scholarly journals Update of a clinical prediction model for serious bacterial infections in preschool children by adding a host-protein-based assay: a diagnostic study

2019 ◽  
Vol 3 (1) ◽  
pp. e000416
Author(s):  
Chantal van Houten ◽  
Josephine Sophia van de Maat ◽  
Christiana Naaktgeboren ◽  
Louis Bont ◽  
R Oostenbrink

ObjectiveTo determine whether updating a diagnostic prediction model by adding a combination assay (tumour necrosis factor-related apoptosis-inducing ligand, interferon γ induced protein-10 and C reactive protein (CRP)) can accurately identify children with pneumonia or other serious bacterial infections (SBIs).DesignObservational double-blind diagnostic study.SettingTwo hospitals in Israel and four hospitals in the Netherlands.Patients591 children, aged 1–60 months, presenting with lower respiratory tract infections or fever without source. 96 of them had SBIs. The original Feverkidstool, a polytomous logistic regression model including clinical variables and CRP, was recalibrated and thereafter updated by using the assay.Main outcome measuresPneumonia, other SBIs or no SBI.ResultsThe recalibrated original Feverkidstool discriminated well between SBIs and viral infections, with a c-statistic for pneumonia of 0.84 (95% CI 0.77 to 0.92) and 0.82 (95% CI 0.77 to 0.86) for other SBIs. The discriminatory ability increased when CRP was replaced by the combination assay; c-statistic for pneumonia increased to 0.89 (95% CI 0.82 to 0.96) and for other SBIs to 0.91 (95% CI 0.87 to 0.94). This updated Feverkidstool improved diagnosis of SBIs mainly in children with low–moderate risk estimates of SBIs.ConclusionWe improved the diagnostic accuracy of the Feverkidstool by replacing CRP with a combination assay to predict pneumonia or other SBIs in febrile children. The updated Feverkidstool has the largest potential to rule out bacterial infections and thus to decrease unnecessary antibiotic prescription in children with low-to-moderate predicted risk of SBIs.

BMJ ◽  
2013 ◽  
Vol 346 (apr02 1) ◽  
pp. f1706-f1706 ◽  
Author(s):  
R. G. Nijman ◽  
Y. Vergouwe ◽  
M. Thompson ◽  
M. van Veen ◽  
A. H. J. van Meurs ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christina A. Rostad ◽  
Neena Kanwar ◽  
Jumi Yi ◽  
Claudia R. Morris ◽  
Jennifer Dien Bard ◽  
...  

Abstract Background Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. Methods We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. Results Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. Conclusions Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4164-4164 ◽  
Author(s):  
Gianpaolo Nadali ◽  
Gessica Marchesini ◽  
Davide Facchinelli ◽  
Francesca Farina ◽  
Maria Chiara Tisi ◽  
...  

