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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 di-agnostics 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. (C) 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

OBJECTIVE To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening. DESIGN Retrospective study and model-based economic evaluation. SETTING Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection. POPULATION Pregnant women who had been tested for hepatitis B, HIV but not HCV. METHODS Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis. MAIN OUTCOME MEASURES Presence of HCV antigen and cost per quality-adjusted life year (QALY). RESULTS In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained. CONCLUSION This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population. TWEETABLE ABSTRACT Universal maternal screening for hepatitis C is cost-effective in this urban Irish population.

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.

The aim of this study was to examine the risk factors for pharyngeal carriage of meningococci in third-level students using an unsupervised machine learning approach. Data were gathered as part of meningococcal prevalence studies conducted by the Irish Meningitis and Sepsis Reference Laboratory (IMSRL). Pharyngeal swab cultures for meningococcal carriage were taken from each student once they had completed a single-page anonymous questionnaire addressing basic demographics, social behaviors, living arrangements, vaccination, and antibiotic history. Data were analyzed using multiple correspondence analysis through a machine learning approach. In total, 16,285 students who had a pharyngeal throat swab taken returned a fully completed questionnaire. Overall, meningococcal carriage rate was 20.6%, and the carriage of MenW was 1.9% (n = 323). Young Irish adults aged under 20 years and immunized with the meningococcal C vaccine had a higher MenW colonization rate (n = 171/1260, 13.5%) compared with non-Irish adults aged 20 years or older without the MenC vaccine (n = 5/81, 6%, chi-square = 3.6, p = .05). Unsupervised machine learning provides a useful technique to explore meningococcal carriage risk factors. The issue is very complex, and asked risk factors only explain a small proportion of the carriage. This technique could be used on other conditions to explore reasons for carriage.

Introduction Bacteraemia in pregnancy and the post-partum period can lead to maternal and newborn morbidly. The purpose of this study was to use machine learning tools to identify if bacteraemia in pregnant or post-partum women could be predicted by full blood count (FBC) parameters other than the white cell count. Methods The study was performed on 129 women with a positive blood culture (BC) for a clinically significant organism, who had a FBC taken at the same time. They were matched with controls who had a negative BC taken at the same time as a FBC. The data were split in to a training (70%) and test (30%) data set. Machine learning techniques such as recursive partitioning and classification and regression trees were used. Results A neutrophil/lymphocyte ratio (NLR) of >20 was found to be the most clinically relevant and interpretable construct of the FBC result to predict bacteraemia. The diagnostic accuracy of NLR >20 to predict bacteraemia was then examined. Thirty-six of the 129 bacteraemia patients had a NLR >20, while only 223 of the 3830 controls had a NLR >20. This gave a sensitivity of 27.9% (95% CI 20.3-36.4), specificity of 94.1% (93.3-94.8), positive predictive value of 13.9% (10.6-17.9) and a negative predictive value (NPV) of 97.4% (97.2-97.7) when the prevalence of bacteraemia was 3%. Conclusion The NLR should be considered for use in routine clinical practice when assessing the FBC result in patients with suspected bacteraemia during pregnancy or in the post-partum period.

Antimicrobial prophylaxis is widely recommended for pregnant women who have preterm premature rupture of the membranes. Erythromycin prophylaxis was used during an initial period (control) and then changed to intravenous amoxicillin for 48 h, followed by 5 days of oral amoxicillin along with a single dose of azithromycin (case). Healthcare records were reviewed retrospectively. The primary outcome was latency (between membrane rupture and delivery) and the secondary outcomes were mode of delivery, maternal high dependency unit (HDU) admission, and several laboratory parameters. There were 78 women in the case group (amoxicillin and azithromycin) and controls were selected on a 1:1 ratio. There was no statistically significant difference between cases and controls with respect to group B Streptococcus or E.coli carriage, previous preterm birth, assissted fertility and parity. No babies had a positive blood culture with Group B Streptococcus. There was a longer latency to delivery for those prescribed amoxicillin and azithromycin (median = 5.5 days), compared with controls on erythromycin (median = 2 days, p < .001). There was no difference in the mode of delivery or maternal HDU admission. Given the potential sequelae of preterm birth, this warrants further prospective investigation in a randomised control trial. IMPACT STATEMENT What is already known on this subject? Antimicrobial prophylaxis is recommended for women who have preterm premature rupture of the membranes (PPROM). It has been shown to increase latency of delivery. However there are different regimens recommended in North America (amoxicillin and a macrolide) and the United Kingdom (macrolide monotherapy). What do the results of this study add? This study has shown that in our population, women who were prescribed the PPROM regimen of amoxicillin with azithromycin had a longer median latency from time of rupture of membranes to delivery, than women in a historical control group who were prescribed erythromycin monotherapy. What are the implications of these findings for clinical practice and/or further research? This retrospective study has shown that there may be a difference in latency between different antimicrobial prophylaxis regimens for PPROM. A randomised control trial, with sufficient patient numbers, is needed to determine the best regimen for prophylaxis, and would allow harmonisation of international guidelines.

The purpose of this study was to investigate H. influenzae epidemiology in the Republic of Ireland. We performed serotyping, multi-locus sequence typing (MLST) and susceptibility testing on H. influenzae isolates received by the Irish Meningitis and Sepsis Reference Laboratory from 2010 to 2018. Three hundred sixty-seven invasive and 41 non-invasive infection (NII) isolates were received. Invasive isolates were mostly recovered from paediatric (21%) and elderly (42%) populations. Invasive disease was more prevalent in females of childbearing age (72%) compared with males the same age (28%). Non-typeable H. influenzae (NTHi) predominated among invasive (83%) and NII (95%). Invasive Hib disease isolates were infrequent (4%, n = 15). Among invasive disease, Hif was the commonest encapsulated serotype (10%, n = 37), and the only encapsulated serotype detected in NII (5%, 2/41). The first PCR-confirmed serotypes d and a in Ireland were characterised among invasive disease in 2017 and 2018, respectively. MLST revealed a diverse NTHi population, while encapsulated serotypes were clonal. Sequence type (ST) 103 (n = 14) occurred exclusively in invasive NTHi disease. Ampicillin resistance (AmpR) was 18% among invasive isolates and 22% in NII. β-Lactamase production was the main source of ampicillin resistance in invasive and NII isolates. We detected β-lactamase negative ampicillin resistance (BLNAR) among invasive isolates. We report an NTHi fluoroquinolone-resistant clone: ST1524 among invasive (n = 2) and NII isolates (n = 2). The Hib vaccine has positively impacted on Hib disease in Ireland, given the low frequency of Hib. The dominance of NTHi, emergence of serotypes a and d and BLNAR suggest a changing H. influenzae epidemiology in Ireland.

