Predicting community acquired bloodstream infection in infants using full blood count parameters and C-reactive protein; a machine learning study.

Early recognition of bloodstream infection (BSI) in infants can be difficult, as symptoms may be non-specific, and culture can take up to 48 h. As a result, many infants receive unneeded antibiotic treatment while awaiting the culture results. In this study, we aimed to develop a model that can reliably identify infants who do not have positive blood cultures (and, by extension, BSI) based on the full blood count (FBC) and C-reactive protein (CRP) values. Several models (i.e. multivariable logistic regression, linear discriminant analysis, K nearest neighbors, support vector machine, random forest model and decision tree) were trained using FBC and CRP values of 2693 infants aged 7 to 60 days with suspected BSI between 2005 and 2022 in a tertiary paediatric hospital in Dublin, Ireland. All models tested showed similar sensitivities (range 47% - 62%) and specificities (range 85%-95%). A trained decision tree and random forest model were applied to the full dataset and to a dataset containing infants with suspected BSI in 2023 and showed good segregation of a low-risk and high-risk group. Negative predictive values for these two models were high for the full dataset (> 99%) and for the 2023 dataset (> 97%), while positive predictive values were low in both dataset (4%-20%).   Conclusion: We identified several models that can predict positive blood cultures in infants with suspected BSI aged 7 to 60 days. Application of these models could prevent administration of antimicrobial treatment and burdensome diagnostics in infants who do not need them. What is Known: • Bloodstream infection (BSI) in infants cause non-specific symptoms and may be difficult to diagnose. • Results of blood cultures can take up to 48 hours. What is New: • Machine learning models can contribute to clinical decision making on BSI in infants while blood culture results are not yet known.

Treatment of Mycoplasma genitalium infection in pregnancy: A systematic review of international guidelines.

BACKGROUND: Mycoplasma genitalium is an emerging pathogen, which has been linked to cervicitis, urethritis and pelvic inflammatory disease (PID). With the advent of multiplex polymerase chain reaction (PCR) panels for sexually transmitted infections, it is increasingly being identified in pregnant women. OBJECTIVES: The aim was to review international guidelines, which had explicit recommendations for treatment of M. genitalium infection in pregnancy and breastfeeding. SEARCH STRATEGY: PubMed, EMBASE and Cochrane databases were reviewed with no age, species, language or date restrictions. SELECTION CRITERIA: Studies were included if they had an explicit recommendation for treatment of M. genitalium in pregnancy. Studies were excluded if there was no recommendation in pregnancy, if they referred to other international guideline recommendations or were historical versions of guidelines. DATA COLLECTION AND ANALYSIS: References were manually reviewed and 50 papers were selected for review. Only four guidelines were included in the final analysis and they were from Europe, UK, Australia and Aotearoa New Zealand. MAIN RESULTS: All studies recommended azithromycin as first-line treatment, and advised against moxifloxacin use. The dosing schedule of azithromycin, varied between guidelines, as did the utility/safety of pristinamycin for macrolide resistant infections. Safety data was generally reassuring for azithromycin but inconsistent for pristinamycin. CONCLUSIONS: Azithromycin is the first-line treatment for macrolide susceptible or unknown resistance infections, but there is a lack of consistency regarding dosing of azithromycin or the utility/safety of pristinamycin for macrolide resistant infections in pregnancy/lactation.

Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study.

BACKGROUND: Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin. METHODS: Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray. RESULTS: The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days). CONCLUSIONS: The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.

Enterovirus Central Nervous System Infection in Infancy, the Value of Routine Testing.

BACKGROUND: Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease. METHODS: Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation. RESULTS: Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis. CONCLUSION: EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters.

To screen or not to screen for asymptomatic bacteriuria in pregnancy: A comparative three-year retrospective review between two maternity centres.

