Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a multicenter clinical experience.

BACKGROUND: severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been increasingly reported over the past few years. Many in vivo and in vitro studies suggest a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: this multicenter, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively from December 2017 to December 2022 in four Hospitals in Italy. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS: during the study period, 102 patients with severe infection caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled: ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteremia in 22%, and CVC-related infection in 16%. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48), and ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced a clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia, and a colistin-containing regimen were independently associated with 30-day mortality, whereas an adequate source control of infection, an early 24 h active in vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteremia were independently associated with clinical failure. Conversely, an adequate source control of infection, a cefiderocol-containing regimen, and an early 24 h active in vitro therapy were associated with clinical success. CONCLUSIONS: Our data showed different antibiotic regimens containing fosfomycin in combination treatment of severe infections caused by CRAB.

Safety and Efficacy of a Single Procedure of Extraction and Reimplantation of Infected Cardiovascular Implantable Electronic Device (CIED) in Comparison with Deferral Timing: An Observational Retrospective Multicentric Study.

(1) Background: Infections are among the most frequent and life-threatening complications of cardiovascular implantable electronic device (CIED) implantation. The aim of this study is to compare the outcome and safety of a single-procedure device extraction and contralateral implantation versus the standard-of-care (SoC) two-stage replacement for infected CIEDs. (2) Methods: We retrospectively included 66 patients with CIED infections who were treated at two Italian hospitals. Of the 66 patients enrolled in the study, 27 underwent a single procedure, whereas 39 received SoC treatment. All patients were followed up for 12 months after the procedure. (3) Results: Considering those lost to follow-up, there were no differences in the mortality rates between the two cohorts, with survival rates of 81.5% in the single-procedure group and 84.6% in the SoC group (p = 0.075). (4) Conclusions: Single-procedure reimplantation associated with an active antibiofilm therapy may be a feasible and effective therapeutic option in CIED-dependent and frail patients. Further studies are warranted to define the best treatment regimen and strategies to select patients suitable for the single-procedure reimplantation.

Hospital Antibiotic Use during COVID-19 Pandemic in Italy.

Antimicrobial resistance (AMR) represents a major issue in healthcare being correlated to global inappropriate use of antibiotics. The aim of this study was to compare the data on hospital antibiotic consumption in 2020-2021 with those related to 2019 in order to evaluate the impact of the COVID-19 pandemic on antibiotic prescriptions and appropriate use at national level and in the different geographical areas. To estimate the consumption of antibiotics, two indicators were calculated: "number of DDD per 1000 inhabitants per day" and "number of DDD per 100 hospitalisation days". Consumption data on antibiotics dispensed in public health facilities were based on the Italian "traceability of medicines" information flow. Data on hospitalisation days were extracted from the Italian "hospital discharge form" flow. Pearson correlation analysis was performed between the number of patients hospitalised for COVID-19 and the consumption of antibiotics in public healthcare facilities. During 2020, about 1.7 DDD/1000 inhabitants per day (12.3% of the overall consumption of reimbursed antibiotics) were dispensed exclusively in Italian hospitals (+0.8% compared to 2019). Considering the number of DDD per 100 hospitalisation days, consumption increased by 19.3% in 2020 compared to 2019. Comparing the first semester of 2020 and 2019, a decrease of DDD/1000 inhabitants per day was observed (-1.6%) at national level, with opposite trends in the different geographical areas; an increase in the use of azithromycin and carbapenems was also observed, with a stable consumption of third-generation cephalosporins. The use of antibiotics in the second semester of 2020 compared to the same period of 2019 showed a clear reduction at national level (-8.5%), appreciable to a similar extent in all geographic areas. In the first semester of 2021 compared to the same period of 2020, there was a huge reduction (-31.4%) in consumption at national level. However, the variations were heterogeneous between different geographical areas. To our knowledge, this study represents the most comprehensive analysis performed on antibiotic consumption data in hospital settings in Italy during the COVID-19 pandemic to date. Despite international and national guideline recommendations, a substantial overall increase in antibiotic prescriptions was observed during the COVID-19 pandemic, with variability in terms of geographical distribution and prescription strategies. These findings may be related to the dichotomy between perceived and real significance of guidelines, expert panels, or consensus. Therefore, new approaches or strategies to antimicrobial stewardship should be proposed.

