Infection with the multidrug-resistant Klebsiella pneumoniae New Delhi metallo-B-lactamase strain in patients with COVID-19: Nec Hercules contra plures?

Background: During the coronavirus disease 2019 (COVID-19) pandemic, in patients treated for SARS-CoV-2 infection, infections with the Klebsiella pneumoniae bacteria producing New Delhi metallo-B-lactamase (NDM) carbapenemase in the USA, Brazil, Mexico, and Italy were observed, especially in intensive care units (ICUs). This study aimed to assess the impact of Klebsiella pneumoniae NDM infection and other bacterial infections on mortality in patients treated in ICUs due to COVID-19. Methods: The 160 patients who qualified for the study were hospitalized in ICUs due to COVID-19. Three groups were distinguished: patients with COVID-19 infection only (N = 72), patients with COVID-19 infection and infection caused by Klebsiella pneumoniae NDM (N = 30), and patients with COVID-19 infection and infection of bacterial etiology other than Klebsiella pneumoniae NDM (N = 58). Mortality in the groups and chosen demographic data; biochemical parameters analyzed on days 1, 3, 5, and 7; comorbidities; and ICU scores were analyzed. Results: Bacterial infection, including with Klebsiella pneumoniae NDM type, did not elevate mortality rates. In the group of patients who survived the acute phase of COVID-19 the prolonged survival time was demonstrated: the median overall survival time was 13 days in the NDM bacterial infection group, 14 days in the other bacterial infection group, and 7 days in the COVID-19 only group. Comparing the COVID-19 with NDM infection and COVID-19 only groups, the adjusted model estimated a statistically significant hazard ratio of 0.28 (p = 0.002). Multivariate analysis revealed that age, APACHE II score, and CRP were predictors of mortality in all the patient groups. Conclusion: In patients treated for SARS-CoV-2 infection acquiring a bacterial infection due to prolonged hospitalization associated with the treatment of COVID-19 did not elevate mortality rates. The data suggests that in severe COVID-19 patients who survived beyond the first week of hospitalization, bacterial infections, particularly Klebsiella pneumoniae NDM, do not significantly impact mortality. Multivariate analysis revealed that age, APACHE II score, and CRP were predictors of mortality in all the patient groups.

Evaluation of the in vitro susceptibility of clinical isolates of NDM-producing Klebsiella pneumoniae to new antibiotics included in a treatment regimen for infections.

Background: Due to the growing resistance to routinely used antibiotics, the search for new antibiotics or their combinations with effective inhibitors against multidrug-resistant microorganisms is ongoing. In our study, we assessed the in vitro drug susceptibility of Klebsiella pneumoniae strains producing New Delhi metallo-ß-lactamases (NDM) to antibiotics included in the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommendations. Methods: A total of 60 strains of NDM-producing K. pneumoniae were obtained from different patients hospitalized at the 4th Military Hospital in Wroclaw between 2019 and 2022 and subjected to drug susceptibility to selected antibiotics, including the effects of drug combinations. Results: Among the tested antibiotics, the highest sensitivity (100%) was observed for cefiderocol, eravacycline (interpreted according to the European Committee on Antimicrobial Susceptibility Testing [EUCAST]), and tigecycline. Sensitivity to intravenous fosfomycin varied depending on the method used. Using the "strip stacking" method, determining cumulative sensitivity to ceftazidime/avibactam and aztreonam demonstrated 100% in vitro sensitivity to this combination among the tested strains. Conclusion: The in vitro susceptibility assessment demonstrated that, the best therapeutic option for treating infections caused by carbapenemase-producing strains seems to be a combination of ceftazidime/avibactam with aztreonam. Due to the safety of using both drugs, cost effectiveness, and the broadest indications for use among the tested antibiotics, this therapy should be the first-line treatment for carbapenemase-producing Enterobacterales infections. Nevertheless, a comprehensive evaluation of the efficacy of treating infections caused by NDM-producing K. pneumoniae strains should include not only in vitro susceptibility assessment but also an analysis of clinical cases.

Aldosterone levels do not predict 28-day mortality in patients treated for COVID-19 in the intensive care unit.

