A Literature Review of Pathophysiology, Clinical Manifestations, Medications and Optimal Dosage, Outpatient, and Post-hospitalization Use of Anticoagulation in COVID-19 Patients.

Since severe acute respiratory syndrome coronavirus 2 led to a world pandemic, extensive research has been conducted to identify its characteristics and form an appropriate management plan. One recognized complication of COVID-19 is coagulation defects that can lead to thromboembolic events. We have reviewed the literature to summarize and present the latest research about the pathophysiology, clinical manifestations, anticoagulation use and appropriate dose in COVID-19 patients, as well as the effect of anticoagulation in outpatient and post-hospital settings. The pathophysiology of coagulation abnormalities in COVID-19 is not fully understood yet, but multiple mechanisms appear to be involved, such as a direct viral attack, hyperinflammation, increased immune response, blood stasis, and endothelial injury. Clinical manifestations are mainly venous thromboembolism (deep vein thrombosis and pulmonary embolism), arterial thromboembolism, ischemic stroke, central venous sinus thrombosis, and central retinal vein occlusion. Anticoagulation is widely used in hospitalized patients with COVID-19, unless it is contraindicated. Heparinoid is the main anticoagulant used. However, the appropriate dosage is still debated as research is trying to find a balance between benefits and risks. In outpatients, it appears that anticoagulation has no benefit in contrast to post-hospitalization use, where benefit could be observed in severely affected patients. We concluded that thromboprophylaxis should be used in treating hospitalized COVID-19 patients, but the dosage is still a matter of debate. More research needs to be done on outpatient and post-hospitalized patients to derive accurate conclusions.

N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis.

BACKGROUND: N-acetylcysteine (NAC) is a mucolytic agents with anti-inflammatory properties that has been suggested as an adjunctive therapy in patients with COVID-19 pneumonia. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate available evidence on the possible beneficial effects of NAC on SARS-CoV-2 infection. METHODS: In September 2022, we conducted a comprehensive search on Pubmed/Medline and Embase on randomized controlled trials (RCTs) and observational studies on NAC in patients with COVID-19 pneumonia. Study selection, data extraction and risk of bias assessment was performed by two independent authors. RCTs and observational studies were analyzed separately. RESULTS: We included 3 RCTs and 5 non-randomized studies on the efficacy of NAC in patients with COVID-19, enrolling 315 and 20826 patients respectively. Regarding in-hospital mortality, the summary effect of all RCTs was OR: 0.85 (95% CI: 0.43 to 1.67, I2=0%) and for non-randomized studies OR: 1.02 (95% CI: 0.47 to 2.23, I2=91%). Need for ICU admission was only reported by 1 RCT (OR: 0.86, 95% CI:0.44-1.69, p=0.66), while all included RCTs reported need for invasive ventilation (OR:0.91, 95% CI:0.54 to 1.53, I2=0). Risk of bias was low for all included RCTs, but certainty of evidence was very low for all outcomes due to serious imprecision and indirectness. CONCLUSION: The certainty of evidence in the included studies was very low, thus recommendations for clinical practice cannot be yet made. For all hard clinical outcomes point estimates in RCTs are close to the line of no effect, while observational studies have a high degree of heterogeneity with some of them suggesting favorable results in patients receiving NAC. More research is warranted to insure that NAC is both effective and safe in patients with COVID-19 pneumonia.

Soluble urokinase plasminogen activator receptor (suPAR) in the emergency department: An update.

Background: The biomarker soluble urokinase plasminogen activator receptor (suPAR) is an indicator of inflammation which is increased in a variety of chronic and acute disease states. Its most promising application in the emergency setting is to aid in the prognostic stratification of patients by identifying those at high risk of deterioration. This is a narrative review of studies evaluating the use of suPAR. Methods: We conducted a Medline search for studies on the use of suPAR in patients acutely admitted to the emergency department. Results: 25 original studies were included in the review. suPAR as a marker of inflammation has been used alone or combined to other inflammatory biomarkers in the assessment of patients suffering from various acute and chronic diseases in an emergency setting. As it is non-specific, it may increase in infectious disease, malignancy or acute coronary syndromes among other conditions, but quantitative suPAR levels correlate with disease severity. It may be useful for the identification of high risk patients regardless of underlying pathology. Conclusion: As the ideal biomarker in the emergency setting has not been identified yet, suPAR may be a promising addition to the established biomarkers for the initial assessment of patients in this setting. Additional research is necessary to evaluate the usefulness of suPAR guided management algorithms.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Percentage Ratio as Predictors of In-hospital Mortality in Sepsis. An Observational Cohort Study.

