cause of infectious endocarditis (IE) following staphylococcal and streptococcal species and reaching up to 20% of all cases. Recently revised guidelines recommend the use of beta-lactams in association with gentamicin administered twice or three times daily for IE due to enterococcal strains that are documented to be susceptible to these compounds [2] and [3]. Enterococci are relatively impermeable to aminoglycosides. Cell wall-active agents (i.e., beta-lactams or glycopeptides) increase the permeability of the enterococcal membrane, and hence a bactericidal effect can be achieved by diffusion of the aminoglycoside at adequate concentrations without excessive toxicity. Thus, high concentration of aminoglycosides in the extracellular milieu during co-treatment with cell wall-active agents might allow increased drug level at the site of the ribosomal target within the bacterial cell for bactericidal activity. Accordingly, gentamicin once-daily administration should optimize Cmax/MIC ratio maximizing the efficacy and reducing the toxicity. Interestingly, favorable clinical outcome in the treatment of Enterococcus faecalis endocarditis using once-daily (OD) aminoglycoside regimen was previously and recently reported [4] and [5]. Our aim was therefore to report clinical and pharmacological data of patients with documented enterococcal IE treated with a single daily dose of gentamicin

Despite advances in the scientific knowledge related to organ transplantation, kidney transplant recipients remain patients who must take immunosuppressive therapy for the rest of their lives to prevent graft rejection. This situation, coupled with the possible need for medical care, whether invasive or noninvasive, and higher hospitalization rates than in the general population, puts the patient with a transplanted kidney at risk of developing infectious diseases. An important threat are bacterial infections of the urinary tract at different levels of severity (from asymptomatic bacteriuria to urinary septicemia), which in recent years have included infections by multidrug-resistant bacteria. Careful attention must be paid therefore to the overall management of kidney transplant recipients with infections and to the "ecological" use of antibiotic therapy, which aims at preventing antibiotic resistance according to the recent concept of antibiotic stewardship. Among the fungal infections candida infections require special consideration. As with bacterial infections, there may be different degrees of severity ranging from candiduria (where some see no indication for treatment) to pyelonephritis and candidemia, conditions that may lead to vascular complications and the possible rupture of blood vessels. The key to success in the fight against infections after kidney transplant lies in the multidisciplinary approach to their management, with the involvement of the nephrologist, transplant surgeon, infectiologist, clinical microbiologist and clinical pharmacologist.

BACKGROUND: The characteristics of patients with infective endocarditis (IE) vary significantly by region of the world. The aim of this study was to evaluate the contemporary epidemiology, characteristics, and outcome of IE in a large, nationwide cohort of Italian patients. METHODS: We conducted a prospective, observational study at 24 medical centers in Italy, including all the consecutive patients with a definite or possible diagnosis of IE (modified Duke criteria) admitted from January 2004 through December 2009. A number of clinical variables were collected through an electronic case report form and analyzed to comprehensively delineate the features of IE. We report the data on patients with definite IE. RESULTS: A total of 1,082 patients with definite IE were included. Of these, 753 (69.6%) patients had infection on a native valve, 277 (25.6%) on a prosthetic valve, and 52 (4.8%) on an implantable electronic device. Overall, community-acquired (69.2%) was more common than nosocomial (6.2%) or non-nosocomial (24.6%) health care-associated IE. Staphylococcus aureus was the most common pathogen (22.0%). In-hospital mortality was 15.1%. From the multivariate analysis, congestive heart failure (CHF), stroke, prosthetic valve infection, S. aureus, and health care-associated acquisition were independently associated with increased in-hospital mortality, while surgery was associated with decreased mortality. CONCLUSIONS: The current mortality of IE remains high, and is mainly due to its complications, such as CHF and stroke.