The immunotropic effects of aldosterone might play a role in COVID-19, as SARS-CoV-2 reportedly uses angiotensin-converting enzyme 2 receptors as an entry point into cells. Aldosterone function is closely linked to its action on mineralocorticoid receptors in kidneys; it increases the renal retention of sodium and the excretion of potassium, which increases blood pressure. Despite the large number of studies examining the effect of Ang-II and its blockers on the course of COVID-19 infection, there is still uncertainty about the role of aldosterone. The aim of the study was to assess the correlation of aldosterone, urea, creatinine, C-reactive protein (CRP), and procalcitonin (PCT) levels with 28 days of mortality in patients treated for COVID19 in an intensive care unit (ICU). This cross-selection study involved 115 adult patients who were divided into two groups: those who died within a 28-day period (n = 82) and those who survived (n = 33). The correlation of aldosterone, urea, creatinine, C-reactive protein (CRP), and procalcitonin (PCT) levels with 28 days of mortality in patients treated for COVID-19 were performed. The patients' age, sex, scores from the APACHE II, SAPS II, and SOFA scales and comorbidities like HA, IHD and DM were also analyzed. Remarkably, the individuals who survived for 28 days were of significantly lower mean age and achieved notably lower scores on the APACHE II, SAPS II, and SOFA assessment scales. Statistically significantly higher CRP levels were observed on days 3, 5, and 7 in individuals who survived for 28 days. Creatinine levels in the same group were also statistically significantly lower on days 1, 3, and 5 than those of individuals who died within 28 days. The investigation employed both univariate and multivariate Cox proportional hazard regression models to explore factors related to mortality. In the univariate analysis, variables with a p value of less than 0.50 were included in the multivariate model. Age, APACHE II, SAPS II, and SOFA demonstrated significance in univariate analysis and were considered to be associated with mortality. The outcomes of the multivariate analysis indicated that age (HR = 1.03, p = 0.033) served as a robust predictor of mortality in the entire study population. In conclusion the plasma aldosterone level is not associated with ICU mortality in patients with COVID-19. Other factors, including the patient's age, creatinine or CRP contribute to the severity and prognosis of the disease. This study was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with registration no. ACTRN12621001300864 (27/09/2021: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382563&isReview=true ).

International Nosocomial Infection Control Consortium (INICC) report of health care associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module.

BACKGROUND: Reporting on the International Nosocomial Infection Control Consortium study results from 2015 to 2020, conducted in 630 intensive care units across 123 cities in 45 countries spanning Africa, Asia, Eastern Europe, Latin America, and the Middle East. METHODS: Prospective intensive care unit patient data collected via International Nosocomial Infection Control Consortium Surveillance Online System. Centers for Disease Control and Prevention/National Health Care Safety Network definitions applied for device-associated health care-associated infections (DA-HAI). RESULTS: We gathered data from 204,770 patients, 1,480,620 patient days, 936,976 central line (CL)-days, 637,850 mechanical ventilators (MV)-days, and 1,005,589 urinary catheter (UC)-days. Our results showed 4,270 CL-associated bloodstream infections, 7,635 ventilator-associated pneumonia, and 3,005 UC-associated urinary tract infections. The combined rates of DA-HAIs were 7.28%, and 10.07 DA-HAIs per 1,000 patient days. CL-associated bloodstream infections occurred at 4.55 per 1,000 CL-days, ventilator-associated pneumonias at 11.96 per 1,000 MV-days, and UC-associated urinary tract infections at 2.91 per 1,000 UC days. In terms of resistance, Pseudomonas aeruginosa showed 50.73% resistance to imipenem, 44.99% to ceftazidime, 37.95% to ciprofloxacin, and 34.05% to amikacin. Meanwhile, Klebsiella spp had resistance rates of 48.29% to imipenem, 72.03% to ceftazidime, 61.78% to ciprofloxacin, and 40.32% to amikacin. Coagulase-negative Staphylococci and Staphylococcus aureus displayed oxacillin resistance in 81.33% and 53.83% of cases, respectively. CONCLUSIONS: The high rates of DA-HAI and bacterial resistance emphasize the ongoing need for continued efforts to control them.

