Correction to: Late Presentation of HIV Infection in the Netherlands: Reasons for Late Diagnoses and Impact on Vocational Functioning.

The original version of this article was published open access. Unfortunately, due to a technical issue, the copyright holder name in the online version (HTML and XML) is incorrectly published as "Springer Science + Business Media, LLC, part of Springer Nature 2018". Instead, it should be "The Author(s) 2018".

Late Presentation of HIV Infection in the Netherlands: Reasons for Late Diagnoses and Impact on Vocational Functioning.

Late diagnosis of HIV remains a major challenge in the HIV epidemic. In Europe, about 50% of all people living with HIV are diagnosed late after infection has occurred. Insight into the reasons for late diagnoses is necessary to increase the number of early diagnoses and optimize treatment options. This qualitative study explored the experiences of 34 late-presenters through in-depth semi-structured interviews. A variety of reasons for late diagnoses emerged from our data and led to a division into four groups, characterized by two dimensions. Regarding vocational functioning, the consequences of late diagnoses were health-related problems prior to and since diagnosis, and problems concealing the HIV status. Healthcare providers should offer HIV tests to groups at risk, and be alert for clinical HIV indicator conditions. It is recommended to increase awareness of HIV transmission routes, symptoms and tests, and the benefits of early testing and early entry to HIV care.

Employment-related concerns of HIV-positive people in the Netherlands: input for a multidisciplinary guideline.

PURPOSE: Finding and keeping employment is difficult for people with HIV. To improve supportive care for people with HIV and employment-related problems, a multidisciplinary guideline was developed in the Netherlands in 2010/2011. To identify the employment-related concerns of people with HIV and to formulate the key questions for the guideline, we conducted a qualitative study. The results of this study are described in this article. METHODS: This study was performed in three HIV-treatment centers in the Netherlands. In total 18 participants participated in three focus-group interviews and nine participants were interviewed individually. The data were transcribed ad verbatim and were analyzed according to the principle of constant comparison. RESULTS: Our findings indicate that people with HIV in the Netherlands face many work-related concerns. The themes which emerged from this study were disclosure, stigma and discrimination, knowledge about HIV, physical and psychological factors, working conditions, absenteeism, reintegration, and dismissal and counselling. CONCLUSIONS: This study provides insight into employment-related concerns for people with HIV living in a Western country. It formed the basis for the key questions which were addressed in a multidisciplinary, evidence-based guideline "HIV and work". Finally, it gives leads for further scientific research and opportunities for improving the vocational guidance of people with HIV.

Post COVID-19 Pandemic Increased Detection of Mycoplasma Pneumoniae in Adults Admitted to the Intensive Care.

Background: Mycoplasma pneumoniae (M. pneumoniae) infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for timely diagnosis, given potential diagnostic method limitations. Methods: A retrospective case series analysis was conducted on M. pneumonia PCR-positive patients admitted to two Dutch secondary hospitals' ICUs between January 2023 and February 2024. Clinical presentations, treatments, outcomes, and mechanical ventilation data were assessed. Results: Seventeen ICU-admitted patients were identified, with a median age of 44 years, primarily due to hypoxia. Non-invasive ventilation was effective for most, while five required invasive mechanical ventilation. None of the patients required extracorporeal membrane oxygenation. No fatalities occurred. Post-PCR, treatment was adjusted to doxycycline or azithromycin; seven received steroid treatment. Discussion: Increased ICU admissions for M. pneumoniae infection were observed. Diverse clinical and radiological findings emphasize heightened clinical awareness. Early molecular diagnostics and tailored antibiotic regimens are crucial since beta-lactam antibiotics are ineffective. Conclusion: This study highlights the escalating challenge of severe M. pneumoniae infections in ICUs, necessitating a multifaceted approach involving accurate diagnostics, vigilant monitoring, and adaptable treatment strategies for optimal patient outcomes.

Presence of procoagulant peripheral blood mononuclear cells in severe COVID-19 patients relate to ventilation perfusion mismatch and precede pulmonary embolism.

