Bacterial Infection In Young Infants Research Articles

Reducing IV Antibiotic Duration for Neonatal UTI Using a Clinical Standard Pathway.

Urinary tract infections (UTIs) are the most common bacterial infections in young infants and are traditionally treated with longer intravenous (IV) antibiotic courses. A growing body of evidence supports shorter IV antibiotic courses for young infants. Our primary aim was to decrease the IV antibiotic treatment to 3 days over 2 years for neonates aged 0 to 28 days who have been hospitalized with UTIs. Using quality improvement methods, our primary intervention was to implement a revised clinical pathway recommending 3 (previously 7) days of IV antibiotics. Our primary outcome measure was IV antibiotic duration, and the secondary outcomes were length of stay (LOS) and costs. The balancing measure was readmission within 30 days of discharge. Neonates were identified by using International Classification of Diseases diagnosis codes and excluded if they were admitted to the ICU or had a LOS >30 days. We used statistical process control to analyze outcome measures for 4 years before (baseline) and 2 years after the pathway revision (intervention) in February 2020. A total of 93 neonates were hospitalized with UTIs in the baseline period and 41 were hospitalized in the intervention period. We found special cause variation, with a significant decrease in mean IV antibiotic duration from 4.7 (baseline) to 3.1 days (intervention) and a decrease in mean LOS from 5.4 to 3.6 days. Costs did not differ between the baseline and intervention periods. There were 7 readmissions during the baseline period, and 0 during the intervention period. The implementation of a revised clinical pathway significantly reduced IV antibiotic treatment duration and hospital LOS for neonatal UTIs without an increase in hospital readmissions.

Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study.

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

Incidence of possible serious bacterial infection in young infants in the three high-burden countries of the Democratic Republic of the Congo, Kenya, and Nigeria: A secondary analysis of a large, multi-country, multi-centre clinical trial.

Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa. This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics. The incidence of PSBI among 0-59-day-old infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0). The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths. Australian New Zealand Clinical Trials Registry: ACTRN12610000286044.

Care-seeking behaviours of mothers and associated factors for possible serious bacterial infection in young infants during COVID-19 pandemic in Ethiopia: mixed-methods formative research

ObjectivesImplementation research was employed to examine rates and contextual factors associated with mothers’ care-seeking for their sick neonates and identify challenges for community-based possible serious bacterial infection (PSBI) services access...

Lessons learnt from community referral and follow up of sick young infants with possible severe bacterial infection in Turkana County, Kenya

IntroductionManagement of possible severe bacterial infections in young infants (0–59 days) requires timely identification of danger signs and prompt administration of efficacious antibiotic treatment. The Possible Severe Bacterial Infection guidelines underscore the importance of close follow up in an outpatient basis to ensure treatment adherence and early detection of illness-related complications. The purpose of this study was to strengthen the follow up and referral of sick young infants on day 4 and 8 by introducing community-led interventions that facilitated community health volunteers to identify sick young infants, conduct community reviews, link data with responsive facilities, and refer appropriately. MethodsSix health facilities were included in a longitudinal, descriptive, mixed methods approach weaved around an initial formative context assessment and three-monthly assessments between October 2019 to January 2020 with a endline assessment in August 2020. Quantitative data was extracted from facility registers to identify gaps in follow up and referral feasibility. Qualitative data was through focus group discussions with community health volunteers and key informant interviews with frontline providers. ResultsQualitative data provided insights into key barriers and facilitators of community follow up and referral. Barriers include community socio-cultural practices, competing tasks, dysfunctional community referral pathway, drivers of common infections, and unavailability of essential commodities. Key facilitators entail indication of competency in identification of danger signs in sick young infants, presence of older women, men, and community resource persons that can leveraged on in community engagement and sensitization, and mothers are the primary decision makers in care seeking. There was increased utilization of decision support tools and an increase in the number of sick young infants managed in dispensaries. The COVID-19 pandemic however negatively impacted community follow up and referral of sick young infants. ConclusionEssential barriers and facilitators to follow up and community referral entwined with facility-based vulnerabilities were highlighted. A two-pronged intervention on improving communication, linkage and subsequent follow up of sick young infants was employed in the six participating facilities. The feasibility, adoption, and fidelity of strengthening community facility linkage through integrated communication strategies was documented, indicative of a successful community-facility linkage in dispensaries and health centers despite the effects of the COVID-19 pandemic.