How to Defeat Multidrug-Resistant Bacteria in Intensive Care Units. A Lesson from the COVID-19 Pandemic. Prevention, Reservoirs, and Implications for Clinical Practice.

Background: Intensive care unit (ICU) patients are at high risk of infection due to multiple invasive procedures, malnutrition, or immunosuppression. The rapid increase in infections with multidrug-resistant organisms (MDRO) during the COVID-19 pandemic caused a dilemma, as the rules of the sanitary regime in ICU rooms were strictly adhered to in the prevailing epidemiological situation. The combat to reduce the number of infections and pathogen transmission became a priority for ICU staff. This study aimed to assess whether eliminating environmental reservoirs and implementing improved procedures for patient care and decontamination and washing equipment in the ICU reduced the incidence of infections caused by MDR strains. Material and methods: The study retrospectively analyzed data in the ICU during the COVID-19 pandemic. The samples were collected based on microbiological culture and medical records in the newly opened ICU (10 stations) and hospital wards where COVID-19 patients were hospitalized. Environmental inoculations were performed during the COVID-19 pandemic every 4-6 weeks unless an increase in the incidence of infections caused by MDR strains was observed. Through microbiological analysis, environmental reservoirs of MDR pathogens were identified. The observation time was divided into two periods, before and after the revised procedures. The relationship between isolated strains of Klebsiella pneumoniae NDM from patients and potential reservoirs within the ICU using ERIC-PCR and dice methods was analyzed. Results: An increased frequency of infections and colonization caused by MDRO was observed compared to the preceding years. A total of 23,167 microbiological tests and 6,985 screening tests for CPE and MRSA bacilli were collected. The pathogen spread was analyzed, and the findings indicated procedural errors. Assuming that the transmission of infections through the staff hands was significantly limited by the restrictive use of personal protective equipment, the search for a reservoir of microorganisms in the environment began. MDR strains were grown from the inoculations collected from the hand-wash basins in the wards and from inside the air conditioner on the ceiling outside the patient rooms. New types of decontamination mats were used in high-risk areas with a disinfectant based on Glucoprotamine. Active chlorine-containing substances were widely used to clean and disinfect surfaces. Conclusions: Infections with MDR strains pose a challenge for health care. Identification of bacterial reservoirs and comprehensive nursing care significantly reduce the number of nosocomial infections.

Decreasing central line-associated bloodstream infections rates in intensive care units in 30 low- and middle-income countries: An INICC approach.

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSIs) occurring in the intensive care unit (ICU) are common and associated with a high burden. METHODS: We implemented a multidimensional approach, incorporating an 11-element bundle, education, surveillance of CLABSI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CLABSI rates and clinical outcomes, and performance feedback in 316 ICUs across 30 low- and middle-income countries. Our dependent variables were CLABSI per 1,000-CL-days and in-ICU all-cause mortality rates. These variables were measured at baseline and during the intervention, specifically during the second month, third month, 4 to 16 months, and 17 to 29 months. Comparisons were conducted using a two-sample t test. To explore the exposure-outcome relationship, we used a generalized linear mixed model with a Poisson distribution to model the number of CLABSIs. RESULTS: During 1,837,750 patient-days, 283,087 patients, used 1,218,882 CL-days. CLABSI per 1,000 CL-days rates decreased from 15.34 at the baseline period to 7.97 in the 2nd month (relative risk (RR) = 0.52; 95% confidence interval [CI] = 0.48-0.56; P < .001), 5.34 in the 3rd month (RR = 0.35; 95% CI = 0.32-0.38; P < .001), and 2.23 in the 17 to 29 months (RR = 0.15; 95% CI = 0.13-0.17; P < .001). In-ICU all-cause mortality rate decreased from 16.17% at baseline to 13.68% (RR = 0.84; P = .0013) at 17 to 29 months. CONCLUSIONS: The implemented approach was effective, and a similar intervention could be applied in other ICUs of low- and middle-income countries to reduce CLABSI and in-ICU all-cause mortality rates.

