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.

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.

Pre- and in-hospital anticoagulation therapy in coronavirus disease 2019 patients: a propensity-matched analysis of in-hospital outcomes.

AIMS: To estimate if chronic anticoagulant (CAC) treatment is associated with morbidity and mortality outcomes of patients hospitalized for SARS-CoV-2 infection. METHODS: In this European multicentric cohort study, we included 1186 patients of whom 144 were on CAC (12.1%) with positive coronavirus disease 2019 testing between 1 February and 30 July 2020. The average treatment effect (ATE) analysis with a propensity score-matching (PSM) algorithm was used to estimate the impact of CAC on the primary outcomes defined as in-hospital death, major and minor bleeding events, cardiovascular complications (CCI), and acute kidney injury (AKI). We also investigated if different dosages of in-hospital heparin were associated with in-hospital survival. RESULTS: In unadjusted populations, primary outcomes were significantly higher among CAC patients compared with non-CAC patients: all-cause death (35% vs. 18% P < 0.001), major and minor bleeding (14% vs. 8% P = 0.026; 25% vs. 17% P = 0.014), CCI (27% vs. 14% P < 0.001), and AKI (42% vs. 19% P < 0.001). In ATE analysis with PSM, there was no significant association between CAC and primary outcomes except for an increased incidence of AKI (ATE +10.2%, 95% confidence interval 0.3-20.1%, P = 0.044). Conversely, in-hospital heparin, regardless of dose, was associated with a significantly higher survival compared with no anticoagulation. CONCLUSIONS: The use of CAC was not associated with the primary outcomes except for the increase in AKI. However, in the adjusted survival analysis, any dose of in-hospital anticoagulation was associated with significantly higher survival compared with no anticoagulation.

A Rare Evolution to Pneumopericardium in Patient with COVID-19 Pneumonia Treated with High Flow Nasal Cannula.

Infection with severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) which was revealed an official pandemic by the World Health Organization on 11 March 2020. The current pandemic, the third of this decade, is the worst in terms of suffering and deaths related. COVID-19 represents an unprecedented challenge for medical communities and patients around the world. High-resolution computed tomography of the chest (HRCT) is a fundamental tool in both management and diagnosis of the disease. Imaging plays an essential role in the diagnosis of all the manifestations of the disease and its complications and the correct use and interpretation of imaging tests are essential. Pneumomediastinum has been reported rarely in COVID-19 patients. We were one of the first groups to share our experiences in uncommon parenchymal complications of COVID-19 with spontaneous pneumothorax and pneumomediastinum, but also with new-onset bronchiectasis and cysts. A finding of pneumopericardium is also unusual. We hereby report a rare case of spontaneous pneumopericardium in a patient with COVID-19 pneumonia treated only with a high-flow nasal cannula (HFNC).

Effectiveness of corticosteroids on chest high-resolution computed tomography features of COVID-19 pneumonia.

OBJECTIVE: The aim of our study was to assess the effect of a short-term treatment with low-moderate corticosteroid (CS) doses by both a quantitative and qualitative assessment of chest HRCT of COVID-19 pneumonia. METHODS: CORTICOVID is a single-center, cross-sectional, retrospective study involving severe/critical COVID-19 patients with mild/moderate ARDS. Lung total severity score was obtained according to Chung and colleagues. Moreover, the relative percentages of lung total severity score by ground glass opacities, consolidations, crazy paving, and linear bands were computed. Chest HRCT scores, P/F ratio, and laboratory parameters were evaluated before (pre-CS) and 7-10 days after (post-CS) methylprednisolone of 0.5-0.8 mg/kg/day. FINDINGS: A total of 34 severe/critical COVID-19 patients were included in the study, of which 17 received Standard of Care (SoC) and 17 CS therapy in add-on. CS treatment disclosed a significant decrease in HRCT total severity score [median = 6 (IQR: 5-7.5) versus 10 (IQR: 9-13) in SoC, p < 0.001], as well in single consolidations [median = 0.33 (IQR: 0-0.92) versus 6.73 (IQR: 2.49-8.03) in SoC, p < 0.001] and crazy paving scores [mean = 0.19 (SD = 0.53) versus 1.79 (SD = 2.71) in SoC, p = 0.010], along with a significant increase in linear bands [mean = 2.56 (SD = 1.65) versus 0.97 (SD = 1.30) in SoC, p = 0.006]. GGO score instead did not significantly differ at the end of treatment between the two groups. Most post-CS GGO, however, derived from previous consolidations and crazy paving [median = 1.5 (0.35-3.81) versus 2 (1.25-3.8) pre-CS; p = 0.579], while pre-CS GGO significantly decreased after methylprednisolone therapy [median = 0.66 (0.05-1.33) versus 1.5 (0.35-3.81) pre-CS; p = 0.004]. CS therapy further determined a significant improvement in P/F levels [median P/F = 310 (IQR: 235.5-370) versus 136 (IQR: 98.5-211.75) in SoC; p < 0.001], and a significant increase in white blood cells, lymphocytes, and neutrophils absolute values. CONCLUSION: The improvement of all chest HRCT findings further supports the role of CS adjunctive therapy in severe/critical COVID-19 pneumonia.