Background: Sepsis remains a major public health problem with increased incidence of mortality. As early recognition and prompt treatment in the first 'golden hour' remain the cornerstone of the septic patient approach, there is a real need for rapid and cost-effective reliable markers. Objective: The aim of the study was to evaluate the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte percentage ratio (PL%R) in patients with sepsis who were initially treated in the Emergency Department and investigate their predictive ability regarding in-hospital mortality and performance comparing them to SOFA, APACHE II, and SAPS II score. Methods: A retrospective observational study in the Emergency Department and Internal Medicine Department in a Mediterranean University Hospital. A total of forty-three patients suffering from sepsis were enrolled in the study. Demographic information, past medical history with pre-existing co-morbidities, physical examination findings, and radiological data were reviewed. Neutrophil to lymphocyte ratio and platelets to lymphocyte percentage ratio was calculated from the complete blood count (CBC). Disease severity was evaluated by calculating SOFA, SAPS II and APACHE II score on admission. The outcome of patients was noted as a primary endpoint. Results: Values of NLR and PL%R were statistically significantly higher in the group of non-survivors and correlate with sepsis prognostic scores. Conclusion: Calculation of NLR and PL%R is easy, fast, and inexpensive in the assessment of patients with sepsis. Their role as prognostic indexes and their validity in the Emergency Department setting should be evaluated with large prospective studies.

High-Flow vs. Low-Flow Nasal Cannula in Reducing Hypoxemic Events During Bronchoscopic Procedures: A Systematic Review and Meta-Analysis.

Introduction: High-flow nasal cannula (HFNC) oxygenation method has been proven to be successful in oxygenation of patients with respiratory failure and has exhibited clinical superiority compared to low-flow nasal cannula (LFNC). Methods: We performed a systematic review and meta-analysis to evaluate the potential favorable impact of HFNC oxygenation during bronchoscopy and related procedures like endobronchial ultrasound-transbronchial needle aspiration. Only randomized control trials (RCTs) were included in the meta-analysis. Results: Six randomized control trials with 1,170 patients were included in this meta-analysis. Patients who underwent bronchoscopy with the use of high-flow nasal cannula experienced less hypoxemic events/desaturations, less procedural interruptions and pneumothoraxes compared to patients under low-flow nasal cannula treatment. This beneficial effect of HFNC in hypoxemic events was persistent 10 min after the end of procedure. Conclusion: The high-flow nasal cannula (HFNC) oxygenation method could reduce hypoxemic events and related peri- and post-bronchoscopic complications.

High-flow versus conventional nasal cannula oxygen supplementation therapy and risk of hypoxia in gastrointestinal endoscopies: a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal endoscopy (GIE) represents a mainstay diagnostic and therapeutic procedure in clinical practice. Hypoxemia constitutes a major complication for endoscopists. Emerging evidence supports the utilization of high-flow nasal cannula (HFNC) over conventional nasal cannula (CNC) for avoidance of hypoxemia. Our aim was to compare the hypoxemia risk in patients undergoing GIE with HFNC versus CNC oxygen supplementation recruited by randomized controlled trials (RCTs). METHODS: We searched in medical databases PubMed, EMBASE and Cochrane to identify RCTs investigating the abovementioned association. Enrolled studies were evaluated for risk of bias and inserted into a random effects model for meta-analysis; subgroup analyses and publication bias were also assessed. RESULTS: Out of 271 articles, five RCTs were eligible (patients n=2656, HFNC 1299 and CNC 1357). A statistically significant reduced relative risk (RR) of hypoxemia among HFNC patients was revealed (RR=0.18, CI95%: 0.05-0.61), whilst with high heterogeneity (I2:79.94%, p<0.01). Patients undergoing upper GIE with HFNC displayed a significantly lower hypoxemia risk (96%, p<0.001, I2:15.59%), even after exclusion of endoscopic retrograde cholangiopancreatography cases (RR:0.03, CI95%:0.01-0.21), albeit with higher heterogeneity (I2:41.82%).    . CONCLUSION: Patients undergoing upper GIE with HFNC experience significantly less hypoxemia burden than CNC counterparts. Further research is warranted to target optimal safety during endoscopy.Abbreviations: ASA, American Society of Anesthesiologists; ASGE, American Society for Gastrointestinal Endoscopy; BMI, Body Mass Index; CI, confidence interval; CNC, conventional nasal cannula; ERCP, endoscopic retrograde cholangiopancreatography; FiO2, fraction of inspired O2; GI, gastrointestinal; GIE, gastrointestinal endoscopies; HFNC, High-Flow nasal cannula; ICU, intensive care unit; PEEP, positive end-expiratory pressure; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis; RCTs, randomized control trials; RR, relative risk (or risk ratio).