Prevalence of life-sustaining treatment limitations in Polish very old intensive care patients (VIPs). A post-hoc analysis of two prospective observational studies.

PURPOSE: Several initiatives have recently focused on raising awareness about limitations of treatment in Poland. We aimed to assess if the propensity to limit LST among elderly patients in 2018-2019 increased compared to 2016-2017. METHODS: We analysed Polish cohorts from studies VIP1 (October 2016 - May 2017) and VIP2 (May 2018 - May 2019) that enrolled critical patients aged >80. We collected data on demographics, clinical features limitations of LST. Primary analysis assessed factors associated with prevalence of limitations of LST, A secondary analysis explored differences between patients with and without limitations of LST. RESULTS: 601 patients were enrolled. Prevalence of LST limitations was 16.1% in 2016-2017 and 20.5% in 2018-2019. No difference was found in univariate analysis (p = 0.22), multivariable model showed higher propensity towards limiting LST in the 2018-2019 cohort compared to 2016-2017 cohort (OR 1.07;95%CI, 1.01-1.14). There was higher mortality and a longer length of stay of patients with limitations of LST compared to the patients without limitations of LST. (11 vs. 6 days, p = 0.001). CONCLUSIONS: The clinicians in Poland have become more proactive in limiting LST in critically ill patients ≥80 years old over the studied period, however the prevalence of limitations of LST in Poland remains low.

Improved oxygenation in prone positioning of mechanically ventilated patients with COVID-19 acute respiratory distress syndrome is associated with decreased pulmonary shunt fraction: a prospective multicenter study.

BACKGROUND: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 (Covid-19) acute respiratory distress syndrome (ARDS). However, physiological mechanisms remain unclear. The aim of this study was to determine whether improved oxygenation was related to pulmonary shunt fraction (Q's/Q't), alveolar dead space (Vd/Vtalv) and ventilation/perfusion mismatch (V'A/Q'). METHODS: This was an international, prospective, observational, multicenter, cohort study, including six intensive care units in Sweden and Poland and 71 mechanically ventilated adult patients. RESULTS: Prone position increased PaO2:FiO2 after 30 min, by 78% (83-148 mm Hg). The effect persisted 120 min after return to supine (p < 0.001). The oxygenation index decreased 30 min after prone positioning by 43% (21-12 units). Q's/Q't decreased already after 30 min in the prone position by 17% (0.41-0.34). The effect persisted 120 min after return to supine (p < 0.005). Q's/Q't and PaO2:FiO2 were correlated both in prone (Beta -137) (p < 0.001) and in the supine position (Beta -270) (p < 0.001). V'A/Q' was unaffected and did not correlate to PaO2:FiO2 (p = 0.8). Vd/Vtalv increased at 120 min by 11% (0.55-0.61) (p < 0.05) and did not correlate to PaO2:FiO2 (p = 0.3). The ventilatory ratio increased after 30 min in the prone position by 58% (1.9-3.0) (p < 0.001). PaO2:FiO2 at baseline predicted PaO2:FiO2 at 30 min after proning (Beta 1.3) (p < 0.001). CONCLUSIONS: Improved oxygenation by prone positioning in COVID-19 ARDS patients was primarily associated with a decrease in pulmonary shunt fraction. Dead space remained high and the global V'A/Q' measure could not explain the differences in gas exchange.

Ultrasound-Guided Pectoserratus Plane Block and Superficial Serratus Anterior Plane Block for Subcutaneous Implantable Cardioverter-Defibrillator Implantation: A Comparative Study.

