Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction.

BACKGROUND: Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity. METHODS: We included patients at or above 18 years with suspected septic shock on admission to the intensive care unit (ICU) during 2014 and 2016 to 2018. Plasma samples were collected from ICU admission and every 4 h for 72 h or until death or ICU discharge and batch analysed for HBP. Mean arterial blood pressure (MAP) and noradrenaline dose (NA dose) were recorded at each sampling time point, and systemic vascular resistance index (SVRI) was recorded when available from non-invasive monitoring. The association between HBP, NA dose, MAP and SVRI was assessed respectively using mixed-effects linear regression models. Procalcitonin (PCT) was used as a comparator. RESULTS: A total of 24 patients were included. The kinetics of plasma HBP was highly variable over time, with occasional >2-fold increases and decreases in between 4-h measurements. Every 100 ng/mL increase in HBP corresponded to a 30% increase in NA dose in a crude model (95% CI 3 to 60%, p = 0.03, nobs = 340), a 1.4-mmHg decrease in MAP in an adjusted model (95% CI - 1 to - 2.3 mmHg, p = 0.04) or a 99 dyne s cm-5 m-2 decrease in SVRI in another adjusted model (95% CI - 36 to - 162, p = 0.002, npat = 13). PCT had a stronger association to NA dose than HBP in a crude model but was not significantly associated to NA dose, MAP or SVRI in any time-adjusted model. CONCLUSIONS: Plasma HBP displayed a highly variable kinetic pattern during septic shock and was significantly associated to cardiovascular organ dysfunction severity over time.

Accelerated treatment of endocarditis-The POET II trial: Rationale and design of a randomized controlled trial.

BACKGROUND: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. OBJECTIVE: The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. METHODS: The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. CONCLUSIONS: The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.

Improved Outcomes After Regional Implementation of Sepsis Alert: A Novel Triage Model.

OBJECTIVES: To assess whether the triage model Sepsis Alert for Emergency Departments results in improved initial care of patients with severe infections. DESIGN: Interventional study comparing patient care before and after the start of a new triage model, including 90-day follow-up. SETTING: Eight emergency departments in Skåne County, Sweden. SUBJECTS: Patients with suspected severe infection. INTERVENTIONS: Patients with severely deviating vital signs and suspected infection were triaged into a designated sepsis line called Sepsis Alert, for rapid evaluation supported by an infectious disease specialist. Also, all emergency department staff participated in a designated sepsis education before the model was introduced. MEASUREMENTS AND MAIN RESULTS: Medical records were evaluated for a 3-month period 1 year before the triage system was started in 2016 and for a 3-month period 1 year after. Of 195,607 patients admitted to these emergency departments during two 3-month periods, a total of 5,321 patients presented severely abnormal vital signs. Of these, 1,066 patients who presented with fever greater thanor equal to 38°C or history of fever/chills were considered to be patients at risk of having severe sepsis. Among patients triaged according to Sepsis Alert, 89.3% received antibiotic treatment within 1 hour after arrival to the emergency department (median time to antibiotics, 26 min), which was significantly better than before the start of the new triage: 67.9% (median time to antibiotics, 37 min) (p < 0.001). Additionally, sepsis treatment quality markers were significantly improved after the introduction of Sepsis Alert, including number of blood cultures and lactate measurements taken, percentage of patients receiving IV fluids, and appropriate initial antibiotic treatment. There were no differences in 28- or 90-day mortality rates. CONCLUSIONS: The implementation of the new triage model Sepsis Alert with special attention to severe sepsis patients led to faster and more accurate antibiotic treatment and improved diagnostic procedures and supportive care.

Scores for sepsis detection and risk stratification - construction of a novel score using a statistical approach and validation of RETTS.

BACKGROUND: To allow early identification of patients at risk of sepsis in the emergency department (ED), a variety of risk stratification scores and/or triage systems are used. The first aim of this study was to develop a risk stratification score for sepsis based upon vital signs and biomarkers using a statistical approach. Second, we aimed to validate the Rapid Emergency Triage and Treatment System (RETTS) for sepsis. RETTS combines vital signs with symptoms for risk stratification. METHODS: We retrospectively analysed data from two prospective, observational, multicentre cohorts of patients from studies of biomarkers in ED. A candidate risk stratification score called Sepsis Heparin-binding protein-based Early Warning Score (SHEWS) was constructed using the Least Absolute Shrinkage and Selector Operator (LASSO) method. SHEWS and RETTS were compared to National Early Warning Score 2 (NEWS2) for infection-related organ dysfunction, intensive care or death within the first 72h after admission (i.e. sepsis). RESULTS: 506 patients with a diagnosed infection constituted cohort A, in which SHEWS was derived and RETTS was validated. 435 patients constituted cohort B of whom 184 had a diagnosed infection where both scores were validated. In both cohorts (A and B), AUC for infection-related organ dysfunction, intensive care or death was higher for NEWS2, 0.80 (95% CI 0.76-0.84) and 0.69 (95% CI 0.63-0.74), than RETTS, 0.74 (95% CI 0.70-0.79) and 0.55 (95% CI 0.49-0.60), p = 0.05 and p <0.01, respectively. SHEWS had the highest AUC, 0.73 (95% CI 0.68-0.79) p = 0.32 in cohort B. CONCLUSIONS: Even with a statistical approach, we could not construct better risk stratification scores for sepsis than NEWS2. RETTS was inferior to NEWS2 for screening for sepsis.

