Unnecessary Antibiotic Treatment Research Articles

48. Local Implementation of an Antibiotic Stewardship Intervention for Asymptomatic Bacteriuria Through Centralized Facilitation Required Minimal Costs and Effort

Abstract Background The cost of an antibiotic stewardship intervention is an important yet often neglected factor in antibiotic stewardship research. We studied the costs associated with successful implementation of the “Kicking CAUTI” intervention to decrease treatment of asymptomatic bacteriuria (ASB). Methods A central coordinating site facilitated roll-out of an audit and feedback intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB in four Veterans Affairs medical centers. Each site had a physician site champion, a part-time research coordinator, and 1-2 additional participants (often pharmacists). Participants kept weekly time-logs to collect the minutes associated with intervention tasks, and percent full-time effort (FTE) and costs were computed. For weeks with missing logs the average minutes for each activity associated with each type of professional was imputed. Salary information was obtained from the Bureau of Labor Statistics and Association of American Medical Colleges. Results Research coordinator time comprised of majority of the personnel time, followed by the physician site champions (Figure 1). Each intervention site required about 10% FTE/year of a research coordinator, and 3.5% FTE/year and 3.8% FTE/year of a physician and pharmacist respectively. The coordinating site required 37% FTE/year of a research coordinator, and 9% FTE of a physician to spearhead the intervention. Research coordinators predominantly spent their time on chart-reviews and project coordination. Physician champions predominantly spent their time on delivering audit and feedback and project coordination. The intervention cost USD 22,299/year per site on average, and USD 45,359/year for the coordinating site. Conclusion The Kicking CAUTI intervention was successful at reducing urine cultures and associated antibiotic use, with minimal time from the local team members. The research coordinators’ time was primarily spent on collection of research data, which will not be necessary outside of a research project. Our model of centralized facilitation makes economic sense for widespread scale-up and dissemination of antibiotic stewardship interventions in integrated healthcare systems. Disclosures Barbara Trautner, MD, PhD, Genentech (Consultant, Scientific Research Study Investigator)

Knowledge and Attitude Toward Lumbar Puncture Among Medina Population

Introduction: Lumbar puncture (LP) is one of the invasive procedures performed to obtain information about cerebrospinal fluid. It has diagnostic and therapeutic purposes for various neurological cases. Previous studies among different populations have indicated that there is a lack of research focusing on individuals’ knowledge and attitude toward LP. Patient who refuse LP may be exposed to unneeded hospital admission, or unnecessary empirical antibiotic treatment. A literature search found a lack of studies regarding LP knowledge and perception among Al-Medina residents. To address that gap, this study aimed at assessing the knowledge and attitude toward LP among the Al-Medina population.
 Methodology: A cross-sectional study was conducted among adults 18 years of age residing in Medina, Saudi Arabia. An online survey using a self-administrated questionnaire that included demographic characteristics, knowledge, and attitude questions was randomly distributed from January 2020 to August 2020. The questionnaire was pretested and validated (Cronbach’s alpha = 0.701).
 Result: A total of 512 participants were included: 51.3% of the participants were aged between 18 and 25 years; 85.5% were female; and 68.6% had a bachelor’s degree. Most participants (65.6%) showed a poor knowledge of LP. Of the total participants, 29.7% had a poor attitude toward LP, while 69.7% had a good attitude. A significant positive correlation was found between knowledge and attitude toward lumbar procedures (r = 0.186, p < 0.001). Respondents who received their information from a healthcare worker had the highest level of knowledge (p < 0.001). A positive significant correlation was found between attitude and age; younger participants had a better attitude (p < 0.001).
 Conclusion: This study assessed the knowledge and attitude toward LP, and the relation between them which leads to a great impact on diagnosis and treatment. The study demonstrated that few participants had a previous experience with LP. There is a crucial need to know how these personal LP experiences affect the decisions and attitude toward LP in the future. The study also showed that the level of knowledge about LP is relatively poor among the public. The level of awareness should be raised to improve patient’s understanding toward LP. Interventions are needed to scale up the level of knowledge about LP. Some potential interventions include: intensifying health promotion campaigns, increasing involvement of physicians in patients’ education to improve knowledge, as well as maintaining the quality and reliability of information provided concerning LP and carrying out further research to evaluate the effect of intervention programs on the knowledge and attitude.