BACKGROUND The combination of pectoserratus plane block (PSP) and superficial serratus anterior plane block (S-SAP) was established to reduce the risk of general anesthesia for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation in patients with high operative risk (American Society of Anesthesiologistsgrade III or IV). This study compared outcomes from ultrasound-guided PSP and S-SAP in 16 patients requiring a subcutaneous implantable cardioverter-defibrillator (S-ICD) at a single center in Poland. MATERIAL AND METHODS A group of 16 patients with ASA grade III and IV qualified for S-ICD implantation was included. The pain assessment using numerical rating scale (NRS), patient's comfort using Quality of Recovery-15 (QoR-15), the operator's satisfaction using Operator's Comfort Scale, adverse event occurrence, and the parameters' stability were evaluated. RESULTS The mean volume of the local anesthetics mixture of PSP block was 19.4 mL; S-SAP was 34.7 mL (mean total volume, 54.1 mL). The mean duration of the block was 21.3 min; the mean time of the S-ICD implantation was 108.4 min. Neither circulatory nor respiratory instability was observed. In 8 patients (50%), non-opioid analgesics were administered intraoperatively; in 11 patients (69%), fentanyl bolus ≤200 µg was administered. The intraoperative NRS score was low (max 2 points); NRS 24 h after the procedure was low (max 4 points). The mean value of QoR-15 was 133.9 points. CONCLUSIONS S-SAP combined with PSP is feasible and safe in providing anesthesia/analgesia during S-ICD implantation and showed good effects in a group of patients with high operative risk (ASA III or IV).

Interleukin-7 and interleukin-15 as prognostic biomarkers in sepsis and septic shock: Correlation with inflammatory markers and mortality.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a syndrome shaped by pathogen and host factors evolving over time. During sepsis, the absolute number of lymphocytes decreases. CD4+ and CD8+ T cells, B cells, and NK cells are reduced. Lymphocytes are an essential element of the body's defence against pathogens. Interleukin 7 has strong anti-apoptotic properties and induces the proliferation of CD4+ and CD8+ T lymphocytes. IL-15 prompts the generation of mature NK cells in the bone marrow, plays an important role in the generation, cytotoxicity, and survival of CD8+ T lymphocytes, and is essential for the survival of natural killer T (NKT) and intestinal intraepithelial lymphocytes (IELs). The study highlights the importance of monitoring IL-7 levels in patients with sepsis and septic shock, as low levels of this cytokine were associated with an increased risk of mortality. Physicians should consider using IL-7 levels as a biomarker to identify patients who are at higher risk of mortality and may require more aggressive treatment.

Multinational prospective study of incidence and risk factors for central-line-associated bloodstream infections in 728 intensive care units of 41 Asian, African, Eastern European, Latin American, and Middle Eastern countries over 24 years.

OBJECTIVE: To identify central-line (CL)-associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs). DESIGN: From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms. SETTING: The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PATIENTS: In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs. METHODS: For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs). RESULTS: The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03-1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03-1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03-1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23-1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31-4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22-3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09-2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11-6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57-3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81-3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71-3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96-2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02-2.18; P = .04). CONCLUSIONS: The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.

Does cognitive function impairment affect the duration of hospitalization and in-hospital mortality in geriatric patients hospitalized for COVID-19?

AIMS: To assess the effect of cognitive function, performance of activities of daily living (ADLs), degree of depression, and fear of infection among geriatric patients hospitalized in internal medicine wards for COVID-19 on the duration of hospitalization and in-hospital mortality. METHODS: This observational survey study was conducted during the second, third, and fourth waves of the COVID-19 pandemic. The study included elderly patients of both sexes, aged ≥ 65 years, hospitalized for COVID-19 in internal medicine wards. The following survey tools were used: AMTS, FCV-19S, Lawton IADL, Katz ADL, and GDS15. The duration of hospitalization and in-hospital mortality were also assessed. RESULTS: A total of 219 patients were included in the study. The results showed that impaired cognitive function in geriatric patients (AMTS) was associated with higher in-hospital mortality among COVID-19 patients. There was no statistical significance between fear of infection (FCV-19S) and risk of death. The impaired ability to perform complex ADLs (Lawton IADL) before the onset of the disease was not associated with higher in-hospital mortality among COVID-19 patients. The diminished ability to perform basic ADLs (Katz ADL) before the onset of the disease was not associated with higher in-hospital mortality in COVID-19. The degree of depression (GDS15) was not associated with higher in-hospital mortality in COVID-19 patients. Statistically, significantly better survival was observed for patients with normal cognitive function (p = 0.005). No statistically significant differences in survival were observed in relation to the degree of depression or independence in performing ADLs. Cox proportional hazards regression analysis showed a statistically significant effect of age on mortality (p = 0.004, HR 1.07). CONCLUSION: In this study, we observe that cognitive function impairments and the older age of patients treated for COVID-19 in the medical ward increase the in-hospital risk of death.

