Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Reduction in the number of neutrophils in the broncho-alveolar aspirate is associated with worse prognosis in elderly patients with severe COVID-19.

The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years). In addition, we have shown that older patients have higher serum concentration of CXCL8 and increased IL-10 expression by neutrophils.

Use of C-reactive protein to guide the antibiotic therapy in hospitalized patients: a systematic review and meta-analysis.

BACKGROUND: C-reactive protein (CRP) is an inflammatory protein used in clinical practice to identify and monitor inflammatory and infectious processes. Recent data suggest CRP might be useful in guiding antibiotic therapy discontinuation among critical care patients. This meta-analysis analyzed the benefits and risks of CRP-guided protocols to guide antibiotic therapy in hospitalized patients in comparison with standard treatment. METHODS: Studies were searched in four databases: CENTRAL, Medline, Embase and LILACS. The search was performed until Jan 25th, 2023. The reference lists of the articles retrieved and related review studies were hand-screened to find eligible trials that might have been missed. Primary endpoints included the duration of antibiotic therapy for the index episode of infection. The secondary endpoint was the all-cause hospital mortality and infection relapses. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Random effects were used to pool the mean differences and odds ratio of individual studies. The protocol was registered in PROSPERO (CRD42021259977). RESULTS: The search strategy retrieved 5209 titles, out of which three studies met the eligibility criteria and were included in this meta-analysis. 727 adult patients were analyzed, of whom 278 were included in the intervention group and 449 were included in the control group. 55,7% of all patients were women. Meta-analysis indicated that experimental groups (CRP-guided) had a lower duration of antibiotic therapy (days) [MMD = -1.82, 95%IC -3.23; -0.40]; with no difference in mortality [OR = 1.19 95%IC 0.67-2.12] or in the occurrence of infection relapse [OR = 3.21 95%IC 0.85-12.05]. CONCLUSION: The use of CRP-guided protocol reduces the total amount of time required for antibiotic therapy when compared to standard protocols of treatment in hospitalized patients with acute bacterial infection. We did not observe statistical differences regarding mortality and infection relapse rates.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials.

Objectives: Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. Methods: We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality. Results: Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5-7.6 days; adjusted difference in days -2.01 [95% CI, -2.45 to -1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI -3.59 to -1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05). Conclusions: This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.

Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a clinical and C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers.

BACKGROUND: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients. METHODS: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics. RESULTS: One hundred thirty patients were included in the CRP (n = 64) and control (n = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0-8.8) days in the CRP and 7.0 (7.0-11.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0-8.0) days for the CRP and 7.0 (7.0-10.0) days for the control (p = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days. CONCLUSIONS: Daily monitoring of CRP levels may allow early interruption of antibiotic therapy in a higher proportion of patients, without an effect on total antibiotic consumption. The clinical and microbiological relevance of this finding remains to be demonstrated. TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT02987790. Registered 09 December 2016.

Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials.

BACKGROUND: Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia. METHODS: We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days. RESULTS: Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days [95% confidence interval [CI], -4.88 to -.84]; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections. CONCLUSIONS: This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.

Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care Unit: The ICU Visits Randomized Clinical Trial.

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain. Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation. Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium. Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.

Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials.

BACKGROUND: The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection. METHODS: For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the "procalcitonin-guided" group) or the current standard of care (the "controls"). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay. RESULTS: Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p <  0.001). CONCLUSION: Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.

Rapid detection of the New Delhi metallo-b-lactamase 1 (NDM-1) gene by loop-mediated isothermal amplification (LAMP).

BACKGROUND: New Delhi Metallo-b-lactamase (NDM-1) is an enzyme emerging around the world conferring resistance to a wide range of ß-lactams agents and whose early detection is extremely important. We proposed to standardize the detection of the blaNDM-1 gene using the LOOP-mediated isothermal amplification technique (LAMP). METHODS: In all, 14 Gram-negative bacterial strains isolated from patients presenting pneumonia associated with mechanical ventilation were used for the blaNDM-1 standardization by LAMP. Klebsiella pneumoniae ATCC BAA-2473 and two clinical strains were used as a positive control. All results were compared to the reaction in polymerase chain reaction (PCR), considered gold standard for this detection. RESULTS: There was an excellent correlation between the two techniques employed, since all measured clinical strains were negative in both employed tests and two clinical, and a reference strains were positive. CONCLUSIONS: The lamp technique seems to be an excellent option for the rapid detection of blaNDM-1. The amplification time is much shorter than other molecular techniques, the PCR machine is not necessary, it is easy of implementation and costs is low.

Post-sepsis cognitive impairment and associated risk factors: A systematic review.

