Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients.

PURPOSE: Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. METHODS: We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. RESULTS: Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. CONCLUSION: Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19.

Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development-Results from the PRO-BAC Cohort.

Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60−79), 68.8% were male, median Charlson score was 5 (IQR 3−7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14−3.12)], haematological malignancy [2.45 (1.20−4.99)], obstructive uropathy [2.86 (1.13−3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10−10.92)] and healthcare-associated BSI [1.85 (1.13−3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

PURPOSE: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. METHODS: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. RESULTS: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65-0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58-0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14-1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61-0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. CONCLUSION: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.

Methodology of a Large Multicenter Observational Study of Patients with COVID-19 in Spanish Intensive Care Units.

INTRODUCTION: The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. METHODS: CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. RESULTS: This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. CONCLUSIONS: We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study).

The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60-81 years) and 3656 (58.3%; 95% confidence interval 57.1-59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients' profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.

Estudio caso-control del impacto clínico de la traqueobronquitis asociada a la ventilación mecánica en pacientes adultos, que no desarrollan neumonía asociada a ventilación mecánica / A case-control study on the clinical impact of ventilator associated tracheobronchitis in adult patients who did not develop ventilator associated pneumonia

Objetivos: El objetivo primario fue determinar si la traqueobronquitis asociada a ventilación mecánica (TAV) está asociada con un aumento de estancia en UCI. Los objetivos secundarios incluyeron prolongación de estancia hospitalaria, así como mortalidad en UCI y hospitalaria. Diseño: Estudio retrospectivo caso-control. Apareamos cada caso con un control en base a los siguientes criterios: periodo de VM al menos tan extenso, como el tiempo en que el caso desarrolla la TAV ± 2 días, gravedad evaluada por la escala APACHE II al ingreso en UCI, igual ± 3, igual motivo de ingreso del paciente, igual edad ± 10 años. Pacientes: Pacientes adultos ingresados en una UCI polivalente de 30 camas, con el diagnóstico de TAV en el periodo 2013-2016. Resultados: Identificamos 76 pacientes con TAV que ingresaron en UCI en el periodo de estudio. No se encontraron controles adecuados para 3 pacientes con TAV. No se encontraron diferencias significativas entre ambos grupos en cuanto a características demográficas, motivo de ingreso y comorbilidades. La estancia media en UCI de los pacientes con traqueobronquitis asociada a ventilación mecánica fue más prolongada en los casos que en los controles, mediana 22d (14-35), comparada con los controles mediana 15d (8-27), p=0,02. Los casos presentaron mayor número de días de VM respecto a los controles, mediana 18 días (9-28) vs. 9 días (5-16) p = 0,03. No encontramos diferencias significativas respecto a la estancia hospitalaria 40d (28-61) vs. 35d (23-54), p= 0,32; mortalidad en UCI (20,5 vs. 31,5% p=0,13) y mortalidad hospitalaria (30,1 vs. 43,8% p= 0,09). Realizamos un análisis del subgrupo de pacientes con TAV con documentación microbiológica y tratamiento empírico adecuado sin encontrar diferencias significativas en ninguno de los aspectos analizados. Conclusiones: La TAV, prolonga los días de estancia en UCI y de ventilación mecánica. Este efecto desaparece cuando los pacientes reciben tratamiento empírico adecuado

Objectives: The main objective was to determine whether ventilator-associated tracheobronchitis (VAT) is related to increased length of ICU stay. Secondary endpoints included prolongation of hospital stay, as well as, ICU and hospital mortality. Design: A retrospective matched case-control study. Each case was matched with a control for duration of ventilation (± 2 days until development of ventilator-associated tracheobronchitis), disease severity (Acute Physiology and Chronic Health Evaluation II) at admission ± 3, diagnostic category and age ±10 years. Patients: Critically ill adults admitted to a polyvalent 30-beds ICU with the diagnosis of VAT in the period 2013-2016. Main results: We identified 76 cases of VAT admitted to our ICU during the study period. No adequate controls were found for 3 patients with VAT. There were no significant differences in demographic characteristics, reasons for admission and comorbidities. Patients with VAT had a longer ICU length of stay, median 22 days (14-35), compared to controls, median 15 days (8-27), p=.02. Ventilator days were also significantly increased in VAT patients, median 18 (9-28) versus 9 days (5-16), p=.03. There was no significant difference in total hospital length of stay 40 (28-61) vs. 35days (23-54), p=.32; ICU mortality (20.5 vs. 31.5% p=.13) and hospital mortality (30.1 vs. 43.8% p=.09). We performed a subanalysis of patients with microbiologically proven VAT receiving adequate antimicrobial treatment and did not observe significant differences between cases and the corresponding controls. Conclusions: VAT is associated with increased length of intensive care unit stay and longer duration of mechanical ventilation. This effect disappears when patients receive appropriate empirical treatment

A case-control study on the clinical impact of ventilator associated tracheobronchitis in adult patients who did not develop ventilator associated pneumonia. / Estudio caso-control del impacto clínico de la traqueobronquitis asociada a la ventilación mecánica en pacientes adultos, que no desarrollan neumonía asociada a ventilación mecánica.

OBJECTIVES: The main objective was to determine whether ventilator-associated tracheobronchitis (VAT) is related to increased length of ICU stay. Secondary endpoints included prolongation of hospital stay, as well as, ICU and hospital mortality. DESIGN: A retrospective matched case-control study. Each case was matched with a control for duration of ventilation (± 2 days until development of ventilator-associated tracheobronchitis), disease severity (Acute Physiology and Chronic Health Evaluation II) at admission ± 3, diagnostic category and age ±10 years. PATIENTS: Critically ill adults admitted to a polyvalent 30-beds ICU with the diagnosis of VAT in the period 2013-2016. MAIN RESULTS: We identified 76 cases of VAT admitted to our ICU during the study period. No adequate controls were found for 3 patients with VAT. There were no significant differences in demographic characteristics, reasons for admission and comorbidities. Patients with VAT had a longer ICU length of stay, median 22 days (14-35), compared to controls, median 15 days (8-27), p=.02. Ventilator days were also significantly increased in VAT patients, median 18 (9-28) versus 9 days (5-16), p=.03. There was no significant difference in total hospital length of stay 40 (28-61) vs. 35days (23-54), p=.32; ICU mortality (20.5 vs. 31.5% p=.13) and hospital mortality (30.1 vs. 43.8% p=.09). We performed a subanalysis of patients with microbiologically proven VAT receiving adequate antimicrobial treatment and did not observe significant differences between cases and the corresponding controls. CONCLUSIONS: VAT is associated with increased length of intensive care unit stay and longer duration of mechanical ventilation. This effect disappears when patients receive appropriate empirical treatment.

A case of pan-resistant Burkholderia cepacia complex bacteremic pneumonia, after lung transplantation treated with a targeted combination therapy.

We describe a case of one patient with cystic fibrosis who developed a pan-resistant Burkholderia cepacia complex rapidly progressive bacteraemic pneunonia, following bilateral lung transplantation. The patient was treated with a targeted combination antibiotic therapy (meropenem plus ceftazidime/avibactam plus high doses of nebulized colistimethate sodium). Evolution of the disease was complicated by multiple organ system dysfunction. Finally, clinical improvement and microbiological cure was achieved.