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.

ObjectiveTo 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.DesignThe BIOmarkers TO diagnose PnEumonia study was a prospective cohort study conducted from March to June 2016.SettingPrimary care in Northern Malawi.Patients494 children aged 2 –59 months with WHO defined pneumonia.Main outcome(s) and measure(s)Number of children with bacterial infection identified and the sensitivity/specificity of WHO markers of severity for need for hospitalisation.Results13 (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 relevanceThe 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.

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.

Public health experts agree that pregnant women who fall into priority groups may be offered a Coronavirus Disease 2019 (COVID-19) vaccine. However, little is known about attitudes of pregnant women toward COVID-19 vaccination. We surveyed 300 pregnant women during the roll out of the Pfizer-BioNTech vaccine in Ireland. Women rated likelihood of receipt of a vaccine during pregnancy, on a 1–10 scale (1 = very unlikely, 10 = very likely). One hundred and thirteen (38%) women responded with a score of ≥8, while a similar proportion (36%) selected a score of ≤2. Safety of their unborn infant was the primary driver of decision making among survey participants, but specific safety concerns differed according to likely acceptance of a vaccine. Communication about COVID-19 vaccines to pregnant women must explicitly address safety. Pregnant women and their health-care providers should be supported with accessible interpretations of data so that they can make the best choice for their individual risk profile.

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 ofSingle-centre, retrospective cohort study.Tertiary paediatric hospital.Children aged 8 days to 2 years, with a pure growth ofPrevalence of coexisting1903 patients had anThe risk of

Objectives: The purpose of this study was to examine the aetiology, investigation and management of ophthalmia neonatorum (ON) presenting to a tertiary referral children’s hospital over 5 years. Methods: The eye swab data of all neonates presenting to Children’s Health Ireland at Temple Street (Dublin, Ireland) between 1st January 2013 and 3rd September 2018 was analysed. The medical records of all patients with positive eye swab results were retrospectively reviewed. Results: A total of 157 neonates had positive eye swab results. 54 cases were identified as ON. Chlamydia trachomatis (20.4%) was the most common organism identified, followed by Staphylococcus aureus (18.5%), Haemophilus influenzae (14.8%), Moraxella catarrhalis (7.4%), Streptococcus pneumoniae (5.6%), Escherischia coli (3.7%), Klebsiella pneumoniae (1.9%) and Pseudomonas aeruginosa (1.9%). A bacterial culture swab was tested in all cases (100%), a C. trachomatis/N. gonorrhoeae PCR swab in 70.4% and a viral PCR swab in 35.2%. On subanalysis of the cases that had C. trachomatis/N. gonorrhoeae PCR testing, C. trachomatis was responsible for 28.9% of cases. 50% of cases were hospitalised, intravenous antibiotics were administered in 46.3% and macrolide therapy was prescribed in 38.9%. Conclusions: C. trachomatis was the most common cause of ON in this study and may be responsible for an even higher proportion of cases due to incomplete testing. In keeping with studies in different populations, S. aureus, H. influenzae and S. pneumoniae were also common. As a result, an improved management algorithm for cases of ON has been introduced in this centre.

Objectives: The genomic epidemiology of group b streptococcus (GBS) isolates from the Rotunda maternity hospital, Dublin, 2008-2017, was investigated. Methods: Whole genome sequences of isolates (invasive, n = 114; non-invasive, n = 76) from infants and women were analysed using the PubMLST database (https://pubmlst.org/sagalactiae/). Results: Serotypes III (36%), Ia (18%), V (17%), II (11%) and Ib, (9%) and sequence types (ST) 17 (23%), ST-23 (14%), ST-1 (12%) and ST-19 (7%) were most common. Core genome MLST (cgMLST) differentiated isolates of the same ST, grouped STs into five lineages congruent with known clonal complexes and identified known mother-baby pairs and suspected linked infant cases. Clonal complex (CC) 17 accounted for 40% and 22% of infant and maternal invasive cases, respectively and 21% of non-invasive isolates. CC23 and CC19 were associated with maternal disease (30%) and carriage (24%), respectively. Erythromycin (26%) and clindamycin (18%) resistance increased over the study period and was associated with presence of the erm(B) gene (55%), CC1 (33%) and CC19 (24%). A multi-resistant integrative conjugative element incorporated in the PI-1 locus was detected in CC17, an ST-12 and ST-23 isolate confirming the global dissemination of this element. All isolates possessed one or more pilus islands. Genes encoding other potential protective proteins including Sip, C5a peptidase and Srr1 were present in 100%, 99.5% and 65.8% of isolates, respectively. The srr2 gene was unique to CC17. Conclusions: The PubMLST.org website provides a valuable framework for genomic GBS surveillance to inform on local and global GBS epidemiology, preventive and control measures.