2134. A Phase 2 Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Booster Dose of a Group B Streptococcus 6-Valent Polysaccharide Conjugate Vaccine (GBS6)

Abstract Background Group B streptococcus (GBS) is a leading cause of invasive bacterial infections in young infants and pregnant women. Pfizer is developing a hexavalent GBS vaccine (GBS6) as a maternal vaccine to prevent invasive GBS disease due to the 6 most prevalent serotypes in young infants. We previously reported Phase 1 safety and immunogenicity data for GBS6. There is precedent for repeat doses of vaccines to augment or sustain circulating antibodies available for placental transfer with each pregnancy; thus, data to inform GBS6 booster strategies were required. Methods This was a Phase 2 open-label extension study to evaluate the safety and immunogenicity of a booster dose of GBS6 (20 μg capsular polysaccharide (CPS)/serotype/dose) with or without AlPO4, given ∼2 years after primary vaccination in 151 healthy nonpregnant adults. Sera taken before and 1-month postbooster were assessed for anti-CPS IgG using a direct Luminex immunoassay. Participants recorded solicited local and systemic events for 14 days after vaccination and unsolicited safety events through 6 months after vaccination. Immunogenicity time points from the Phase 1 study are referred to as primary dose. Results Immunogenicity results For all serotypes, serotype-specific IgG geometric mean concentrations (GMCs) remained elevated compared to baseline at the prebooster time point and were higher 1-month postbooster than 1 month post primary. The 1-month postbooster IgG GMCs were 10- to 59-fold higher than at the prebooster time point. There were similar responses between the 2 formulations. Safety and tolerability results The most frequently reported local reaction was mild to moderate pain at the injection site. Greater pain was associated with AlPO4 formulation. The most frequently reported systemic events were mild to moderate headache and fatigue. The frequency of adverse events was low. Figure 1Antibody Response Line Plot of IgG GMCs by Vaccine Group - All SerotypesFigure 2.Reverse Cumulative Distribution Curves (RCDCs) for IgG 1 Month After Primary and Booster Vaccination, by Vaccine Group – All SerotypesFigure 3.IgG Geometric Mean Fold Rises (GMFRs) at 1 Month Postbooster Vaccination Conclusion A booster dose of GBS6 given ∼2 years after a primary dose to healthy nonpregnant adults was safe and elicited robust immune responses that were also consistently higher than after primary dose. This study suggests that repeat vaccination with GBS6 may confer additional benefit in pregnant women in subsequent pregnancies. Disclosures Babalwa Jongihlati, MD, MBA, Pfizer: Stocks/Bonds Judith Absalon, MD, MPH, Pfizer: Stocks/Bonds Samantha Munson, MPH, MBA, Pfizer: Stocks/Bonds Yasmin Sanchez-Pearson, PhD, Pfizer: Stocks/Bonds Raphael Simon, PhD, Pfizer: Stocks/Bonds Natalie Silmon de Monerri, PhD, Pfizer: Stocks/Bonds David Radley, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Emily A. Gomme, Ph.D., Pfizer: Stocks/Bonds Michelle Gaylord, PhD, Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Salary|Pfizer, Inc.: Stocks/Bonds Kathrin U. Jansen, PhD, Pfizer: Stocks/Bonds Daniel A. Scott, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Stocks/Bonds.

Temperature threshold in the screening of bacterial infections in young infants with hypothermia

BackgroundYoung infants with hypothermia presenting to the emergency department (ED) are at risk for serious bacterial infections (SBI), however there is no consensus temperature to prompt evaluation for SBI among...

Differentiating vaccine reactions from invasive bacterial infections in young infants presenting to the emergency department in the 4CMenB era: a retrospective observational comparison

BackgroundDifferentiating infants with adverse events following immunisation (AEFIs) or invasive bacterial infection (IBI) is a significant clinical challenge. Young infants post vaccination are therefore often admitted to the hospital for...

Management of bacterial infections in young infants in Ethiopia: Facility preparedness, health workers' knowledge and quality of care.