PURPOSE: Pulmonary emboli (PE) contribute substantially to coronavirus disease 2019 (COVID-19) related mortality and morbidity. Immune cell-mediated hyperinflammation drives the procoagulant state in COVID-19 patients, resulting in immunothrombosis. To study the role of peripheral blood mononuclear cells (PBMC) in the procoagulant state of COVID-19 patients, we performed a functional bioassay and related outcomes to the occurrence of PE. Secondary aims were to relate this functional assay to plasma D-dimer levels, ventilation perfusion mismatch and TF expression on monocyte subsets. METHODS: PBMC from an ICU biobank were obtained from 20 patients with a computed tomography angiograph (CTA) proven PE and compared to 15 COVID-19 controls without a proven PE. Functional procoagulant properties of PBMC were measured using a modified fibrin generation time (MC-FGT) assay. Tissue factor (TF) expression on monocyte subsets were measured by flow cytometry. Additional clinical data were obtained from patient records including end-tidal to arterial carbon dioxide gradient. RESULTS: MC-FGT levels were highest in the samples taken closest to the PE detection, similar to the end-tidal to arterial carbon dioxide gradient (ETCO2 - PaCO2), a measurement to quantify ventilation-perfusion mismatch. In patients without proven PE, peak MC-FGT relates to an increase in end-tidal to arterial carbon dioxide gradient. We identified non-classical, CD16 positive monocytes as the subset with increased TF expression. CONCLUSION: We show that the procoagulant state of PBMC could aid in early detection of PE in COVID-19 ICU patients. Combined with end-tidal to ETCO2 - PaCO2 gradient, these tests could improve early detection of PE on the ICU.

Review: Viral infections and mechanisms of thrombosis and bleeding.

Viral infections are associated with coagulation disorders. All aspects of the coagulation cascade, primary hemostasis, coagulation, and fibrinolysis, can be affected. As a consequence, thrombosis and disseminated intravascular coagulation, hemorrhage, or both, may occur. Investigation of coagulation disorders as a consequence of different viral infections have not been performed uniformly. Common pathways are therefore not fully elucidated. In many severe viral infections there is no treatment other than supportive measures. A better understanding of the pathophysiology behind the association of viral infections and coagulation disorders is crucial for developing therapeutic strategies. This is of special importance in case of severe complications, such as those seen in hemorrhagic viral infections, the incidence of which is increasing worldwide. To date, only a few promising targets have been discovered, meaning the implementation in a clinical context is still hampered. This review discusses non-hemorrhagic and hemorrhagic viruses for which sufficient data on the association with hemostasis and related clinical features is available. This will enable clinicians to interpret research data and place them into a perspective.

Epidemiology of febrile diseases in the emergency department of a Caribbean island: the Curaçao experience.

OBJECTIVE: The aetiology of febrile diseases in tropical countries often remains poorly characterized. We aim to describe the aetiology and outcome of febrile illnesses at the Emergency Department (ED) in Curaçao. METHODS: From April 2008 - April 2009, all adult febrile patients (T> 38.5 degrees C) at the ED of the St Elisabeth Hospital, Curaçao, Netherlands Antilles, were included. Clinical data were recorded, routine laboratory measurements and blood cultures were taken. Final diagnoses were made at discharge by an independent physician and in retrospect by the main investigator RESULTS: Four hundred and three patients were included: 223 patients (55.6%) were hospitalized, 32 patients (7.9%) died and 18 patients (4.5%) were admitted to the Intensive Care Unit. In 129 febrile patients (32.0%), infection was proven; 84.4% of patients had bacterial (29.0% urinary tract infection, 23.2% pneumonia infection), 5.6% viral and 10.0% parasitic or fungal infections. Twenty-one patients (5.2%) were discharged with a non-infectious diagnosis and 172 patients (42.7%) without a clear diagnosis. CONCLUSION: A high mortality rate of 7.9% was observed. We found a high prevalence of bacterial infections, with pneumonia and urinary tract infections as the most common causes of fever. One in 20 patients did not have an infectious disease.

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department.

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings.

COVID-19 related stigma and health-protective behaviours among adolescents in the Netherlands: An explorative study.