The Role of Plasminogen Activator Inhibitor 1 in Predicting Sepsis-Associated Liver Dysfunction: An Observational Study.

Sepsis-associated liver dysfunction (SALD) is associated with a poor prognosis and increased mortality in the intensive care unit. Bilirubin is one of the components of Sequential Organ Failure Assessment used in Sepsis-3 criteria. Hyperbilirubinemia is a late and non-specific symptom of liver dysfunction. This study aimed to identify plasma biomarkers that could be used for an early diagnosis of SALD. This prospective, observational study was conducted on a group of 79 patients with sepsis and septic shock treated in the ICU. Plasma biomarkers-prothrombin time, INR, antithrombin III, bilirubin, aspartate transaminase (AST), alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, albumin, endothelin-1, hepcidin, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex, and interferon-gamma inducible protein (10 kDa) were analysed. Plasma samples were obtained within 24 h after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival. A total of 24 patients (30.4%) developed SALD. PAI-1 with a cut-off value of 48.7 ng/mL was shown to be a predictor of SALD (AUC = 0.671, sensitivity 87.3%, and specificity 50.0%) and of 28-day survival in patients with sepsis/septic shock (p = 0.001). Measuring PAI-1 serum levels at the onset of sepsis and septic shock may be useful in predicting the development of SALD. This should be verified in multicenter prospective clinical trials.

Multinational prospective cohort study of rates and risk factors for ventilator-associated pneumonia over 24 years in 42 countries of Asia, Africa, Eastern Europe, Latin America, and the Middle East: Findings of the International Nosocomial Infection Control Consortium (INICC).

Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16-1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07-1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23-1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57-15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21-9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34-7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17-1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15-1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22-5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78-3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79-3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51-0.77; P < .0001). Conclusions: Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

The impact of healthcare-associated infections on mortality in ICU: A prospective study in Asia, Africa, Eastern Europe, Latin America, and the Middle East.

BACKGROUND: The International Nosocomial Infection Control Consortium has found a high ICU mortality rate. Our aim was to identify all-cause mortality risk factors in ICU-patients. METHODS: Multinational, multicenter, prospective cohort study at 786 ICUs of 312 hospitals in 147 cities in 37 Latin American, Asian, African, Middle Eastern, and European countries. RESULTS: Between 07/01/1998 and 02/12/2022, 300,827 patients, followed during 2,167,397 patient-days, acquired 21,371 HAIs. Following mortality risk factors were identified in multiple logistic regression: Central line-associated bloodstream infection (aOR:1.84; P<.0001); ventilator-associated pneumonia (aOR:1.48; P<.0001); catheter-associated urinary tract infection (aOR:1.18;P<.0001); medical hospitalization (aOR:1.81; P<.0001); length of stay (LOS), risk rises 1% per day (aOR:1.01; P<.0001); female gender (aOR:1.09; P<.0001); age (aOR:1.012; P<.0001); central line-days, risk rises 2% per day (aOR:1.02; P<.0001); and mechanical ventilator (MV)-utilization ratio (aOR:10.46; P<.0001). Coronary ICU showed the lowest risk for mortality (aOR: 0.34;P<.0001). CONCLUSION: Some identified risk factors are unlikely to change, such as country income-level, facility ownership, hospitalization type, gender, and age. Some can be modified; Central line-associated bloodstream infection, ventilator-associated pneumonia, catheter-associated urinary tract infection, LOS, and MV-utilization. So, to lower the risk of death in ICUs, we recommend focusing on strategies to shorten the LOS, reduce MV-utilization, and use evidence-based recommendations to prevent HAIs.

Analysis of Mortality in Unvaccinated Patients with COVID-19 and Cardiovascular Risk.