The Role of High Flow Nasal Oxygen in the Management of Severe COVID-19: A Systematic Review.

INTRODUCTION: Oxygen therapy remains the cornerstone for managing patients with severe SARS-CoV-2 infection and several modalities of non-invasive ventilation are used worldwide. High-flow oxygen via nasal canula is one therapeutic option which may in certain cases prevent the need of mechanical ventilation. The aim of this review is to summarize the current evidence on the use of high-flow nasal oxygen in patients with severe SARS-CoV-2 infection. MATERIAL AND METHODS: We conducted a systematic literature search of the databases PubMed and Cochrane Library until April 2021 using the following search terms: "high flow oxygen and COVID-19" and "high flow nasal and COVID-19". RESULTS: Twenty-three articles were included in this review, in four of which prone positioning was used as an adjunctive measure. Most of the articles were cohort studies or case series. High-flow nasal oxygen therapy was associated with a reduced need for invasive ventilation compared to conventional oxygen therapy and led to an improvement in secondary clinical outcomes such as length of stay. The efficacy of high-flow nasal oxygen therapy was comparable to that of other non-invasive ventilation options, but its tolerability is likely higher. Failure of this modality was associated with increased mortality. CONCLUSION: High flow nasal oxygen is an established option for respiratory support in COVID-19 patients. Further investigation is required to quantify its efficacy and utility in preventing the requirement of invasive ventilation.

Introdução: A oxigenoterapia continua a ser o pilar do tratamento de doentes com infecção grave por SARS-CoV-2 e várias modalidades de ventilação não invasiva são usadas em todo o mundo. O oxigénio de alto fluxo via cânula nasal é uma opção terapêutica que pode, em certos casos, evitar a necessidade de ventilação mecânica. Material e Métodos: Realizámos uma pesquisa sistemática da literatura nas bases de dados PubMed e Cochrane Library até abril de 2021 usando os seguintes termos de pesquisa: "oxigénio de alto fluxo e COVID-19" e "alto fluxo nasal e COVID-19". Resultados: Vinte e três artigos foram incluídos nesta revisão, em quatro dos quais a posição de decúbito ventral foi usada como medida adjuvante. A maioria dos artigos eram estudos de coorte ou séries de casos. A oxigenoterapia nasal de alto fluxo pode reduzir a necessidade de ventilação invasiva em comparação com a oxigenoterapia convencional e pode melhorar os resultados clínicos. A eficácia da oxigenoterapia nasal de alto fluxo é comparável à de outras opções de ventilação não invasiva, embora a sua tolerabilidade seja provavelmente superior. O insucesso dessa modalidade está associado ao aumento da mortalidade. Conclusão: O oxigénio nasal de alto fluxo é uma opção estabelecida para suporte respiratório em doentescom COVID-19. É necessária investigação adicional para medir a sua eficácia e utilidade na prevenção da necessidade de ventilação invasiva.

Evaluation of four novel prognostic scores on admission for COVID-19 mortality. An experience from a Mediterranean tertiary center.

