Rapid Decrease in Fluoroquinolones Consumption following Implementation of a Simple Antimicrobial Stewardship Bundled Intervention in a University Hospital during the COVID-19 Pandemic.

Fluoroquinolones (FQs) represent an class of antibiotics of medical importance, but their use has been restricted due to their ecologic impact and associated side effects. The reduction of FQs use is an important goal of antimicrobial stewardship programs (ASP). This work describes an ASP focused on overall antibiotics and FQs consumption reduction. From January 2021, an ASP was implemented in a 700-bed teaching hospital. The ASP was based on: (i) antibiotics consumption monitoring system (DDD/100 bed days); (ii) mandatory antibiotic prescription-motivation (using a dedicated informatic format) with the goal of >75% of motivated prescriptions; and (iii) data feedback and training on FQs use indications. We evaluated the impact of the intervention on overall systemic antibiotics and FQs consumption according to the objectives posed by Italian PNCAR (National Action Plan on Antimicrobial Resistance). A decrease of 6.6% in antibiotic use was observed (2019 vs. 2021). Notably, the FQs consumption fell by 48.3% from 7.1 DDD/100 bd in 2019 to 3.7 DDD/100 bd in 2021 (p < 0.001). After six months of mandatory antibiotic prescription-indication, all units achieved the target set. The study suggests that a simple, bundled ASP intervention can be rapidly effective obtaining the objectives of PNCAR on the reduction of overall antibiotics and FQs consumption.

Relationship between intensive care surge capacity and hospital factors: an extensive experience.

As a prolonged surge scenario, the COVID-19 pandemic has offered an unparalleled opportunity to improve hospital surge capacity (SC) understanding and the ability to manage it. In this study, the authors report the experience of a large hospital network and evaluate potential relationships between Intensive Care Units SC (ICU-SC) and some hospital-related variables: bed occupancy, emergency department admissions, ward admission from ED, and elective surgery procedures. Pearson's partial correlation coefficient (r) has been used to define the relationship between SC and the daily values of the above variables, collected through a dedicated digital platform that also ensured a regular quality check of the data. The observation has concerned several levels of analysis, namely two different types of SC calculation (SC base-SCb and SC actual-SCa), hospital category level and multi-hospital level, and two consecutive pandemic waves. Among the 16 hospitals observed, the correlation was shown to be moderate-positive with non-ICU bed occupancy (r/ = 0.62, r/ = 0.54), strong/moderate with ICU bed occupancy (r/ = 0.72, r/ = 0.54), and moderate with ward admissions from ED (r/ = 0.50, r/ = 0.51) On the contrary, the correlation proved to be moderate-negative with ED admissions (r/ = - 0.69, r/ = - 0.62) and low with the number of elective surgery procedures (r/ = - 0.10, r/ = - 0.16). This study identified a positive correlation between SC and three variables monitored: ICU bed occupancy, non-ICU bed occupancy, and ward admissions from ED. On the contrary, the correlation was negative for ED admission and the number of elective surgery procedures. The results have been confirmed across all levels of analysis adopted.

Dynamic assessment of surge capacity in a large hospital network during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has provided an unprecedented scenario to deepen knowledge of surge capacity (SC), assessment of which remains a challenge. This study reports a large-scale experience of a multi-hospital network, with the aim of evaluating the characteristics of different hospitals involved in the response and of measuring a real-time SC based on two complementary modalities (actual, base) referring to the intensive care units (ICU). METHODS: Data analysis referred to two consecutive pandemic waves (March-December 2020). Regarding SC, two different levels of analysis are considered: single hospital category (referring to a six-level categorization based on the number of hospital beds) and multi-hospital wide (referring to the response of the entire hospital network). RESULTS: During the period of 114 days, the analysis revealed a key role of the biggest hospitals (>Category-4) in terms of involvement in the pandemic response. In terms of SC, Category-4 hospitals showed the highest mean SC values, irrespective of the calculation method and level of analysis. At the multi-hospital level, the analysis revealed an overall ICU-SC (base) of 84.4% and an ICU-SC (actual) of 106.5%. CONCLUSIONS: The results provide benchmarks to better understand ICU hospital response capacity, highlighting the need for a more flexible approach to SC definition.

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Hyperimmune plasma in three immuno-deficient patients affected by non-severe, prolonged COVID-19: a single-center experience.

