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Background The COVID-19 pandemic has severely impacted healthcare delivery and there are growing concerns that the pandemic will accelerate antimicrobial resistance. Objectives To evaluate the impact of the COVID-19 pandemic on antibiotic prescribing in a tertiary paediatric hospital in London, UK. Methods Data on patient characteristics and antimicrobial administration for inpatients treated between 29 April 2019 and Sunday 28 March 2021 were extracted from the electronic health record (EHR). Interrupted time series analysis was used to evaluate antibiotic days of therapy (DOT) and the proportion of prescribed antibiotics from the WHO ‘Access’ class. Results A total of 23 292 inpatient admissions were included. Prior to the pandemic there were an average 262 admissions per week compared with 212 during the pandemic period. Patient demographics were similar in the two periods but there was a shift in the specialities that patients had been admitted to. During the pandemic, there was a crude increase in antibiotic DOTs, from 801 weekly DOT before the pandemic to 846. The proportion of Access antibiotics decreased from 44% to 42%. However, after controlling for changes in patient characteristics, there was no evidence for the pandemic having an impact on antibiotic prescribing. Conclusions The patient population in a specialist children’s hospital was affected by the COVID-19 pandemic, but after adjusting for these changes there was no evidence that antibiotic prescribing was significantly affected by the pandemic. This highlights both the value of routine, high-quality EHR data and importance of appropriate statistical methods that can adjust for underlying changes to populations when evaluating impacts of the pandemic on healthcare.

Objective To review the epidemiology of Coagulase-negative staphylococci (CoNS) in England over the recent 12-year period. Methods Laboratory confirmed CoNS reported from sterile sites in patients in England to the UK Health Security Agency (UKHSA) between 2010 and 2021 were extracted from the national laboratory database and analysed. Results Overall, 668,857 episodes of CoNS were reported. Unspeciated CoNS accounted for 56% (374,228) of episodes, followed by Staphylococcus epidermidis (26%; 174,050), S. hominis (6.5%; 43,501) and S. capitis (3.9%; 25,773). Unspeciated CoNS increased by 8.2% (95% CI, 7.1-9.3) annually between 2010 and 2016, then decreased annually by 6.4% (95% CI: -4.8 to -7.9) until 2021. Speciated CoNS increased by 47.6% (95% CI, 44.5-50.9) annually between 2010 and 2016 and increased annually by 8.9% (95% CI: 5.1 to 12.8) until 2021. Antimicrobial susceptibility profiles differed by species. Conclusions Reports of CoNS from normally sterile body sites in patients in England increased between 2010 and 2016 and remained stable between 2017 and 2021. There has been a striking improvement in species-level identification of CoNS in recent years. Monitoring trends in CoNS epidemiology is crucial for development of observational and clinical intervention studies on individual species.

Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogenStaphylococcus aureus. The reported prevalence of these resistances vary, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures.We exploredS. aureusAMR diversity in 70,000 isolates from a UK paediatric hospital between 2000-2020, using electronic datasets containing multiple routinely collected isolates per patient with phenotypic antibiograms, hospitalisation information, and antibiotic consumption.At the hospital-level, the proportion of isolates that were meticillin-resistant (MRSA) increased between 2014-2020 from 25 to 50%, before sharply decreasing to 30%, likely due to a change in inpatient demographics. Temporal trends in the proportion of isolates resistant to different antibiotics were often correlated in MRSA, but independent in meticillin-susceptibleS. aureus. Ciprofloxacin resistance in MRSA decreased from 70% to 40% of tested isolates between 2007-2020, likely linked to a national policy to reduce fluoroquinolone usage in 2007. At the patient level, we identified frequent AMR diversity, with 4% of patients ever positive forS. aureussimultaneously carrying, at some point, multiple isolates with different resistances. We detected changes over time in AMR diversity in 3% of patients ever positive forS. aureus. These changes equally represented gain and loss of resistance.Within this routinely collected dataset, we found that 65% of changes in resistance within a patient’sS. aureuspopulation could not be explained by antibiotic exposure or between-patient transmission of bacteria, suggesting that within-host evolution via frequent gain and loss of AMR genes may be responsible for these changing AMR profiles. Our study highlights the value of exploring existing routine surveillance data to determine underlying mechanisms of AMR. These insights may substantially improve our understanding of the importance of antibiotic exposure variation, and the success of singleS. aureusclones.