AIM: To assess the performance of four novel prognostic scores on admission in predicting in-hospital mortality in patients with confirmed SARS-CoV-2 infection and compare it to NEWS2 and respiratory SOFA score. METHODS: A total of 85 adult patients admitted to a tertiary hospital in Western Greece with positive SARS-CoV-2 PCR test, were enrolled and divided into the non-survivor (n = 10) and survivor (n = 75) groups. Receiver Operating Characteristic (ROC) analysis was conducted to determine the predictive effect of the COVID-19 Mortality Score, COVID-19 Severity Index, 4 C Mortality Score and COVID-IRS NLR. Subsequently, they were compared to the respiratory component of the SOFA score and NEWS2. RESULTS: ROC curve analysis showed that the COVID-19 Mortality Score (score ≥4) had the highest combination of sensitivity and specificity values for predicting in-hospital mortality (Sensitivity = 0.8, Specificity = 0.853). The Area Under Curve (AUC) for predicting in hospital mortality for the COVID-19 Mortality Score, COVID-19 Severity Index, 4 C Mortality Score and COVID-IRS NLR were 0.846, 0.815, 0.789 and 0.787, respectively. Comparison between the AUC of the four novel COVID-19 scores, respiratory SOFA and NEWS2 showed no significant differences. CONCLUSION: All four novel prognostic scores had acceptable to excellent AUC values for predicting in hospital mortality. Out of the four novel prognostic scores for patients with COVID-19, the COVID-19 mortality score showed the best results in our cohort. Its prognostic ability was superior to that of the NEWS2 and respiratory SOFA score.

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis.

OBJECTIVE: Osteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), of patients with COPD. METHODS: A PubMed/Medline search was conducted using the search terms "chronic obstructive pulmonary disease", "osteoporosis" and "vertebral compression fracture". Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335. RESULTS: Of the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I2=89%, P<0.01), decreased FEV1/FVC with a mean difference of -4.80% (95% CI: -6.69; -2.90, I2=83%, P<0.01) and decreased FEV1, with a mean difference of -4.91% (95% CI: -6.51; -3.31, I2=95%, P<0.01) and -0.41 L (95% CI: -0.59; -0.24, I2=97%, P<0.01), compared to control subjects. Apart from FEV1 (liters) in subgroup 1 (P=0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies. CONCLUSION: Osteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.

Evaluation of Plasma Soluble Urokinase Plasminogen Activator Receptor Levels in Patients With COVID-19 and Non-COVID-19 Pneumonia: An Observational Cohort Study.

BACKGROUND: The respiratory system is the main system affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a great number of infected people need hospitalization. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker indicative of acute and chronic inflammation. Current literature supports that suPAR has great predictive ability for mortality in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to compare the value of suPAR and other laboratory biomarkers in patients with chest infection and suspected COVID-19. METHODS: A total of 41 consecutive patients with chest infection were enrolled in the study and were assigned into two groups according to the real-time polymerase chain reaction (PCR) result for SARS-CoV-2. The two groups had no significant difference in baseline data (age, sex), arterial oxygen partial pressure (PO2)/fraction of inspired oxygen (FiO2) ratio and mortality. RESULTS: Among patients with chest infection who required hospitalization, suPAR was significantly higher on admission in those with COVID-19 when compared to patients with non-COVID-19. suPAR had a great prognostic ability for in-hospital mortality in the COVID-19 subgroup. CONCLUSIONS: A single measurement of suPAR on admission can provide prognostic information for patients with suspected COVID-19 pneumonia. In the subgroup of patients with positive real-time PCR result for SARS-CoV2, suPAR was significantly higher and had an excellent prognostic value for the in-hospital mortality.

Evaluation of Admission Chest X-Ray Findings in Patients With Respiratory Infection During the COVID-19 Pandemic.

AIMS: To evaluate the prevalence of X-ray findings in hospitalized patients requiring hospitalization with suspected Coronavirus disease 2019 (COVID-19) infection and potential differences in the laboratory values and clinical outcomes related to the presence of abnormal chest X-ray (CXR) findings. METHODS:  A total of 117 patients suspected of COVID-19 pneumonia and hospitalized with symptoms of lower respiratory tract disease were included in this study. Patients were divided into subgroups according to COVID-19 diagnosis and statistical comparisons were made according to CXR findings. RESULTS:  In our cohort, CXR abnormalities were more common in patients with confirmed COVID-19 diagnosis and were associated with increased mortality. Patients with abnormal chest X-rays had a significantly lower PaO2/FiO2 ratio both in the COVID-19 and non-COVID-19 groups. CONCLUSION: CXR is a routine examination in all patients with symptoms of lower respiratory tract disease and its findings relate to in-hospital mortality and PaO2/FiO2 ratio. Thus, it can be a significant measure of disease severity, especially in resource restrained settings and emergency situations such as the COVID-19 pandemic.