Background: Early onset group B streptococcal (GBS) disease can cause significant neonatal morbidity and mortality. There is currently no Irish national guideline for GBS screening, and protocols vary across maternity units. Polymerase chain reaction (PCR) testing at induction or labour onset informs triage for antibiotic prophylaxis; however, there are human and infrastructural resource requirements to enable widespread implementation. Aim: Our aim was to identify current standard practices for GBS prevention in Irish obstetric and neonatal services and to utilise this data to inform the need for, and potential impact of implementation of, a national guideline. Methods: A questionnaire on GBS screening, management and existing resources was completed by an informed staff member from each of the 19 Irish maternity units, including questions regarding timing and method of screening, antibiotic usage, and neonatal management. Results: One unit (5.2%) performs routine GBS screening at 35–37 weeks of gestation. Twelve units (63%) screen for GBS following spontaneous rupture of membranes (SROM) after 37 weeks, of which two (17%) perform PCR and ten (83%) culture testing. Seventeen units (89.3%) have access to a GeneXpert PCR machine, and of these, two (11.7%) use the machine for rapid GBS testing. Two units screen patients for GBS at either the start of labour or induction of labour. Four units (21%) use the neonatal early onset sepsis (EOS) calculator. Sixteen units (84%) do not treat asymptomatic infants born to GBS-positive mothers. Conclusion: There is a lack of consistency in the methods for GBS screening and disease prevention across the country, highlighting the need for a national guideline accompanied by an implementation plan and budget to standardise care.

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.

Culture yield in osteomyelitis and septic arthritis is low, emphasising the role for molecular techniques. The purpose of this study was to review the laboratory investigation of childhood osteomyelitis and septic arthritis. A retrospective review was undertaken in an acute tertiary referral paediatric hospital from January 2010 to December 2016. Cases were only included if they had a positive culture or bacterial PCR result from a bone/joint specimen or blood culture, or had radiographic evidence of osteomyelitis. Seventy-eight patients met the case definition; 52 (66%) were male. The median age was 4.8 years. Blood cultures were positive in 16 of 56 cases (29%), with 11 deemed clinically significant (Staphylococcus aureus = 8, group A Streptococcus = 3). Thirty-seven of 78 (47%) bone/joint samples were positive by culture with S. aureus (n = 16), coagulase-negative Staphylococcus (n = 9) and group A Streptococcus (n = 4), being the most common organisms. Sixteen culture-negative samples were sent for bacterial PCR, and four were positive (Kingella kingae = 2, Streptococcus pneumoniae = 1, group A Streptococcus = 1). Sequential culture and PCR testing can improve the detection rate of causative organisms in paediatric bone and joint infections, particularly for fastidious microorganisms such as K. kingae. PCR testing can be reserved for cases where culture is negative after 48 h. These results have been used to develop a standardised diagnostic test panel for bone and joint infections at our institution.

Summary Objectives Group A streptococcus (GAS) is responsible for mild to very severe disease. The epidemiology of an upsurge in invasive GAS (iGAS) infections in Ireland, 2012–2015 was investigated. Methods Epidemiological typing of iGAS (n = 473) isolates was performed and compared to non-invasive (n = 517) isolates. Clinical data of notified iGAS was obtained from the national infectious disease information system. Results Annual incidences of iGAS cases (n = 561) were 2.33–3.66 per 100,000 population. Bacteraemia was the most common clinical presentation (75%) followed by focus without bacteraemia (19%) and necrotizing faciitis (7%). Streptococcal toxic shock syndrome occurred in 19% of presentations. The main invasive emm types in rank order were emm1, emm3, emm28, emm12 and emm89 whereas emm4, emm28, emm3, emm12, emm89 and emm1 predominated in non-invasive infections. Invasive emm1 and emm3 showed annual fluctuations (15–48% and 4–37%, respectively) and predominated in most clinical presentations of iGAS. Superantigens speA, speG, speJ was associated with iGAS disease and, speC, speI and ssa with non-invasive infections. There was 4.3% erythromycin and 5.6% tetracycline resistance. The main resistant types were emm11, emm28 and emm77. Conclusions Cyclic increases in emm1 and emm3 occurred during the iGAS upsurge. Continued surveillance of GAS is therefore essential given the epidemiological changes that occur in a short time period.

Rubella is caused by the rubella virus, a single-stranded RNA virus of the Togaviridae family. The most severe complications of rubella in adult women occur during pregnancy when infection can lead to miscarriage, stillbirth or congenital rubella syndrome. Antenatal rubella susceptibility screening is no longer performed in England, Scotland or Wales but continues in Northern Ireland. The aims of this seroprevalence study were to (1) determine amongst women presenting for antenatal care the percentage of women who are rubella susceptible, rubella immune and those with equivocal rubella antibody levels by year of birth and (2) to consider how rubella vaccination resources can best be utilised. A retrospective study was performed analysing all antenatal rubella IgG antibody tests performed between January 2015 and June 2017 inclusive (n = 19,000; excluding duplicate tests). All antenatal women were included regardless of the country of origin and age. From our analysis, 88.7% (n = 16,868) women had plasma concentrations of anti-rubella IgG > 10 IU/ml. 7.3% of women (n = 1403) had rubella IgG levels between 5 and 9.99 IU/ml, and 2.8% (n = 729) had IgG levels

The aim of this retrospective study was to review the diagnostic accuracy of real-time polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) samples for Streptococcus pneumoniae DNA in comparison with traditional bacterial culture. The hypothesis was that PCR is more sensitive than culture and would detect more cases of pneumococcal meningitis, particularly in children treated with antimicrobials before CSF sampling occurred. Patients younger than 16 years of age who had a CSF sample tested for S. pneumoniae DNA by PCR between 2004 and 2015 were included. A total of 2025 samples were included, and the PCR had a sensitivity of 100% and specificity of 98% for the detection of S. pneumoniae DNA in comparison with culture. Of the 28 culture negative/PCR positive cases, 25 (89%) were probable meningitis cases and only 3 (11%) were suspected false positive results. Nineteen (76%) of the 25 probable cases required ICU admission, and 3 died (12%). Six different serotypes were found in the culture positive patients (18C, 6B, 14, 22F, 7F and 33F). This study demonstrates that PCR testing of CSF samples for S. pneumoniae is sensitive and specific when compared with culture. PCR is particularly useful in detecting those cases where culture is negative, perhaps relating to pre-CSF sampling administration of antimicrobials.