Unnecessary antibiotic treatment of children hospitalised with respiratory syncytial virus (RSV) bronchiolitis: risk factors and prescription patterns

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections, especially in young children. Antibiotics are often unnecessarily prescribed for the treatment of RSV. Such treatments affect antibiotic resistance in future bacterial infections of treated patients and the general population. This study aimed to understand risk factors for and patterns of unnecessary antibiotic prescription in children with RSV. In a single-centre, retrospective study in Israel, we obtained data for children aged ≤2 years (n=1016) hospitalised for RSV bronchiolitis during 2008-2018 and ascertained not to have bacterial co-infections. Antibiotic misuse was defined as prescription of antibiotics during hospitalisation of the study population. Demographic and clinical variables were assessed as predictors of unnecessary antibiotic treatment in a multivariable logistic regression model. The unnecessary antibiotic treatment rate of children infected with RSV and ascertained not to have a bacterial co-infection was estimated at 33.4% (95% CI 30.5-36.4%). An increased likelihood of antibiotic misuse was associated with drawing bacterial cultures and with variables indicative of a severe patient status such as lower oxygen saturation, higher body temperature, tachypnoea and prior recent emergency room visit. Older age and female sex were also associated with an increased likelihood of unnecessary antibiotic treatment. Unnecessary antibiotic treatment in RSV patients was very common and may be largely attributed to physicians' perception of patients' severity. Improving prescription guidelines, implementing antibiotic stewardship programmes and utilising decision support systems may help achieve a better balance between prescribing and withholding antibiotic treatment.

Outcomes of nontuberculous mycobacteria isolation among lung transplant recipients: A matched case-control with retrospective cohort study.

Lung transplant recipients are at increased risk for acquiring nontuberculous mycobacteria (NTM), but the clinical significance of NTM isolation, particularly among patients not meeting guideline-endorsed diagnostic criteria for NTM pulmonary disease, is unclear. A case-control study of lung transplant recipients culture-positive for NTM at a large transplant center during a 7-year period (2013-2019) was performed. Twenty-nine cases were matched 1:2 to non-NTM controls. The median time to NTM isolation was 10.7 months post transplant. Only 34.5% of all cases, and half of treated cases, met diagnostic criteria for NTM pulmonary infection. All-cause mortality at 12 months was numerically higher among NTM cases versus controls (20.7% vs 8.6%, P = 0.169); however, no deaths were attributed to NTM. No increase in the 12-month rate of acute rejection was observed (27.6% vs 36.2%, P = 0.477). Recent augmented immunosuppression was associated with increased odds of NTM isolation, while azithromycin prophylaxis was associated with reduced odds of NTM isolation and was not associated with macrolide resistance. Both adverse events and actual or potential drug-drug interactions occurred in more than 90% of treated cases; these events included ocular toxicity, hearing loss, and supratherapeutic calcineurin inhibitor concentrations. Eight of the 14 treated cases (57.1%) required early antibiotic discontinuation due to adverse events or drug-drug interactions. Among lung transplant recipients, most patients with NTM isolation did not meet guideline criteria for infection and had outcomes similar to non‒NTM-infected patients, which may reflect transient lung colonization by NTM rather than true disease. As adverse events are common with NTM therapy, limiting unnecessary antibiotic treatment represents an area for future antimicrobial stewardship efforts.

Parechovirus Genotype 3 Outbreak Among Young Infants in Portugal.

