Epidemiology and risk factors of 28-day mortality of hospital-acquired bloodstream infection in Turkish intensive care units: a prospective observational cohort study.

OBJECTIVES: To uncover clinical epidemiology, microbiological characteristics and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs) in Turkish ICU patients. METHODS: The EUROBACT II was a prospective observational multicontinental cohort study. We performed a subanalysis of patients from 24 Turkish ICUs included in this study. Risk factors for mortality were identified using multivariable Cox frailty models. RESULTS: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78]. Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599), 67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp. and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329), SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI 1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08), COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality. However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI 1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality, whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with survival. CONCLUSIONS: Considering high antimicrobial resistance rate, importance of source control and availability of clinical pharmacists, a multifaceted management programme should be adopted in Turkish ICUs.

Evaluation of the implementation of WHO infection prevention and control core components in Turkish health care facilities: results from a WHO infection prevention and control assessment framework (IPCAF)-based survey.

BACKGROUND: The core components (CCs) of infection prevention and control (IPC) from World Health Organization (WHO) are crucial for the safety and quality of health care. Our objective was to examine the level of implementation of WHO infection prevention and control core components (IPC CC) in a developing country. We also aimed to evaluate health care-associated infections (HAIs) and antimicrobial resistance (AMR) in intensive care units (ICUs) in association with implemented IPC CCs. METHODS: Members of the Turkish Infectious Diseases and Clinical Microbiology Specialization Association (EKMUD) were invited to the study via e-mail. Volunteer members of any healt care facilities (HCFs) participated in the study. The investigating doctor of each HCF filled out a questionnaire to collect data on IPC implementations, including the Infection Prevention and Control Assessment Framework (IPCAF) and HAIs/AMR in ICUs in 2021. RESULTS: A total of 68 HCFs from seven regions in Türkiye and the Turkish Republic of Northern Cyprus participated while 85% of these were tertiary care hospitals. Fifty (73.5%) HCFs had advanced IPC level, whereas 16 (23.5%) of the 68 hospitals had intermediate IPC levels. The hospitals' median (IQR) IPCAF score was 668.8 (125.0) points. Workload, staffing and occupancy (CC7; median 70 points) and multimodal strategies (CC5; median 75 points) had the lowest scores. The limited number of nurses were the most important problems. Hospitals with a bed capacity of > 1000 beds had higher rates of HAIs. Certified IPC specialists, frequent feedback, and enough nurses reduced HAIs. The most common HAIs were central line-associated blood stream infections. Most HAIs were caused by gram negative bacteria, which have a high AMR. CONCLUSIONS: Most HCFs had an advanced level of IPC implementation, for which staffing was an important driver. To further improve care quality and ensure everyone has access to safe care, it is a key element to have enough staff, the availability of certified IPC specialists, and frequent feedback. Although there is a significant decrease in HAI rates compared to previous years, HAI rates are still high and AMR is an important problem. Increasing nurses and reducing workload can prevent HAIs and AMR. Nationwide "Antibiotic Stewardship Programme" should be initiated.

Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial.

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18-60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

What is the context? The timing of the primary and booster doses for each vaccine differs.We aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as homologous booster dose after CoronaVac primary vaccination.What is new? The neutralizing antibody titers against the Wuhan variant decreased below 1/6- the seropositivity threshold value- in more than 55% of the participants 4 months after administration of two doses of CoronaVac vaccine.Immunogenicity was re-stimulated and the neutralizing antibody titers increased rapidly and markedly with the administration of the CoronaVac or TURKOVAC as a booster dose 4 months after the second dose.While the increase in neutralizing antibodies against the Wuhan variant was similar with both CoronaVac and TURKOVAC, more antibodies developed against the Delta variant with TURKOVAC.What is the impact? With the Hybrid COV-RAPEL TR study, after the primary vaccination consisting of two doses of inactivated vaccine, antibody titers decreased in the long term; however, higher antibody titers are achieved than the primary vaccination after the booster dose administered after 4­6 month interval.Booster application with TURKOVAC provides antibodies at least as much as the CoronaVac booster dose, with an acceptable safety profile.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Efficiencies of Laboratory Parameters in Covid-19 Patients Follow up: Turkish Journal of Medical and Surgical Intensive Care Medicine