The COVID-19 pandemic has forced many governments to impose social distancing measures upon its citizens, including in the Netherlands. Motivating adolescents to adhere to measures such as social distancing can be challenging, since adolescents are relatively more affected by them, while experiencing virtually no personal health benefit. In addition, the COVID-19 pandemic seems to impact the social environment of adolescents in schools, as some media sources have reported bullying and stigmatisation of students with an Asian appearance. This study aims to explore the experiences of adolescents regarding their Health-Protective Behaviour (HPB), as well as the prevalence and expression of stigma towards ethnic minorities within the context of the first wave of COVID-19 pandemic. We performed a cross-sectional mixed-methods study, including two independent online questionnaires. An adapted version of the "HPB" questionnaire (n = 528) and the "Measure of Disease-Related Stigma (MDRS)" questionnaire (n = 380), were administered to Dutch adolescents of 10-16 years old, attending primary or secondary school. Furthermore, 15 interviews were held with eight male and seven female adolescents. All data collection took place between March 17 and April 20, 2020. Results show that adolescents perceive COVID-19 as a threat to other peoples' health, rather than their own, and report adherence to public health measures in the interest of older and more vulnerable members of their community. We found no convincing evidence for widespread misinformation or stigmatising of certain ethnic groups among adolescents related to COVID-19 during this study. Participants acknowledged such behaviour happened in the early stages of the pandemic, before this study was initiated. Adolescents are a vital group for public health researchers to engage with during a pandemic, even when reaching them can be challenging.

Coagulation disorders in patients with severe leptospirosis are associated with severe bleeding and mortality.

OBJECTIVE: To determine the involvement of coagulation in bleeding and poor outcome in patients with severe leptospirosis. METHODS: In a prospective study, parameters of the coagulation system were measured on admission and during follow-up in 52 consecutive patients with severe leptospirosis. RESULTS: All patients showed coagulation disorders, such as prolonged prothrombin time (PT) and activated partial thromboplastin time, marked procoagulant activity [thrombin-antithrombin (TAT) complexes, prothrombin fragment 1+2, D-dimer], reduced levels of anticoagulant markers (protein C, antithrombin) and increased (anti-) fibrinolytic activity [plasmin-antiplasmin (PAP) complexes, plasminogen activator inhibitor-1]. These disorders were more pronounced in patients who died eventually. PT prolongation was associated with mortality (OR 1.4, 95% CI: 1.0-1.8, P = 0.04). Bleeding occurred in 31 subjects (60%). Of these, 24 had mild bleeding and seven had severe haemorrhages. Thrombocytopenia (platelets

[Human T-cell lymphotropic virus type 1 (HTLV-1): a forgotten pathogen]. / Het humaan T-cellymfotroop virus type 1.

HTLV-1 is a retrovirus endemic to different parts of the world that causes a variety of symptoms, ranging from asymptomatic infection to severe diseases such as lymphoma/leukaemia and myelopathy. HTLV-1 is transmitted from mother to child through breastfeeding, sexually and via blood and organ donation. We describe 3 patients as examples of the distinct clinical problems related to HTLV-1: a 53-year-old woman with HTLV-1-associated myelopathy, a 43-year-old woman with acute T-cell lymphoma and a 34-year-old pregnant woman who is an asymptomatic carrier. It is not known how many people are infected in the Netherlands, but it is probably more prevalent among immigrants from the Caribbean and Surinam and likely to be underdiagnosed. Diagnosis is important because it alters treatment and because measures to prevent transmission can be implemented, e.g. refraining from breastfeeding and safe sex precautions.

Identification and profiling of circulating metabolites of atazanavir, a HIV protease inhibitor.

Atazanavir is a commonly prescribed protease inhibitor for treatment of HIV-1 infection. Thus far, only limited data are available on the in vivo metabolism of the drug. Three systemic circulating metabolites have been reported, but their chemical structures have not been released publicly. Atazanavir metabolites may contribute to its effectiveness but also to its toxicity and interactions. Thus, there is a need for extensive metabolic profiling of atazanavir. Our goals were to screen and identify previously unknown atazanavir metabolites and to develop a sensitive metabolite profiling method in plasma. Five atazanavir metabolites were detected and identified in patient samples using liquid chromatography coupled to linear ion trap mass spectrometry: one N-dealkylation product (M1), two metabolites resulting from carbamate hydrolysis (M2 and M3), a hydroxylated product (M4), and a keto-metabolite (M5). For sensitive semiquantitative analysis of the metabolites in plasma, the method was transferred to liquid chromatography coupled to triple quadrupole mass spectrometry. In 12 patient samples, all the metabolites could be detected, and possible other potential atazanavir keto-metabolites were found. Atazanavir metabolite levels were positively correlated with atazanavir levels, but interindividual variability was high. The developed atazanavir metabolic screening method can now be used for further clinical pharmacological research with this antiretroviral agent.

Quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cell lysate using liquid chromatography coupled with tandem mass spectrometry.

For pharmacokinetic monitoring, measurement of antiretroviral agents in plasma is the gold standard. However, human immunodeficiency virus protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) exert their action within the infected cell. Cell-associated concentrations may therefore more adequately reflect therapy outcome. Therefore, for the quantification of nine PIs (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir and tipranavir), 1 active PI metabolite (nelfinavir M8) and 2 NNRTIs (efavirenz and nevirapine) in lysate of peripheral blood mononuclear cells (PBMCs) an assay was developed and validated, using liquid chromatography coupled with tandem mass spectrometry. Analytes were extracted from a PBMC pellet by means of a one-step extraction with 50% methanol containing the internal standards D6-indinavir, D5-saquinavir, 13C6-efavirenz and dibenzepine. Chromatographic separation was performed on a reversed phase C18 column (150mmx2.0mm, particle size 5microm) with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.25mL/min. The analytical run time was 10min. The triple quadrupole mass spectrometer was operated in the positive ion-mode and multiple reaction monitoring was used for drug quantification. The method was validated over a range of 1-500ng/mL in PBMC lysate for all analytes. The method was proven to be specific, accurate, precise and robust. The mean precision and accuracy was less than +/-12% at all concentration levels. Using the developed assay and a previously developed assay for these analytes in plasma, the relationship between plasma and intracellular pharmacokinetics and their relationship with therapy outcome can now be determined.

Effect of HIV viral load, CD4 cell count and antiretroviral therapy on human papillomavirus prevalence in urine samples of HIV-infected men.

HIV-infected patients are at increased risk for persistent human papillomavirus (HPV) infection, the major cause of anogenital cancer. The present study describes the HPV prevalence in urine samples of 243 HIV-infected men and a control group of 231 men. HPV DNA was amplified by the SPF10 polymerase chain reaction primer set. The overall HPV prevalence in HIV-infected men was 27.5% compared with 12.6% in controls (P < 0.01). Infections with high-risk and multiple HPV genotypes were present in both groups. Differences were not statistically significant. A multivariate logistic regression model showed a decreased HPV prevalence associated with use of a nucleoside and a non-nucleoside reverse transcriptase inhibitor combination (P = 0.03). A trend was observed towards a higher HPV prevalence and a lower CD4 cell count. Further prospective studies are needed to determine the role of HPV DNA testing in urine in future screening programmes for anal cancer in men.

Quantification of etravirine (TMC125) in plasma, dried blood spots and peripheral blood mononuclear cell lysate by liquid chromatography tandem mass spectrometry.

For the quantification of the novel non-nucleoside reverse transcriptase inhibitor etravirine in human plasma, dried blood spots and peripheral blood mononuclear cell (PBMC) lysate, an assay was developed and validated, using liquid chromatography coupled with tandem mass spectrometry. Etravirine was extracted from plasma by means of protein precipitation with a mixture of methanol and acetonitrile using only 50 microL plasma. Extraction from dried blood spots was performed with a one-step extraction with a mixture of methanol, acetonitrile and 0.2M zinc sulphate in water (1:1:2, v/v/v) and extraction from cell lysate was performed in 50% methanol in water. Chromatographic separation was performed on a reversed phase C18 column (150mmx2.0mm, particle size 5microm) with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.25mL/min. (13)C(6)-efavirenz was used as an internal standard. The analytical run time was only 10min. The triple quadrupole mass spectrometer was operated in the positive ion-mode and multiple reaction monitoring was used for drug quantification. The method was validated over a range of 25-5000ng/mL in plasma, 50-10,000ng/mL in dried blood spots and a range of 5-2500ng/mL in PBMC lysate. Accuracies ranged from 89% to 106% in plasma, from 94% to 109% in dried blood spots and from 91% to 105% in PBMC lysate. Precisions at the all concentration levels ranged from 1.9% to 14% in plasma, 4.7% to 20% in dried blood spots and from 3.1% to 11% in PBMC lysate. The bioanalytical assay was successfully incorporated with previously developed assays for the determination of all currently approved PIs and NNRTIs in plasma and dried blood spots and it is now applied for therapeutic drug monitoring and pharmacological research in HIV-infected patients treated with etravirine.