Background: Subdural empyema is a neurosurgical emergency requiring prompt diagnosis and treatment. There is a debate between the benefits and risks of starting early antibiotics prior to surgical drainage as this is purported to reduce the rate of microbiological diagnosis. Here, we describe our experience of treating this potentially life-threatening condition, advocating for the early commencement of antibiotics and importance of source control in its treatment. Methods: Retrospective review of a prospectively collected electronic departmental database included all patients who were admitted to our unit with a diagnosis of subdural empyema over an 11-year period (2008–2018). Basic demographic data were collected. Further data pertaining to mode of presentation, surgical approach, causative organism, post-operative antibiotic regime, anti-seizure medications, length of hospital stay, further surgery, and neurological outcomes were extracted. Results: Thirty-six children underwent 44 operations for subdural empyema at our institution during the study period. Median age was 11.0 (range 0.2–15.8); 47.2% (17/36) were female. Over time, there was decreasing use of burr holes and increasing use of craniectomy as the index surgery. Using a combination of extended culture and polymerase chain reaction, a microbiological diagnosis was achieved in all 36 cases; the commonest causative microorganism was of the Streptococcus anginosus group of bacteria. Seven patients underwent repeat surgery, and 4 patients underwent a concurrent ENT procedure. No risk factors were significant in predicting the likelihood of re-operation (location of subdural empyema, age, index surgery type, inflammatory markers, concurrent ENT procedure, and microorganism) although it was notable that none of the patients undergoing a concurrent ENT procedure underwent repeat surgery (p = 0.29). Median length of stay was 12 days (range 3–74), and there were no inpatient or procedure-related mortalities. Clinical outcomes were good with 94.4% (34/36) categorized as modified Rankin Scale 0–3 at discharge and there were 2 cranioplasty-related complications. Conclusions: We observed an evolution of practice from limited surgical approaches towards more extensive index surgery over the study period. Given that a microorganism was isolated in all cases using a comprehensive approach, initiation of antibiotic therapy should not be delayed on presentation. Concurrent ENT surgery may be an important factor in providing aggressive source control thereby reducing the need for repeat surgery.

Background Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to neutralize the virus in vitro and prevent disease in animal challenge models on reexposure. However, the current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. Methods The COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike protein (S), receptor-binding domain, and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Meso Scale Discovery Assay. Survival analysis determined the proportion of seroreversion, while 2 hierarchical gamma models predicted the upper and lower bounds of long-term antibody trajectory. Results A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days after symptoms, >95% of participants had detectable S antibodies, compared with 75% with detectable N antibodies. S antibody was predicted to remain detectable in 95% of participants until 465 days (95% confidence interval, 370–575 days) using a “continuous-decay” model and indefinitely using a “decay-to-plateau” model to account for antibody secretion by long-lived plasma cells. S-antibody titers were correlated strongly with surrogate neutralization in vitro (R2 = 0.72). N antibodies, however, decayed rapidly with a half-life of 60 days (95% confidence interval, 52–68 days). Conclusions The Co-Stars data presented here provide evidence for long-term persistence of neutralizing S antibodies. This has important implications for the duration of functional immunity after SARS-CoV-2 infection. In contrast, the rapid decay of N antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics after SARS-CoV-2 infection. Clinical Trials Registration NCT04380896.

Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 non-transplanted cases. Low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), both of which enable AAV2 lytic replication, were also found in the five explanted livers and blood from 15/17 and 6/9 respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained hepatitis in children infected in the recent HAdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of HAdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with HAdV-F41 and/or HHV-6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.

Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches to reconstruct outbreaks exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is stable among repeated serial samples from the same host, is transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.

Strongyloides stercoralis is a common parasitic infection in tropical and subtropical areas which may result in fatal hyperinfection syndrome in immunosuppressed patients. Infection occurs through skin or mucous membrane contact with material contaminated with infected human faeces. Sexual transmission of other gastrointestinal infections has been observed in men who have sex with men (MSM), with human immunodeficiency virus (HIV) a known risk factor. We present a case series of strongyloidiasis in seven HIV-positive MSM living in a non-endemic area. We found high rates of concomitant sexually transmitted infection and chemsex drug use, suggesting high-risk sexual behaviour.