BACKGROUND: Current national guidance in Ireland states that asymptomatic bacteriuria (AB) should be screened for at 12-16 weeks' gestation and treated with a seven-day course of antimicrobials, due to the potential risk of preterm birth and low birth weight infants (LBWI), however, this is based on low quality evidence. METHODS: Over a three-year period (2018-2020), a retrospective review was undertaken in two neighbouring maternity hospitals; one of which screens for AB (Rotunda hospital (RH)) and one which does not (National Maternity Hospital (NMH)). Patients were included on the basis of fulfilling the IDSA definition for pyelonephritis and requiring admission for intravenous antibiotics. Rates of antenatal pyelonephritis were compared between hospitals, and between screened and unscreened populations. Secondary outcomes including rates of preterm births and LBWI were compared across sites. RESULTS: A total of 47,676 deliveries between the two centres (24,768 RH; 22,908 NMH) were assessed, of which 158 patients met inclusion criteria for antenatal pyelonephritis (n = 88 RH, n = 70 NMH). There was no statistically significant difference in the rate of antenatal pyelonephritis (p = 0.34) or preterm births (p = 0.21) across sites. RH had a significantly higher rate of LBWI at 6.45% versus 5.68% of all births in NMH (p=<0.004). Given the screening rate in RH was below 100%, this cohort was further subdivided into 'RH screened' and 'RH unscreened'. There was no statistically significant difference in the rate of antenatal pyelonephritis both between the 'NMH unscreened' group (n = 70) versus the 'RH screened' group (n = 62) (p = 0.53), or in the 'RH screened' group (n = 62) versus the 'RH unscreened' group (n = 26) (p = 0.53). CONCLUSION: Omission of a screening programme for AB in NMH did not result in higher rates of antenatal pyelonephritis, preterm birth or LBWI. Our findings may inform decision-making on screening protocols and whether selective screening (i.e. screening in high-risk patients only) could be more cost-effective without compromising best quality of care.

Antenatal pyelonephritis: a three-year retrospective cohort study of two Irish maternity centres.

Pyelonephritis affects 1-2% of pregnant women, and is associated with significant maternal and fetal morbidity. Antenatal pyelonephritis has been associated with PPROM (preterm premature rupture of membranes), preterm labour, low birth weight (LBW) and prematurity. A three-year retrospective dual-centre cohort study of antenatal pyelonephritis cases was conducted in two neighbouring Irish maternity hospitals - the Rotunda Hospital (RH) and the National Maternity Hospital (NMH). Patient demographics, clinical presentation, investigations, management and maternal/neonatal outcomes were recorded. A total of 47,676 deliveries (24,768 RH; 22,908 NMH) were assessed. 158 cases of antenatal pyelonephritis were identified (n = 88 RH, n = 70 NMH), with an incidence of 0.33%. The median age was 28 years. The median gestation was 27 + 6 weeks, with 51% presenting before 28 weeks' gestation. Risk factors included; obesity (18.4%), diabetes mellitus (13.3%) and self-reported clinical history of recurrent urinary tract infection (28.5%). Rate of relapse with UTI in the same pregnancy was 8.2%. Renal ultrasound was performed in 30.4%. Predominant uropathogens were Escherichia coli (60%), Klebsiella pneumoniae (11%) and Proteus mirabilis (5%). 7.5% of cases had a concurrent bloodstream infection, 13.3% of cases were complicated by sepsis and 1.9% with septic shock. Complications including PPROM (6.3%), preterm delivery < 37 weeks' gestation (11%), LBW < 2,500 g (8.2%) were comparable between sites. Delivery within 72 hours of diagnosis was noted in 7% (n = 11) of patients, of which three were preterm and one had LBW. Appropriate and prompt investigation and management of antenatal pyelonephritis is essential given the associated maternal and neonatal morbidity.

Preparing for Group B Streptococcus vaccine. Attitudes of pregnant women in two countries.