This pilot study assessed the diagnostic accuracy and potential impact of a rapid PCR-based screening test for the detection of group B Streptococcus (GBS) at the onset of labour for the purpose of optimising intrapartum antibiotic prophylaxis (IAP). Vaginal and rectal swabs from a convenience sample of 158 women were analysed by conventional broth-enriched culture and a rapid PCR test. Overall, GBS carriage was 18.98% by culture and 19.62% by PCR. PCR for the detection of GBS had a sensitivity of 93.1%, specificity of 96.67% and area under the curve (AUC) of 0.95. Only 19.3% GBS-positive women received IAP. Three-fourths of babies born to GBS-positive mothers did not receive surveillance for early-onset GBS disease. Of the women who received IAP, only 32.5% were GBS carriers. Seventy-four percent of the GBS-positive mothers delivered more than 5 h after recruitment, which gives adequate swab to delivery interval for appropriate antibiotic prophylaxis in labour. Impact statement What is already known about this subject: Appropriate intra-partum treatment of colonized mothers reduces the risk of GBS transmission to neonates. Universal ante partum screening of pregnant women or IAP based on risk factors in labour for GBS prevention fail to accurately identify and treat the woman who actually harbors GBS in the birth canal in labour. A PCR based rapid test, allows for real-time assessment of GBS carriage in labour.This study highlights the fact that a large number of GBS carriers in labour, who could potentially infect their babies, do not receive IAP, and most of their babies do not receive added surveillance in the neonatal period for EOGBS disease. It also confirms that PCR testing at onset of labour is a highly sensitive and reliable test that identifies the women who are GBS carriers in labour and hence need IAP. What the implications are of these findings for clinical practice and/or further research: Timely provision of IAP for the appropriate woman is possible by adopting universal GBS screening at the onset of labor using GBS-PCR. This would involve additional costs to health care facilities and added work to laboratory personnel.

Rotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains. This study was a collaboration between the Temple Street Children’s University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital. In the 2015/2016 period (July 2015–June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised. The results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%). This distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

The aim of this project was to assess the implementation of a quality improvement project regarding the introduction of on-site influenza PCR testing in a stand-alone obstetric hospital.As part of a quality improvement project on the management of influenza in obstetric patients, the Xpert Flu assay (Cepheid Inc., Sunnyvale, CA) was introduced on-site and it replaced the previous method of PCR testing which was off-site. The main outcome measures were duration of antimicrobials, rate of admission and administration of oseltamavir in the emergency department.Twenty-eight patients were included in the pre-intervention period and 45 patients were included in the post-intervention period. Following the introduction of the test, there was a statistically significant reduction seen in commencement of antimicrobials (76% pre- and 33% post-intervention), and also rate of admission (88% pre- and 45% post-intervention) while there was a statistically significant improvement in the commencement of oseltamavir in the emergency department (72% pre-and 95% post-intervention) (p .01 for all outcomes).Introduction of on-site rapid influenza PCR testing can lead to a significant improvement in patient management and should be considered for introduction to other sites.

Allplex Bacterial vaginosis assay (Seegene, South Korea) is a molecular test for bacterial vaginosis (BV). A machine learning algorithm was devised on 200 samples (BV = 23, non-BV = 177) converting 7 identified bacterial strains polymerase chain reaction results to binary output of BV detected or not. Comparing algorithm interpretation of molecular results to the consensus Gram stain (Hay's criteria), the sensitivity was 65% [95% confidence interval (CI) 42–83%], specificity was 98% (95% CI 95–99%), positive predictive value was 83% (95% CI 58–96%), and negative predictive value was 95% (91–98%) with area under the curve of 0.82 (95% CI 0.76–0.87). For the second phase, 100 samples were processed using the 2 techniques in parallel, with the scientists blinded to the result of the other method. There was agreement 90% of the cases (n = 90/100). The samples that were called BV by the algorithm but non-BV by Gram stain all cluster with the concordant BV samples, suggesting that the molecular test was correct.

Group B Streptococcus (GBS) is the most common cause of early-onset neonatal sepsis and meningitis. In babies with no clinical suspicion of infection, who are at risk of early-onset invasive disease based on maternal risk factors, blood cultures are taken to detect bacteraemia. In our institution, lumbar punctures are performed in infants with clinical signs of sepsis but not in infants who are well at the time of screening. Between 2001 and 2014, there were 112,361 live births weighing >500 g, of whom 13,959 (12.4%) infants had a blood culture taken on the first or second day of life, and 1971 (14.1%) of these infants had lumbar punctures on these first two days of life. Fifty-three cases of early-onset GBS disease were identified. Only three patients with invasive GBS disease had no clinical suspicion for sepsis at the time of testing. Thus, the number of blood cultures taken to detect one case of GBS bacteraemia in an infant who is well at the time of testing was 3996.

Using the Allplex™ 2019-nCoV assay (Seegene, South Korea), 285 samples were tested; 49 (17%) were positive for 3 genes, 4 (1.4%) samples were positive for 2 genes (all N gene and RdRP gene), 8 (3%) samples were positive for 1 gene (all N gene only), and 224 (78.5%) samples were negative., Highlights • All patients with detected PCR result were positive for all 3 gene targets. • 12 of 61 positive staff were detected in only 1 or 2 of the 3 gene targets. • Positive results with high cycle threshold values were only seen in healthcare workers.

A point-prevalence study of antimicrobial use among inpatients at 5 public hospitals in Sri Lanka revealed that 54.6% were receiving antimicrobials: 43.1% in medical wards, 68.0% in surgical wards, and 97.6% in intensive care wards. Amoxicillin-clavulanate was most commonly used for major indications. Among patients receiving antimicrobials, 31.0% received potentially inappropriate therapy.