Human parechovirus type 3 has been recognized as a cause of pediatric infection, occasionally associated with seriousillness, including sepsis and meningitis, particularly among young infants. The aim of this study is to report the first known humanparechovirus type 3 outbreak in Portugal. Descriptive study of an outbreak that occurred between the 8th June to the 12th August 2016. Laboratory diagnosiswas made by reverse transcription - polymerase chain reaction in the cerebrospinal fluid and/or in stools. Genotyping was madeby reverse transcription - polymerase chain reaction and sequencing in stool samples from infants and family members. Human parechovirus type 3 infection was detected in seven infants, of which six were male. Median age was 23 days (5 - 52).One had seizures, with a magnetic resonance imaging scan showing white matter diffusion restriction. The mean duration of admissionwas 5.6 days (3 - 11), with favourable outcome in all. In three cases there were symptomatic close family members. Human parechovirustype 3 was identified in the stools of three mothers. Even though human parechovirus type 3 infection has been well described in the presented age group, most Portuguesehospitals do not have this laboratory diagnosis. Our results are comparable to those obtained in other countries. Besides detection ofthe virus in the cerebrospinal fluid, there were no raised local or systemic inflammatory markers. This study reports the first known outbreak, in infants, of human parechovirus type 3 in Portugal. Although there is nospecific treatment, this diagnosis can avoid unnecessary empirical antibiotic treatment and prolonged admissions.

High rate of bacterial respiratory tract co-infections upon admission amongst moderate to severe COVID-19 patients

Background The role of bacterial and viral co-infection in the current COVID-19 pandemic remains elusive. The aim of this study was to describe the rates and features of co-infection on admission of COVID-19 patients, based on molecular and routine laboratory methods. Methods A retrospective study of COVID-19 and non-COVID-19 patients undergoing Biofire®, FilmArray® Pneumonia Panel, bioMérieux, and routine cultures during the first 3 days from admission, between June 2019 and March 2021. Results FilmArray tests were performed in 115 COVID-19 and in 61 non-COVID-19 patients. Most (>99%) COVID-19 patients had moderate-critical illness, 37% required mechanical ventilation. Sputa and endotracheal aspirates were the main samples analyzed. Positive FilmArray tests were found in 60% (70/116) of the tests amongst COVID-19 patients and 62.5% (40/64) amongst non-COVID-19 patients. All 70 cases were positive for bacterial targets, while one concomitant virus (Rhinovirus/Enterovirus) and one Legionella spp. were detected. The most common bacterial targets were Haemophilus influenzae (36%), Staphylococcus aureus (23%), Streptococcus pneumoniae (10%) and Enterobacter cloacae (10%). Correlation between FilmArray and cultures was found in 81% and 44% of negative and positive FA tests, respectively. Positive FilmArray results typically (81%) triggered the administration of antibiotic therapy and negative results resulted in antimicrobials to be withheld in 56% of cases and stopped in 8%. Bacterial cultures of COVID-19 patients were positive in 30/88 (34%) of cases. Conclusions Bacterial co-infection is common amongst moderate-critical COVID-19 patients on admission while viral and atypical bacteria were exceedingly rare. Positive FilmArray results could trigger potentially unnecessary antibiotic treatment. KEY POINT We found high rates of on-admission bacterial co-infection amongst hospitalized moderate to severe COVID-19 patients. Molecular tests (Biofire, FilmArray) and routine microbiological tests revealed 60% and 34% bacterial co-infection, respectively, while viral and fungal co-infections were rare.

Management of Pediatric Thoracic Empyema in the North Queensland Region of Australia and Impact of a Local Evidence-based Treatment Guideline.

The North Queensland region of Australia has a high incidence of pediatric thoracic empyema (pTE). We describe the management of empyema at the Townsville University Hospital which is the regional referral center for these children. The impact of a newly developed institutional guideline is also discussed. This retrospective audit included children under the age of 16 years treated for empyema between 1 Jan 2007 and 31 December 2018. Demographic and management-related variables were correlated to outcomes. A local guideline was introduced at the beginning of 2017 and patient outcomes characteristics pre, and post introduction of this guideline are compared. There were 153 children with pTE (123 before and 30 after the introduction of a local guideline). Nonsurgical management was associated with a higher treatment failure rate. Median length of stay (LOS) was 11.8 (IQR 9.3-16) days. Longer hospital LOS was associated with younger age (r2 -0.16, P = 0.04), Aboriginal and/or Torres Strait (ATSI) ancestry (13.8 vs. 10.5 days, P = 0.002) and concomitant respiratory viral infections (14.4 vs. 10.9 days, P = 0.003). The introduction of local guideline was associated with significant decrease in the use of empirical chest CT scans (54.4% before vs. 6.7% after, P < 0.001) and duration of intravenous antibiotics (14 days before vs. 10 days after, P = 0.02). There was no significant change in the hospital LOS (12.1 days pre and 11.7 post, P = 0.8). Younger age, concomitant viral respiratory infections and ATSI ancestry were identified as potential risk factors for increase LOS. Hospital LOS following the adoption of an institutional guideline was unchanged. However, such a guideline may identify populations at risk for an unfavorable course and avoid unnecessary antibiotic treatment and radiation exposure.

