Meropenem plus Ertapenem and Ceftazidime-Avibactam plus Aztreonam for the Treatment of Ventilator Associated Pneumonia Caused by Pan-Drug Resistant Klebsiella pneumonia.

INTRODUCTION: Gram-negative bacteria (GNB) account for about 70% of infections in the intensive care unit (ICU) setting and are associated with significant morbidity and mortality. In recent years, pan-drug resistant (PDR) strains, strains that are not susceptible to any antibiotic, have been emerged and new treatment strategies are required. RESULTS: Fifty eligible patients were recruited in the three groups. A statistically significant reduction in the Sequential Organ Failure Assessment (SOFA) score was observed in the control group on day 4 in comparison to day 0 of VAP (p = 0.005). The Clinical Pulmonary Infection Score (CPIS) was also reduced on day 4 (p = 0.0016) and day 7 in comparison to day 0 (p = 0.001). Patients that received combination therapy, CAZ-AVI + ATM and DCT, presented with a lower SOFA score and CPIS on day 7 in comparison to day 0 (p = 0.0288 and p = 0.037, respectively). No differences in the ΔSOFA score and ΔCPIS were found between the groups. The control group presented with a significantly lower ICU stay and duration of mechanical ventilation (p = 0.03 and p = 0.02, respectively). There was no difference in mortality. MATERIALS AND METHODS: This is a retrospective analysis. This study was conducted in a mixed ICU in the University Hospital of Larissa, Thessaly, Greece during a three-year period (2020-2022). Patients suffering from ventilator associated pneumonia (VAP) due to carbapenem-resistant K. pneumonia (CR-KP) were divided in three different groups: the first one was treated using ceftazidime-avibactam plus aztreonam (CAZ-AVI + ATM group), the second was treated using double carbapenems (DCT group), and the last one (control group) received appropriate therapy since the strain was susceptible in vitro to at least to one antibiotic. CONCLUSIONS: Treatment with CAZ-AVI +ATM or DCT may offer a clinical benefit in patients suffering with infections due to PDR K. pneumoniae. Larger studies are required to confirm our findings.

Incidence and Risk Factors for Blood Stream Infection in Mechanically Ventilated COVID-19 Patients.

It is widely known that blood stream infections (BSIs) in critically ill patients may affect mortality, length of stay, or the duration of mechanical ventilation. There is scarce data regarding blood stream infections in mechanically ventilated COVID-19 patients. Preliminary studies report that the number of secondary infections in COVID-9 patients may be higher. This retrospective analysis was conducted to determine the incidence of BSI. Furthermore, risk factors, mortality, and other outcomes were analyzed. The setting was an Intensive Care Unit (ICU) at a University Hospital. Patients suffering from SARS-CoV-2 infection and requiring mechanical ventilation (MV) for >48 h were eligible. The characteristics of patients who presented BSI were compared with those of patients who did not present BSI. Eighty-four patients were included. The incidence of BSI was 57%. In most cases, multidrug-resistant pathogens were isolated. Dyslipidemia was more frequent in the BSI group (p < 0.05). Moreover, BSI-group patients had a longer ICU stay and a longer duration of both mechanical ventilation and sedation (p < 0.05). Deaths were not statistically different between the two groups (73% for BSI and 56% for the non-BSI group, p > 0.05). Compared with non-survivors, survivors had lower baseline APACHE II and SOFA scores, lower D-dimers levels, a higher baseline compliance of the respiratory system, and less frequent heart failure. They received anakinra less frequently and appropriate therapy more often (p < 0.05). The independent risk factor for mortality was the APACHE II score [1.232 (1.017 to 1.493), p = 0.033].

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort.

BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.

Transesophageal echocardiography during endovascular procedures for thoracic aorta diseases: sensitivity and specificity analysis.