Decolonization of drug-resistant Enterobacteriaceae carriers: A scoping review of the literature.

The ESCMID-EUCIC guideline on decolonization of multidrug-resistant Gram-negative bacteria carriers does not recommend routine decolonization and highlights the necessity of well-powered and designed randomized clinical trials. Based on this limited evidence, we decided to conduct a scoping review with the aim of describing and discussing the last published studies investigating the efficacy and safety of decolonization therapies in drug-resistant Enterobacteriaceae carriers. Studies published in PubMed from January 1, 2017 to December 28, 2021 were retrieved. A PICO (population, intervention, comparator, outcome) framework was used for article selection as follows: Population defined as any patient of any age in any setting with screening sample yielding for drug-resistant Enterobacteriaceae; Intervention defined as any decolonization; Controls defined as patients receiving no intervention (spontaneous decolonization) or a different decolonization therapy; Outcomes defined as a microbiological, clinical, epidemiological and adverse event. A total of 679 records were initially identified, of which 647 were excluded because they were not related to decolonization therapies. Other 18 records were excluded because not related to our aims, target bacteria, or study design. A total of 12 clinical studies were included, of which 4 were randomized clinical trials and 8 were non-randomized studies. The majority of studies evaluated selective decontamination of the digestive tract or selective oropharyngeal decontamination regimens. Selected studies were characterized by high heterogeneity. Further high-quality studies with proper design and sample size calculation are warranted.

Respiratory Intensive Care Unit management and efficacy during the COVID-19 outbreak in Naples, Italy.

The World Health Organization declared the Coronavirus Diseases 2019 (COVID-19) outbreak a global pandemic on March 11, 2020. COVID-19 had an impact on over 500 million people worldwide. According to the American Thoracic Society criteria, the respiratory spectrum of this disease ranges from mild illness to severe pneumonia, with the latter occurring in a not insignificant 15% of patients. A rapid increase in the incidence of COVID-19 pneumonia cases has been observed all over the world, resulting in a saturation of the Intensive Care Unit's capacity (ICUs). Because of this impressive outbreak, the ICU beds and invasive mechanical ventilators reached their capacity. Non-invasive supportive care has become an important option for keeping respiratory conditions under control. As a result, proper healthcare resource management was required to ensure adequate patient care. Respiratory Intensive Care Units (RICUs) have become a useful resource for managing complex patients due to a shortage of ICU capacity. This highlighted the importance of RICUs, where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support rather than being admitted to the ICU. The clinical outcomes and baseline characteristics of patients admitted to the RICU of Cotugno Hospital, a tertiary referral center in Naples (Italy), from January 2021 to October 2021 are described in this report.

Monkeypox Clinical Features and Differential Diagnosis: First Case in Campania Region.

As of 15 June, there have been, globally, a total of 2103 laboratory-confirmed cases and one probable case of Monkeypox, including one death. We report two cases of vesicular infectious diseases, one of those is the first case of Monkeypox in the Campania Region. The report, therefore, highlights a recrudescent infection disease that could represent a challenge in differential diagnosis with other vesicular infectious diseases such as Varicella Zoster Virus, during a pandemic season that does not seem to end. Indeed, varicella should be carefullu considered in differential diagnosis according to its vesicular or pustular rash to have a prompt diagnosis and public health response in case of monkeypox infection.

Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study.

INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.

Pathophysiology of Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT) and Vaccine-Induced Thrombocytopenic Thrombosis (VITT) and Their Diagnostic Approach in Emergency.

SARS-CoV-2 induced a pandemic that is reported to have started in Asia and was then extended to other countries in the world. Main clinical aspects of this viral infection have been lung injuries with severe pneumonia requiring prolonged hospitalization and associated morbidities such as venous thromboembolism and/or superinfection by bacteria, fungus or other pests. Immediately there was a need to develop a sustainable therapeutic strategy, such as vaccination. Vaccines against Covid-19, in fact, exert a protective action for common people and reduce viral diffusion. Yet, vaccination of a large number of people raises the question of a well-known complication of several types of vaccines; this complication is immune thrombocytopenia, which is sometimes associated with thrombosis as well. In this short review, we summarized mechanisms involved in the pathogenesis of vaccine-induced prothrombotic immune thrombocytopenia and vaccine-induced thrombocytopenic thrombosis.