Procalcitonin and lung ultrasonography point-of-care testing to determine antibiotic prescription in patients with lower respiratory tract infection in primary care: pragmatic cluster randomised trial

ObjectiveTo assess whether point-of care procalcitonin and lung ultrasonography can safely reduce unnecessary antibiotic treatment in patients with lower respiratory tract infections in primary care.DesignThree group, pragmatic cluster randomised controlled...

Reducing Unnecessary Antibiotic Treatment for Acute Bronchitis Using Virtual Primary Care

Objective: Reducing antibiotic overuse is a point of emphasis of the Centers for Disease&#x0D; Control and Prevention (CDC). Despite this, both telemedicine and traditional in-person&#x0D; medical care struggle to meet national guidelines. This study evaluates antibiotic&#x0D; prescribing practices at 98point6, a Seattle-based provider of virtual primary care. This&#x0D; paper reviews a novel combination of machine learning with a physician-led virtual&#x0D; platform and smartphone interface to exceed published benchmarks for the avoidance&#x0D; of antibiotics in the treatment of bronchitis.&#x0D; &#x0D; Design: This retrospective cohort study looks at patients ages 18–64 who presented to&#x0D; 98point6 with “acute bronchitis/bronchiolitis” diagnosed between December 1, 2019&#x0D; and November 30, 2020. Visits were categorized by whether systemic antibiotics were&#x0D; or were not given. Cases in which systemic antibiotics were given were categorized as&#x0D; “broad spectrum” or “narrow spectrum”. The results are presented as descriptive&#x0D; statistics with demographic information and compared to published reports of&#x0D; antibiotic use for the treatment of bronchitis.&#x0D; &#x0D; Results: Of the 1,238 visits with a bronchitis/bronchiolitis diagnosis, 99 (8.0%) were&#x0D; treated with prescribed systemic antibiotics. The rate of antibiotic avoidance of 92.0%&#x0D; compares favorably with published benchmarks from the National Committee for&#x0D; Quality Assurance and is significantly lower than rates in previously published samples&#x0D; for telemedicine, primary care and urgent care.&#x0D; &#x0D; Conclusion: Virtual primary care administered by 98point6 resulted in a high rate of&#x0D; adherence to the established standard for the treatment of bronchitis, greatly exceeding&#x0D; benchmarks and published results from both telemedicine and in-person medical&#x0D; practice.

Decreasing Blood Culture Contamination Rates When Using an Initial Peripheral IV: Implementing the 5 P's and Using a Closed System Device

Blood culture remains the gold standard for the diagnosis and treatment of bacteraemia and is the first-line tool for detecting bloodstream infections [1]. Research shows that the emergency department (ED) is an essential component of the health care system and subject to workflow challenges, which may hinder ED personnel adherence to guideline-based infection prevention practices [2]. This impact has wide-reaching effects. Moreover, a fast-paced ED presents a host of challenges with competing priorities. In addition, EDs are perceived as 24/7 portals where rapid and efficient diagnosis, urgent attention, primary care, and inpatient admission is provided for stabilizing seriously ill and wounded patients [3]. Blood culture contaminants are common, and they have a significant impact on patients and staff, contributing to unnecessary or inappropriate antibiotic treatment, increased length of stay, and costly economic burden [4]. The aim of this study was to evaluate the use of an automated blood culture collection system when drawing blood cultures from a peripheral IV and to evaluate the effectiveness of implementing evidence-based policies, procedures, practice, products, and patient care to reduce blood culture contamination rates.

A Panel Comprising Serum Amyloid A, White Blood Cells and Nihss for the Triage of Patients at Low Risk of Post-Stroke Infection.