Diagnosis of wild-type rotavirus disease may be complicated by the detection of vaccine-derived virus which can be detected in stool samples following immunisation. We evaluate an immunochromatographic assay and real-time RT-PCR to determine which is more suitable for the detection of wild-type rotavirus.To compare the Ct values of wild-type rotavirus and Rotarix determined by real-time RT-PCR. To establish the Ct value corresponding to the limit of detection of the immunochromatographic Combi-Strip method (Coris, BioConcept).Retrospective review of real-time RT-PCR Ct values was performed on 100 samples tested by a pan-rotavirus assay (n = 50 wild-type, n = 50 Rotarix). Secondly the limit of detection of the Combi-Strip assay was determined by testing; wild-type rotavirus (n = 33, Ct range 6.85-34.26) samples, Rotarix (n = 9, Ct range 20.86-34.26) samples and rotavirus negative (n = 21) samples.The median Ct of 50 wild-type rotavirus was Ct 12.43; range 6.11-32.66 compared with the median of 50 Rotarix, Ct 29.09; range 18.91-35.28, p=0.0001. The limit of detection of the Combi-Strip method was approximately Ct 18. The 21 rotavirus negative samples were negative by real-time RT-PCR and Combi-Strip.We found the Ct value was significantly lower, and therefore the viral load higher, for wild-type rotavirus compared to detectable Rotarix. The Combi-Strip assay detects most wild-type infections; however, it lacks sensitivity to detect low-level wild-type rotavirus and, beneficially, is unlikely to detect Rotarix. It is not a more suitable method than real-time RT-PCR when a definitive rotavirus result is required.

Global spread of aggressive mycobacteria Many mycobacteria, in addition to those causing leprosy and tuberculosis, are capable of infecting humans. Some can be particularly dangerous in patients suffering from immunosuppression or chronic disease, such as cystic fibrosis (CF). Bryant et al. observed clusters of near-identical isolates of drug-resistant Mycobacterium abscessus in patients reporting to CF clinics. The similarity of the isolates suggests transmission between patients, rather than environmental acquisition. Although this bacterium is renowned for its environmental resilience, the mechanism for its long-distance transmission among the global CF patient community remains a puzzle. Science , this issue p. 751

Group B streptococcus (GBS) is a leading cause of invasive disease in infants. Accurate and rapid diagnosis is crucial to reduce morbidity and mortality. Real-time polymerase chain reaction (PCR) targeting the dltR gene was utilised for the direct detection of GBS DNA in blood and cerebrospinal fluid (CSF) from infants at an Irish maternity hospital. A retrospective review of laboratory and patient records during the period 2011–2013 was performed in order to evaluate PCR and culture for the diagnosis of invasive GBS disease. A total of 3570 blood and 189 CSF samples from 3510 infants had corresponding culture and PCR results. Culture and PCR exhibited concordance in 3526 GBS-negative samples and 13 (25 %) GBS-positive samples (n = 53). Six (11 %) and 34 (64 %) GBS-positive samples were positive only in culture or PCR, respectively. Culture and PCR identified more GBS-positive infants (n = 47) than PCR (n = 43) or culture (n = 16) alone. Using culture as the reference standard, the sensitivity, specificity, and positive and negative predictive values for PCR on blood samples were 71.4 %, 99.2 %, 25 % and 99.9 %, and for CSF samples, they were 60 %, 97.8 %, 42.9 % and 98.9 %, respectively. The sensitivity and positive predictive values were improved (blood: 84.6 % and 55 %; CSF: 77.8 % and 100 %, respectively) when maternal risk factors and other laboratory test results were considered. The findings in this study recommend the use of direct GBS real-time PCR for the diagnosis of GBS infection in infants with a clinical suspicion of invasive disease and as a complement to culture, but should be interpreted in the light of other laboratory and clinical findings.

Objective To establish the number of outbreaks of extended spectrum beta-lactamase (ESBL) producing organisms in neonatal intensive care units (NICUs), to determine causes, mortality rates, proportions of infants colonised and infected and the interventions that terminated outbreaks. Methods A systematic review of the literature in English, Spanish and French was undertaken with searches in four databases. The review conformed to the PRISMA guidelines, and the data extraction was modelled on the ORION criteria for studies of nosocomial infection. Results 75 studies fulfilled the inclusion criteria. There were 1185 cases of colonisation, 860 infections and 139 deaths. The median outbreak duration was 6.2 months (IQR 2.0–7.5 months). Klebsiella pneumoniae was the most frequently implicated pathogen. Understaffing was the most frequent risk factor for outbreaks. The most commonly identified source was admission of an ESBL-colonised infant with subsequent horizontal dissemination. The main interventions described were improved infection-control procedures and screening of staff and the environment. 26 studies were included in the quantitative analysis. Random effects meta-analysis indicated high mortality rates in infants who developed infection (31%, 95% CI 20% to 43%). Conclusion ESBL outbreaks in NICUs are associated with significant mortality and prolonged disruption. Understaffing is a major risk factor, but is infrequently addressed by interventions. Poor infection-control procedures are frequently implicated as contributing to ESBL spread. Better reporting of outbreaks may help clarify the role for routine ESBL screening in NICUs.

Influenza is a significant cause of childhood morbidity and death; it contributes to up to 16% of hospitalizations for respiratory illnesses worldwide. Novel rapid viral diagnostic tests, including molecular diagnostic tests, have the potential to significantly affect both time to diagnosis and selection of optimal anti-infective therapy. However, little is known about current treatment algorithms used in US hospitals. In this study, for hospitalized children in the United States, we aimed to define the current approaches to influenza diagnosis and treatment and to explore reasons for their potential variation. In this study, we aimed to define the current approaches to pediatric influenza diagnosis and treatment in US hospitals, and to explore reasons for their potential variation. Our results suggest a rise in the availability and use of rapid molecular diagnostic testing in addition to continued variability in anti-infective management, particularly with regard to antiviral use.