Cytokine production and outcome in MDR versus non-MDR gram-negative bacteraemia and sepsis.

BACKGROUND: Sepsis represents a life-threatening syndrome characterized by a cytokine storm. Whether cytokine levels are related to the susceptibility pattern of invasive micro-organism remains a matter of debate. The purpose of this study is to investigate the immune response in multidrug resistant (MDR) and non-MDR sepsis patients by measuring cytokine levels, compare the outcome and determine predictors of mortality. MATERIALS AND METHODS: A total of 128 septic patients, treated in intensive care unit (ICU) were enrolled in the study. Epidemiological and ICU data were recorded. Plasma concentrations of angiopoietin-2 (Ang-2), interleukin (IL)-6, IL-10, tumour necrosis factor-α (TNF-α) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) were measured on admission. RESULTS: A total of 90 patients suffered from non-MDR and 38 from MDR gram-negative sepsis. Levels of TNF-α were significantly higher (p = .017) in non-MDR sepsis patients. All pro-inflammatory cytokines were significantly increased in severely ill patients compared to patients with lower acute physiology and chronic health evaluation (APACHE) II score. MDR positive patients had a significantly lower 28-d survival (p = .008). Factors that were independently associated with higher 28-d mortality were carbapenem resistance (OR 5.38 [1.032 - 28.12], p = .046), male gender (OR 2.76 [1.156 - 6.588], p = .022), APACHE II score (OR 1.126 [1.048 - 1.21], p = .001) and Ang-2 (OR 1.025 [1.001 - 20.1], p = .048). CONCLUSIONS: Sepsis evolution and outcome are influenced by multiple factors. Although MDR pathogens induced a weaker immune response characterized by lower TNF-α levels this was not accompanied by better survival. Increased Ang-2 levels, APACHE II score and carbapenem resistance are important factors associated with higher mortality.

Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis.

Sepsis is a condition characterized by high morbidity and mortality which is commonly encountered in an emergency and critical care setting. Despite a substantial body of research, the ideal biomarker for the diagnosis and prognostic stratification of septic patients remains unknown. This review aimed to summarize the publications referring to the validity of the biomarker presepsin when used for the detection, monitoring and prognosis in patients suffering with sepsis. This work is a narrative review based on a PubMed/Medline search conducted in order to identify all relevant publications referring to the use of presepsin in sepsis. Search was not limited by year of publication so all articles archived in the database would be retrieved. No article from before 2010 was identified. A total of 57 publications of the last decade were included, all of which support the use of presepsin as a biomarker for the assessment of septic patients. It has been used alone or in combination with commonly used biomarkers in the evaluation of patients with sepsis in settings such as the emergency department and the intensive care unit. It is useful in the initial workup of patients with suspected sepsis in the emergency setting and may be a predictive factor of mortality and the most severe complication of sepsis. Presepsin seems to be a valuable tool for the laboratory workup of sepsis, especially when used in conjunction with other biomarkers and clinical rating scores with an established role in this population. Further research is needed to evaluate the clinical implications of utilizing presepsin measurements in the workup of sepsis.

Continuous positive airway pressure in the treatment of COVID-19 patients with respiratory failure. A report of six cases with excellent outcome.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently considered a significant threat to global health and global economy. This new rapidly spreading virus causes enormous stress to healthcare systems as large number of patients present with respiratory failure, needing intubation and mechanical ventilation. While the industry is racing to meet the rising demand for ventilators, all the alternative respiratory support modalities are employed to save lives in hospitals around the globe. We hereby report 6 patients who were diagnosed with SARS-CoV-2 and treated with continuous positive airway pressure in a negative pressure isolated room in a tertiary center in western Greece. The rapid progression of mild flu-like symptoms to respiratory failure in all patients was controlled with the use of continuous positive airway pressure making this strategy a reasonable alternative to respiratory failure due to SARS-CoV-2 as it may avert intubation and mechanical ventilation.

The use of soluble urokinase plasminogen activator receptor (suPAR) as a marker of sepsis in the emergency department setting. A current review.

