At the emergency department (ED) a urinary tract infection (UTI) is frequently suspected as the cause of inflammation or illness.1 Accurate confirmation or exclusion of a UTI in the ED time window can be challenging since urine culture (UC) results are unavailable during an ED visit. In addition, the results are disconcordant, especially in an ED population, as part of the UC results do not reflect the presence or absence of a UTI.2 Presumed UTI diagnosis and effective patient management should therefore rely on both clinical characteristics and interpretation of available urinary parameters.

by Per Venge, Christer Peterson, Shengyuan Xu, Anders Larsson, Joakim Johansson, Jonas Tydén Introduction Sepsis is a growing problem worldwide and associated with high mortality and morbidity. The early and accurate diagnosis and effective supportive therapy are critical for combating mortality. The aim of the study was to compare the kinetics of four biomarkers in plasma in patients admitted to ICU including sepsis and during antibiotics treatment. Methods The biomarkers evaluated were HBP (Heparin-binding protein), HNL Dimer (Human Neutrophil Lipocalin), HNL Total and PCT (Procalcitonin). Plasma was obtained at admission to ICU and during follow-up at days 2 and 3. Antibiotic treatment was started or reviewed on admission to ICU. The results were compared to SOFA and KDIGO-scores and to survival. 277 patients admitted to ICU were included of which 30% had sepsis. The other groups were categorized as miscellaneous, other medical and trauma. Results The plasma concentrations of all four biomarkers were highly elevated with the highest concentrations in sepsis patients. During the follow-up period HNL Dimer decreased already day 2 and further so day 3 (p…

Abstract Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-Cmin) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-Cmin. In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-Cmin (p 

Abstract Purpose A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. Methods This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral ( 65) infections. Results Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score  65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores 

Abstract Purpose A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. Methods This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral ( 65) infections. Results Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score  65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores 

Abstract Background The clinical significance of the presence or absence of Mycoplasma pneumoniae (MP) in pleural effusion in Mycoplasma pneumoniae pneumonia (MPP) children has not yet been elucidated. Herein, we investigated the clinical implication of pleural fluid MP positive in children with MPP. Methods A total of 165 MPP children with pleural effusion requiring thoracocentesis were enrolled in this study. They were subsequently divided into two groups according to the presence or absence of MP in pleural effusion, namely positive group (n = 38) and negative group (n = 127). Information on their clinical manifestations, laboratory findings, radiological characteristics and treatment modalities was retrospectively collected from medical chart reviews. Results The length of hospitalization (15.00 (10.75–19.25) vs. 11.00 (9.00–14.00) days, p=0.001) and total course of illness (23.00 (18.00–28.00) vs. 20.00 (17.00–24.00) days, p=0.010) were significantly longer in the positive group than in the negative group. The occurrence of pericardial effusion (23.7% vs. 7.9%, p=0.017), atelectasis (73.7% vs. 53.5%, p=0.027) and necrotizing pneumonia (23.7% vs. 7.9%, p=0.017) were more frequent in the positive group compared to the negative group. The levels of neutrophil percentages (82.35% (75.40%-85.78%) vs. 72.70% (64.30%-79.90%), p

Abstract Purpose The IL-6 receptor inhibitor tocilizumab reduces mortality and morbidity in severe cases of COVID-19 through its effects on hyperinflammation and was approved as adjuvant therapy. Since tocilizumab changes the levels of inflammatory markers, we aimed to describe these changes in patients treated with tocilizumab, analyse their value in predicting death and bacterial superinfection and determine their influence on mortality rates. Methods A retrospective analysis of 76 patients who were treated with tocilizumab for severe COVID-19 in 2020 and 2021 was conducted. Inflammatory markers (IL-6, C-reactive protein (CRP), procalcitonin) were documented before and up to seven days after tocilizumab administration. Results The overall mortality was 25% and 53.8% in patients who required invasive respiratory support. Deceased patients had higher baseline IL-6 (p = 0.026) and peak IL-6 levels after tocilizumab vs those who survived (p  1000 pg/dl after tocilizumab administration was a good predictor of mortality (AUC = 0.812). Of the deceased patients 41.1% had a renewed CRP increase after an initial decrease following tocilizumab administration, compared to 7.1% of the surviving patients (p = 0.0011). Documented bacterial superinfections were observed in 35.5% (27/76) of patients, of whom 48.1% (13/27) died. Conclusion CRP-decline and IL-6 increase after tocilizumab treatment occurs regularly. An increase of IL-6 levels exceeding tenfold of baseline IL-6 levels, an absolute peak of 1000 pg/ml or a renewed increase of CRP are associated with higher mortality. Suppressed CRP synthesis can impede the diagnosis of bacterial superinfections, thus increasing the risk for complications. …

Abstract Background Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion. Case presentation The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem. Conclusions This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion. …