We assessed primary care facility preparedness, health workers' knowledge and their classification and treatment of possible serious bacterial infection and local bacterial infection in young infants aged 0-59days. A cross-sectional survey was conducted in four regions of Ethiopia, including 169health posts with 276health extension workers and 155health centres with 175staff. Registers of 1058sick young infants were reviewed. Antibiotics to treat possible serious bacterial infection were available in 71% of the health centres and 38% of the health posts. Nine of ten health extension workers and eight of ten health centre staff mentioned at least one sign of possible serious bacterial infection and local bacterial infection. Among the registered cases with signs of bacterial infections, the health extension workers classified 49% as having a possible serious bacterial infection and 88% as local bacterial infection. The health centre staff classified 25% as possible serious bacterial infections and 86% as local bacterial infections. One-fourth (26%) of possible serious bacterial infection received the recommended treatment at health posts and 35% at health centres. Many health posts lacked antibiotics. The classification and treatment of possible serious bacterial infection did not follow guidelines. The lack of medicines and poor adherence compromise the quality of care.

Implementation research to increase treatment coverage of possible serious bacterial infections in young infants when a referral is not feasible: lessons learnt.

The objective was to achieve high coverage of possible serious bacterial infections (PSBI) treatment using the World Health Organization (WHO) guideline for managing it on an outpatient basis when referral to a hospital is not feasible. We implemented this guideline in the programme settings at 10 Basic Health Units (BHU) in two rural districts of Sindh in Pakistan using implementation research. A Technical Support Unit supported the programme to operationalize guidelines, built capacity of health workers through training, monitored their clinical skills, mentored them and assured quality. The community-based health workers visited households to identify sick infants and referred them to the nearest BHU for further management. The research team collected data. Of 17600 identified livebirths, 1860 young infants with any sign of PSBI sought care at BHUs and 1113 (59.8%) were brought by families. We achieved treatment coverage of 95%, assuming an estimated 10% incidence of PSBI in the first 2 months of life and that 10% of young infants came from outside the study catchment area. All 923 infants (49%; 923/1860) 7-59days old with only fast breathing (pneumonia) treated with outpatient oral amoxicillin were cured. Hospital referral was refused by 83.4% (781/937) families who accepted outpatient treatment; 92.2% (720/781) were cured and 0.8% (6/781) died. Twelve (7.6%; 12/156) died among those treated in a hospital. It is feasible to achieve high coverage by implementing WHO PSBI management guidelines in a programmatic setting when a referral is not feasible.

Frequency of serious bacterial infections in young infants with and without viral respiratory infections.

The goal of our investigation was to describe the incidence of serious bacterial infection (SBI, defined as bacteremia, urinary tract infection (UTI), or meningitis) in young infants with and without documented viral pathogens. This was a retrospective cross-sectional study (1/2016-12/2017) in 3 emergency departments (EDs). Previously healthy 0-60-day-old infants were included if at least respiratory viral testing and a blood culture was obtained. The frequency of SBI, the primary outcome, was compared among infants with/without respiratory viral infections using the Pearson Chi-square test (or Fisher's Exact Test) and unadjusted odds ratios (OR). The median age of the 597-infant cohort was 32days (interquartile range: 20-45days); 42% were female. Eighty-three percent were well appearing in the ED and 72% were admitted. ED triage vitals commonly revealed tachypnea (68%), pyrexia (45%), and tachycardia (28%); hypoxemia (5%) was uncommon. Twenty-eight percent had positive viral testing, most commonly RSV (93/169, 55%), parainfluenza (29, 17%), and influenza A (23, 14%). Eighty-three infants (13.9%) had SBI: 8.4% (n=50) had UTI alone, 2.8% (n=17) had bacteremia alone, 1.2% (n=7) had bacteremia + UTI, 1.0% (n=6) had bacteremia + meningitis, and 0.5% (n=3) had meningitis alone. Infants with documented respiratory viral pathogens were less likely to have any SBI (OR: 0.23; 95% CI: 0.11-0.50), UTI (OR 0.22, 95% CI: 0.09-0.56), or bacteremia (OR 0.27, 95% CI: 0.08-0.9) than infants with negative viral testing. There was no difference in meningitis frequency based on viral status (OR: 0.13, 95% CI: 0.008-2.25). The frequency of bacteremia and UTI was lower in young infants with respiratory viral infections compared to infants with negative respiratory viral testing.