Acute Pancreatitis and COVID-19: A Single-Center Experience.

Gastrointestinal involvement in SARS-CoV-2 disease (COVID-19) can occur and evolve fatally. Reports are emerging that SARS-CoV-2 virus attacks the pancreatic cells, causing the boost of amylase and lipase serum activity and rarely frank pancreatitis. We retrospectively assessed all the patients admitted to the respiratory sub-intensive care and evaluated pancreatitis cases and their course. In our study, we included all patients admitted to our respiratory sub-intensive care unit from 1st to 30th November. All patients had a confirmed diagnosis of COVID-19 and a CT finding of interstitial pneumonia associated with signs of respiratory failure. We observed the course and evaluated who developed acute pancreatitis according to standard definitions. In this study, etiology of acute pancreatitis was defined on the basis of risk factors (ie, biliary pancreatitis was defined in presence of common bile duct stone or sludge at CT or MR). According to the Revised Atlanta Classification, we diagnosed and classified the patients and evaluated the radiological severity according to the Balthazar index and a computed tomography severity index. We found that 19% (15 of 78 patients) met the criteria for acute pancreatitis. The mortality rate among patients with pancreatitis was 20%. Interestingly, in our population, cholelithiasis' imaging findings were found in only 7% of the patients, whereas no patient-reported alcohol consumption. Considering that alcohol and biliary stones represent the two major causes of AP in the general population, it is reasonable to hypothesize that SARS-CoV-2 could play a role in the etiology of acute pancreatitis in a subgroup of these patients.

Diagnosis and treatment of pneumonia, a common cause of respiratory failure in patients with neuromuscular disorders.

Patients with neuromuscular diseases, during their illness are more susceptible to respiratory infections due to predisposing factors. Ineffective cough and the presence of atelectasis and hypoventilation, dysphagia and drooling can represent risk factors for the development of respiratory infection and fatal respiratory failure. Infections of respiratory tract with acute respiratory failure are the most common reason for hospitalizations, and pneumonia is among the leading causes of morbidity and mortality worldwide. The setting in which pneumonia is acquired heavily influences diagnostic and therapeutic choices. We will focus on aetiopathogenesis, diagnosis and treatment of pneumonia in these subjects, particularly considering the disease severity, rates of antibiotic resistance and the possible complications. In this case consultations with specialized physicians are strongly recommended.

Remdesivir in Severe COVID-19 and Non-Invasive Ventilation: A Real-Life Experience.

BACKGROUND: Antiviral treatment is a hot topic regarding therapy for COVID-19. Several antiviral drugs have been tested in the months since the pandemic began. Yet only Remdesivir obtained approval after first trials. The best time to administer Remdesivir is still a matter for discussion and this could also depend upon the severity of lung damage and the staging of the infection. METHODS: We performed a real-life study of patients hospitalized forCOVID-19 and receiving non-invasive ventilation (NIV). In this single-center study, a 5 day course of Remdesivir was administered as compassionate use. Further therapeutic supports included antibiotics, low molecular weight heparin and steroids. Data collection included clinical signs and symptoms, gas exchange, laboratory markers of inflammation, and radiological findings. Major outcomes were de-escalation of oxygen-support requirements, clinical improvement defined by weaning from ventilation to oxygen therapy or discharge, and mortality. Adverse drug reactions were also recorded. All data were collected during hospitalization and during a 20-day follow up after treatment. RESULTS: 51 patients were enrolled. A global clinical improvement was recorded in 22 patients (43%) at 12 days, and 36 (71%) at 20 days; in particular, at 12 days, 27 patients (53%) also had a de-escalation of oxygen-support class from a therapeutic point of view. Remdesivir use was associated with a lower hazard ratio for clinical improvement in the elderly (older than 70 years) and in subjects with more extensive lung involvement (total severity score at HRCT of more than 14). The 20-day mortality was 13%. CONCLUSIONS: Results demonstrated that Remdesivir is associated with an improvement in clinical, laboratory and radiological parameters in patients with severe COVID-19 and showed an overall mortality of 13%. We conclude that, in this cohort, Remdesivir was a beneficial add-on therapy for severe COVID-19, especially in adults with moderate lung involvement at HRCT.