BACKGROUND: Improving the diagnosis of serious bacterial infections (SBIs) in the children’s emergency department is a clinical priority. Early recognition reduces morbidity and mortality, and supporting clinicians in ruling out SBIs may limit unnecessary admissions and antibiotic use. METHODS: A prospective, diagnostic accuracy study of clinical and biomarker variables in the diagnosis of SBIs (pneumonia or other SBI) in febrile children RESULTS: There were 1101 children studied, of whom 264 had an SBI. A diagnostic model discriminated well between pneumonia and no SBI (concordance statistic 0.84, 95% confidence interval 0.78–0.90) and between other SBIs and no SBI (0.77, 95% confidence interval 0.71–0.83) on internal validation. A published model discriminated well on external validation. Model updating yielded good calibration with good performance at both high-risk (positive likelihood ratios: 6.46 and 5.13 for pneumonia and other SBI, respectively) and low-risk (negative likelihood ratios: 0.16 and 0.13, respectively) thresholds. Extending the model with procalcitonin and resistin yielded improvements in discrimination. CONCLUSIONS: Diagnostic models discriminated well between pneumonia, other SBIs, and no SBI in febrile children in the emergency department. Improvements in the classification of nonevents have the potential to reduce unnecessary hospital admissions and improve antibiotic prescribing. The benefits of this improved risk prediction should be further evaluated in robust impact studies.

Both Staphylococcus aureus and coagulase negative Staphylococci are common causes of late-onset neonatal sepsis in the neonatal intensive care unit (NICU), usually relating to intravascular access device infections. This project aimed to review the impact on antimicrobial treatment and clinical outcome in the NICU setting, of the introduction of the Xpert MRSA/SA BC test (Cepheid, USA) for the identification of staphylococci in blood cultures. A retrospective audit was carried out of the pre- and post-intervention periods; the intervention was the introduction of the Xpert MRSA/SA BC test. In total, 88 neonates had positive blood cultures with Staphylococcus spp., comprising 42 neonates in the pre-intervention and 46 in the post-intervention groups. The pre-intervention group had a higher birth weight (1.541 kg vs. 1.219 kg, p = 0.05) and higher platelet count (288 vs. 224 × 109/L, p = 0.05). There was a trend towards a shorter duration of antimicrobial therapy in term infants and in the length of admission; however, this was not statistically significant (p = 0.2). All of the nine infants post-intervention with significant bacteraemia (S. aureus =3, CoNS =6) were changed to the optimal antimicrobial at the time the result was available. This study shows that the introduction of the Xpert MRSA/SA BC test can lead to a reduction in the length of admission and duration of antimicrobials in term infants; however, the difference was not statistically significant. All nine infants with clinically significant bacteraemia were treated with the appropriate antimicrobial when the Xpert MRSA/SA BC test result was available.

Of the 551 extended spectrum β-lactamase-producing isolates characterized, the MIC90 for Escherichia coli, Klebsiella spp., and Enterobacter spp. were in the susceptible range when tested against meropenem, but were in the resistant range for all other antimicrobials tested excluding E coli and Klebsiella spp. against ertapenem and ciprofloxacin, and for Enterobacter spp. against ciprofloxacin.

Susceptibility testing on 60 isolates of Staphylococcus epidermidis and 20 isolates of Staphylococcus hominis was performed using the Sensititre (Trek Diagnostics, Cleveland, OH, USA) method and compared with Vitek-2 automated susceptibility testing (bioMèrieux, Marcy l'Etoile, France), MICE strips for minimum inhibitory concentration determination (Oxoid, Basingstoke, UK), and disc diffusion (MAST, Bootle, UK). The categorical agreement between Vitek and Sensititre was greater than 90% for agents tested against S. epidermidis except for tetracycline (52%) and oxacillin (67%), and for S. hominis, the agreement was greater than 90% except for tetracycline (80%), gentamicin (65%), and oxacillin (75%). The categorical agreement between disc diffusion and Sensititre was greater than 90% for antimicrobials tested against S. epidermidis except for tetracycline (45%), moxifloxacin (70%), clindamycin (88%), and cefoxitin (80%), while against S. hominis, the categorical agreement was greater than 90% for antimicrobials tested except for gentamicin (65%), tetracycline (75%), moxifloxacin (80%), and ciprofloxacin (75%). Categorical agreement between MICE strips and Sensititre for S. epidermidis and S. hominis was greater than 95% for vancomycin and daptomycin. Sensititre method shows good categorical agreement with other standard methods for susceptibility testing of S. hominis and S. epidermidis.

The aim of this systematic review was to review studies that existed from 1993 to 2012 regarding antimicrobial treatment options of paediatric neurosurgical shunt.Studies were identified from MEDLINE, Scopus and Cochrane databases using a search strategy that was registered on the PROSPERO database. Studies were included if they had two or more patients, aged less than 18 years, and also specified the organism and antimicrobial treatment that was used.The search yielded 2,985 articles, and 76 articles were suitable for full review. In the final qualitative analysis, only eight studies were included, involving 86 participants. The most common antimicrobial regimens for Gram-positive infections was intravenous and intrathecal vancomycin (n = 7), followed by intravenous vancomycin monotherapy.This systematic review has shown that there are no prospective randomised studies of antimicrobial treatment options for paediatric neurosurgical patients in the last 20 years, and larger prospective studies are urgently required for this serious infection. There is some limited case series showing the benefits of certain antimicrobials such as vancomycin and ceftriaxone, but a larger case series or randomised controlled trial is required, particularly to establish the benefit, if any, of additional intraventricular antimicrobials.

Summary Background Carbapenem-resistant Enterobacteriaceae are an emerging global infection threat. However, there are few data describing their clinical importance in children. Aim This retrospective study reviewed the prevalence and resistance mechanisms of carbapenem-resistant Enterobacteriaceae grown from clinical and surveillance samples in a large tertiary referral children's hospital in the UK. Methods Carbapenem-resistant Enterobacteriaceae were sought in specimens submitted for diagnostic and surveillance purposes at Alder Hey Children's NHS Foundation Trust, Liverpool, between September 2011 and August 2012. Mechanisms of resistance were identified using phenotypic and/or molecular methods. Variable number tandem repeat profiling was used to type carbapenemase-producing strains. Findings During the 12-month study period, carbapenem-resistant Enterobacteriaceae were recovered from 24 patients. Five isolates were from clinical diagnostic specimens whereas 19 of 421 patients had positive rectal surveillance swabs (4.5%). Of the 24 isolates, seven (all Klebsiella spp.) harboured carbapenemases: three had bla KPC and four bla NDM , whereas 17 had resistance due to combinations of AmpC or extended-spectrum β-lactamase activity plus impermeability. Conclusion Carbapenem-resistant Enterobacteriaceae and, in particular, those with carbapenemases, are an emerging infection problem in a major paediatric hospital in the UK. Active surveillance is required to monitor and control their spread.