NEWS2 is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department.

Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75-0.83) and 0.70 (95% CI 0.65-0.74), than qSOFA, AUC 0.70 (95% CI 0.66-0.75) and 0.62 (95% CI 0.57-0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.

[Endocarditis team in the Scania region - experiences from the first year]. / Multidisciplinärt endokarditteam på plats i Skåne - Första årets erfarenhet visar riktningen framåt.

International guidelines recommend that the treatment of patients with infective endocarditis (IE) should be directed by a multidisciplinary endocarditis team. The aim of this study was to describe the first-year experience of multidisciplinary rounds by the endocarditis team in Scania, Sweden. This was a retrospective study on all possible and definitive IE episodes that were assessed by the endocarditis team from January 1st to December 31st, 2017. Descriptive statistics were used. A total of 145 multidisciplinary rounds were held and addressed 100 episodes in 97 patients. The median age was 71 years and 66% were males. The most common causative pathogens were alpha-hemolytic streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and enterococci. The endocarditis team recommended surgery in 40 % of episodes. The transfer of patients between different hospitals was facilitated by the team.  The IE team evaluated a large proportion of patients with IE in the region and provided a rapid expert opinion on the optimal management of complicated cases of IE.

Heparin-Binding Protein as a Prognostic Biomarker of Sepsis and Disease Severity at the Emergency Department.

OBJECTIVE: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department. DESIGN: Prospective, international multicenter, convenience sample study. SETTING: Four general emergency departments at academic centers in Sweden, Switzerland, and Canada. PATIENTS: All emergency encounters among adults where one of the following criteria were fulfilled: respiratory rate >25 breaths per minute; heart rate >120 beats per minute; altered mental status; systolic blood pressure <100 mm Hg; oxygen saturation <90% without oxygen; oxygen saturation <93% with oxygen; reported oxygen saturation <90%. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A total of 524 emergency department patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a noninfectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 h, 54 patients (10%) were admitted to an intensive care unit, and 23 patients (4%) died within 72 h. For the primary outcome, detection of infected-related organ dysfunction within 72 h, the area under the receiver operating curve (AUC) for HBP was 0.73 (95% CI 0.68-0.78) among all patients and 0.82 (95% CI 0.76-0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12-24 h) HBP had an AUC of 0.87 (95% CI 0.79-0.95) among all patients and 0.88 (95% CI 0.77-0.99) among patients confidently adjudicated to either infection or noninfection. CONCLUSIONS: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.

A population-based study on the treatment and outcome of enterococcal prosthetic joint infections. A consecutive series of 55 cases.

AIM: Enterococci cause 2-11% of all prosthetic joint infections (PJI) and are generally considered difficult to treat. However, study-results are not consistent. In this study we present a population-based case series of 55 cases with enterococcal PJI, investigating treatment and outcome, as well as describing the affected patient population regarding demography and co-morbidities. METHODS: We identified all enterococcal PJIs in the Region of Skåne, Sweden, during a five-year period (2011-2015) and reviewed the patients' medical records. RESULTS: Fifty-five enterococcal PJIs were found. Enterococcus faecalis was the most frequently isolated species (84%), and poly-microbial infections were common (64%). Treatment with intention to cure was given to 43 (78%) cases. Debridement with retention of the implant and antibiotics (DAIR) was the most common surgical treatment strategy (71%), with a cure-rate of 72%. Overall cure-rate was 67%, and in cases where cure was intended, this was achieved in 80%. CONCLUSIONS: When cure is aimed for, the prognosis for enterococcal PJI is not so poor, and DAIR treatment can provide adequate results in many cases.

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) throat carriage: a randomised trial comparing topical treatment with rifampicin-based systemic therapy.