INTRODUCTION: Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. This cognitive impairment can be global or may affect specific domains. A better understanding of these deficits and associated risk factors could influence the care of patients with sepsis. OBJECTIVE: To perform a systematic review to investigate the presence of cognitive impairment and its associated risk factors among patients who survived sepsis. METHODS: The search was conducted in MEDLINE (1966 to March 2017) and EMBASE (1988 to March 2017). We included studies with individuals who were 18 years or older with post-sepsis cognitive impairment. RESULTS: We analysed 577 articles. Sixteen studies met the inclusion criteria. More than 74,000,000 patients were evaluated in the selected studies. Significant variation was observed in the definition of sepsis and cognitive impairment. Twelve studies used ACCP/SCCM criteria for sepsis, while cognitive impairment was defined per test used. Post-sepsis cognitive impairment was observed in 12.5 to 21% of survivors of sepsis. Attention, cognitive flexibility, processing speed, associative learning, visual perception, work memory, verbal memory, and semantic memory were the specific domains affected. Depressive symptoms, central nervous system infection, length of hospitalisation due to infection, and temporal proximity to the last period of infection were associated with cognitive impairment. CONCLUSION: The studies are heterogeneous, and there is urgent need for a common language, including definitions and neuropsychological tests, for the investigation of post-sepsis cognitive impairment. Despite this, there is mounting evidence for the clinical relevance of post-sepsis cognitive impairment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017054583 (www.crd.york.ac.uk/PROSPERO).

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.

BACKGROUND: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES: The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS: Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis. MAIN RESULTS: From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results. AUTHORS' CONCLUSIONS: This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.

Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.

Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective.

BACKGROUND: Whether or not antibiotic stewardship protocols based on procalcitonin levels results in cost savings remains unclear. Herein, our objective was to assess the economic impact of adopting procalcitonin testing among patients with suspected acute respiratory tract infection (ARI) from the perspective of a typical US integrated delivery network (IDN) with a 1,000,000 member catchment area or enrollment. METHODS: To conduct an economic evaluation of procalcitonin testing versus usual care we built a cost-impact model based on patient-level meta-analysis data of randomized trials. The meta-analytic data was adapted to the US setting by applying the meta-analytic results to US lengths of stay, costs, and practice patterns. We estimated the annual ARI visit rate for the one million member cohort, by setting (inpatient, ICU, outpatient) and ARI diagnosis. RESULTS: In the inpatient setting, the costs of procalcitonin-guided compared to usual care for the one million member cohort was $2,083,545, compared to $2,780,322, resulting in net savings of nearly $700,000 to the IDN for 2014. In the ICU and outpatient settings, savings were $73,326 and $5,329,824, respectively, summing up to overall net savings of $6,099,927 for the cohort. RESULTS were robust for all ARI diagnoses. For the whole US insured population, procalcitonin-guided care would result in $1.6 billion in savings annually. CONCLUSIONS: Our results show substantial savings associated with procalcitonin protocols of ARI across common US treatment settings mainly by direct reduction in unnecessary antibiotic utilization. These results are robust to changes in key parameters, and the savings can be achieved without any negative impact on treatment outcomes.

Prognostic value of procalcitonin in respiratory tract infections across clinical settings.

INTRODUCTION: Whether the inflammatory biomarker procalcitonin provides prognostic information across clinical settings and different acute respiratory tract infections (ARIs) is poorly understood. In the present study, we investigated the prognostic value of admission procalcitonin levels to predict adverse clinical outcome in a large ARI population. METHODS: We analysed data from 14 trials and 4,211 ARI patients to study associations of admission procalcitonin levels and setting specific treatment failure and mortality alone at 30 days. We used multivariable hierarchical logistic regression and conducted sensitivity analyses stratified by clinical settings and ARI diagnoses to assess the results' consistency. RESULTS: Overall, 864 patients (20.5%) experienced treatment failure and 252 (6.0%) died. The ability of procalcitonin to differentiate patients with from those without treatment failure was highest in the emergency department setting (treatment failure area under the curve (AUC): 0.64 (95% confidence interval (CI): 0.61, 0.67), adjusted odds ratio (OR): 1.85 (95% CI: 1.61, 2.12), P <0.001; and mortality AUC: 0.67 (95% CI: 0.63, 0.71), adjusted OR: 1.82 (95% CI: 1.45, 2.29), P <0.001). In lower respiratory tract infections, procalcitonin was a good predictor of identifying patients at risk for mortality (AUC: 0.71 (95% CI: 0.68, 0.74), adjusted OR: 2.13 (95% CI: 1.82, 2.49), P <0.001). In primary care and intensive care unit patients, no significant association of initial procalcitonin levels and outcome was found. CONCLUSIONS: Admission procalcitonin levels are associated with setting specific treatment failure and provide the most prognostic information regarding ARI in the emergency department setting.