Accurate and early prediction of poststroke infections is important to improve antibiotic therapy guidance and/or to avoid unnecessary antibiotic treatment. We hypothesized that the combination of blood biomarkers with clinical parameters could help to optimize risk stratification during hospitalization. In this prospective observational study, blood samples of 283 ischemic stroke patients were collected at hospital admission within 72 h from symptom onset. Among the 283 included patients, 60 developed an infection during the first five days of hospitalization. Performance predictions of blood biomarkers (Serum Amyloid-A (SAA), C-reactive protein, procalcitonin (CRP), white blood cells (WBC), creatinine) and clinical parameters (National Institutes of Health Stroke Scale (NIHSS), age, temperature) for the detection of poststroke infection were evaluated individually using receiver operating characteristics curves. Three machine learning techniques were used for creating panels: Associative Rules Mining, Decision Trees and an internal iterative-threshold based method called PanelomiX. The PanelomiX algorithm showed stable performance when applied to two representative subgroups obtained as splits of the main subgroup. The panel including SAA, WBC and NIHSS had a sensitivity of 97% and a specificity of 45% to identify patients who did not develop an infection. Therefore, it could be used at hospital admission to avoid unnecessary antibiotic (AB) treatment in around half of the patients, and consequently, to reduce AB resistance.

Is peripartum maternal fever alone a reliable predictor of neonatal sepsis? A single-centre, retrospective cohort study.

To determine the incidence rate of early-onset neonatal sepsis (EONS) among term neonates (gestation greater than 37 weeks) admitted to the neonatal intensive care unit for suspected sepsis and the association of EONS with maternal fever (temperature greater than 38°C). A single-centre retrospective cohort study of all term neonates (gestation >37 weeks) admitted to and treated in the neonatal unit at the Townsville University Hospital between March 2015 and March 2020. Neonatal sepsis was confirmed with positive neonatal blood culture. Data on neonatal birth/stay and maternal pregnancy were collected from the electronic medical records and neonatal database. Data from 737 neonates who were admitted for treatment of EONS were analysed. Sixty % (426) reported maternal intrapartum fever, with 1.1% (5) of neonates developing blood culture-proven sepsis. Forty % did not report intrapartum fever (311), with 3% (9) of neonates developing sepsis. As such, the sensitivity and specificity of maternal fever are 1.14% and 97%, respectively. The positive predictive value was 35.7%, and the negative predictive value was 40.1%. Fourteen neonates developed EONS, and all of them were symptomatic. Seventy-eight % (334/426) of the women in the febrile group received epidural analgesia compared to 5% (16/311) in the afebrile group. Of the 95 neonates born to women with chorioamnionitis, one (1.0%) of the neonates born to women with chorioamnionitis developed sepsis. Intrapartum maternal fever is an unreliable predictor for EONS and leads to unnecessary antibiotic treatment. Symptoms in the neonate are a more reliable indicator of an ill neonate with blood culture-proven sepsis.

Serum β2-microglobulin may be a viral biomarker by analyzing children with upper respiratory tract infections and exanthem subitum: a retrospective study.

BackgroundDue to the lack of effective and feasible viral biomarkers to distinguish viral infection from bacterial infection, children often receive unnecessary antibiotic treatment. To identify serum β2-microglobulin that distinguishes bacterial upper respiratory tract infection from viral upper respiratory tract infection and exanthem subitum in children.MethodsThis retrospective study was conducted from January 1, 2019 to September 30, 2020 in Yancheng Third People’s Hospital. Children with upper respiratory tract infection and exanthem subitum were recruited. The concentration of serum β2-microglobulin in the viral and bacterial infection groups were statistically analyzed.ResultsA total of 291 children included 36 with bacterial upper respiratory tract infection (median age, 13 months; 44.4% female), 197 with viral upper respiratory tract infection (median age, 12 months; 43.7% female) and 58 with exanthem subitum (median age, 13 months; 37.9% female). When the concentration of β2-microglobulin was 2.4mg/L, the sensitivity to distinguish viral from bacterial upper respiratory tract infection was 81.2% (95% CI [75.1–86.4%]), and the specificity was 80.6% (95% CI [64.0–91.8]%). When the cutoff was 2.91 mg/L, the sensitivity of β2-microglobulin to distinguish exanthem subitum from bacterial upper respiratory tract infection was 94.8% (95% CI [85.6–98.9]%), and the specificity was 100% (95% CI [90.3–100]%).ConclusionsSerum β2-microglobulin may be a significant biological indicator in children with upper respiratory tract infection and exanthem subitum.