Group B Streptococcus (GBS) vaccines, designed to be given to pregnant women, are in clinical trials. There is an opportunity to conduct preparatory research now to understand the drivers of and barriers to GBS vaccine acceptance. This will enable targeted interventions so that delays in vaccine uptake might be avoided. A multicenter, mixed-methodology, cross-sectional study evaluated the acceptability of a hypothetical GBS vaccine among pregnant women in two countries with differing health systems. Pregnant women in Philadelphia, US, and Dublin, Ireland, completed an electronic survey and a Discrete Choice Experiment. Five hundred and two women were included in the final analysis. Fifty-three percent of US and 30% of Irish participants reported both awareness and understanding of GBS. The median likelihood score for vaccine receipt (measured on a 10-point scale) was 9 (US: 9 (IQR 7-10), IRL: 9 (IQR 6-10)). Among the US participants, identifying as Black or African American was associated with a lower likelihood of vaccine receipt. Possession of a college degree was associated with increased likelihood of vaccine receipt. Perceived infant benefit was the most important driver of GBS vaccine acceptance. Safety concerns about a novel vaccine was the most prominent barrier identified. Good GBS vaccine uptake is achievable through strong messaging that highlights vaccine safety and the potential infant benefits. Preparation for vaccine implementation should include efforts to increase awareness among pregnant women about GBS infection and a continued focus on improving acceptability of currently recommended maternal vaccines, particularly in population subgroups with low uptake of maternal immunizations.

Redefining Clostridioides difficile infection antibiotic response and clinical outcomes.

With the approval and development of narrow-spectrum antibiotics for the treatment of Clostridioides difficile infection (CDI), the primary endpoint for treatment success of CDI antibiotic treatment trials has shifted from treatment response at end of therapy to sustained response 30 days after completed therapy. The current definition of a successful response to treatment (three or fewer unformed bowel movements [UBMs] per day for 1-2 days) has not been validated, does not reflect CDI management, and could impair assessments for successful treatment at 30 days. We propose new definitions to optimise trial design to assess sustained response. Primarily, we suggest that the initial response at the end of treatment be defined as (1) three or fewer UBMs per day, (2) a reduction in UBMs of more than 50% per day, (3) a decrease in stool volume of more than 75% for those with ostomy, or (4) attainment of bowel movements of Bristol Stool Form Scale types 1-4, on average, by day 2 after completion of primary CDI therapy (ie, assessed on day 11 and day 12 of a 10-day treatment course) and following an investigator determination that CDI treatment can be ceased.

Maternity care provider acceptance of a future Group B Streptococcus vaccine - A qualitative study in three countries.

INTRODUCTION: There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its' uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake. METHODS: This study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions. RESULTS: Thirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine. CONCLUSION: Maternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.

The full blood count in screening asymptomatic infants for early-onset sepsis: A cross-sectional study.

AIM: The full blood count (FBC) is commonly measured as part of a partial septic work-up in asymptomatic infants at increased risk of early-onset neonatal sepsis (EOS). To determine the impact of FBC parameters on infants' subsequent management a retrospective cross-sectional study was performed. METHODS: Infants, born at ≥34 weeks gestation, asymptomatic at birth, undergoing a partial septic work-up and receiving prophylactic antibiotics due to increased risk of EOS in a single centre over a 2-year period, were included. The primary outcome measure was frequency of FBC result impacting on duration of antibiotic therapy. Secondary outcome measures included frequency of FBC parameters outside of the reference range and incidental diagnoses. RESULTS: In total, 16 726 live-born infants were delivered during the study period. A total of 802 (4.8%) were included. Thirteen infants (1.6%) received a prolonged course of antibiotics due to suspicion for EOS. Two of these infants had elevated white cell counts. All had normal neutrophil counts. In no case did the FBC result influence the decision to prolong the antibiotic course. CONCLUSION: In a cohort of 802 infants, asymptomatic at birth and at increased risk of EOS, the FBC result did not impact on the decision to prolong the course of antibiotics for suspicion of EOS.

Haemophilus influenzae type f in the post-Haemophilus influenzae type b vaccination era: a systematic review.

