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.

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.

Candida palmioleophila isolation in Italy from two cases of systemic infection, after a CHROMagar and Vitek system mis-identification as C. albicans.

A correct, fast, reliable identification method is pivotal in nosocomial environments to guide treatment strategies, whereas misidentification might lead to treatment failure. For routine identifications the Vitek system and CHROMagar are widely used but not always reliable, especially now with an increasing number of new emerging fungal pathogens that need careful identification. Here we describe two cases of candidemia, due to Candida palmioleophila previously misidentified as Candida albicans by using the Vitek2 system and CHROMagar. The first case is a 54-year-old man with an infected ulcer in the lower right limb, treated with a targeted therapy using a central venous catheter (CVC). After two months he developed a CVC-related candidemia MDR identified as C. albicans. The second case is a 2-month-old male baby that was admitted to the neonatal unit with acute respiratory failure due to a severe community-acquired bilateral pneumonia; blood cultures were all positive for C. albicans MDR. The isolated strains where re-identified with Maldi-Tof and DNA sequencing as C. palmioleophila. From the identification point of view, CHROMagar can be clearly misleading, especially because CHROMagar types currently available are not designed to discriminate new emerging species, suggesting that systems other than MALDI-TOF and marker sequencing may be inadequate even for routine identification and could contribute to producing misleading identifications and therapeutically wrong practices, leading to failures and patient death.

Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Neonatal pertussis diagnosis: low procalcitonin level and high lymphocyte count are able to discriminate pertussis from bacterial and viral infections.

Pertussis is quite frequent and severe among infants; therefore, rapid diagnosis and timely targeted therapy are essential. Although a molecular test for etiological diagnosis is now available, it may not be available everywhere, and therefore adjunctive diagnostic tests are still useful for presumptive diagnosis. We describe the use of procalcitonin (PCT) and lymphocyte count to discriminate among pertussis, bacterial and viral infections. Fourteen infants per group were studied. The decision tree, built considering all available variables, showed a major role of PCT in predicting the different groups. A PCT value equal to or greater than 0.75 ng/ml selected for bacterial infections. A PCT value lower than 0.75 ng/ml and a lymphocyte count equal to or greater than 10,400/mm3 selected the subjects with pertussis, while a lymphocyte count lower than 10,400/mm3 selected for viral etiology. PCT should be used in the diagnosis of infants suspected of having pertussis.

Neurobrucellosis: diagnostic and clinical management of an atypical case.

Brucellosis is the most common zoonosis in the world and it is caused by ingestion of foods contaminated by Brucella spp. that is able to avoid the immune system and can involve every organ system. The bacteria may affect the Central Nervous System (CNS) directly or using phagocytic cells with the way of the "Trojan Horse Model". Meningitis is the most common form of neuro-brucellosis (NB) but other neurological manifestation, with variable onset, such as severe encephalic involvement, neuropathy, vascular damage, radiculitis and hydrocephalus might happened. NB may manifest itself with an acute or chronic onset and could be the only manifestation of the infection or appearance during the systemic disease. Frequently the diagnosis might be very difficult and the clinical characteristics and the microbiological demonstration in the blood and in the CSF are necessary. The prognosis of brucella meningitis is generally better than other forms of chronic meningitis except for encephalitis or spinal cord involvement. The treatment is based on the combination of two or three antibiotics to achieve normalization of the cerebrospinal fluid parameters otherwise relapse are relatively frequent. We describe an atypical case of brucellar meningitis with many stroke-like signs, think as recurrent cerebrovascular events and treated with antithrombotic therapy, but without meningeal syndrome.

Invasive listeriosis in a patient with several episodes of antibiotic associated colitis presumably due to Clostridium difficile.

A 62-year-old man developed a blood stream infection and meningitis due to Listeria monocytogenes, 20 days after an episode of pseudo-membranous colitis. The patient, hospitalized for the first time for transurethral prostatectomy, was readmitted 20 days later with watery diarrhea. Pseudo-membranous colitis was diagnosed and treated successfully, without testing for Clostridium difficile infection (CDI). After 15 more days, the patient developed again diarrhea, fever and confusion. Hospitalized again, blood and cerebrospinal fluid cultures resulted positive for L. monocytogenes. The patient was treated successfully and a diagnosis of recurrent CDI was confirmed following culture and nucleic acid amplification assays both positive for C. difficile. This is the first report of an invasive listeriosis after CDI underlines the importance of taking greater awareness in complicated blood stream infections that may arise after CDI.

A high PCT level correlates with disease severity in Plasmodium falciparum malaria in children.

Most clinicians in developed countries have limited experience in making clinical assessments of malaria disease severity and/or monitoring high-level parasitemia in febrile patients with imported malaria. Hyperparasitemia is a risk factor for severe P. falciparum malaria, and procalcitonin (PCT) has recently been related to the severity of malaria. In developed countries, where not all hospital have skilled personnel to count parasitemia, a rapid test might be useful for the prompt diagnosis of malaria but unfortunately these tests are not able to count the number of parasites. In this context, PCT might have a prognostic value for the assessment of severe malaria, especially in children with cerebral malaria. We describe two children with severe cerebral malaria, who were directly admitted to the ICU with a high level of PCT and extremely high (>25%) parasitemia. Our conclusion is that PCT may also be a measure of severity of P. falciparum malaria in children.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

BACKGROUND: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. 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: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, 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 bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

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.

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.

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.

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.

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.

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.

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.

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.