Usefulness of the HACOR score in predicting success of CPAP in COVID-19-related hypoxemia.

INTRODUCTION: In COVID-19 associated hypoxemic acute respiratory failure (ARF) without mandatory indication for urgent endotracheal intubation, a trial of CPAP may be considered. We aimed to evaluate HACOR (heart rate, acidosis, consciousness, oxygenation, respiratory rate) score performance in these patients as predictor of CPAP failure. METHODS: Prospective observational multicentric study (three centers in different countries), including adult patients with SARS-CoV-2 pneumonia admitted to a respiratory intermediate care unit, presenting PaO2/FiO2 < 300 and PaCO2 < 45 mmHg, who received CPAP. One hour after starting CPAP, HACOR was calculated. RESULTS: We enrolled 128 patients, mean age 61,7 years. Mean HACOR at 1 h after starting CPAP was 3,27 ± 3,84 and mean PaO2/FiO2 was 203,30 ± 92,21 mmHg; 35 patients (27,3 %) presented CPAP failure: 29 underwent oro-tracheal intubation and 6 died due to COVID-19 (all having a do-not-intubate order). HACOR accuracy for predicting CPAP failure was 82,03 %, while PaO2/FiO2 accuracy was 81,25 %. CONCLUSION: Although HACOR score had a good diagnostic performance in predicting CPAP failure in COVID-19-related ARF, PaO2/FiO2 has also shown to be a good predictor of failure.

The Role of High Flow Nasal Cannula in COVID-19 Associated Pneumomediastinum and Pneumothorax.

BACKGROUND: Pneumomediastinum, subcutaneous emphysema and pneumothorax are not rarely observed during the COVID-19 pandemic. Such complications can worsen gas exchange and the overall prognosis in critical patients. The aim of this study is to investigate what predisposing factors are related to pneumomediastinum and pneumothorax in SARS-CoV2-Acute Respiratory Distress Syndrome (ARDS), what symptoms may predict a severe and potentially fatal complication and what therapeutical approach may provide a better outcome. METHODS: In this single center cohort study, we recorded data from 45 critically ill COVID-19 patients who developed one or more complicating events among pneumomediastinum, subcutaneous emphysema and pneumothorax. All patients showed ARDS and underwent non-invasive ventilation (NIV) at baseline. Patients with mild to moderate ARDS and pneumomediastinum/pneumothorax (n = 25) received High Flow Nasal Cannula (HFNC), while patients with severe ARDS and pneumomediastinum/pneumothorax underwent HFNC (n = 10) or invasive mechanical ventilation (IMV) (n = 10). RESULTS: Pneumomediastinum/pneumothorax developed in 10.5% of subjects affected by SARS-coV2-ARDS. Dyspnea affected 40% and cough affected 37% of subjects. High resolution computed tomography of the chest showed bilateral diffuse ground glass opacities (GGO) in 100% of subjects. Traction bronchiolectasis, reticulation, crazy paving and distortion were observed in 64%. Furthermore, 36% showed subcutaneous emphysema. Non-severe ARDS cases received HFNC, and 76% patients recovered from pneumomediastinum/pneumothorax over a median follow up of 5 days. Among severe ARDS cases the recovery rate of pneumomediastinum/pneumothorax was 70% with the HFNC approach, and 10% with IMV. CONCLUSION: HFNC is a safe and effective ventilatory approach for critical COVID-19 and has a positive role in associated complications such as pneumomediastinum and pneumothorax.

Daytime alternatives for non-invasive mechanical ventilation in neuromuscular disorders.