Since the introduction of Haemophilus influenzae (Hi) serotype b (Hib) vaccination, reports of increasing incidence rates of non-Hib serotypes have emerged. A systematic review was performed to investigate whether the Hi serotype f (Hif) incidence rate has increased globally and to describe its associated disease burden. In the post-Hib vaccine era, evidence shows that the incidence rate of Hif infection is increasing worldwide. In total 94 studies including 2 701 patients reported Hif infections. The estimated pooled incidence rate of Hif infection was 0.15/100 000 population per year (range: 0.05-0.40/100 000), with a median case fatality ratio of 14.3 %. Invasive infections most frequently presented as pneumonia (45 %), septicaemia (34 %) and meningitis (20 %). Of 191 Hif isolates, 87 % were ampicillin-susceptible. Multi-locus sequence typing revealed that Hif were relatively clonal, with the majority belonging to clonal complex 124. Hif causes invasive infections of significant variance in both severity and presentation. Globally, the Hif population shows little genetic variability and currently appears to possess low resistance to antimicrobials.

How to: Clostridioides difficile infection in children.

BACKGROUND: Clostridioides difficile infections (CDI) are traditionally attributed to an older adult patient group but children can also be affected. Although the causative pathogen is the same in both populations, the management of CDI may differ. OBJECTIVES: To discuss the current literature on CDI in the paediatric population and to provide CDI diagnostics and treatment guidance. SOURCES: The literature was drawn from a search of PubMed from January 2017 to July 2021. CONTENT: In the paediatric population, laboratory diagnostics for CDI should preferably be combined with laboratory diagnostics for other gastrointestinal pathogens. Coinfections of CDI are also possible. Though the detection of toxigenic C. difficile using a molecular assay may simply reflect colonisation rather than infection, detection of C. difficile free toxins A/B in faeces is much more indicative of true infection. CDI in children below 2 years of age and in the absence of risk factors is very difficult to diagnose and requires careful clinical judgement pending additional studies. Fidaxomicin has been shown to be superior to vancomycin with a sustained clinical response up to 30 days after the end of CDI treatment in children. Metronidazole is less effective than vancomycin in adults and there are no supporting data for its use in children. In recurrent CDI, treatment should be adjusted according to the drug or drug regimen used for the treatment of a previous episode(s). In multiple recurrent CDI, faecal microbiota transplantation can be effective. IMPLICATIONS: If CDI laboratory testing is indicated in children with diarrhoea, the likelihood of C. difficile colonisation and coinfection with other intestinal pathogens should be considered. The currently available data support a change in the treatment strategy of CDI in children.

Infant Escherichia coli urinary tract infection: is it associated with meningitis?

OBJECTIVES: Determine the prevalence of coexisting bacterial meningitis (BM) and sterile cerebrospinal fluid (CSF) with raised white cell count relative to age ('pleocytosis') in the presence of Escherichia coli urinary tract infection (UTI), with the addition of CSF E. coli PCR analysis. DESIGN: Single-centre, retrospective cohort study. SETTING: Tertiary paediatric hospital. PARTICIPANTS: Children aged 8 days to 2 years, with a pure growth of E. coli from urine and a CSF sample taken within 48 hours of a positive urine culture between 1 January 2014 and 30 April 2019. MAIN OUTCOME MEASURE: Prevalence of coexisting E. coli BM with UTI, defined as a pure growth E. coli from urine and a CSF culture with pure growth E. coli and/or positive E. coli PCR. RESULTS: 1903 patients had an E. coli UTI, of which 314 (16%) had a CSF sample taken within 48 hours. No cases of coexisting E. coli BM were identified. There were 71 (23%) cases of pleocytosis, 57 (80%) of these had PCR analysis, all of which were E. coli PCR not detected. Patients aged 1-6 months accounted for 72% of all lumbar punctures (LPs). CONCLUSION: The risk of E. coli UTI and coexisting E. coli BM is low. There is potential to reduce the number of routine LPs in infants with a diagnosis of E. coli UTI with the greatest impact in children up to 6 months of age. CSF E. coli PCR can help further reduce post-test probability of BM in the setting of pleocytosis.

Neurological involvement in children with hemolytic uremic syndrome.