Introduction: Diagnostic efficiencies of laboratory parameters used in COVID-19 patients and their association with disease severity were evaluated. Materials and Methods: Laboratory parameters of COVID-19 patients hospitalized in Dr. Lütfi Kırdar Kartal City Hospital between March and August 2020 were evaluated. The patients were grouped as non-severe and severe according to the interim guidance of the World Health Organization (WHO). The diagnostic performances of NLR, D-dimer, CRP, procalcitonin, IL-6, LDH, and ferritin in discrimination of severe cases were evaluated by Receiver operator’s characteristics (ROC) analysis. Generalized lineer model Analysis (GLM) was performed with mortality as a dependent variable and age, gender, NLR, D-dimer, CRP, Procalcitonin, IL-6, LDH, and ferritin as an independent variables. Results: A total of 257 patients were evaluated and there was a significant difference between non-severe and severe cases in terms of NLR, D-dimer, CRP, Procalcitonin, IL-6, LDH, and Ferritin values. All the parameters showed comparable performances in discriminating severe disease;D-dimer with the least (AUC 73.5%), and NLR with the highest (AUC 80.7%) efficiency. Values above 4.5 for NLR, 930 ug/L for D-dimer, 64 mg/L for CRP, 0.136 ug/L for procalcitonin, 44.3 pg/mL for IL-6, 304 IU for LDH, and 312 ug/L for ferritin were associated with severe disease. Contribution of age, NLR, D-dimer, and CRP were found significant on the model. Conclusions: NLR, D-dimer, CRP, procalcitonin, IL-6, LDH, and ferritin showed comparable performances in discriminating severe cases with predefined cut-offs. Age, NLR, D-dimer, and CRP may be considered as predictors of mortality in COVID-19 patients.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

Correlation of neuroimaging and thorax CT findings in patients with COVID-19: A large single-center experience

Background/aim: The aim of this current study was to describe the neuroimaging findings among patients with COVID-19 and to compare them with thorax CT imaging findings and clinicobiological profiles. Materials and methods: Between the period March 11 and December 31, 2020, we evaluated brain computed tomography (CT) and magnetic resonance (MR) images of patients with COVID-19. A total of 354 patients (mean age 65.2 ± 16.6, 52% female, 42% male) who had brain imaging were included in the study. Of this total sample, 218 had thorax CT scanning (65.5%). Neuroimaging and thorax CT findings, clinical course, neurologic findings, and laboratory data were evaluated. White matter lesions (WML) and thorax CT scans were scored. Participants were divided according to whether or not they had an infarction. Results: The neuroimaging findings indicated infarcts, parenchymal hemorrhage, encephalitis, cortical signal abnormality, posterior reversible encephalopathy syndrome (PRES), and cranial nerve involvement. WML significantly positively correlated with age (p < 0.01) but not with sex (p > 0.05). Thorax CT findings did not demonstrate significant correlations with infarcts, WML, or hemorrhages (p> 0.05). D-dimer and ferritin levels were significantly higher among patients with infarcts (p < 0.05). Conclusion: Immune-mediated prothrombic state and cytokine storm appear to be more responsible for etiopathogenesis than direct viral neurotropism. Neuroimaging and thorax CT findings were not correlated among patients with COVID-19 in our study. These results suggest that neurological manifestations may occur independently of pulmonary involvement and age.

Pulse steroid treatment for hospitalized adults with COVID-19

Background/aim: High-dose steroid has been shown to reduce the mortality rate in Corona virus disease 2019 (COVID-19) patients who need oxygen support. Here, we evaluated the effectiveness of pulse-steroid in case of unresponsiveness to treatment with high dose steroid. Materials and methods: The study is a retrospective controlled trial. We divided the patients in 3 groups: standard-care therapy alone, high-dose steroid treatment (6 mg/day dexamethasone equivalent), and pulse-steroid treatment (250 mg/day methyl-prednisolone). One hundred and fifty patients were enrolled in each group. All patients were hospitalized and needed oxygen support. We matched the patients according to disease severity at the onset of hypoxia, weight of co-morbidities, age, and sex. We then compared 3 groups in terms of mortality, length of hospitalization, need for intensive care unit (ICU) admission and mechanical ventilation (MV), length of stay in ICU, and duration of MV. Results: The pulse-steroid group had shorter ICU stay. The median ICU stay was 9.0 (CI 95% 6.0­12.0) days in standard-care group, 8.0 (CI 95% 5.0­13.0) days in high-dose steroid group and 4.5(CI %95 3.0­8.0) days in pulse-steroid group. Moreover, although patients in pulse-steroid group were initially unresponsive to high dose steroid therapy, they achieved similar results compared to the high-dose steroid group in other outcomes except for length of hospital stay. Conclusion: Pulse-steroid treatment would be an option for COVID-19 patients who do not respond to the initial high-dose steroid treatment.