BACKGROUND: Convalescent plasma (CP) and hyperimmune plasma (HP) are passive immunotherapies consisting in the infusion of plasma from recovered people into infected patients. Following pre-existing evidence in many other viral diseases, such as SARS, MERS and Ebola, CP and HP have also been proposed for the treatment of COVID-19. Nevertheless, due to the lack of large, well-designed, clinical trials, no clear-cut guidelines exist about what subtype of patient CP and HP should be administered to. CASE PRESENTATION: We have reported the cases of 3 patients, all immunosuppressed and affected by non-severe, prolonged COVID-19. They were treated with HP, whose neutralizing titer was higher than 1/80. The first patient was a 55-year-old male, who had undergone lung transplant. He was under therapy with Tacrolimus and developed non-neutralizing antibodies against SARS-CoV2. The second patient was a 77-year-old female, affected by follicular lymphoma. She had tested positive for SARS-CoV2 after 6 months. The third was a 60-year-old patient, affected by chronic leukemia. He did not develop antibodies after 2-month disease. All 3 patients received HP and had tested negative for SARS-CoV2 within 2 weeks. CONCLUSION: Despite encouraging initial data, no strong evidence exist in support of CP and HP to treat COVID-19. In our experience, although limited due to the reduced number of patients, we found a good safety and efficacy of HP in 3 immuno-deficient subjects. Further data are needed in order to assess whether this subtype of patients may particularly benefit from passive immunization.

Right Ventricular Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to describe the features of right ventricular impairment and pulmonary hypertension in coronavirus disease (COVID-19) and assess their effect on mortality. DESIGN: The authors carried out a systematic review and meta-analysis of observational studies. SETTING: The authors performed a search through PubMed, the International Clinical Trials Registry Platform, and the Cochrane Library for studies reporting right ventricular dysfunction in patients with COVID-19 and outcomes. PARTICIPANTS: The search yielded nine studies in which the appropriate data were available. INTERVENTIONS: Pooled odds ratios were calculated according to the random-effects model. MEASUREMENTS AND MAIN RESULTS: Overall, 1,450 patients were analyzed, and half of them were invasively ventilated. Primary outcome was mortality at the longest follow-up available. Mortality was 48.5% versus 24.7% in patients with or without right ventricular impairment (n = 7; OR = 3.10; 95% confidence interval [CI] 1.72-5.58; p = 0.0002), 56.3% versus 30.6% in patients with or without right ventricular dilatation (n = 6; OR = 2.43; 95% CI 1.41-4.18; p = 0.001), and 52.9% versus 14.8% in patients with or without pulmonary hypertension (n = 3; OR = 5.75; 95% CI 2.67-12.38; p < 0.001). CONCLUSION: Mortality in patients with COVID-19 requiring respiratory support and with a diagnosis of right ventricular dysfunction, dilatation, or pulmonary hypertension is high. Future studies should highlight the mechanisms of right ventricular derangement in COVID-19, and early detection of right ventricular impairment using ultrasound might be important to individualize therapies and improve outcomes.

Portable Pocket-Sized Ultrasound Scanner for the Evaluation of Lung Involvement in Coronavirus Disease 2019 Patients.

Ultrasound imaging of the lung (LUS) and associated tissues has demonstrated clinical utility in coronavirus disease 2019 (COVID-19) patients. The aim of the present study was to evaluate the possibilities of a portable pocket-sized ultrasound scanner in the evaluation of lung involvement in patients with COVID-19 pneumonia. We conducted 437 paired readings in 34 LUS evaluations of hospitalized individuals with COVID-19. The LUS scans were performed on the same day with a standard high-end ultrasound scanner (Venue GO, GE Healthcare, Chicago, IL, USA) and a pocket-sized ultrasound scanner (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). Fourteen scans were performed on individuals with severe cases, 11 on individuals with moderate cases and nine on individuals with mild cases. No difference was observed between groups in days since onset of symptoms (23.29 ± 10.07, 22.91 ± 8.91 and 28.56 ± 11.13 d, respectively; p = 0.38). No significant differences were found between LUS scores obtained with the high-end and the portable pocket-sized ultrasound scanner. LUS scores in individuals with mild respiratory impairment were significantly lower than in those with moderate and severe cases. Our study confirms the possibilities of portable pocket-sized ultrasound imaging of the lung in COVID-19 patients. Portable pocket-sized ultrasound scanners are cheap, easy to handle and equivalent to standard scanners for non-invasive assessment of severity and dynamic observation of lung lesions in COVID-19 patients.