Our objective was to establish the rate of neurological involvement in Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS) and describe the clinical presentation, management and outcome. A retrospective chart review of children aged ≤ 16 years with STEC-HUS in Children's Health Ireland from 2005 to 2018 was conducted. Laboratory confirmation of STEC infection was required for inclusion. Neurological involvement was defined as encephalopathy, focal neurological deficit, and/or seizure activity. Data on clinical presentation, management, and outcome were collected. We identified 240 children with HUS; 202 had confirmed STEC infection. Neurological involvement occurred in 22 (11%). The most common presentation was seizures (73%). In the neurological group, 19 (86%) were treated with plasma exchange and/or eculizumab. Of the 21 surviving children with neurological involvement, 19 (91%) achieved a complete neurological recovery. A higher proportion of children in the neurological group had renal sequelae (27% vs. 12%, P = .031). One patient died from multi-organ failure.Conclusion: We have identified the rate of neurological involvement in a large cohort of children with STEC-HUS as 11%. Neurological involvement in STEC-HUS is associated with good long-term outcome (complete neurological recovery in 91%) and a low case-fatality rate (4.5%) in our cohort. What is Known: • HUS is associated with neurological involvement in up to 30% of cases. • Neurological involvement has been reported as predictor of poor outcome, with associated increased morbidity and mortality. What is New: • The incidence of neurological involvement in STEC-HUS is 11%. • Neurological involvement is associated with predominantly good long-term outcome (90%) and a reduced case-fatality rate (4.5%) compared to older reports.

Evaluation of molecular testing for Mycoplasma genitalium for symptomatic women.

Mycoplasma genitalium is an emerging cause of sexually transmitted infections (STI) with a capacity to rapidly develop antibiotic resistance. The aim of this work was to carry out an evaluation and descriptive analysis of routine molecular testing of M. genitalium in symptomatic women at the Rotunda Hospital, Dublin January 2018-December 2019. 1972 specimens were tested from1291 individual symptomatic female patients > 18 years old. The median age was 29 (range 18-71). There were 10 confirmed positive specimens (0.77%); median patient age 26 (range 18-34); seven were obstetrics/gynaecology patients and three were attendees at a sexual assault treatment unit (SATU). The prevalence of positive cases in the ≥ 18 ≤ 30-year-old age group (n = 683) was six times that of the ≥ 30 year-old age group (n = 608) at 1.3% versus 0.2%. Patient symptoms included: discharge in five (50%); pelvic pain on examination in five (50%); abdominal pain in two (20%); pelvic bleeding in two (20%); dyspareunia in two (20%) patients. Co-infections were present in three patients (30%). Macrolide resistance was detected in two positives (28.6%). This initial pilot study prompts the following recommendations which require further study and consideration: 1. promotion of M. genitalium status to notifiable disease; 2 widespread screening of female population not warranted; 3. M. genitalium testing for women symptomatic for STIs; 4. antibiotic resistance testing of all positive cases. 5. Further research into other potential risk groups.

The Effect of COVID-19 Infection During Pregnancy; Evaluating Neonatal Outcomes and the Impact of the B.1.1.7. Variant.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection during pregnancy has been associated with adverse perinatal outcomes. We aim to evaluate the neonatal outcomes including the incidence of preterm birth, admission to the neonatal unit and incidence of congenital anomalies in this cohort. We will also describe these outcomes in the context of the B.1.1.7. variant outbreak, the dominant variant in Ireland since January 2021, which has had a greater impact on pregnant patients. METHODS: This was a retrospective study of liveborn infants, delivered between 1st March 2020 and 1st March 2021, to women with a severe acute respiratory syndrome coronavirus 2 diagnosis during pregnancy, in a tertiary maternity hospital (8,500 deliveries/year). Clinical data were collected, and analyses were performed to evaluate the impact of maternal symptom status, time from diagnosis to delivery and the B.1.1.7. variant on neonatal outcome. RESULTS: In total 133 infants (1.6%) were born to women with severe acute respiratory syndrome coronavirus 2 identified during pregnancy. The median birth weight was 3.45 kg and gestational age at birth was 39.3 weeks. 14 infants (10.5%) were preterm. 22 infants (16.5%) required admission to the neonatal unit and 7 (5.3%) were small for gestational age. There was no difference in growth, preterm birth or neonatal unit admission based on maternal symptom status or infection after the outbreak of B.1.1.7. as the dominant strain. CONCLUSIONS: Following a COVID-19 infection in pregnancy, there was no increase in the incidence of preterm birth or neonatal intensive care unit admission compared with 5-year hospital data. Maternal symptom status did not influence neonatal outcomes. Further studies to evaluate the impact of COVID-19 in early pregnancy, the variants of concern, particularly the emerging Delta variant and COVID-19 placentitis are required.