Mechanical ventilation in recent years has benefited from the development of new techniques and interfaces. These developments allowed clinicians to offer increasingly personalised therapies with the combination of different complementary techniques for treating respiratory insufficiency in patients with neuromuscular diseases. The mouthpiece ventilation, intermittent abdominal pressure ventilator and the negative pressure ventilation can offer many patients alternative therapy options when ventilation is required for many hours a day. In this non-systematic review, we will highlight the use of alternative methods to non-invasive mechanical ventilation at positive pressure in neuromuscular patients, to ensure the optimal interface for each patient.

Clinical outcomes of high-flow nasal cannula in COVID-19 associated postextubation respiratory failure. A single-centre case series.

INTRODUCTION: A high-flow nasal cannula (HFNC) is an alternative device for oxygena-tion, which improves gas exchange and reduces the work of breathing. Postextubation respiratory failure causes increased morbidity and mortality. HFNC has been widely employed during the COVID-19 pandemic. The purpose of this paper is to report a single-centre experience on the effectiveness and safety of HFNC in weaning COVID-19 patients. MATERIAL AND METHODS: Nine patients showed severe acute respiratory failure and interstitial pneumonia due to SARS-CoV-2. After mechanical ventilation (5 Helmet CPAP, 4 invasive mechanical ventilation), they were de-escalated to HFNC. Settings were: 34-37°C, flow from 50 to 60 L min-1. FiO2 was set to achieve appropriate SpO2. RESULTS: Nine patients (4 females; age 63 ± 13.27 years; BMI 27.2 ± 4.27) showed a baseline PaO2/FiO2 of 109 ± 45 mm Hg. After a long course of ventilation all patients improved (PaO2/FiO2 336 ± 72 mm Hg). Immediately after initiation of HFNC (2 hours), PaO2/FiO2 was 254 ± 69.3 mm Hg. Mean ROX index at two hours was 11.17 (range: 7.38-14.4). It was consistent with low risk of HFNC failure. No difference was observed on lactate. After 48 hours of HFNC oxygen therapy (day 3), mean PaO2/FiO2 increased to 396 ± 83.5 mm Hg. All patients recovered from respiratory failure after 7 ± 4.1 days. CONCLUSIONS: HFNC might be helpful in weaning COVID-19 respiratory failure. Effectiveness and comfort should be assessed between 2 and 48 hours. Clinical outcomes, oxygenation, and ROX index should be considered, to rule out the need for intubation. Further evidence is required for firm conclusions.

Different presentation of pulmonary parenchymal disruption in COVID-19 pneumonia. Case series of Sub-Intensive Care Unit in Naples, Italy.

The coronavirus disease 2019 (COVID-19) is a recent pandemic that affected more than 5 million people worldwide. Chest high resolution computed tomography (HRCT) is an essential tool in diagnosis and management of the disease. Pulmonary parenchymal opacity is a typical sign of the disease, but not the only one. Pneumothorax, pneumomediastinum, bronchiectasis and cysts are probably underrated complications of COVID-19 that can worsen prognosis, in terms of prolonged hospitalization and need of oxygen therapy. In our single center case series, we outline four different manifestations of pneumothorax, pneumomediastinum and cysts in hospitalized patients with COVID-19 pneumonia.

Successful intravenous immunoglobulin treatment in severe COVID-19 pneumonia.

We describe a 42-year old woman, admitted to our Department after 15 days of persistence of respiratory failure and treated with infusion of intravenous immunoglobulin with a successful outcome.

Circulating dendritic cells are severely decreased in idiopathic pulmonary fibrosis with a potential value for prognosis prediction.

Dendritic cells (DCs) accumulate in the lung of patients affected by idiopathic pulmonary fibrosis (IPF). We measured the frequencies of circulating conventional CD1c + and CD141+ cells (namely, cDC2 and cDC1) and of plasmacytoid CD303+ DCs in a cohort of 60 therapy naive IPF patients by flow cytometry. Peripheral levels of reactive oxygen species (ROS) and of pro-inflammatory and Th1/Th2 polarizing cytokines were also analyzed. All blood DC subtypes were significantly reduced in IPF patients in comparison to age- and sex-matched controls, while ROS and interleukin (IL-6) levels were augmented. IL-6 expression increased along with disease severity, according to the gender-age-physiology index, and correlated with the frequency of cDC2. IL-6 and cDC2 were not influenced by anti-fibrotic therapies but were associated with a reduced survival, the latter being an independent predictive biomarker of worse prognosis. Deciphering the role of DCs in IPF might provide information on disease pathogenesis and clinical behavior.

Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction.

BACKGROUND: Hypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset. METHODS: Conventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry. RESULTS: Despite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (- 13.4 ± 3.8 vs - 18.4 ± 3.3 in controls, P <  0.001) and at peak exercise (- 15.8 ± 2.6 vs - 23.4 ± 4.3, P <  0.001). Systolic pulmonary artery pressure (sPAP) and E/E' ratios increase during effort were higher in OSA than in controls (ΔsPAP 44.3% ± 6.4 vs 32.3% ± 5.5, P <  0.0001, and ΔE/E' 87.5% ± 3.5 vs 25.4% ± 3.3, P <  0.0001, respectively). The best correlate of E/E' at peak stress was peak exertion capacity (r = - 0.50, P <  0.001). OB was also increased in OSA patients (P = 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction. CONCLUSIONS: Evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.

Severe depletion of peripheral blood dendritic cell subsets in obstructive sleep apnea patients: A new link with cancer?

Recent evidence suggests that alterations of the immune responses are associated with the inflammatory nature of obstructive sleep apnea (OSA) and of its related co-morbidities. In this scenario, we asked whether circulating dendritic cell (DC) subsets may be possible players as their role has not yet been detailed. The frequency distribution of peripheral blood myeloid (mDC1 and mDC2) and plasmacytoid (p) DCs was investigated by mean of multi-parametric flow cytometry in 45 OSA patients (mean age: 53 yrs; M = 29) at the time of the first diagnosis and compared to 30 age- and sex-matched healthy controls. Oxidative burst (OB) and serum levels of tumor necrosis factor (TNF)-α, (interleukin) (IL)-6, interferon (INF)-γ, IL-2, IL-4, IL-10 and vascular endothelial growth factor (VEGF) were also analyzed. All subsets of circulating DCs were significantly depleted in OSA patients as compared to healthy subjects (p < 0.01, in all instances), with mDC2 and pDC subtypes being more severely compromised. These findings were co-existing with higher levels of OB along with an increased expression of IL-6, IL-10, TNF-α, IFN-γ, and VEGF (p < 0.005 in all instances). In particular, IL6 levels were significantly higher (p = 0.013) in severe OSA patients (apnea/hypopnea index >30) and were inversely correlated with both mDC2 (r = -0.802, p < 0.007) and pDC (r = -0.317, p = 0.04) subsets. We first provide evidence for a constitutive reduction of all circulating DC subsets in OSA patients. Perturbation of DCs coexists with an inflammatory milieu and is negatively correlated with the expression of IL-6, which is actually recognized as a pivotal inhibitor of DC maturation. Future studies exploring the contribution of DCs in the pathogenesis of OSA and of its complications should be encouraged.

First Description of the Hyperpnea-Hypopnea Periodic Breathing in Patients with Interstitial Lung Disease-Obstructive Sleep Apnea: Treatment Implications in a Real-Life Setting.

There is evidence that hypopneas are more common than apneas in obstructive sleep apnea (OSA) related to idiopathic pulmonary fibrosis (IPF). We investigated the frequency distribution of hypopneas in 100 patients with interstitial lung diseases (ILDs) (mean age 69 yrs ± 7.8; 70% males), including 54 IPF cases, screened for OSA by home sleep testing. Fifty age- and sex-matched pure OSA patients were included as controls. In ILD-OSA patients the sleep breathing pattern was characterized by a high prevalence of hypopneas that were preceded by hyperpnea events configuring a sort of periodic pattern. This finding, we arbitrarily defined hyperpnea-hypopnea periodic breathing (HHPB), was likely reflecting a central event and was completely absent in control OSA. Also, the HHPB was highly responsive to oxygen but not to the continuous positive pressure support. Thirty-three ILD-OSA patients (42%) with a HHPB associated with a hypopnea/apnea ratio ≥3 had the best response to oxygen with a median residual AHI of 2.6 (1.8-5.6) vs. 28.3 (20.7-37.8) at baseline (p < 0.0001). ILD-OSA patients with these characteristics were similarly distributed in IPF (54.5%) and no-IPF cases (45.5%), the most of them being affected by moderate-severe OSA (p = 0.027). Future studies addressing the pathogenesis and therapy management of the HHPB should be encouraged in ILD-OSA patients.