Aim: The purpose of this review is to summarize all relevant publications regarding the use and validity of the soluble urokinase plasminogen activator receptor (suPAR) when used by clinicians in the emergency department (ED) for the detection and monitoring of patients with sepsis syndrome. Methods: A PubMed search was conducted in order to identify all publications related to the use of suPAR in sepsis patients in the ED setting. Results: Although suPAR is actively involved in the pathophysiology of sepsis, over the last 15 years, only a few studies have been published referring to its predictive validity in the ED. Conclusions: SuPAR can be easily and rapidly measured in an ED setting, and its role in the exclusion of an infection and the management of sepsis, alone or in combination to other biomarkers, should be further evaluated. The optimal cut-off value, the timing of the measurement and the role of the suPAR in an ED setting should be further investigated.

High flow nasal cannula oxygen therapy in adults with COVID-19 respiratory failure. A case report.

The novel corona virus (SARS-CoV-2) continuous to spread around the globe causing high mortality, tremendous stress on healthcare systems and an unprecedented disruption of everyday life with unpredictable socioeconomic ramifications. The diseaseis typically affecting the respiratory system and some patients will develop refractory hypoxemic respiratory insufficiency requiring mechanical ventilation. The role of non-invasive ventilation (NIV), high flow nasal cannula (HFNC) or continuous positive airway pressure devices (C-PAP) in the treatment of the 2019 corona virus disease (COVID-19) is not yet clear. We hereby report a case of a 44-year-old COVID-19 positive male patient suffering from hypoxic respiratory failure that was successfully treated with high flow nasal cannula oxygen therapy in a negative pressure intensive care room. Although specific criteria for the use of high flow nasal canula devices COVID-19 are not available at this time, clinicians could use this non-invasive modality as analternative method of respiratory support in selected patients presenting with respiratory failure.

Molecular characteristics and predictors of mortality among Gram-positive bacteria isolated from bloodstream infections in critically ill patients during a 5-year period (2012-2016).

To identify the molecular characteristics of Gram-positive cocci isolated from blood cultures and clinical outcome among critically ill patients. This retrospective study was conducted in the general intensive care unit of the University General Hospital of Patras, Greece, during a 5-year period (2012-2016). All adult patients with a Gram-positive BSI were included. PCR was applied to identify mecA gene (staphylococci); vanA, vanB, and vanC genes (enterococci). Linezolid-resistant S. epidermidis, MRSA, and VRE were further typed by multilocus sequence typing. Mutations in region V of 23S rDNA and ribosomal protein L4were investigated by PCR and sequencing analysis. The presence of the cfr gene was tested by PCR. In total, 141 Gram-positive BSIs were included. Coagulase-negative staphylococci predominated (n = 69; 65 methicillin-resistant, 23 linezolid-resistant carrying both C2534T and T2504A mutations and belonging to the ST22 clone), followed by enterococci (n = 46; 11 vancomycin-resistant carrying vanA gene, classified into four clones), S. aureus (n = 22; 10 methicillin-resistant, classified into three clones) and streptococci (n = 4). The most common type of infection was catheter-related (66; 46.8%), followed by primary BSI (28; 19.9%). Overall 14-day fatality was 24.8%. Multivariate analysis revealed septic shock as independent predictor of fatality, while appropriate empiric antimicrobial treatment and catheter-related BSI were identified as a predictor of good prognosis. Even though most of Gram-positive cocci were multidrug-resistant, fatality rate was low, associated with catheter-related BSIs. Among CNS, LR isolates represented one-third of BSIs due to the dissemination of ST22 S. epidermidis propagated by utilization of linezolid.

Risk factors for acute kidney injury in critically ill patients with bacteraemia by carbapenem non-susceptible Gram negative bacteria.

The objectives of the present study were to identify risk factors for development of acute kidney injury (AKI) during the treatment of bacteraemia due to carbapenem non-susceptible Gram-negative bacteria (CnS-GNB) and its role on mortality. Data of all patients with bacteraemia by CnS-GNB in the intensive care unit of a tertiary hospital from 2012 to 2016 were included. AKI was defined by AKIN criteria. Secondary outcomes were AKI development in patients treated with colistin and predictors of 14-day mortality. Among 285 episodes of bacteraemia due to CnS-GNB, 84 (29.5%) developed AKI. Multivariate analysis revealed that obesity, septic shock, maximum noradrenaline dose and eGFR<60 mL/min/1.73m² upon bacteraemia onset were independently associated with development of AKI. Out of 228 patients receiving colistin, 64 (28.1%) developed AKI. Multivariate analysis found the same factors as before in addition to voriconazole administration. Fourteen-day mortality was 34.2% and was independently associated with bacteraemia by Pseudomonas aeruginosa, AKI during bacteraemia treatment, maximum noradrenaline dose, SAPS II and SOFA scores upon bacteraemia onset, whereas appropriate combination therapy and catheter-related bacteraemia were independently associated with better survival. AKI was a frequent complication of bacteraemia by CnS-GNB and was associated with septic shock and baseline renal function impairment. Mortality was higher among patients that developed AKI due to bacteraemia. Colistin should be considered a safe therapeutic option for treating such infections.