COVID-19 is a contagious disease that has spread globally, killing millions of people around the world. In order to reduce the likelihood of in-hospital death due to COVID-19, it is reasonable to select a group of patients with a low probability of survival and to implement measures in advance to minimize the risk of death. One way to do this is to establish cut-off values for the most commonly performed blood laboratory tests, above or below which the likelihood of death increases significantly. The aim of the study was to determine the basic laboratory parameters among unvaccinated patients hospitalized for COVID-19 with concomitant cardiovascular disease, which are the predictors of in-hospital death. Out of 1234 patients, 446 people who met the specific inclusion criteria were enrolled in the study. The multivariate regression analysis has shown that the independent predictors of death are: troponin levels of at least 0.033 µg/L (OR = 2.04 [1.10; 3.79]), creatinine of at least 1.88 mg/dL (OR = 2.88 [1.57; 5.30]), D-dimers of at least 0.97 g/L (OR = 2.04 [1.02; 4.07]), and C-reactive protein minimum of 0.89 mg/L (OR = 2.28 [1.24; 4.18]).

Measurement of Serum Levels of 5 Amino Acids and Dimethylamine Using Liquid Chromatography-Tandem Mass Spectrometry in Patients without Septic Associated Acute Kidney Injury and with Septic Associated Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

BACKGROUND Acute kidney injury (AKI) is one of the most common organ failures. An early diagnosis of AKI using specific biomarkers is essential for effective treatment. This study determined the serum concentrations of selected amino acids and amines using targeted liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in patients with AKI during sepsis and septic shock treated in the Intensive Care Unit (ICU). MATERIAL AND METHODS A sample of 41 patients was divided into 2 groups: (1) patients with sepsis and septic shock along required continuous renal replacement therapy (CRRT) due to AKI (n=13), and (2) patients with sepsis and septic shock but without AKI (n=28). LC-MS/MS was used to measure a serum concentration of 6 amino acids and amines: arginine, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine (DMA), and citrulline. RESULTS There was a statistically significantly higher median DMA level in AKI patients compared to those without AKI (8.1 vs 5.2 umol/L; P=0.022). The results for the remaining molecules showed no significant differences (P>0.05). Patients with DMA ≥14.95 umol/L (n=5; 100%) and treated with CRRT presented DMA level below the cut-off point (n=7; 20%). Subjects with creatinine levels ≥1.19 mg/dL (n=11; 28%) and treated with CRRT presented creatinine levels below the cut-off point (n=1; 3%). CONCLUSIONS In patients with sepsis, increased serum levels of DMA were significantly associated with AKI requiring CRRT. It remains unclear whether increased DMA concentrations are secondary to sepsis-induced AKI or are a cause.

Renin as a Marker of Tissue Perfusion, Septic Shock and Mortality in Septic Patients: A Prospective Observational Study.

Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the host's response to an infection, where the dominant mechanism is tissue hypoperfusion. Currently, the marker used to define tissue disorders is lactate levels, which may be elevated in other disease states as well. Renin is an essential hormone for the proper functioning of the renin-angiotensin-aldosterone (RASS) system. It is secreted in the glomerular apparatus in response to hypoperfusion. This study aimed to assess the usefulness of renin as a marker of tissue hypoperfusion in patients with sepsis and septic shock. A final group of 48 patients treated for sepsis and septic shock in the intensive care unit was included. Blood samples for renin quantification were collected in the morning as a part of routine blood analysis on the first, third, and fifth days. Sepsis was diagnosed in 19 patients (39.6%), and septic shock was diagnosed in 29 patients (60.4%). There was no significant difference in renin concentration between patients who received and did not receive continuous renal replacement therapy (CRRT) on any study day. Therefore, all samples were analyzed together in subsequent analyses. There was a significant difference in renin concentration between sepsis survivors and non-survivors on the third (31.5 and 119.9 pg/mL, respectively) and fifth (18.2 and 106.7 pg/mL, respectively) days. As a survival marker, renin was characterized by 69% and 71% overall accuracy if determined on the third and fifth days, respectively. There was a significant difference in renin concentration between sepsis and septic shock patients on the first (45.8 and 103.4 pg/mL, respectively) and third (24.7 and 102.1 pg/mL, respectively) days. At an optimal cut-off of 87 pg/mL, renin had very good specificity and a positive likelihood ratio. Renin was a strong predictor of mortality in patients with sepsis and septic shock. Further, the level of renin in patients with septic shock was significantly higher than in patients with sepsis. In combination with the assessment of lactate concentration, renin seems to be the optimal parameter for monitoring tissue hypoperfusion and could be helpful for septic shock diagnosis, as well as for identifying candidate patients for CRRT.