Using procalcitonin to guide antimicrobial duration in sepsis: asking the same questions will not bring different answers.

Severe sepsis is a major healthcare problem and the early initiation of antimicrobials is one of the few measures associated with improved outcomes. However, antibiotic overuse is an increasing problem in critical care. Of several potential biomarkers for antibiotic stewardship, procalcitonin represents the most widely studied and validated. In this commentary we address the current literature on the use of biomarkers to guide antimicrobial therapy in the critically ill and discuss its limitations and future directions.

Utrasound as a method for confirming the positioning of enteral catheters in critically ill patients.

AIM: To evaluate the agreement between the bedside ultrasound in a single epigastric window and the plain X-ray to confirm the positioning of the enteral catheter in critically ill patients. MATERIAL AND METHODS: This was an observational, cross-sectional study conducted in two Intensive Care Units of a university hospital. The ultrasound exams were carried out immediately after the introduction of the enteral catheter, using only the epigastric window, with an injection of 5 ml of air associated with 5 ml of saline solution. In all cases, the plain radiography was taken to confirm the positioning of the enteral catheter and to define the beginning of nutritional therapy. RESULTS: This study included 83 patients, the positioning of the enteral catheter was confirmed by plain radiography in all cases and by ultrasound in 81 (97.6%) patients. The median duration of the ultrasound exam was 2 (2-3) minutes, while the time spent between the request for the X-ray and the release of the exam for a doctor's appointment was 225 (120-330) minutes. CONCLUSION: Bedside ultrasound proved to be an effective, quick, and safe method to confirm the position of the enteral catheter in critically ill patients.

Use of point-of-care ultrasound to assess the severity of scorpion stings in hospitalized patients.

INTRODUCTION: Scorpionism is a public health problem, especially in tropical regions. In Brazil, the prevalence of envenomation by scorpions is high, and the average national lethality is around 0.16 percent. The Tityus serrulatus scorpion is the primary species of medical importance. However, objective tools to predict and define the severity of these envenomations are lacking. MATERIALS AND METHODS: This was an observational study conducted among patients aged 0-19 years with scorpionism. Patients were admitted to a reference hospital between December 2020 and May 2022. Point-of-care ultrasound was performed within 24 hours of the scorpion sting. RESULTS: Forty-nine patients were included, with a median age of 3.6 (interquartile range 2.3-5.3) years and a predominance of females (51 percent). Fifteen patients (30.6 percent) presented major life-threatening signs, 32 (65.3 percent) minor systemic manifestations, and two (4.1 percent) only local manifestations. Left ventricular dysfunction was identified in 13 patients (26.5 percent). Ten patients (20.4 percent) presented pattern B (visualization of three or more B lines in the evaluated quadrant) in at least one lung window. The sensitivity and specificity of cardiac and pulmonary ultrasound to identify the most severely ill patients were 86 percent and 94 percent, respectively. DISCUSSION: The changes found on point-of-care ultrasound were associated with life-threatening signs. All patients with class III envenomation were referred to the intensive care unit, showing the importance of early identification of this subgroup. The main limitations were the small sample size and the fact that admission to intensive care was not based on systematic criteria. CONCLUSIONS: Point-of-care ultrasound is able to identify early signs of pulmonary congestion and heart failure in scorpionism. It can be useful for the objective selection of patients who are at a higher risk of complications and death and who require intensive support; it may also be valuable for periodic reassessments. Point-of-care ultrasound is a valuable tool for identifying and monitoring severe cases of scorpionism.

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.

AB2CO risk score for in-hospital mortality of COVID-19 patients admitted to intensive care units.

PURPOSE: To develop a mortality risk score for COVID-19 patients admitted to intensive care units (ICU), and to compare it with other existing scores. MATERIALS AND METHODS: This retrospective observational study included consecutive adult patients with laboratory-confirmed COVID-19 admitted to ICUs of 18 hospitals from nine Brazilian cities, from September 2021 to July 2022. Potential predictors were selected based on the literature review. Generalized Additive Models were used to examine outcomes and predictors. LASSO regression was used to derive the mortality score. RESULTS: From 558 patients, median age was 69 years (IQR 58-78), 56.3 % were men, 19.7 % required mechanical ventilation (MV), and 44.8 % died. The final model comprised six variables: age, pO2/FiO2, respiratory function (respiratory rate or if in MV), chronic obstructive pulmonary disease, and obesity. The AB2CO had an AUROC of 0.781 (95 % CI 0.744 to 0.819), good overall performance (Brier score = 0.191) and an excellent calibration (slope = 1.063, intercept = 0.015, p-value = 0.834). The model was compared with other scores and displayed better discrimination ability than the majority of them. CONCLUSIONS: The AB2CO score is a fast and easy tool to be used upon ICU admission.