Relation Between Central Venous, Peripheral Venous and Arterial Lactate Levels in Patients With Sepsis in the Emergency Department.

BACKGROUND: Sepsis and multi-organ failure remain a major clinical problem with high morbidity and mortality worldwide. Lactate measurement remains part of the initial assessment and management of patients with sepsis. Although arterial blood is most commonly used for lactate measurement, there is increasing use of peripheral venous lactate for initial assessment and for monitoring of response to treatment in patients with sepsis. The aim of this study was to evaluate the relation between lactate levels measured from central line, peripheral vein and arterial line in patients treated for sepsis in the emergency department (ED). METHODS: This prospective study enrolled 31 patients with diagnosis of sepsis who were evaluated and treated in the ED of a university hospital. During initial resuscitation, blood samples from the artery, peripheral vein and central vein (when available) were collected and lactate concentrations were measured. Correlation between lactate values from the three different locations was assessed using Pearson correlation. Bland-Altman plots were used to evaluate agreement between lactate measurements in different sampling locations. All patients were eventually admitted to the Internal Medicine Department ward or to the intensive care unit (ICU) for further treatment. RESULTS: Our data showed strong, highly significant correlation between arterial and peripheral venous lactate levels (r = 0.880, P < 0.0001), between arterial and central venous blood lactate (r = 0.898, P < 0.0001) and between central and peripheral venous blood lactate (r = 0.941, P < 0.0001). CONCLUSIONS: In this study we observed strong correlation between arterial, central vein and peripheral vein lactate concentrations in 31 patients assessed and treated for sepsis. We suggest that lactate measurement in peripheral venous blood could be used for screening and for monitoring response to therapy in sepsis patients. However, because this is a small study in only 31 patients and published data are limited, larger studies are needed in order to confirm the validity of our findings.

Breakthrough bloodstream infections in critically ill non-neutropenic patients: higher incidence and better survival than non-breakthrough infections.

Introduction. Breakthrough bloodstream infections (BSIs) are rare among non-neutropenic patients.Aim. Our goal was to determine the risk factors associated with development of breakthrough BSIs among critically ill non-neutropenic patients and its role in mortality.Methodology. During a 24-month period (August 2016 to July 2018), all BSIs among non-neutropenic patients hospitalized at the University General Hospital of Patras, Greece, were included. Antimicrobial resistance of isolates was interpreted according to EUCAST guidelines. BSIs were considered as breakthrough when blood cultures yielded a pathogen in a patient who, for at least the previous 72 h, had been receiving at least one antibiotic to which the isolated microorganism was susceptible.Results. Among 217 episodes of BSI, 118 (54.4 %) developed a breakthrough infection. Primary BSIs predominated (101; 46.5 %), followed by catheter-related BSIs (56; 25.8 %). Gram-negative bacteria represented the most common pathogens isolated (157; 72.4 %), followed by Gram-positive bacteria (36; 16.6 %) and fungi (36; 16.6 %). Factors independently associated with the development of breakthrough BSIs were immunosuppressive therapy, obesity (body mass index ≥30 kg m- 2), infection by Gram-positive bacteria, noradrenaline dose during 24 h from BSI onset, prior use of colistin and antifungal treatment. Overall 14-day mortality was 23.0 % (50 patients). Multivariate analysis revealed noradrenaline dose during 24 h from BSI onset as an independent predictor of mortality, while appropriate empiric antimicrobial treatment and breakthrough BSI were identified as predictors of good prognosis.Conclusion. Breakthrough BSIs were common among critically ill non-neutropenic patients and these patients were associated with better survival because they were de facto receiving appropriate antibiotics.