Abstract Introduction: in the last 5 years new "target drugs" to treat lymphoproliferative disorders have been introduced in clinical practice, such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab), BTK inhibitors (ibrutinib) and PI3K inhibitors (idelalisib). Efficacy and safety of these drugs were assessed in registrative trials and data regarding infectious complications in the "real life" experience are currently unavailable. We aimed to assess the incidence of major infections in patients treated with the above mentioned drugs. Methods: 555 patients were treated, for registered indications, with idelalisib, ibrutinib, brentuximab, ofatumumab and obinutuzumab (single agents or in combination as licensed) in 13 hematology centres in Italy, from time of their commercial availability to December 2016. The observation period was one year after study entry. Patients in clinical trials or treated within patient named programs were excluded as well as patients with active infections at beginning of treatment. Results: in 132/555 patients (24%) infections occurred for a total number of 187 events, 56% of whom were of grade 3. The median age was 64 years (range 20-86), 46,2% (61/132) of patients were treated with 3 or more previous lines of therapy, 55/132 (42%) experienced 2 or more infective episodes. A bacterial cause of infection was reported in 35% of cases, viral in 22% and an invasive fungal infection (IFI) in 9% (17/187). In 2% of cases the infection was of mixed origin (bacterial/viral or bacterial/fungal) while in 32% of cases there was not microbiological documentation. The lower respiratory tract was the most frequent site of infection in 39% of cases (73/187) while the upper respiratory tract was involved in 30% of events (39/187). The urinary tract infections were 13% (24/187). Other sites involved were skin and soft tissue 7%, sepsis 7%, gastrointestinal site 5%, central nervous system 2% and fever of unknown origin 6%. Patients treated with idelalisib were 106 (80% affected by chronic lymphocytic leukemia - CLL- and 20% follicular lymphoma) and 35 (33%) experienced one ore more infections for a total of 49 episodes. The incidence of bacterial infections was 37%, of viral infections 37% and of IFI 6%. In 235 patients treated with ibrutinib, 70 (30%) had one ore more events for a total of 102 infective episodes. 60/70 (86%) patients had CLL and 10/70 (14%) had indolent or mantle cell lymphoma The incidence of bacterial infections was 50%, viral 20% and IFI 16%. Focusing on IFI, 17 events were reported in 15 patients. According to the EORTC criteria, 11 cases (4 possible, 1 probable, 6 proven) were reported in patients treated with ibrutinib, 3 cases of possible IFI in patients treated with idelalisib and 3 cases of proven IFI in patients treated with brentuximab. The incidence of IFI in patients treated with ibrutinib (11/102 events) and idelalisib (3/49 events) was not different (11% vs. 6% respectively; p-value = 0.55) even considering proven/probable cases only (3% in ibrutinib vs. 0% in idelalisib p-value = 0.11). The incidence of bacterial infections in patients treated with ibrutinib (35/102) was not statistically different compared to patients treated with idelalisib (18/49) (34% vs. 37% respectively p-value =0.87). Noteworthy, the incidence of viral infections in patients treated with idelalisib (18/49) was significantly higher compared to patients treated with ibrutinib (14/102) (37% vs. 14% respectively; p-value =0.015). Brentuximab was used in 175 patients, 70% of cases for Hodgkin Lymphoma and 30% for T cell lymphoma. The rate of infections was 11% for a total of 27 infection episodes. The incidence of bacterial, viral and fungal infections was 37%, 30% and 11% respectively. In 22% of cases the cause of infection could not be established. Patients treated with ofatumumab or obinutuzumab were 39 and in 7/39 (18%) an infective episode was reported (four of bacterial origin, one viral and four undetermined). All patients were affected by CLL. Conclusions: this "real life" experience confirm that the incidence of infections in patients treated with "target drugs" is not negligible. Ongoing analysis that take into account patient's clinical and demographical characteristics, may give insights on risk factors that will contribute to better characterizing patients at different risk levels. Figure. Figure. Disclosures Cattaneo: GILEAD: Other: Advisory Board. Candoni:Pfizer: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Merck SD: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau. Fanci:Gilead: Honoraria; Pfizer Pharmaceuticals: Honoraria; Merck: Consultancy, Honoraria, Speakers Bureau. Del Principe:Gilead: Membership on an entity's Board of Directors or advisory committees. Busca:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merk: Honoraria, Speakers Bureau; Pfizer Pharmaceuticals: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria; Novartis: Speakers Bureau.


2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S16-S16
Author(s):  
Sara Kim ◽  
Avni Bhatt ◽  
Silvana Carr ◽  
Frances Saccoccio ◽  
Judy Lew

Abstract Background Procalcitonin (PCT) and c-reactive protein (CRP) have been utilized in children to assess risk for serious bacterial infections. However, there have been different cut-offs reported for PCT and CRP, which yield different sensitivity and specificity. This study aims to compare the sensitivity and specificity of PCT and CRP in detecting serious bacterial infections (SBIs), specifically urinary tract infections, bacteremia and meningitis. Methods In this retrospective, single center cohort study from January 2018 to June 2019, we analyzed children with a fever greater than 38C with both PCT and CRP value within 24 hours of admission. Each patient had a blood, urine and/or cerebrospinal fluid culture collected within 48 hours of admission. No antibiotics were administered from the admitting hospital prior to collection of the PCT or CRP. Our gold standard was a positive culture obtained from blood, cerebrospinal fluid, or urine. The statistical analysis included categorical variables as percentages and compared them using the Fisher exact test. The optimal cutoff values for PCT or CRP were based on ROC curve analysis and Youden Index. Sensitivity and specificity analysis were based on literature review cut offs and ROC curves cut offs. Results Among 202 children, we had 45 culture positive patients (11 urinary tract infections, 4 meningitis, and 32 bacteremia). The patients with culture positivity had higher PCT levels (7.9 ng/mL vs 2.5 ng/mL, P=0.0111), CRP levels (110.9 mg/L vs 49.6 mg/L, P<0.0001) and temperature (39.2C vs 39C, P<0.0052). The area under the curve (AUC) comparing culture positivity vs negativity for all culture types was 0.72 (p<0.0001) for PCT and 0.66 (p=0.001) for CRP. In Figure 1, the AUC for culture positive bacteremia was 0.68 (p=0.0011) for PCT and 0.70 (p=0.0003). The AUC for culture positive urinary tract infections (UTI) only was 0.86 (p=0.0001) for PCT and 0.70 (p=0.3607). For the cut-off value for PCT at 0.5 ng/mL, the sensitivity and specificity was 64% (95% confidence interval [CI] 0.5–0.77) and 70% (95% CI 0.62–0.77) respectively in identifying children with bacterial infection. For the cut-off value for CRP at 20 mg/L, the sensitivity and specificity was 67% (95% CI 0.52–0.79) and 52% (95% CI 0.44–0.59) respectively in identifying children with bacterial infection. Conclusion In this study, PCT and CRP are nearly equivalent classifiers for detecting SBIs as a group and bacteremia, but PCT is statistically better for urinary tract infections; however, the clinical utility is unknown.