Quantification of the HIV-integrase inhibitor raltegravir and detection of its main metabolite in human plasma, dried blood spots and peripheral blood mononuclear cell lysate by means of high-performance liquid chromatography tandem mass spectrometry.

For the quantification of the HIV-integrase inhibitor raltegravir in human plasma, dried blood spots and peripheral blood mononuclear cell (PBMC) lysate, an assay was developed and validated, using liquid chromatography coupled with tandem mass spectrometry. The assay also allowed detection, but no quantification due to absence of reference substance, of the main metabolite, raltegravir-glucuronide. Raltegravir was extracted from plasma by means of protein precipitation with a mixture of methanol and acetonitrile using only 50microL plasma. Extraction from dried blood spots was performed with a simple one-step extraction with a mixture of methanol, acetonitrile and 0.2M zincsulphate in water (1:1:2, v/v/v) and extraction from cell lysate was performed in 50% methanol in water. Chromatographic separation was performed on a reversed phase C18 column (150mmx2.0mm, particle size 5microm) with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.25mL/min. The analytical run time was 10min. The triple quadrupole mass spectrometer was operated in the positive ion-mode and multiple reaction monitoring was used for drug quantification. The method was validated over a range of 50-10,000ng/mL in plasma and dried blood spots and a range of 1-500ng/mL in PBMC lysate. Dibenzepine was used as the internal standard. The method was proven to be specific, accurate, precise and robust. Accuracies ranged from 104% to 105% in plasma, from 93% to 105% in dried blood spots and from 82% to 113% in PBMC lysate. Precision over the complete concentration range was less than 6%, 11% and 13% in plasma, dried blood spots and PBMC lysate, respectively. The method is now applied for therapeutic drug monitoring and pharmacological research in HIV-infected patients treated with raltegravir.

Ciprofloxacin strongly inhibits clozapine metabolism: two case reports.

We report on two cases of drug-drug interactions between ciprofloxacin and clozapine. The first case was a 46-year-old male patient receiving a daily dose of clozapine 900 mg. He was admitted to hospital with urosepsis and was treated with a 5-day course of ciprofloxacin and amoxicillin. Two days after completion of antibacterial therapy, the patient developed symptoms of rhabdomyolysis. Clozapine therapy was discontinued and measurement of the patient's clozapine plasma concentration 1 day after cessation of clozapine therapy and 3 days after cessation of ciprofloxacin treatment showed that it was in excess of recommended therapeutic levels. The second patient was a 58-year-old male patient treated with a daily dose of clozapine 300 mg. He was admitted to hospital because of delirium and suspected urinary tract infection or pneumonia. Treatment with ciprofloxacin was initiated. Measurement of clozapine plasma concentrations prior to and 3 days after commencement of ciprofloxacin showed that clozapine concentrations doubled over that time period. We suggest that inhibition of cytochrome P450 (CYP) enzymes 1A2 and 3A4 by ciprofloxacin resulted in delayed clozapine metabolism and elevated clozapine plasma concentrations. This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin.

Dutch healthcare professionals' opinion on vaccination and education to prevent infections in immunocompromised patients: A mixed-method study with recommendations for daily practice.