Mondor Disease in a Patient With Recurrent Deep Venous Thromboses.

Despite representing 3.3% of adult emergency department (ED) visits, dermatologic presentations can be challenging even to the astute emergency physician (EP). Although approximately one-half of dermatologic complaints in the ED result in a diagnosis of cellulitis or abscess, there are numerous other less common conditions (1). A thorough differential diagnosis for skin conditions in the ED may prevent misdiagnosis and unnecessary antibiotic treatment. We present a case of Mondor disease in a man with a history of recurrent deep venous thromboses (DVTs).

43745 A pilot survey to assess the practices, attitudes and beliefs around endotracheal aspirate culture use in a pediatric intensive care unit

ABSTRACT IMPACT: Optimizing the use of endotracheal aspirate cultures (EACs) has the potential to improve the care of complex mechanically ventilated children by improving testing practices and avoiding unnecessary antibiotic treatment for false-positive results. OBJECTIVES/GOALS: An electronic survey has previously been employed to characterize the practices and attitudes around blood cultures among critically ill children. The objective of this work was to develop and pilot a new survey as a tool to understand practices and attitudes that could inform quality improvement initiatives to optimize EAC practices. METHODS/STUDY POPULATION: Informed by prior experience of diagnostic stewardship of EAC in other settings and using a similar structure to the blood culture practice survey, we developed an electronic self-administered survey sent to respiratory therapists, advanced practice providers, and physicians at the Johns Hopkins All Children’s pediatric intensive care unit. RESULTS/ANTICIPATED RESULTS: A total of 27 of 87 clinicians (37%) responded to the survey (22 respiratory therapists, 9 attending physicians and 1 advanced practice provider). Responses indicated samples are typically collected by respiratory therapists via in-line (endotracheal) or open suctioning (tracheostomy). Most respondents did not feel EACs could lead to unintended negative consequences (71%), agreed practices vary between people (89%), and felt an algorithm would help align the clinical team (79%). Most respondents agreed some clinicians may be reluctant to change practice (82%) and may not change practice due to concern for missing diagnosis of ventilator-associated pneumonia or tracheitis (78%). Surveillance cultures were not used in this unit and there were no prior EAC diagnostic stewardship efforts. DISCUSSION/SIGNIFICANCE OF FINDINGS: This survey captured practices, perceptions and barriers to changes that will inform the implementation of quality improvement initiatives to optimize EAC use in this unit. Future studies can consider utilizing an electronic survey to describe practice variation, clinician believes and attitudes about EAC testing in ventilated patients.

Urgent Bordetella PCR in infants under 3 months, a useful tool in the Pediatric Department

IntroductionWhooping cough in patients aged under 3 months has higher rates of morbimortality. Hospitalisation and treatment with azithromycin is generally recommended. Many patients with cough without other signs of alarm, are admitted and started antibiotic therapy until a result of Bordetella-PCR is available. This technique, when performed urgently, can provide the diagnosis in a few hours. The objective of this study is to determine if its generalisation in the Emergency Department allows to improve patient management. MethodsRetrospective cohort study of patients aged under 3 months who underwent Bordetella-PCR testing from upper respiratory tract secretions since March 2011 to December 2017. From December 2015 the test was performed urgently. ResultsOne hundred and fifty-eight PCR were performed, 16 (10%) were positive for B. pertussis. Negative results (142; 90%) were divided in 2 cohorts: conventional-PCR, with 74 cases, and urgent-PCR, with 68 cases. The 2 groups were homogeneous in terms of clinical and analytical characteristics. In the urgent-PCR group there was 18% reduction in chest X-rays performed (p=0.008). There were 33 (48.5%) patients admitted in the urgent-PCR group, compared to 49 (66.2%) in the conventional-PCR (p=0.042). Antibiotic treatment was initiated in 32% of the patients in the urgent-PCR group compared to 67% in the conventional-PCR group (p=0.000047), without observing any significant increase in the number of visits to the Emergency Department or worse clinical performance. ConclusionsThe introduction of urgent PCR in the Emergency Department is a useful tool in the management of infants under 3 months of age with suspected pertussis, since it can avoid unnecessary admissions, diagnostic tests and antibiotic treatments.