Abstract Purpose The IL-6 receptor inhibitor tocilizumab reduces mortality and morbidity in severe cases of COVID-19 through its effects on hyperinflammation and was approved as adjuvant therapy. Since tocilizumab changes the levels of inflammatory markers, we aimed to describe these changes in patients treated with tocilizumab, analyse their value in predicting death and bacterial superinfection and determine their influence on mortality rates. Methods A retrospective analysis of 76 patients who were treated with tocilizumab for severe COVID-19 in 2020 and 2021 was conducted. Inflammatory markers (IL-6, C-reactive protein (CRP), procalcitonin) were documented before and up to seven days after tocilizumab administration. Results The overall mortality was 25% and 53.8% in patients who required invasive respiratory support. Deceased patients had higher baseline IL-6 (p = 0.026) and peak IL-6 levels after tocilizumab vs those who survived (p  1000 pg/dl after tocilizumab administration was a good predictor of mortality (AUC = 0.812). Of the deceased patients 41.1% had a renewed CRP increase after an initial decrease following tocilizumab administration, compared to 7.1% of the surviving patients (p = 0.0011). Documented bacterial superinfections were observed in 35.5% (27/76) of patients, of whom 48.1% (13/27) died. Conclusion CRP-decline and IL-6 increase after tocilizumab treatment occurs regularly. An increase of IL-6 levels exceeding tenfold of baseline IL-6 levels, an absolute peak of 1000 pg/ml or a renewed increase of CRP are associated with higher mortality. Suppressed CRP synthesis can impede the diagnosis of bacterial superinfections, thus increasing the risk for complications. …

Abstract Aim This study aimed to discover risk factors for death in patients with critical COVID-19 infection in order to identify patients with a higher risk of death at an early stage. Methods We retrospectively analyzed the clinical data of patients with critical COVID-19 infection from April 2022 to June 2022. Data were collected from the electronic medical records. Propensity matching scores were used to reduce the effect of confounding factors, such as patient baseline variables. Independent risk factors affecting patient prognosis were assessed using univariate logistic regression and multivariate logistic regression analysis. Restricted cubic spline curves were used to assess the relationship between independent and dependent variables. Results The data of 132 patients with critical COVID-19 infection were included in the study. Of the 132 patients, 79 survived and 53 died. Among laboratory indicators, patients who died had higher proportions of abnormalities in procalcitonin, aspartate aminotransferase (AST), creatinine, cardiac troponin I, and myoglobin. Univariate and multivariate logistic regression analyses suggested that abnormal AST (OR = 4.98, P = 0.02), creatinine (OR = 7.93, P = 0.021), and myoglobin (OR = 103.08, P = 0.002) were independent risk factors for death. After correction for AST and creatinine, a linear relationship between myoglobin and risk of death in patients was found using restricted cubic splines. Conclusion High myoglobin level is an independent risk factor for death and is therefore a prognostic marker in elderly patients with severe COVID-19 infection. …

Abstract Purpose This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. Methods The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. Results The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7–8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. Conclusion The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany. …

Abstract Purpose This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. Methods The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. Results The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7–8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. Conclusion The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany. …

IMPORTANCE: Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES: To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES: The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS: Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE: Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.

Objectives: In sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide antibiotic cessation, but solid evidence is insufficient. Recently, concerns were raised that this strategy would increase recurrence. Additionally, optimal protocol or difference from the commonly used C-reactive protein (CRP) are uncertain. We aimed to compare the effectiveness and safety of procalcitonin- or CRP-guided antibiotic cessation strategies with standard of care in sepsis. Data Sources: A systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform. Study Selection: Randomized controlled trials involving adults with sepsis in intensive care. Data Extraction: A systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty. Data Synthesis: Eighteen studies involving 5023 participants were included. Procalcitonin-guided and CRP-guided strategies shortened antibiotic treatment (–1.89 days [95% CI, –2.30 to –1.47], –2.56 days [95% CI, –4.21 to –0.91]) with low- to moderate-certainty evidence. In procalcitonin-guided strategies, this benefit was consistent even in subsets with shorter baseline antimicrobial duration (7–10 d) or in Sepsis-3, and more pronounced in procalcitonin cutoff of “0.5 μg/L and 80% reduction.” No benefit was observed when monitoring frequency was less than half of the initial 10 days. Procalcitonin-guided strategies lowered mortality (–27 per 1000 participants [95% CI, –45 to –7]) and this was pronounced in Sepsis-3, but CRP-guided strategies led to no difference in mortality. Recurrence did not increase significantly with either strategy (very low to low certainty). Conclusions: In sepsis, procalcitonin- or CRP-guided antibiotic discontinuation strategies may be beneficial and safe. In particular, the usefulness of procalcitonin guidance for current Sepsis-3, where antimicrobials are used for more than 7 days, was supported. Well-designed studies are needed focusing on monitoring protocol and recurrence.