INTRODUCTION: The widespread use of endovascular repair in thoracic aorta (TEVAR) pathologies has ameliorated postoperative outcomes. This meta-analysis was designed to investigate the intra-operative use of transesophageal echocardiography (TEE) compared to angiography in patients undergoing TEVAR. EVIDENCE ACQUISITION: The meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines. A data search of the English literature was conducted, using PubMed, EMBASE and CENTRAL databases, until November 30, 2019. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence and the summary of findings for each of the included outcomes. EVIDENCE SYNTHESIS: The final analysis included 7 articles (183 patients). All patients underwent TEVAR using intra-operative TEE and angiography. The sensitivity and specificity rates of entry points were 0.624 (95% CI: 0.145-0.97) and 0.377 (95% CI: 0.029-0.856), respectively. Regarding the detection of adequate guidewire advancement, the sensitivity was 0.778 (95% CI: 0.288-939) and specifity 0.346 (95% CI: 0.019-0.844). TEE could detect endograft incomplete deployment within acceptable rates of sensitivity and specifity, estimated at 0.616 (95% CI: 0.141-0.971) and 0.365 (95% CI: 0.028-0.845), respectively. The intra-operative detection of endoleaks presented a sensitivity estimated at 0.875 (0.51-0.998) and specificity at 0.698 (95% CI: 0.284-0.904). CONCLUSIONS: Despite the limitations of this analysis, TEE may be evaluated in the current endovascular era, as a useful tool, providing adequate information, on graft deployment and early endoleaks.

Noninvasive ventilation in chronic respiratory failure: effects on quality of life.

BACKGROUND: Noninvasive ventilation (NIV) has been found to be an essential technique to treat chronic respiratory failure (CRF) resulting from restrictive thoracic disorders (RTD). The last decades were characterized by the expansion of NIV to treat patients suffering from various other conditions, such as chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). OBJECTIVES: The aim of this study was to evaluate the effect of NIV on health-related quality of life (HRQoL) of patients with CRF during 2 years and to identify parameters associated with changes in HRQoL. METHODS: Ninety-one patients with CRF [35 COPD; 17 RTD; 28 OHS; 11 neuromuscular diseases (NMD)] participated. HRQoL was assessed with the SF-36 questionnaire. Additional measurements included blood gases, pulmonary function tests, dyspnea, daytime sleepiness, exacerbations and hospitalizations. The patients were evaluated every 3-6 months. RESULTS: Improvements in SF-36 physical component summary (PCS, p < 0.0001) and mental component summary (MCS, p < 0.0001) scores in RTD and MCS in OHS (p = 0.01) and COPD (p = 0.003) were observed by the third month. PCS in OHS and COPD patients improved by the sixth month (p = 0.003 and p < 0.0001, respectively). NMD patients did not present improvements in HRQoL. Improvements in HRQoL were associated with improvements in PaO(2) and dyspnea in COPD patients, and with total hours of daily ventilator use, improvement in dyspnea, pressure support and expiratory positive airway pressure in RTD patients. CONCLUSION: Home NIV is consistently effective in improving HRQoL and physiological parameters in patients with CRF. Randomized trials to identify subgroups of COPD responders are justified by our results.

Diagnostic accuracy of biomarkers of oxidative stress in parapneumonic pleural effusions.

BACKGROUND: The imbalance between oxidants and antioxidants is referred to as oxidative stress and has been associated with various respiratory disorders. The aim of this study was the assessment of 8-isoprostane (8-iso-PGF(2α)) and Cu/Zn superoxide dismutase (Cu/Zn SOD) in exudative pleural effusions in order to examine the diagnostic accuracy of these markers in the differentiation between complicated and uncomplicated parapneumonic effusions. METHODS: The study included 214 consecutive patients with pleural effusions [68 parapneumonic (31 uncomplicated parapneumonic, 20 complicated parapneumonic, 17 empyemas), 24 tuberculous, 88 malignant and 34 transudates]. 8-Isoprostane and Cu/Zn SOD were determined by ELISA in pleural fluid and serum. RESULTS: Parapneumonic effusions were characterized by higher pleural fluid 8-isoprostane levels compared to transudative, malignant and tuberculous effusions. Pleural fluid Cu/Zn SOD levels were lower in transudates, while serum levels were higher in transudative compared to all exudative pleural effusions. Both pleural fluid 8-isoprostane and Cu/Zn SOD were higher in complicated parapneumonic effusions and empyemas compared to uncomplicated parapneumonic effusions. Pleural fluid 8-isoprostane was the most accurate test to differentiate between complicated and uncomplicated parapneumonic pleural effusions with a sensitivity of 100% and a specificity of 58·1% at a cut-off point of 35·1 (AUC = 0·848). CONCLUSIONS: Pleural fluid 8-isoprostane and Cu/Zn SOD may provide useful information for the differentiation between uncomplicated and complicated parapneumonic effusions and empyemas.