The Xpert MRSA/SA blood culture assay (Cepheid, USA) is a rapid PCR test which can be used for positive blood cultures where Gram-positive cocci in clusters are seen. It can detect Staphylococcus aureus and also the mecA gene, which encodes for β-lactam resistance. The assay was introduced into the Rotunda Hospital for positive blood cultures to allow earlier detection of MRSA and methicillin susceptible S. aureus. To assess the impact of the Xpert MRSA/SA blood culture assay on the management of obstetric patients with a positive blood culture where Gram-positive cocci in clusters were seen. The main outcome measures were duration of intravenous antimicrobials and length of admission. Pre-intervention and post-intervention groups were identified relating to whether or not the test was in use at the time. A standardised form was used to retrospectively review the medical notes and laboratory results. There were 35 obstetric patients with positive blood cultures with Gram-positive cocci in clusters in the pre-intervention group and 22 cases in the post-intervention group. All 22 positive blood cultures in the post-intervention period were correctly identified. The antimicrobial duration was reduced from a median of 55.5–43.5 h and length of admission reduced from a median of 66.5–56 h (Mann–Whitney U value = 161, p = 0.46 and U value = 256, p = 0.15, respectively). This study has shown a reduction in the median duration of intravenous antimicrobials and admission; however, larger multi-centre studies are needed to evaluate this potential benefit further.

Shahid Husain, MD, MS, Martha L. Mooney, MD, MS, FACP, Lara Danziger-Isakov, MD, MPH, Frauke Mattner, MD, PhD, Nina Singh, MD, Robin Avery, MD, FIDSA, Michael Ison, MD, MS, Atul Humar, MD, MSc, Robert F. Padera, MD, PhD, Leo P. Lawler, MD, FRCR, Andy Fisher, PhD, FRCP, Richard J. Drew, MD, Kate F. Gould, MBBS, MRCP, FRCP, Amparo Sole, MD, PhD, Sean Studer, MD, MSc, Patricia Munoz, MD, Lianne G. Singer, MD, FRCPC, and Margaret Hannan, MD, FRCP, FRCPath, for the ISHLT Infectious Diseases Council Working Group on Definitions From the Division of Infectious Diseases, Transplant Infectious Diseases, University Health Network, University of Toronto, Toronto, Ontario, Canada; Eastern Virginia Medical School, Sentara Norfolk Transplant Center, Norfolk, Virginia; Center for Pediatric Infectious Diseases, Department of Infectious Disease, Medicine Institute, The Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio; Infection Control and Hospital Epidemiology, Institute for Medical Microbiology, Hannover Medical School, Hannover, Germany; Division of Infectious Diseases, Veteran Affairs Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania; Divisions of Infectious Diseases and Organ Transplantation, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Respiratory Transplant Medicine, Newcastle University, Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Mater Misericordiae University Hospital, Dublin, Ireland; Health Protection Agency Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK; Hospital Universitario La Fe, Valencia, Spain; Division of Pulmonary & Critical Care, Newark Beth Israel Medical Center, Newark, New Jersey; and Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, Spain.

In 2009, the International Society for Heart and Lung Transplantation (ISHLT) recognized the importance of infectionrelated morbidity and mortality in patients using ventricular assist devices (VADs) and the growing need for a consensusbased expert opinion to provide standard definitions of infections in these patients. The aim of these standard definitions is to improve clinical-investigator communication, allowing meaningful comparison in practice and outcomes between different centers and different VAD devices. In 2010, a core group of experts, including infectious diseases specialists, cardiologists, pathologists, radiologists, and cardiothoracic surgeons, formed an ISHLT Infectious Diseases Working Group to develop agreed criteria for definitions of infections in VAD patients. These definitions have been created by adapting and expanding on existing standardized definitions, which are based on the pathophysiology of equivalent infectious processes in prosthetic devices, such as cardiac prosthetic valve infections, intravascular catheter-related infections, and prosthetic joint infections. These definitions have been divided into 3 sections: VAD-specific infections, VAD-related infections, and non-VAD infections. Owing to the constant shortage of donor organs, new allocation systems, and improved medical therapies for congestive cardiac failure, the overwhelming trend in cardiac transplantation has been toward listing principally the most critically ill patients, that is, those requiring inpatient inotropic therapy for mechanical circulatory support (MCS). The ventricular assist device (VAD) has an expanding role in the management of these patients, both as a bridge to transplantation and as a destination therapy (ie, alternative to transplantation). According to United Network of Organ Sharing (UNOS) registry data, 9,000 transplant candidates have undergone MCS since 1999, comprising 33% of all listed patients and 75% of all listed inpatients. 1

Background Blood cultures are a common investigation for children admitted to hospital. In routine practice, it takes at least 24 hours to identify an organism as a contaminant or clinically significant. FilmArray Blood Culture Identification Panel (FA-BCIP) is a multiplex polymerase chain reaction that can detect 24 pathogens within 1 hour. We assessed whether results from FA-BCIP lead to changes in clinical management in a tertiary referral paediatric hospital. Methods We prospectively studied children having blood cultures taken at our tertiary children's hospital. Blood cultures were monitored and organisms identified using standard methods. FA-BCIP was performed when growth was initially detected in first positive blood cultures per episode, between January 1 and June 30, 2014. Assessment of whether the FA-BCIP result altered clinical management was made, specifically focused on antimicrobial stewardship and length of stay. Results FA-BCIP was done on 117 positive blood cultures; 74 (63%) grew clinically significant organisms, 43 (37%) grew contaminants. FA-BCIP results were judged to alter clinical management in 63 of the 117 episodes (54%). Antimicrobials were started/altered in 23 (19%) episodes and de-escalated/withheld/stopped in 29 (25%) episodes. Ten children were discharged from hospital earlier, which saved a cumulative total of 14 bed days. Conclusions Rapid identification of microorganisms in pediatric blood cultures by FA-BCIP, led to changes in clinical management for half of the episodes. This improved antimicrobial stewardship and allowed early discharge from hospital for 10% of children. Future studies should focus on how best to use this technology in a cost-effective manner.