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonisation may prevent transmission of strains between patients and reduces the risk of clinical infection. Colonisation of the throat is associated with prolonged carriage and is more difficult to eradicate. An open randomised study was conducted to evaluate two eradication protocols. Patients with pharyngeal carriage of MRSA were enrolled at six Swedish centres during 4 years. One treatment group received oral rifampicin and either clindamycin or trimethoprim/sulfamethoxazole (SXT) for 7 days in combination with nasal mupirocin. Patients in the other group were treated with nasal mupirocin only. Patients in the same household were randomised together. Both groups followed a hygiene protocol including chlorhexidine washing. Cultures from the nares, perineum and throat were taken at baseline and then at 2 weeks, 2 months and 6 months after the end of treatment. A total of 28 patients received rifampicin-based systemic antibiotics and 24 subjects received mupirocin only. At follow-up 6 months after the end of treatment, 61% of patients and 50% of households in the systemic antibiotics group had culture results negative for MRSA. Significantly less patients (12%) and households (10%) became decolonised in the group receiving topical treatment only. A combination of rifampicin and either clindamycin or SXT was more effective in eliminating pharyngeal MRSA carriage compared with topical treatment with mupirocin only.

Urine concentrations of human beta-defensins and ribonuclease 7 in urinary tract infection and asymptomatic bacteriuria.

Antimicrobial peptides (AMPs) provide a first line of defense against bacterial infections. Here we report that urine levels of AMPs, locally produced in the urinary tract, are lower in individuals with asymptomatic bacteriuria (ABU) compared to patients with urinary tract infection (UTI).

Sepsis Alert - a triage model that reduces time to antibiotics and length of hospital stay.

OBJECTIVE: To study if a modified triage system at an Emergency Department (ED) combined with educational efforts resulted in reduced time to antibiotics and decreased length of hospital stay (LOS) for patients with severe infection. METHODS: A retrospective, observational study comparing patients before and after the start of a new triage model at the ED of a University Hospital. After the implementation of the model, patients with fever and abnormal vital signs were triaged into a designated sepsis line (Sepsis Alert) for rapid evaluation by the attending physician supported by a infectious diseases (IDs) specialist. Also, all ED staff participated in a designated sepsis education before Sepsis Alert was introduced. Medical records were evaluated for patients during a 3-month period after the triage system was started in 2012, and also during the corresponding months in 2010 and 2014. RESULTS: A total of 1837 patients presented with abnormal vital signs. Of these, 221 patients presented with fever and thus at risk of having severe sepsis. Among patients triaged according to the new model, median time to antibiotics was 58.5 at startup and 24.5 minutes at follow-up two years later. This was significantly less than for patients treated before the new model, 190 minutes. Also, median LOS was significantly decreased after introduction of the new triage model, from nine to seven days. CONCLUSIONS: A triage model at the ED with special attention to severe sepsis patients, led to sustained improvements of time to antibiotic treatment and LOS.

Distinguishing asymptomatic bacteriuria from urinary tract infection in the elderly - the use of urine levels of heparin-binding protein and interleukin-6.

Asymptomatic bacteriuria (ABU) is highly prevalent among elderly patients. It can be difficult to distinguish ABU from symptomatic urinary tract infection (UTI) in this population, which leads to unnecessary antibiotic treatment. Urinary heparin-binding protein (U-HBP) and urinary interleukin-6 (U-IL-6) have previously been studied as diagnostic markers for UTI. In this study, biomarkers were measured in the urine of 134 nursing home residents. The prevalence of ABU in this population, excluding patients with urinary catheter, was 32.8%. Levels of U-HBP and IL-6 were significantly lower among residents with ABU when compared to 49 patients with verified UTI. When previously defined cut-off limits were used, U-HBP had a high negative predictive value for UTI (93%), however, the specificity for differentiating patients with UTI and ABU was low. Discriminatory values were better for U-IL-6 with a sensitivity of 80% and specificity of 82% for the differentiation between the subgroup of pyelonephritis and ABU.

Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department.

OBJECTIVES: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. DESIGN: A prospective international multicenter cohort study. SETTING: Seven different emergency departments in Sweden, Canada, and the United States. PATIENTS: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort. CONCLUSION: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

Heparin-binding protein: a diagnostic biomarker of urinary tract infection in adults.