Severe bacterial infection in young infants with pyrexia admitted to the emergency department.

The objectives of this study were to understand the clinical presentations of febrile young infants with severe bacterial infection (SBI), and to investigate the pathogen variations throughout the vaccine era and after antenatal group B Streptococcus (GBS) screening.All infants < 90 days old with a body temperature of ≥38.0°C and admitted to the emergency department were retrospectively enrolled in our study. SBI was defined as a positive culture of urine, blood, or cerebrospinal fluid. All clinical variables were analyzed and compared between the SBI group and the non-SBI group, to identify the relevant risk factors for SBI in infants with pyrexia.A total of 498 infants were studied, 279 of whom (56%) had SBI. The body temperature at triage was higher in the SBI group, and the difference was highly obvious in the neonatal group. White blood cell count and C-reactive protein levels were both significantly higher in the SBI group (P < .05), whereas neutrophil percentage and band percentage demonstrated no significant differences. Escherichia coli was the most common pathogen and plasmid-mediated extended-spectrum lactamases were detected in up to 9.1%. GBS was detected in 16 cases of bacteremia (6 cases with concurrent meningitis).The body temperature at triage may provide a clue for differentiating sick babies, especially in the neonatal group. Complete serum analysis is required for infection survey, especially white blood cell and C-reactive protein. Escherichia coli is the most common pathogen, and clinician should raise awareness of drug resistance in some patients. The prevalence of GBS infection in the young infant group remains high after routine antenatal GBS screening

#70: Comparing Prospectively Identified Etiologic Agents of Neonatal Sepsis in Southwest Ethiopia with WHO Empiric Antibiotic Guidelines

Abstract Background Neonatal sepsis accounts for one third of global neonatal mortality. To improve access to treatment for neonatal sepsis, in 2015 the World Health Organization (WHO) released guidance for outpatient treatment (when referral is not possible or refused) of Possible Serious Bacterial Infection (PSBI).1 However, studies from low and middle-income countries suggest that bacteria causing neonatal infection differ from high-income countries, with higher rates of Staphylococcus aureus, Escherichia coli, and Klebsiella species and high rates of antimicrobial resistance. For this reason, local surveillance is vital to develop local antibiograms and tailor appropriate prescribing. Methods This is an analysis of the first 6 months of a prospective study of young infants admitted to Jimma University Hospital with PSBI. Young infants admitted to Jimma University Hospital with PSBI (defined by WHO danger signs: poor feeding, seizures, fever, lethargy, hypothermia, tachypnea, and increased work of breathing) are being recruited over a 12-month period. Blood cultures are obtained on admission, incubated in the BACTEC system and positive cultures evaluated for antibiotic susceptibility by Kirby-Bauer Disc diffusion. Primary outcomes are culture positivity, organism identification, and rates of antimicrobial resistance. Secondary outcomes include mortality rates and duration of hospital stay. The data included in this analysis were collected from March 21, 2019, through September 20, 2019. Data collection is ongoing. Results In total, 196 infants have been enrolled with a culture positivity rate of 58%. At this time, most frequently identified organisms are Klebsiella spp. (43.4%) and Staphylococcus aureus (12.2%). Gram-negative rods represent 67.8% of the isolates and gram-positive cocci 32.2%. Less than half the isolates (44.4%) were susceptible to either first-line antibiotic (ampicillin and gentamicin). Only 17.4% of the gram-positive cocci were sensitive to oxacillin. In-hospital mortality rates for those with positive cultures approached 15% (compared with 5% for culture negative). The average hospital stay for infants with positive cultures was 13.9 days compared with 10.1 for those with negative cultures. Conclusion Klebsiella spp. are responsible for a plurality of neonatal sepsis admissions at Jimma University Hospital. The organisms responsible for neonatal sepsis in southwest Ethiopia are highly resistant to the WHO recommended first-line antibiotics. It is possible that adoption of the WHO guidelines may be inappropriate in this population, which could be better served by tailoring empiric antibiotics to the identified organisms. Reference 1. World Health Organization. Guideline: Managing possible serious bacterial infection in young infants when a referral is not feasible. (2015) Geneva, CH.

Costs and cost-effectiveness of management of possible serious bacterial infections in young infants in outpatient settings when referral to a hospital was not possible: Results from randomized trials in Africa.

Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens. Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made. The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs. Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality. The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Frequency of Serious Bacterial Infections in Young Infants with and without Viral Respiratory Infections

Frequency of Serious Bacterial Infections in Young Infants with and without Viral Respiratory Infections

Innovation to Increase Treatment Coverage of Possible Serious Bacterial Infections in Young Infants When a Referral is Not Feasible Implemented in the Existing Health System in Sindh, Pakistan

BackgroundNeonatal infections are a leading cause of mortality globally. They should ideally be treated in a hospital. However, in resource constraint settings refusal to hospitalization is high. To address this, the World Health Organization (WHO) developed a guideline for managing Possible Serious Bacterial Infections (PSBI) on an outpatient basis when referral to a hospital is not feasible. The objective of this research was to achieve high coverage of PSBI treatment and evaluate enablers and barriers to implementation of WHO guideline. Methods: We implemented the WHO PSBI guideline in the programme setting at 10 Basic Health Units (BHU) in two rural districts of Sindh (Thatta and Sujawal) in Pakistan using implementation research. We conducted policy dialogue with federal and provincial decision-makers and held discussions with programme managers and community leaders. A Technical Supporting Unit supported the programme to operationalize guidelines, capacity building of health workers, monitored their skills and mentored them and assured quality. The community-based health workers visited households to identify sick infants and referred them to the nearest BHU for further management. Data was collected by the research team. Results: Of 17,600 identified births, 1860 young infants with any sign of PSBI sought care at study BHUs and 1113 (59.8%) were brought by families. We achieved treatment coverage of 95%, assuming an estimated 10% incidence of PSBI in the first two months of life and that 10% of young infants came from outside the study catchment area. A total of 923 infants (49%; 923/1860) 7-59 days old with only fast breathing (pneumonia) were treated with oral amoxicillin without referral and all survived. A hospital referral was offered to 937 young infants, but 781 families (83.4%, 781/937) refused and accepted outpatient treatment. Among 344 (18.5%; 344/1860) <7 days old young infants with severe pneumonia, 335 (97.4%; 335/344) received outpatient treatment, 24 (7.2%; 24/335) failed treatment while one died. Among 495 (26.6%; 495/1860) with clinical severe infection 440 (88.9%; 440/495) received outpatient treatment, 34 (7.7%; 34/440) failed treatment, whereas 4 (0.9%; 4/440) died. Among 98 (4.9%; 98/1860) infants with critical illness, 6 (6.1%; 6/98) refused referral and received outpatient treatment, 3 (50%; 3/6)) failed treatment and one died. Twelve (7.6%; 12/156) deaths were recorded amongst those treated in a hospital. Conclusion: It is feasible to implement WHO PSBI management guidelines in a programmatic setting when a referral is not feasible. However, a scale-up of the guideline will require strong government commitment, system strengthening and capacity building of health workers along with adequate supervision and monitoring. Trial Registration: The trial is registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369. Funding: This study was funded by the Bill and Melinda Gates Foundation to the Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland through grant number OPP1114815. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interest: The authors have declared that no competing interests exist. Ethical Approval: This study was approved by the AKU Ethical Review Committee (ERC Number: 3936-Ped-ERC-15) and WHO Research Ethics Review Committee. Caregivers of infants provided informed, signed consent before enrolment in the study. Those who were unable to sign provided a thumb impression to express consent.

Management of possible serious bacterial infection in young infants closer to home when referral is not feasible: Lessons from implementation research in Himachal Pradesh, India.