BACKGROUND: The fast-growing population of immunocompromised patients (ICP) is more vulnerable to infectious diseases, demanding strategies to protect them. These strategies seem inconsistent in available guidelines and in practices. We aim to evaluate healthcare professionals' (HCP) opinions on vaccination to reduce the number and severity of infections in ICP. METHODS: A mixed-method study, with an exploratory sequential design, was performed. Medical specialists from various departments in a tertiary care center in the Netherlands were invited for semi-structured interviews to explore their perspective on preventive care of ICP. Topics that play a substantial role in daily practice for ICP were translated into a survey to gain insight into what extent opinions were generalizable to Erasmus Medical Center. RESULTS: Surveys were completed by 689 HCP (43% of the invitees), 269 of them treated at least two ICP weekly on average and were considered eligible for further analysis. Quantitative data showed that according to 80 percent of HCP, preventive care for ICP can be improved. Education was chosen by 40 percent as the most important intervention to reduce the number and severity of infections. Vaccinations were valued as important by seventeen percent of HCP. Except for influenza, vaccinations were not regularly discussed during routine consultations. Difficulties to administer vaccinations were experienced by 75 percent of HCP. CONCLUSION: According to our respondents, education is the most promising intervention to reduce the number and severity of infections in ICP. To reach a higher vaccine uptake, we recommend HCP to address vaccinations more frequently during consultations and to search for solutions to alleviate barriers to vaccinate.

Quantification of protease inhibitors and non-nucleoside reverse transcriptase inhibitors in dried blood spots by liquid chromatography-triple quadrupole mass spectrometry.

A bioanalytical method for the determination of most commonly prescribed protease inhibitors (atazanavir, darunavir, lopinavir and ritonavir) and non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) was developed and validated according to FDA guidelines. In brief, dried blood spots were punched out of a collection paper with a 0.25 in. diameter punch. The analytes were extracted from the punched-out disc using a mixture of acetonitrile, methanol and 0.2M zinc sulphate in water (1:1:2, v/v/v) containing the internal standards dibenzepine, 13C6-efavirenz and D5-saquinavir. 20 microL of the extract was injected onto the reversed-phase C18 column (150 mm x 2.0 mm) for separation from endogenous compounds and the analytes were quantified using a triple quadrupole mass spectrometer. The analytical run time was only 10 min. Validated concentration ranges covered the ranges encountered in routine clinical practice. The assay was linear over the concentration ranges tested (0.1-20 mg/L for atazanavir, lopinavir, nevirapine and efavirenz and 0.05-10 mg/L for darunavir and ritonavir). Accuracies and inter- and intra-run precisions at all levels ranged from 96.2 to 113.9% and 3.1 to 13.3%, respectively. Analytes in dried blood spots were stable for at least 7 days at 30 degrees C. The method enabled patient-friendly sample collection, easy and cheap sample shipment and non-hospital based sampling for therapeutic drug monitoring and pharmacokinetic studies.

Identifying patients with bacterial infections using a combination of C-reactive protein, procalcitonin, TRAIL, and IP-10 in the emergency department: a prospective observational cohort study.

OBJECTIVES: The aim was to effectively reduce the unnecessary use of broad spectrum antibiotics in the emergency department (ED), patients with bacterial infections need to be identified accurately. We investigated the diagnostic value of a combination of biomarkers for bacterial infections, C-reactive protein (CRP), and procalcitonin (PCT), together with biomarkers for viral infections, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and interferon-gamma-induced protein-10 (IP-10), in identifying suspected and confirmed bacterial infections in a general ED population with fever. METHODS: This is a sub-study in the HiTEMP cohort. Patients with fever were included during ED triage, and blood samples were obtained. Using both diagnostics and expert panel analysis, all patients were classified as having either suspected or confirmed bacterial infections, or non-bacterial disease. Using multivariable logistic regression analysis, three biomarker models were analysed: model 1, CRP, TRAIL, IP-10; model 2, PCT, TRAIL, IP-10; and model 3, CRP, PCT, TRAIL, IP-10. RESULTS: A total of 315 patients were included, of whom 228 patients had a suspected or confirmed bacterial infection. The areas under the curve for the combined models were the following: model 1, 0.730 (95% CI 0.665-0.795); model 2, 0.748 (95% CI 0.685-0.811); and model 3, 0.767(95% CI 0.704-0.829). CONCLUSIONS: These findings show that a combination of CRP, PCT, TRAIL and IP-10 can identify bacterial infections with higher accuracy than single biomarkers and combinations of a single bacterial biomarkers combined with TRAIL and IP-10.