Stratification of Culture-Proven Early-Onset Sepsis Cases by the Neonatal Early-Onset Sepsis Calculator: An Individual Patient Data Meta-Analysis

To provide a comprehensive assessment of case stratification by the Neonatal Early-Onset Sepsis (EOS) Calculator, a novel tool for reducing unnecessary antibiotic treatment. A systematic review with individual patient data meta-analysis was conducted, extending PROSPERO record CRD42018116188. Cochrane, PubMed/MEDLINE, EMBASE, Web of Science, Google Scholar, and major conference proceedings were searched from 2011 through May 1, 2020. Original data studies including culture-proven EOS case(s) with EOS Calculator application, independent from EOS Calculator development, and including representative birth cohorts were included. Relevant (individual patient) data were extracted from full-text and data queries. The main outcomes were the proportions of EOS cases assigned to risk categories by the EOS Calculator at initial assessment and within 12hours. Evidence quality was assessed using Newcastle-Ottawa scale, Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies, and GRADE tools. Among 543 unique search results, 18 were included, totaling more than 459 000 newborns. Among 234 EOS cases, EOS Calculator application resulted in initial assignments to (strong consideration of) empiric antibiotic administration for 95 (40.6%; 95% CI, 34.2%-47.2%), more frequent vital signs for 36 (15.4%; 95% CI, 11.0%-20.7%), and routine care for 103 (44.0%; 95% CI, 37.6%-50.6%). By 12hours of age, these proportions changed to 143 (61.1%; 95% CI, 54.5%-67.4%), 26 (11.1%; 95% CI, 7.4%-15.9%), and 65 (27.8%; 95% CI, 22.1%-34.0%) of 234 EOS cases, respectively. EOS Calculator application assigns frequent vital signs or routine care to a substantial proportion of EOS cases. Clinical vigilance remains essential for all newborns.

The microbiome in urinary tract infections in children - an update.

Urinary tract infection (UTI) is one of the most common pediatric infections worldwide. Recently introduced 16S rRNA sequencing allows detailed identification of bacteria involved in UTI on a species-based level. The urogenital microbiome in children is scarcely investigated, with underlying conditions differing from adults. Improvement in diagnostic and therapeutic approaches can help to minimize unnecessary antibiotic treatments, thereby protecting the physiological microbiome. Healthy bladders of children display a distinct microbiome than those of adults. UTI is characterized by changes in bacterial composition, with a high prevalence of Enterobacterales. There is a correlation between bacterial species and the pH of the urine, so a characteristic age-related pathogen pattern can be found due to the acidic urine in infants and more alkaline urine in older children. Recently, new methods were proposed to overcome the suboptimal diagnostic performance of urine cultures and urine dipstick test. This allows precise treatment decisions and helps to prevent chronification of UTI, related voiding dysfunctions and renal scaring, systemic abiosis, and the development of antibiotic resistance. Uropathogens involved in UTIs in children should be identified with precision to allow targeted therapeutic decisions. This can also help preventing the destruction of the microbiome homeostasis, which could result in a life-long dysbiosis. New treatment approaches and recolonization with probiotics are necessary due to increasing intrinsic antibiotic resistance of bacteria.

Short Versus Extended Treatment with a Carbapenem in Haematology Patients with High Risk Fever of Unknown Origin During Neutropenia: An Open-Label Multicentre Randomised Clinical Trial