Government of India and the World Health Organization have guidelines for outpatient management of young infants 0-59 days with signs of Possible Serious Bacterial Infection (PSBI), when referral is not feasible. Implementation research was conducted to identify facilitators and barriers to operationalizing these guidelines. Himachal Pradesh government implemented the guidelines in program settings supported by Centre for Health Research and Development, Society for Applied Studies. The strategy included community sensitization, skill enhancement of Accredited Social Health Activists (ASHA), Auxiliary Nurse Midwives (ANMs) and Medical Officers (MOs) to identify PSBI and treat when referral was not feasible. The research team collected information on facilitators and barriers. A technical support unit provided training and oversight. Among 1997 live births from June 2017 to January 2019, we identified 160 cases of PSBI in young infants resulting in a coverage of 80%, assuming an incidence of 10%. Of these,29(18.1%) had signs of critical illness (CI), 92 (57.5%) had clinical severe infection (CSI), 5 (3.1%)had severe pneumonia (only fast breathing in young infants 0-6 days), while 34 (21%) had pneumonia (only fast breathing in young infants 7-59 days). Hospital referral was accepted by 48/160 (30%), whereas 112/160 (70%) were treated with the simplified treatment regimens at primary level facilities. Of the 29 infants with CI, 18 (62%) accepted referral; 26 (90%) recovered while 3 (10%) who had accepted referral, died. Of the 92 infants who had CSI, 86 (93%) recovered, 65 (71%) received simplified treatment and one infant who had accepted referral, died. All the five infants who had severe pneumonia, recovered; 3 (60%) had received simplified treatment. Of the 34 pneumonia cases, 33 received simplified treatment of which 5 (15%) failed treatment; two out of these 5 died. Overall, 6/160 infants died (case-fatality-rate 3.4%); 2 in the simplified treatment (case-fatality-rate 1.8%) and 4 in the hospital group (case-fatality-rate 8.3%). Delayed identification and care-seeking by families and health system weaknesses like manpower gaps and interrupted supplies were challenges in implementation. Implementation of the guidelines in program settings is possible and acceptable. Scaling up would require creating community awareness, early identification and appropriate care-seeking, strengthening ASHA home-visitation program, building skills and confidence of MOs and ANMs, uninterrupted supplies and a dependable referral system.

Diagnosis and Management of UTI in Febrile Infants Age 0-2 Months: Applicability of the AAP Guideline.

Urinary tract infections (UTIs) are the most common bacterial infection in young infants. The American Academy of Pediatrics' (AAP) clinical practice guideline for UTIs focuses on febrile children age 2-24 months, with no guideline for infants <2 months of age, an age group commonly encountered by pediatric hospitalists. In this review, we assess the applicability of the AAP UTI Guideline's action statements for previously healthy, febrile infants <2 months of age. We also discuss additional considerations in this age group, including concurrent bacteremia and routine testing for meningitis.

Diagnostic Accuracy of Procalcitonin for the Detection of Bacterial Infections in Young Infants.

Diagnostic Accuracy of Procalcitonin for the Detection of Bacterial Infections in Young Infants.

Bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infection: a systematic review.

Urinary tract infections, the most common severe bacterial infections in young infants, may be associated with co-existing meningitis. There is no consensus on when to perform a lumbar puncture in these infants. Our aim was to quantify the frequency of co-existing bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infections. We systematically reviewed PubMed, EMBASE, and the Cochrane Library for studies including infants ≤ 3months with suspected/confirmed urinary tract infections, who underwent a lumbar puncture. Two investigators independently reviewed articles for inclusion and extracted relevant data. Our outcomes were culture-confirmed meningitis and identification of low-/high-risk criteria of meningitis. Overall 20/2079 studies, including 4191 infants, met inclusion criteria. A total of 11 infants had bacterial meningitis (frequency between 0 and 2.1% across studies) and were mostly neonates. Of 253 infants meeting the low-risk criteria (well-appearing, age > 21days, procalcitonin ≤ 0.5ng/ml, and C reactive protein ≤ 20mg/L) none developed meningitis, but only 15 underwent lumbar puncture.Conclusion: Co-existing bacterial meningitis in febrile young infants with urinary tract infection is rare. In those meeting low-risk criteria, a lumbar puncture may not be indicated. A case by case assessment should be made in infants not meeting low-risk criteria.Trial registration: CRD42018105339 What is known: • When caring for febrile infants ≤ 3months with urinary tract infections, clinicians may have uncertainty on whether to perform a lumbar puncture (LP) for possible co-existing meningitis What is new: • An up-to-date systematic review of 20 studies found the frequency of co-existing meningitis in this population to be between 0 and 2.1% • Despite limited data, an LP may not be indicated in infants meeting low-risk criteria (being well-appearing, age > 21days, procalcitonin ≤ 0.5ng/ml, C reactive protein ≤ 20 mg/L). Ill-appearance and neonatal age appear to be significant risk factors of co-existing meningitis.