BACKGROUND: Urinary tract infections (UTIs) are associated with significant morbidity and high frequency of antibiotic prescription. Diagnosing UTI is often difficult, particularly in the critically ill patient and in patients with unspecific and mild symptoms. The standard rapid tests have limited value, and there is a need for more reliable diagnostic tools. Heparin-binding protein (HBP) is released from neutrophils and has previously been studied as a diagnostic and predictive biomarker in different bacterial infections. METHODS: This prospective survey enrolled adult patients at 2 primary care units and 2 hospital emergency departments, to investigate in urine HBP as a biomarker of UTI. In addition, urine levels of interleukin-6, white blood cells, and nitrite were analyzed and compared with HBP. Based on symptoms of UTI and microbiological findings, patients were classified into different groups, UTI (cystitis and pyelonephritis) and no UTI. RESULTS: Three hundred ninety patients were evaluated. The prevalence of UTI in the study group was 45.4%. The sensitivity and specificity for HBP in urine as a marker for UTI were 89.2% and 89.8%, respectively. The positive and negative predictive values were 90.2% and 88.8%, respectively. Heparin-binding protein was the best diagnostic marker for UTI, with an area-under-curve value of 0.94 (95% confidence interval, 0.93-0.96). Heparin-binding protein was significantly better in distinguishing cystitis from pyelonephritis, compared with the other markers. CONCLUSIONS: An elevated level of HBP in the urine is associated with UTI and may be a useful diagnostic marker in adult patients with a suspected UTI.

Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock.

INTRODUCTION: Rapid detection of, and optimized treatment for, severe sepsis and septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcome in patients with severe infections. Our aim was to study the systemic release and dynamics of HBP in the plasma of patients with severe sepsis and septic shock in the ICU. METHODS: A prospective study was conducted of two patient cohorts treated in the ICU at Karolinska University Hospital Huddinge in Sweden. A total of 179 patients was included, of whom 151 had sepsis (126 with septic shock and 25 patients with severe sepsis) and 28 a non-septic critical condition. Blood samples were collected at five time points during six days after admission. RESULTS: HBP levels were significantly higher in the sepsis group as compared to the control group. At admission to the ICU, a plasma HBP concentration of ≥ 15 ng/mL and/or a HBP (ng/mL)/white blood cell count (109/L) ratio of >2 was found in 87.2% and 50.0% of critically ill patients with sepsis and non-septic illness, respectively. A lactate level of >2.5 mmol/L was detected in 64.9% and 56.0% of the same patient groups. Both in the sepsis group (n = 151) and in the whole group (n = 179), plasma HBP concentrations at admission and in the last measured sample within the 144 hour study period were significantly higher among 28-day non-survivors as compared to survivors and in the sepsis group, an elevated HBP-level at baseline was associated with an increased case-fatality rate at 28 days. CONCLUSIONS: Plasma HBP levels were significantly higher in patients with severe sepsis or septic shock compared to patients with a non-septic illness in the ICU. HBP was associated with severity of disease and an elevated HBP at admission was associated with an increased risk of death. HBP that rises over time may identify patients with a deteriorating prognosis. Thus, repeated HBP measurement in the ICU may help monitor treatment and predict outcome in patients with severe infections.

Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes.

INTRODUCTION: Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol. METHODS: Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test. RESULTS: ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients. CONCLUSIONS: During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS.

Elevated urine levels of heparin-binding protein in children with urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is a common infection diagnosis in children, and efficient diagnosis and treatment are important to avoid serious complications. In this study we investigated whether urinary levels of neutrophil-derived heparin-binding protein (HBP) can be used as a marker of UTI in children. These results were compared to those of dipstick analysis, interleukin-6 (IL-6) analysis in urine, and bacterial culturing. METHODS: Seventy-eight children aged 0-18 years with fever and/or symptoms indicating UTI were enrolled in a prospective consecutive study. Urine samples were cultured and analyzed with dipstick, and concentrations of HBP and IL-6 were measured. RESULTS: Fifteen patients were classified as having UTI, 30 patients had fever but were diagnosed with a non-urinary tract infection, and 33 patients had neither UTI nor fever. Using a urine HBP (U-HBP) cut-off level of 32 ng/mL, the sensitivity and specificity for detecting UTI were 93.3 and 90.3 %, respectively. Receiver operating characteristic curves demonstrated that U-HBP levels were a higher specificity indicator of UTI than urine white blood cell counts or urine IL-6 levels; they also showed a higher sensitivity than the results of the urine nitrite test. All patients with significant growth of clinically relevant bacteria had elevated U-HBP levels. CONCLUSION: The results indicate that rapid analysis of U-HBP can provide helpful guidance in the management of children with suspected UTI.

Heparin-binding protein: a diagnostic marker of acute bacterial meningitis.

BACKGROUND: The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. OBJECTIVE: In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis. DESIGN: One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed. SETTING AND PATIENTS: Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12-858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0-41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2-10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4-8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters. CONCLUSION: Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.