The efficacy of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA)-related infections has been called into question by recent findings of higher rates of failure of vancomycin treatment of infections caused by strains with high MICs. Continuous infusion may be the best way to maximize the time-dependent activity of vancomycin. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL Cr ) estimates for use in daily clinical practice to target the steady-state concentrations ( C ss s) of vancomycin during continuous infusion at 15 to 20 mg/liter (after the administration of an initial loading dose of 15 mg/kg of body weight over 2 h). The correlation between vancomycin clearance (CL v ) and CL Cr was retrospectively assessed in a cohort of critically ill patients (group 1, n = 70) to create a formula for dosage calculation to target C ss at 15 mg/liter. The performance of this formula was prospectively validated in a similar cohort (group 2, n = 63) by comparison of the observed and the predicted C ss s. A significant relationship between CL v and CL Cr was observed in group 1 ( P < 0.001). The application of the calculated formula to vancomycin dosing in group 2 {infusion rate (g/24 h) = [0.029 × CL Cr (ml/min) + 0.94] × target C ss × (24/1,000)} led to a significant correlation between the observed and the predicted C ss s ( r = 0.80, P < 0.001). Two dosing nomograms based on CL Cr were created to target the vancomycin C ss at 15 and 20 mg/liter in critically ill patients. These nomograms could be helpful in improving the vancomycin treatment of MRSA infections, especially in the presence of borderline-susceptible pathogens and/or of pathophysiological conditions which may enhance the clearance of vancomycin, while potentially avoiding the increased risk of nephrotoxicity observed with the use of high intermittent doses of vancomycin.

Recent articles have described an increasing number of infections due to Panton-Valentine leukocidin PVL-positive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) worldwide. We report a case of necrotizing pneumonia successfully treated with levofloxacin in Italy, sustained by a PVL-positive CA-MRSA, belonging to ST88 and carrying a staphylococcal chromosomal cassette mec type V. Further molecular characterization of isolates revealed that they were PVL positive, belonged to the agr IV allele, possessed a capsular type 8, and had an almost complete pathotype composed of leukocidins and numerous adhesins. In addition, the strains were strong biofilm producers.

We report a visceral leishmaniasis case in an immunocompetent immigrant with acute renal failure. Parasites were demonstrated in bone marrow, peripheral blood, and kidney samples. A collapsing focal segmental glomerulosclerosis was documented, which was successfully treated with a single infusion of 10 mg/kg liposomal amphotericin B.

The purpose of this study was to assess the clinical efficacy of high-dose levofloxacin plus rifampicin in the empirical treatment of non-tuberculous spondylodiscitis in an epidemiological context of low incidence of staphylococcal fluoroquinolone resistance. All consecutive adult patients with spondylodiscitis (January 2003 to December 2006) were empirically treated with high-dose levofloxacin (500 mg every 12 h normalised to renal function and optimised by means of therapeutic drug monitoring whenever feasible) plus rifampicin 600 mg every 24 h. Trough and peak plasma concentrations were targeted at 1-3 mg/L and 6-9 mg/L, respectively, to maximise the concentration-dependent activity of levofloxacin in bone. Follow-up was performed until 9 months after the end of therapy. Forty-eight patients were included. Eleven patients underwent a surgical approach for spine stabilisation. Among the 29 bacterial isolates, Staphylococcus aureus was the most frequent (65.5%) (all meticillin-susceptible strains). Tailored levofloxacin plasma exposure over time was ensured in most cases. Median treatment duration was 15.1 weeks. Overall response rates were: 77.1% at the intent-to-treat analysis; 84.1% among patients who completed therapy (N = 44); and 96.3% among those receiving targeted therapy against documented levofloxacin-susceptible isolates (N = 27). No patient had evidence of disease relapse at follow-up. Our findings suggest that high-dose levofloxacin regimens may be highly effective in the treatment of non-tuberculous spondylodiscitis and support its putative role in combination with rifampicin against S. aureus. © 2008 Elsevier B.V. and the International Society of Chemotherapy.

and pulmonary and rheumatologic presentations were more frequent in Group I, whereas in Group II cardiac and abdominal presentations were more common. During hospitalization, septic shock (12.7% vs 18.9%; p = 0.021) was observed more frequently in Group II. There were no differences in periannular complications, heart failure, valvular dysfunction, persistent infection and embolism. In Group II the need of cardiac surgery was higher than in Group I (49.3 vs 58.7%; p 0.011). No differences were observed in hospital mortality (28.1% vs 28%). Conclusions: In the last years the incidence of infective endocarditis was higher in older patients with a higher degree of comorbidity. Prosthetic valve IE increased and IE in IVDU was less frequent. The need for cardiac surgery has also increased. Mortality remained similar.