2020 ◽  
pp. 75-81
Author(s):  
Paul Ishimine

Fever is the most common complaint of children who present to the emergency department. Approximately 12% of febrile neonates (aged 0–28 days) and young infants (aged 29—56 days) have serious bacterial infections (bacteremia, meningitis, urinary tract infections, pneumonia, bacterial gastroenteritis, and osteomyelitis). The evaluation and management of the febrile neonate and febrile young infant can be confusing. All febrile neonates require diagnostic testing, treatment with antibiotics, and hospital admission. The workup of the febrile young infant is more controversial. These patients should undergo blood and urine testing, but the need for lumbar puncture is controversial, as is the need for empiric antibiotic treatment. The disposition of these patients will depend on the results of these screening tests.


2017 ◽  
Vol 17 (4) ◽  
pp. 431-440 ◽  
Author(s):  
Chantal B van Houten ◽  
Joris A H de Groot ◽  
Adi Klein ◽  
Isaac Srugo ◽  
Irena Chistyakov ◽  
...  

2012 ◽  
Vol 52 (6) ◽  
pp. 313
Author(s):  
Ni Putu Veny Kartika Yantie ◽  
BNP Arhana ◽  
Purnomo Suryantoro

Background There is a debate on the use of high fever \\lith othermorbidities to predict serious bacterial infection (SBI). Bacterialinfection occurs in 3􀁉15% of children with fever of 2: 39°C.Various laboratory parameters including increased C􀁉reactiveprotein (CRP) levels, leukocyte counts, and absolute neutrophilcounts (AN C) have been studied for their usefulness in predictingthe occurrence of SBI, but with varied results. The ability todiscriminate whether a patient has a SBI can lead to improvedpatient management.Objective To evaluate fever of 2: 39°C, leukocyte counts of2: 15,000/mm3, ANC of 2: 1O,000/mm3 and CRP of 2: 10 mgiL aspredictors of SBI in children aged 1 month􀁉 18 years.Methods A case􀁉controlled study was conducted by collectingdata from medical records at Sanglah Hospital, Denpasar. Subjectsin the case group were diagnosed \\lith SBls (bacterial meningitis,bacterial pneumonia, bacteremia or sepsis, urinary tract infections,or bacterial gastroenteritis), and subjects in the control group nonserious bacterial infections (non􀁉SBI). Data was analyzed usingbivariate and multivariate methods \\lith 95% confidence intervalsand a statistical significance value ofP <0.05.Results Sixty subjects were studied, \\lith 30 subjects in the casegroup and 30 in the control group. Baseline characteristics ofsubjects were similar between the two groups. Fever and CRP werepredictors ofSBI [OR8.71 (95% CI 1.61 t046.98), P 􀀁 0.009; andOR 6.20 (95% CI 1.58 to 24.24), P 􀀁 0.012, respectively].Conclusion Fever 2: 39°C and CRP 2: 10 mgiL were significantpredictors of serious bacterial infections in children. [Paediatrrndones, 2012;52:313-6].


2005 ◽  
Vol 49 (1) ◽  
pp. 195-201 ◽  
Author(s):  
J. P. Shaw ◽  
J. Seroogy ◽  
K. Kaniga ◽  
D. L. Higgins ◽  
M. Kitt ◽  
...  

ABSTRACT The pharmacokinetics, tolerability, and serum inhibitory and bactericidal titers of telavancin, a new rapidly bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens, were assessed in a two-part, randomized, double-blind, placebo-controlled, ascending-dose study with 54 healthy men. In part 1, single ascending intravenous doses of 0.25 to 15 mg/kg of body weight were studied. In part 2, multiple ascending doses (30-min infusions of 7.5 to 15 mg/kg/day) were studied over 7 days. Following the administration of multiple doses, steady state was achieved by days 3 to 4. At day 7 after the administration of telavancin at 7.5, 12.5, and 15 mg/kg/day, peak concentrations in plasma were 96.7, 151.3, and 202.5 μg/ml, respectively, and steady-state area-under-the-curve values were 700, 1,033, and 1,165 μg · h/ml, respectively. The elimination half-life ranged from 6.9 to 9.1 h following the administration of doses ≥5 mg/kg. Most adverse events were mild in severity. At 24 h postinfusion, serum from subjects given telavancin demonstrated potent bactericidal activity against methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae strains. The results suggest that telavancin may be an effective once-daily therapy for serious bacterial infections caused by these pathogens.


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