Acute Limb Ischemia in Hospitalized COVID-19 Patients.

BACKGROUND: COVID-19 is a multisystemic disorder. Hematologic and cardiovascular involvement of COVID-19 causes thromboembolic events across multiple organs which mainly manifest as venous thromboembolism, and rarely, peripheral arterial thromboembolic events. In-situ thrombosis of a healthy, non-atherosclerotic native artery is rare, and COVID-19 has been reported to be a cause of this phenomenon. We aimed to report our institutional experience with COVID-19 patients who developed acute limb ischemia (ALI) during hospitalization or after discharge. METHODS: This was a single-center cross-sectional study. Records of all patients ≥18 years of age admitted to a tertiary center with a confirmed diagnosis of COVID-19 infection between September 1 and December 31, 2020 were retrospectively examined. Data regarding patient demographics, co-morbidities and outcomes were collected. Patients were followed-up during index hospitalization and for 30 days postdischarge. Acute limb ischemia was diagnosed by means of duplex ultrasound and computed tomography angiography in the presence of a clinical suspicion. RESULTS: A total of 681 consecutive patients (38.5% women) were hospitalized with a confirmed diagnosis of COVID-19 during the study period. Median age was 63 years (IQR, 52-74). In-hospital mortality occurred in 94 (13.8%) patients. Ninety (13.2%) patients required intensive care unit admission at some point of their hospital stay. Six (0.9%) patients (one woman) with a median age of 62 years experienced ALI (IQR, 59-64.3). All patients were receiving low molecular weight heparin when they developed ALI. The median of duration between COVID-19 diagnosis and ALI symptom onset was 13 days (IQR, 11.3-14). Three patients underwent emergent surgical thrombectomy combined with systemic anticoagulation, and 3 received systemic anticoagulation alone. Two patients with ALI did not survive to hospital discharge. Among survivors, 1 patient underwent bilateral major amputations, and another underwent a minor amputation within 1 month of hospital discharge. Symptoms of ALI completely resolved in 2 patients without sequelae. CONCLUSIONS: COVID-19 is a multisystemic disorder with involvement of hematologic and cardiovascular systems. Despite widespread use of thromboprophylaxis, hospitalized patients with COVID-19 are at increased risk of ALI, and subsequent limb loss or even death.

Should CT be used for the diagnosis of RT-PCR-negative suspected COVID-19 patients?

INTRODUCTION: The diagnosis of patients with Coronavirus disease 2019 (COVID-19) suspicion but negative reverse transcriptase-polymerase chain reaction (RT-PCR) test is challenging. OBJECTIVE: We aimed to investigate the diagnostic value of chest computed tomography (CT) in RT-PCR-negative patients with suspected COVID-19. MATERIALS AND METHODS: The study included patients who were admitted to our hospital with the suspicion of COVID-19 between 1 April 2020 and 30 April 2020 and tested negative after RT-PCR test, and underwent CT for further diagnosis. Initial CT findings were classified as typical, indeterminate, and atypical for COVID-19, and negative for pneumonia. Incidental findings on CT were noted. RESULTS: Of the 338 patients with a mean age of 57 years (min 18 years-max 96 years), 168 (49.70%) were male and 170 (50.29%) were female. The most common symptoms were cough (58.87%), fever (40.82%), and dyspnea (39.34%). The CT findings were typical for COVID-19 in 109 (32.24%) patients, indeterminate in 47 (13.90%) patients, and atypical in 77 (22.78%) patients. The CT findings of 105 (31.06%) patients were negative for pneumonia. Incidental lung nodules suspicious of malignancy were identified in seven patients. Seventy-seven patients (22.78%) had extrapulmonary incidental findings CONCLUSION: The diagnostic value of CT in RT-PCR-negative patients with suspected COVID-19 is not very high. Based on clinical, laboratory, and chest x-ray findings, it may be more appropriate to refer patients to CT after the first triage, when necessary.