A Systematic Review of Clinical Prediction Rules to Predict Hospitalisation in Children with Lower Respiratory Infection in Primary Care and their Validation in a New Cohort.

Background: Our goal was to identify existing clinical prediction rules for predicting hospitalisation due to lower respiratory tract infection (LRTI) in children in primary care, guiding antibiotic therapy. A validation of these rules was then performed in a novel cohort of children presenting to primary care in Malawi with World Health Organisation clinically defined pneumonia. Methods: MEDLINE & EMBASE databases were searched for studies on the development, validation and clinical impact of clinical prediction models for hospitalisation in children with lower respiratory tract infection between January 1st1946-June 30th 2021. Two reviewers screened all abstracts and titles independently. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews & Meta-Analyses guidelines. The BIOTOPE cohort (BIOmarkers TO diagnose PnEumonia) recruited children aged 2-59 months with WHO-defined pneumonia from two primary care facilities in Mzuzu, Malawi. Validation of identified rules was undertaken in this cohort. Findings: 1023 abstracts were identified. Following the removal of duplicates, a review of 989 abstracts was conducted leading to the identification of one eligible model. The CHARMS checklist for prediction modelling studies was utilized for evaluation. The area under the curve (AUC) of the STARWAVe rule for hospitalisation in BIOTOPE was found to be 0.80 (95% C.I of 0.75-0.85). The AUC of STARWAVe for a confirmed diagnosis of bacterial pneumonia was 0.39 (95% C.I 0.25-0.54). Interpretation: This review highlights the lack of clinical prediction rules in this area. The STARWAVe rule identified was useful in predicting hospitalisation from bacterial infection as defined. However, in the absence of a gold standard indicator for bacterial LRTI, this is a reasonable surrogate and could lead to reductions in antibiotic prescription rates, should clinical impact studies prove its utility. Further work to determine the clinical impact of STARWAVe and to identify diagnostic tests for bacterial LRTI in primary care is required.

Haematological parameters and coagulation in umbilical cord blood following COVID-19 infection in pregnancy.

OBJECTIVE: The aim of this study was to evaluate infants, born to women with SARS-CoV-2 detected during pregnancy, for evidence of haematological abnormalities or hypercoagulability in umbilical cord blood. STUDY DESIGN: This was a prospective observational case-control study of infants born to women who had SARS-CoV-2 RNA detected by PCR at any time during their pregnancy (n = 15). The study was carried out in a Tertiary University Maternity Hospital (8,500 deliveries/year) in Ireland. This study was approved by the Hospital Research Ethics Committee and written consent was obtained. Umbilical cord blood samples were collected at delivery, full blood count and Calibrated Automated Thrombography were performed. Demographics and clinical outcomes were recorded. Healthy term infants, previously recruited as controls to a larger study prior to the outbreak of COVID-19, were the historical control population (n = 10). RESULTS: Infants born to women with SARS-CoV-2 had similar growth parameters (birth weight 3600 g v 3680 g, p = 0.83) and clinical outcomes to healthy controls, such as need for resuscitation at birth (2 (13.3%) v 1 (10%), p = 1.0) and NICU admission (1 (6.7%) v 2 (20%), p = 0.54). Haematological parameters (Haemoglobin, platelet, white cell and lymphocyte counts) in the COVID-19 group were all within normal neonatal reference ranges. Calibrated Automated Thrombography revealed no differences in any thrombin generation parameters (lag time (p = 0.92), endogenous thrombin potential (p = 0.24), peak thrombin (p = 0.44), time to peak thrombin (p = 0.94)) between the two groups. CONCLUSION: In this prospective study including eligible cases in a very large population of approximately 1500 women, there was no evidence of derangement of the haematological parameters or hypercoagulability in umbilical cord blood due to COVID-19. Further research is required to investigate the pathological placental changes, particularly COVID-19 placentitis and the impact of different strains of SARS-CoV-2 (particularly the B.1.1.7 and the emerging Delta variant) and the severity and timing of infection on the developing fetus.