Use of Ultrasound-Guided Interfascial Plane Blocks in Anterior and Lateral Thoracic Wall Region as Safe Method for Patient Anesthesia and Analgesia: Review of Techniques and Approaches during COVID-19 Pandemic.

Ultrasound-guided interfascial plane blocks performed on the anterior and lateral thoracic wall have become an important adjuvant method to general anesthesia and an independent method of local anesthesia and pain management. These procedures diminish the harmful effects of anesthesia on respiratory function and reduce the risk of phrenic nerve paralysis or iatrogenic pneumothorax. In postoperative pain management, interfascial plane blocks decrease the dosage of intravenous drugs, including opioids. They can also eliminate the complications associated with general anesthesia when used as the sole method of anesthesia for surgical procedures. The following procedures are classified as interfascial plane blocks of the anterior and lateral thoracic wall: pectoral nerve plane block (PECS), serratus anterior plane block (SAP), transversus thoracic muscle plane block (TTP), pectoral interfascial plane block (PIF), and intercostal nerve block (ICNB). These blocks are widely used in emergency medicine, oncologic surgery, general surgery, thoracic surgery, cardiac surgery, orthopedics, cardiology, nephrology, oncology, palliative medicine, and pain medicine. Regional blocks are effective for analgesic treatment, both as an anesthesia procedure for surgery on the anterior and lateral thoracic wall and as an analgesic therapy after trauma or other conditions that induce pain in this area. In the era of the COVID-19 pandemic, ultrasound-guided interfascial plane blocks are safe alternatives for anesthesia in patients with symptoms of respiratory distress related to SARS-CoV-2 and appear to reduce the risk of COVID-19 infection among medical personnel.

Does the Serum Concentration of Angiotensin II Type 1 Receptor Have an Effect on the Severity of COVID-19? A Prospective Preliminary Observational Study among Healthcare Professionals.

SARS-CoV-2 is a virus that causes severe respiratory distress syndrome. The pathophysiology of COVID-19 is related to the renin-angiotensin system (RAS). SARS-CoV-2, a vector of COVID-19, uses angiotensin-converting enzyme 2 (ACE-2), which is highly expressed in human lung tissue, nasal cavity, and oral mucosa, to gain access into human cells. After entering the cell, SARS-CoV-2 inhibits ACE-2, thus favouring the ACE/Ang II/angiotensin II type 1 receptor (AT1R) axis, which plays a role in the development of acute lung injury (ALI). This study aimed to analyse the influence of angiotensin 1 receptor (AT1R) levels in the serum on the course of the severity of symptoms in healthcare professionals who had a SARS-CoV-2 infection. This prospective observational study was conducted on a group of 82 participants. The study group included physicians and nurses who had a COVID-19 infection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2. The control group consisted of healthy medical professionals who had not had a SARS-CoV-2 infection or who had no symptoms of COVID-19 and who tested negative for SARS-CoV-2 on the day of examination. We analysed the correlation between AT1R concentration and the severity of COVID-19, as well as with sex, age, blood group, and comorbidities. There were no statistically significant differences in the mean values of AT1R concentration in the recovered individuals and the non-COVID-19 subjects (3.29 vs. 3.76 ng/mL; p = 0.32). The ROC curve for the AT1R assay showed an optimal cut-off point of 1.33 (AUC = 0.44; 95% CI = 0.32-0.57; p = 0.37). There was also no correlation between AT1R concentration and the severity of symptoms associated with COVID-19. Blood type analysis showed statistically significantly lower levels of AT1R in COVID-19-recovered participants with blood group A than in those with blood group O. In conclusion, AT1R concentration does not affect the severity of symptoms associated with COVID-19 among healthcare professionals.