Home Management of Patients with Moderate or Severe Respiratory Failure Secondary to COVID-19, Using Remote Monitoring and Oxygen with or without HFNC.

BACKGROUND: Home treatment of patients affected by COVID-19 is still a matter of daily debate. During the clinical evolution of the disease, there are high risks of lung failure, which requires oxygen therapy. Here, we report our clinical experience with at-home treatment using high-flow nasal cannula in non-hospitalised patients with confirmed COVID-19. PATIENTS AND METHODS: In this study, 18 patients with moderate-to-severe respiratory failure secondary to COVID-19 were monitored at home daily for temperature and SpO2 measurements. Other parameters such as saturation of peripheral oxygen (SpO2), SpO2/FiO2 (fraction of inspired oxygen), temperature, and lung performance were monitored periodically. Depending on oxygen requirements, the patients also received either standard oxygen via a face mask or, if higher FiO2 required, high-flow nasal cannula (HFNC). RESULTS: All 18 patients had favourable outcomes and recovered from COVID-19. No death was recorded in this group. CONCLUSION: Our clinical experience proves that high-flow nasal cannula oxygen therapy may be considered for at-home treatment of COVID-19 patients with moderate lung failure. This could be useful for further treatment during the pandemic and may also be considered in future epidemics.

Therapeutic approach for severe COVID-19 and immunocompromised patients. A case series.

BACKGROUND: COVID-19 is a potentially critical infectious disease. Inflammatory response and disease severity may vary according to immune system status. The aim of this case series is to investigate different presentation of COVID-19 in immunocompromised patients. METHODS: this is a single centre case series about 17 immunocompromised patients admitted to our respiratory department during the recent COVID-19 pandemic. White blood cell count, C reactive protein, interleukin 6, lymphocytic subpopulation count (CD4+, CD8+, CD20+) and immunoglobulin count (IgG, IgM, IgA) were measured at hospitalization. RESULTS: the most common causes of immunosuppression observed in our severe COVID-19 population are hematological malignancies, immunosuppressant drugs for transplant, primary immunodeficiency and inflammatory bowel disease. Onset symptoms were fever (88%), cough (53%), dyspnoea (24%), asthenia (35%), anosmia and/or ageusia (17%), expectoration (12%). Compared to benign conditions, patients with malignancies show a lower lymphocytic count (490 vs 1100 cells/uL) and higher interleukin 6 (33 vs 13 pg/mL). CONCLUSIONS: immunocompromised patients are at risk of adverse outcome from COVID-19. Hematological malignancies and anti-CD20 therapies induce a high risk. Primary immunodeficiency and classical immunosuppressant such as calcineurin inhibitors and antimetabolites share an intermediate risk.

Incidence and Prognosis of Ventilator-Associated Pneumonia in Critically Ill Patients with COVID-19: A Multicenter Study.

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, p < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.

Daptomycin-based aminoglycoside-sparing therapy for streptococcal endocarditis: a retrospective multicenter study.

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.

Prognostic Value of Fibrinogen among COVID-19 Patients Admitted to an Emergency Department: An Italian Cohort Study.

INTRODUCTION: A highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19); the disease became pandemic after a few months. Little is still known about the laboratory prognostic markers in COVID-19 patients. The aim of our study was to describe the prognostic value of clotting parameters for the prediction of severe form of COVID-19 characterized by acute respiratory distress syndrome (ARDS) at hospital admission. MATERIAL AND METHODS: From a large cohort of 152 patients consecutively admitted from February to March 2020 for fever and dyspnea to the emergency departments (ED) of three Italian hospitals, we evaluated 85 patients with confirmed diagnosis of COVID-19 and 67 patients with acute illness. All patients underwent medical history checks, physical examination, and laboratory evaluation. Prothrombin time (PT), activated thromboplastin time (aPTT), fibrinogen and D-dimer tests were performed and compared, first, between COVID-19 and control groups, and then between COVID-19 patients with or without ARDS. RESULTS: COVID-19 patients were more likely to show abnormal baseline levels of PT, aPTT, D-dimer, and fibrinogen at admission compared to the control group. COVID-19 patients with ARDS showed a statistically significant increase in levels of fibrinogen compared to those without ARDS (720 (621-833) vs. 490 (397.5-601.5); p= 1.8653 × 10-9 (0.0765). A cut-off value of 617 mg/dL had a sensitivity of 76% and a specificity of 79% in identifying COVID-19 patients with ARDS. CONCLUSION: A serum level of fibrinogen of 617 mg/dL in COVID-19 patients admitted to emergency department may help to identify early those with ARDS.