Background: Early antibiotic discontinuation in haematology patients with fever of unknown origin during chemotherapy-induced neutropenia has been advocated to reduce unnecessary antibiotic treatment, but the safety of this strategy is unknown. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment. Methods: In this randomised, multicentre, non-inferiority trial we assigned 292 haematology patients with fever of unknown origin during high-risk neutropenia (≥7 days) to short treatment, with carbapenem discontinuation after 72 hours (± 12 hours), or extended treatment, with carbapenem continuation for ≥ 9 days until being afebrile for 5 days or neutrophil recovery. The composite primary endpoint was treatment failure, defined as recurrent fever or a carbapenem-sensitive infection between day 4 and day 9 and septic shock/respiratory failure or death from day 4 until neutrophil recovery. Findings: Treatment failure in the intention-to-treat analysis (281 patients) was 19·4% (28/144) in the short treatment versus 15·3% (21/137) in the extended treatment arm (adjusted risk difference 4·0%, 90% confidence interval [CI] -1·7% to 9·7%, excluding the 10% non-inferiority threshold). Mortality until 30 days after neutrophil recovery occurred in five patients (3·5%) in the short treatment group and in one (0·7%) in the extended treatment group (adjusted risk difference 2·6%, 95% CI % 1·2 to 5·4%), of which none were related to infections with carbapenem-sensitive microorganisms. Interpretation: Early discontinuation of carbapenem treatment in neutropenic patients with fever was non-inferior to extended treatment with regard to treatment failure, but all-cause mortality before 30 days after neutrophil recovery was significantly higher in patients with persistent fever at day 3. Early discontinuation of carbapenem treatment is therefore possible in afebrile patients, but caregivers should be vigilant of other non-carbapenem susceptible infections in patients with persistent fever.: Clinical Trial Registration Details: This trial is registered with ClinicalTrials.gov (number NCT02149329). Funding Information: Dutch Research Council (ZonMw) and Fonds NutsOhra. Declaration of Interests: The authors 408 declare no competing interests. Ethics Approval Statement: The protocol was approved by the research ethics review committee of VU university medical centre (current name: Amsterdam University medical centres, location VUmc) and ethical bodies of each participating centre. An independent data and safety monitoring board oversaw study procedures and data quality during conduct of the study and performed a planned interim safety analysis. All participants provided written informed consent.

1357. Urinary Symptom Management in Children with Neuropathic Bladder Presenting to the Emergency Department

BackgroundChildren with neuropathic bladders are at high risk for developing urinary tract infections (UTIs). The accurate diagnosis of UTI is complicated by altered sensation and the ubiquity of bacterial colonization. As a result, overdiagnosis and overtreatment for presumed UTIs is common. The objective of this study is to estimate potential overdiagnosis and unnecessary antibiotic treatment in children with neuropathic bladder presenting to the Emergency Department (ED) with urinary symptoms.MethodsRetrospective cohort study of patients with neuropathic bladder presenting to the Children’s National Hospital ED between October 2008 and December 2019. Chart review was used to determine presenting symptoms, urinary evaluation, and antibiotic treatment. We used the validated urinary symptoms questionnaire (USQNB-IC) to categorize ED visits as ‘evaluation warranted’ if the patient presented with at least one of the actionable symptoms on the USQNB-IC. We used the Spina Bifida Association’s (SBA) published definitions for UTI to determine which patients warranted presumptive antibiotic treatment.ResultsThere were 211 visits by 82 patients (43% female), with a mean of 4.6 visits per patient (IQR 6). Mean age at ED visit was 5.2 years (SD 4.2 years). The most common presenting symptoms were fever (57%), emesis (32%), abdominal pain (24%), foul-smelling urine (11%), and cloudy urine (8%). Of the total visits, 122 (58%) had a urinary evaluation and 31% were treated with antibiotics. Sixteen ED visits (8%) resulted in a urinary evaluation that was not warranted. Of the 122 ED visits with urinary evaluation, 32 patients (26%) did not meet SBA criteria for UTI but were treated empirically with antibiotics.Table 1: Urinary evaluation in children with neuropathic bladder seen in CNH ED between October 2008 and December 2019. Table 2: UTI treatment in children with neuropathic bladder seen in CNH ED between October 2008 and December 2019. ConclusionMost children with neuropathic bladder presenting to the ED were appropriately evaluated and treated for presumed UTI. One-quarter of evaluated children received empiric antibiotics despite not meeting SBA criteria for UTI, indicating this may be a target for educational initiatives to promote antibiotic stewardship. Further research is needed to generate and validate clinical guidelines for emergency department providers to limit unnecessary testing and antibiotic therapy in this population.Disclosures All Authors: No reported disclosures