SARS-CoV-2 in pleural fluid in a kidney transplant patient.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread all over the globe from China. Pleural involvement is not common; around 5-10% of patients can develop pleural effusion and little is known about the involvement of pleural structures in this new infection.A 61-year-old male kidney transplant patient with a history of multiple biopsy-confirmed acute rejections and chronic allograft rejection was admitted to our COVID-19 Unit with dry cough, exertional dyspnea, oliguria, and abdominal distension. Lung ultrasound imaging, chest X-ray, and CT scan showed left pleural effusion and atelectasis of the neighboring lung parenchyma. RT-PCR was positive for SARS-CoV-2 in the pleural fluid and cytology showed mesothelial cells with large and multiple nuclei, consistent with a cytopathic effect of the virus.This is one of few reports describing detection of SARS-CoV-2 in the pleural fluid and to the best of our knowledge, is the first to document the simultaneous presence of a direct cytopathic effect of the virus on mesothelial cells in a kidney transplant patient with COVID-19 pneumonia. The pleura proved to be a site of viral replication where signs of a direct pathological effect of the virus on cells can be observed, as we report here. RT-PCR for SARS-CoV-2 should be part of routine examination of pleural effusion even in patients with mild respiratory symptoms or with comorbidities that seem to explain the cause of effusion.

Ruxolitinib Rapidly Reduces Acute Respiratory Distress Syndrome in COVID-19 Disease. Analysis of Data Collection From RESPIRE Protocol.

Background: The Coronavirus disease (COVID-19) pandemic is causing millions of infections and hundreds of thousands of deaths worldwide. Cumulative clinical and laboratory evidence suggest that a subset of patients with severe COVID-19 may develop a cytokine storm syndrome during the course of the disease, with severe respiratory impairment requiring ventilatory support. One field of research nowadays is to identify and treat viral-induced hyperinflammation with drugs used in other clinical conditions characterized by an hyperinflammation status. These drugs might help to reduce COVID19 mortality. Methods: Ruxolitinib, a JAK1 and JAK2 inhibitor, has been successfully used to treat severe immune-mediated diseases, such as graft vs. host disease and Hemophagocytic lymphohistiocytosis. We used ruxolitinib in 18 patients with clinically progressive COVID-19 related acute respiratory distress syndrome, with a primary endpoint to rapidly reduce the degree of respiratory impairment and as a secondary endpoint to rapidly restore the PaO2/FiO2 ratio, as an evaluation of clinical status, and monitoring of drug related Adverse Events. Parameters of inflammation responses and organ functions were assessed and monitored. The treatment plan was ruxolitinib 20 mg bid for the first 48 h and subsequent two-step de-escalation at 10 mg bid and 5 mg bid for a maximum of 14 days of treatment. Results: Our data collection shows a rapid clinical response with no evolution from non-invasive ventilation to mechanical ventilation in 16/18 patients and no response in two patients (overall response rate-ORR 89%). Already after 48 h of ruxolitinib treatment 16/18 patients showed evident clinical improvement, and after 7 days of treatment 11/18 patients showed fully recovered respiratory function (pO2 > 98% in spontaneous breathing), 4/18 patients had minimal oxygen requirement (2-4 L/m), 1/18 patient showed stable disease, and 2/18 patient showed progressive disease. After 14 days, 16/18 patients showed complete recovery of respiratory function (ORR 89%). Compliance to ruxolitinib planned treatment was 100% and no serious adverse event was recorded. In our case series of 18 critically ill patients with COVID-19 and ARDS, administration of ruxolitinib resulted in a clinical improvement that concurred to modify the standard course of disease. Ruxolitinib can be a therapeutic option for patients with respiratory insufficiency in COVID-19 related ARDS. RESPIRE Study (Ruxolitinib for the treatment of acute rESPIratory distREss syndrome, ClinicalTrials.gov Identifier: NCT04361903).

Serum KL-6 concentrations as a novel biomarker of severe COVID-19.

Severe acute respiratory syndrome coronavirus 2-induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen-6 (KL-6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL-6 in patients with coronavirus disease (COVID-19) to verify its potential as a prognostic biomarker of severity. Twenty-two patients (median age [interquartile range] 63 [59-68] years, 16 males) with COVID-19 were enrolled prospectively. Patients were divided into mild-moderate and severe groups, according to respiratory impairment and clinical management. KL-6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut-off value was 119 cells/µL. KL-6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL-6 serum levels and the best cut-off value was 406.5 U/mL. NK cell analysis and assay of KL-6 in serum can help identify severe COVID-19 patients. Increased KL-6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL-6 measurement to evaluate COVID-19 patients' prognosis.