Late Reactivation of SARS-CoV-2: A Case Report.

SARS-CoV-2 is a betacoronavirus that belongs to the family Coronaviridae and the order Nidovirales (1). During December 2019, a series of pneumonia cases caused by a SARS-CoV-2 outbreak was identified in Wuhan, Hubei, China, and rapidly spread across the world. The spectrum of SARS-CoV-2 disease (COVID 19) varies from asymptomatic or paucisymptomatic forms to clinical conditions characterized by respiratory failure that necessitate mechanical ventilation and support in an intensive care unit (ICU), multiorgan and systemic manifestations, and, in terms of sepsis, septic shock, and multiple organ dysfunction syndromes (MODS) (2). Whilst many reports have characterized the clinical, epidemiological, laboratory, and radiological features, as well as treatment and clinical outcomes of patients with COVID-19 pneumonia, information on SARS-CoV-2 reactivation remains unreported. Curative and eradicative therapy for COVID-19 is not currently available (3). We report a case of a patient with PCR-confirmed COVID-19 pneumonia who experienced reactivation after 43 days and negative PCR sampling.

Administration of Immunoglobulins in SARS-CoV-2-Positive Patient Is Associated With Fast Clinical and Radiological Healing: Case Report.

Polyclonal preparation of IgM as an adjuvant therapy has been reported as a relevant immunomodulant therapy in several infectious diseases, exhibiting, in most cases, improvement of the clinical course. No drug has demonstrated therapeutic efficacy for COVID-19. Immunomodulatory treatment with hydroxychloroquine and biologics as tocilizumab, in fact, has not proven to show satisfactory results in several reports. We therefore treated a selected patient with interstitial multifocal pneumonia, positive to COVID-19, with polyclonal preparation of immunoglobulins as an adjuvant therapy, obtaining in few days clinical remission and improvements in radiological findings. Based on this case report, we suggest that clinical trials are conducted to test the efficacy and safety of polyclonal immunoglobulins for adjunctive therapy of COVID-19.

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study).

BACKGROUND: Few data are reported in the literature about the outcome of patients with severe extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. METHODS: A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. RESULTS: C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success. CONCLUSIONS: Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.

Clotting Factors in COVID-19: Epidemiological Association and Prognostic Values in Different Clinical Presentations in an Italian Cohort.

INTRODUCTION: A novel highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19) outbreak, which has spread rapidly from China to other countries. Little is known about laboratory prognostic markers in COVID-19 patients. The aim of our study was to describe the basic clotting parameters in COVID-19 patients and their prognostic role in different clinical forms of the disease. MATERIAL AND METHODS: We enrolled 67 COVID-19 patients admitted to the Emergency Department. A cohort of 67 age- and sex-matched non-COVID-19 patients with acute respiratory illness was used as a control group. For all patients, platelet count (PLT), prothrombin time (PT), activated thromboplastin time (aPTT), C-reactive protein (PCR), fibrinogen, and D-dimer were determined. The COVID-19 population was divided in two groups according to the presence or absence of SARS. The clotting factors values were compared between the groups. RESULTS: At admission, the COVID-19 patients showed statistically significant increased levels of fibrinogen (601.5 (480-747) vs. 455 (352.5-588.5) mg/dL; p = 0.0000064), and a higher percentage of patients had fibrinogen levels >400 mg/dL (86% vs.58%; p = 0.0054) compared to the control group. The levels of fibrinogen were higher in COVID-19 patients with SARS compared to those without SARS (747 (600.0-834.0) vs. 567 (472.5-644.50); p = 0.0003). CONCLUSION: Fibrinogen seems to increase early in COVID-19 patients and may be used as a risk stratification marker for the early detection of a subgroup of COVID-19 patient at increased risk to develop SARS, who might benefit from a different and thorough clinical surveillance and treatment.