Epidemiological typing of methicillin resistant Staphylococcus aureus recovered from patients attending a maternity hospital in Ireland 2014-2019.

It has previously been reported that maternity hospitals have lower levels of MRSA compared to other healthcare facilities, due to the patient population - mostly healthy patients with limited healthcare contact. In this epidemiological study, all MRSA isolates recovered from patients attending a maternity hospital from 2014 - 2019 were investigated. 171 isolates from adults (n=120) and babies (n=51) from diagnostic and screening investigations were submitted to the National MRSA Reference Laboratory (NMRSARL). Investigations included: spa typing, antimicrobial susceptibility testing, detection of the mecA/mecC genes and lukS-PV and lukF-PV. All were susceptible to glycopeptides, linezolid, rifampicin and mupirocin, while 29 of 171 (17%) were resistant to ß-lactam agents only. Thirteen isolates (8%) were resistant to two classes of antibiotic; one resistant to three. All isolates harboured mecA and 33 of 171 (19%) harboured PV-lukF/S. Among the collection, 21 multilocus sequence types (ST) were inferred from 63 spa types. EARS-NET data shows that ST22-MRSA-IV accounts for approximately 75% of MRSA recovered in Irish hospitals. Here, it accounted for only 25.7%. MLST types associated with community acquired MRSA accounted for the remaining 74.3%. These included ST8, ST30, ST1, ST5 and ST88, suggesting a diverse population, harbouring multiple resistance and virulence genes, some of which have been previously associated with outbreaks in Ireland. This study exposes a reservoir of MRSA in the community which may be imported into hospitals, leading to outbreaks. The diversity of MRSA lineages with enhanced virulence factors highlights the need for regular surveillance to ensure appropriate infection prevention and control interventions are implemented promptly.

Aetiology and severity of childhood pneumonia in primary care in Malawi: a cohort study.

OBJECTIVE: To determine the aetiology of community acquired pneumonia in children presenting to primary care in Northern Malawi, and to ascertain predictors for identification of children requiring hospitalisation. DESIGN: The BIOmarkers TO diagnose PnEumonia study was a prospective cohort study conducted from March to June 2016. SETTING: Primary care in Northern Malawi. PATIENTS: 494 children aged 2 -59 months with WHO defined pneumonia. MAIN OUTCOMES AND MEASURES: Number of children with bacterial infection identified and the sensitivity/specificity of WHO markers of severity for need for hospitalisation. RESULTS: 13 (2.6%) children had a bacterium consistent with pneumonia identified. A virus consistent with pneumonia was identified in in 448 (90.7%) of children. 56 children were admitted to hospital and two children died within 30 days. 442 (89.5%) received antibiotic therapy. Eleven children (2.6%) had HIV. WHO severity markers at baseline demonstrated poor sensitivity for the need for hospitalisation with a sensitivity of 0.303 (95% CI 0.188 to 0.441) and a specificity 0.9 (95% CI 0.868 to 0.926). A prediction rule to indicate the need for hospitalisation was developed. CONCLUSIONS AND RELEVANCE: The low rate of bacterial infection and high use of antibiotics in the setting of high immunisation rates highlights the changing profile of childhood pneumonia. Similarly, the markers of need for hospitalisation may have changed in the setting of extended immunisation. Further studies are required to examine this.