Maternal sepsis is a significant problem in obstetrics, with almost one in four maternal deaths related to severe sepsis. We carried out a retrospective review of clinically significant bacteraemia in obstetric patients attending Rotunda Hospital over 14 years. From 2001 to 2014, there were 252 clinically significant positive blood culture episodes in obstetric patients. There were 112,361 live births >500 g during the study period giving an overall rate of 2.24 clinically significant positive maternal blood culture episodes per 1000 live births >500 g. The median rate over the 14 years was 2.12 episodes per 1000 live births >500 g, with an interquartile range of 1.74–2.43 per 1000 live births >500 g. There was no discernable increasing or decreasing trend over the 14 years.E. coliwas the most commonly isolated organism (n= 92/252, 37%), followed by group BStreptococcus(n= 64/252, 25%),Staphylococcus aureus(n= 28/252, 11%), and anaerobes (n= 11/252, 4%). These top four organisms represented three-quarters of all positive blood culture episodes (n= 195/252, 77.3%). Of note, there were only five cases of listeriosis, representing a rate of 4.4 cases per 100,000 live births >500 g. The rate of invasive group A streptococcal infection was also very low at 5.3 cases per 100,000 live births >500 g.

There are currently no Irish guidelines on screening for Chlamydia trachomatis infection in pregnancy. Prevalence rates in the antenatal population are not known which has prevented the development of screening recommendations for this group. The objective of this study was to determine the prevalence of asymptomatic urogenital C. trachomatis infection in young women attending for care at a large maternity hospital. All patients aged 25 years and under attending the Hospital between December 2011 and December 2013 were offered screening for urogenital C. trachomatis infection. Nucleic acid amplification testing of the C. trachomatis cryptic plasmid was performed on either endocervical swabs or first void urine samples. There were 2687 women tested for C. trachomatis infection, 83.4 % (2241/2687) through the antenatal clinics, 7.1 % (193/2687) through the gynaecology clinic, and 9.4 % (253/2687) through the emergency department. The rate of a positive test result was 5.6 % (151/2687) overall. The rates in women ages 16–18, 19–21 and 22–25 years were 9.1 % (31/340), 6.5 % (50/774) and 4.4 % (69/1561), respectively. A positive test result was more likely in those who were unemployed (p = 0.04), those who were Irish (p = 0.03) and those who were unmarried (p

BACKGROUND: Bacteremia is now an uncommon presentation to the children’s emergency department (ED) but is associated with significant morbidity and mortality. Its evolving etiology may affect the ability of clinicians to initiate timely, appropriate antimicrobial therapy. METHODS: A retrospective time series analysis of bacteremia was conducted in the Alder Hey Children’s Hospital ED between 2001 and 2011. Data on significant comorbidities, time to empirical therapy, and antibiotic susceptibility were recorded. RESULTS: A total of 575 clinical episodes were identified, and Streptococcus pneumoniae (n = 109), Neisseria meningitidis (n = 96), and Staphylococcus aureus (n = 89) were commonly isolated. The rate of bacteremia was 1.42 per 1000 ED attendances (95% confidence interval: 1.31–1.53). There was an annual reduction of 10.6% (6.6%–14.5%) in vaccine-preventable infections, and an annual increase of 6.7% (1.2%–12.5%) in Gram-negative infections. The pneumococcal conjugate vaccine was associated with a 49% (32%–74%) reduction in pneumococcal bacteremia. The rate of health care–associated bacteremia increased from 0.17 to 0.43 per 1000 ED attendances (P = .002). Susceptibility to empirical antibiotics was reduced (96.3%–82.6%; P < .001). Health care–associated bacteremia was associated with an increased length of stay of 3.9 days (95% confidence interval: 2.3–5.8). Median time to antibiotics was 184 minutes (interquartile range: 63–331) and 57 (interquartile range: 27–97) minutes longer in Gram-negative bacteremia than in vaccine-preventable bacteremia. CONCLUSIONS: Changes in the etiology of pediatric bacteremia have implications for prompt, appropriate empirical treatment. Increasingly, pediatric bacteremia in the ED is health care associated, which increases length of inpatient stay. Prompt, effective antimicrobial administration requires new tools to improve recognition, in addition to continued etiological surveillance.

A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan.

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment ( K cp ), 0.474/3.876 h −1 (8.16 h −1 ); and first-order rate constant from peripheral to central compartment ( K pc ), 0.292/3.994 h −1 (8.93 h −1 ). The percentage of patients with a minimum concentration of drug in serum ( C min ) of 10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. IMPORTANCE (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.)

Conjunctivitis is a very common presentation to general practitioners and general paediatricians. The investigation of conjunctivitis can be a significant cost to microbiology laboratories due to the high volume of samples that can be submitted, particularly from patients in the community. The key issue is to send eye swabs in clinical situations where it can make a difference to management, and limiting the use of eye swabs in routine cases of conjunctivitis which are likely to be due to viruses. For investigation of neonatal conjunctivitis we recommend sending a bacterial swab for routine culture, and also a swab for molecular detection of Chlamydia trachomatis and Neisseria gonorrhoeae. In older children with mild conjunctivitis no swab is necessary unless there is marked conjunctival injection. In this article we also highlight patient populations that require specialist tests to be sent as part of their assessment such as contact lens wearers and sexually active teenagers.

Laboratory methods of diagnosis were examined for 266 children with invasive meningococcal disease. Seventy-five (36%) of 207 cases with bloodstream infection had both positive blood culture and blood meningococcal polymerase chain reaction (PCR), 130 (63%) negative blood culture and positive blood PCR, and 2 (1%) had positive blood culture and negative blood PCR. Sixty-three percent of cases were diagnosed by PCR alone.