Clinical, functional and biochemical changes during recovery from COPD exacerbations.

The pathways underlying chronic obstructive pulmonary disease exacerbations (ECOPD) remain unclear. This study describes the clinical, functional and biochemical changes during recovery from ECOPD. Thirty hospitalized patients with Anthonisen's type-I ECOPD were evaluated on days 0 (admission), 3, 10 and 40. A five-symptom score (TSS), performance status and quality of life were evaluated. Post-bronchodilator spirometry, blood gases, oxidative stress, C-reactive protein (CRP), serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and fibrinogen were also measured. Patients were classified as early- or late-recoverers, based on whether dyspnea had returned to pre-exacerbation level by day 10. Most clinical, functional and biochemical parameters improved during follow-up. CRP and IL-6 levels reduced on Day 3 (p<0.05), whereas SAA on Day 10 (p<0.01). TNF-alpha was reduced on Days 3 and 10, but on Day 40 its levels returned to baseline. Fibrinogen and WBC reduced only by day 40. TSS and dyspnea were correlated inversely with FEV(1) on days 3, 10 and 40. Although late-recoverers had lower FEV(1) on admission, none of the reported measurements on admission and day 3 predicted early recovery. During recovery from ECOPD, symptomatic improvement correlates only with post-bronchodilator FEV(1) whereas systemic inflammatory burden subsidence does not correlate with clinical and functional changes. Although late-recoverers have lower FEV(1) on admission, none of the measured parameters is able to predict early symptomatic recovery.

Non-invasive ventilation in chronic hypercapnic COPD patients with exacerbation and a pH of 7.35 or higher.

BACKGROUND: Current guidelines suggest the use of non-invasive ventilation (NIV) in hypercapnic chronic obstructive pulmonary disease (COPD) exacerbations in patients presenting with a pH of 7.25-7.35. The aim of this study was to investigate the role of NIV in COPD patients with chronic hypercapnic respiratory failure admitted to the hospital with acute exacerbations and an arterial pH of 7.35 or higher. METHODS: Forty-seven COPD patients with chronic hypercapnic respiratory failure admitted for exacerbations and with a pH of 7.35 or higher were randomized to receive standard medical therapy (control group) or medical therapy plus NIV (NIV group). Arterial blood gases were measured at baseline, after 1 h, 6 h, 12 h, 24 h, 48 h, and at discharge. Need for admission to intensive care unit (ICU), death, and duration of hospitalization were recorded. The final analysis included 42 patients (21 controls and 21 NIV patients). RESULTS: NIV resulted in a shorter hospital stay (5.5+/-2.6 vs 10.1+/-4.4 days for controls, p=0.0004). Two patients from the control group were admitted to the ICU and one eventually died, whereas all NIV patients were successfully discharged. The NIV group showed a faster improvement in PaCO(2) and pH. At discharge, the NIV group had a lower PaCO(2) (6.5+/-0.6 kPa vs 7.5+/-1.1 kPa, p=0.01) but a comparable pH (7.43+/-0.03 vs 7.43+/-0.04, p=0.93). PaO(2) and PaO(2)/FiO(2) levels showed similar improvement in both groups at discharge. CONCLUSION: Early administration of NIV in COPD patients with chronic hypercapnic respiratory failure admitted for acute exacerbations with a pH of 7.35 or higher results in a reduced hospital stay and faster improvement of arterial blood gases.