Congenital toxoplasmosis occurs following transplacental transfer of Toxoplasma gondii. Irrespective of symptom status at birth, infants with congenital infection may develop serious long-term sequelae, including learning disability, seizures, hydrocephalus, motor and hearing deficits, chorioretinitis and retinal scarring with impaired vision. Timely diagnosis facilitates early initiation of therapy, aimed at prevention or amelioration of adverse clinical consequences. Diagnosis can be difficult, however, since acutely infected mothers are often asymptomatic and laboratory testing can be complex. Moreover, any decision to start treatment in the newborn must include careful consideration of the benefits and risks. This paper outlines a structured approach for managing an infant born to a woman with possible or confirmed T. gondii infection during pregnancy, including key aspects of the antenatal history, interpretation and timing of investigations, treatment and appropriate follow-up. Our recommendations are based on current evidence in the literature, consensus from two UK paediatric infectious disease centres and the UK specialist Toxoplasma Reference Unit.

BackgroundAntibodies to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been shown to neutralize the virusin-vitro. Similarly, animal challenge models suggest that neutralizing antibodies isolated from SARS-CoV-2 infected individuals prevent against disease upon re-exposure to the virus. Understanding the nature and duration of the antibody response following SARS-CoV-2 infection is therefore critically important.MethodsBetween April and October 2020 we undertook a prospective cohort study of 3555 healthcare workers in order to elucidate the duration and dynamics of antibody responses following infection with SARS-CoV-2. After a formal performance evaluation against 169 PCR confirmed cases and negative controls, the Meso-Scale Discovery assay was used to quantify in parallel, antibody titers to the SARS-CoV-2 nucleoprotein (N), spike (S) protein and the receptor-binding-domain (RBD) of the S-protein. All seropositive participants were followed up monthly for a maximum of 7 months; those participants that were symptomatic, with known dates of symptom-onset, seropositive by the MSD assay and who provided 2 or more monthly samples were included in the analysis. Survival analysis was used to determine the proportion of sero-reversion (switching from positive to negative) from the raw data. In order to predict long-term antibody dynamics, two hierarchical longitudinal Gamma models were implemented to provide predictions for the lower bound (continuous antibody decay to zero, “Gamma-decay”) and upper bound (decay-to-plateau due to long lived plasma cells, “Gamma-plateau”) long-term antibody titers.ResultsA total of 1163 samples were provided from 349 of 3555 recruited participants who were symptomatic, seropositive by the MSD assay, and were followed up with 2 or more monthly samples. At 200 days post symptom onset, 99% of participants had detectable S-antibody whereas only 75% of participants had detectable N-antibody. Even under our most pessimistic assumption of persistent negative exponential decay, the S-antibody was predicted to remain detectable in 95% of participants until 465 days [95% CI 370-575] after symptom onset. Under the Gamma-plateau model, the entire posterior distribution of S-antibody titers at plateau remained above the threshold for detection indefinitely. Surrogate neutralization assays demonstrated a strong positive correlation between antibody titers to the S-protein and blocking of the ACE-2 receptorin-vitro[R2=0.72, pDiscussionThis study has demonstrated persistence of the spike antibody in 99% of participants at 200 days following SARS-CoV-2 symptoms and rapid decay of the nucleoprotein antibody. Diagnostic tests or studies that rely on the N-antibody as a measure of seroprevalence must be interpreted with caution. Our lowest bound prediction for duration of the spike antibody was 465 days and our upper bound predicted spike antibody to remain indefinitely in line with the long-term seropositivity reported for SARS-CoV infection. The long-term persistence of the S-antibody, together with the strong positive correlation between the S-antibody and viral surrogate neutralizationin-vitro, has important implications for the duration of functional immunity following SARS-CoV-2 infection.

While changes in SARS-CoV-2 viral load over time have been documented, detailed information on the impact of remdesivir and how it might alter intra-host viral evolution is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 recovered from the upper respiratory tract of hospitalised children revealed that remdesivir treatment suppressed viral RNA levels in one patient but not in a second infected with an identical strain. Evidence of drug resistance to explain this difference was not found. Reduced levels of subgenomic (sg) RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication that is independent of viral RNA levels. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. We conclude that these are likely to have arisen from within-host evolution, and not co-transmission, although superinfection cannot be excluded in one case. Sample-to-sample heterogeneity in the abundances of variant genotypes is best explained by the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalisation is well described in serious lung infections caused by influenza and Mycobacterium tuberculosis and has been associated with poor drug penetration, suboptimal treatment and drug resistance. Our data provide evidence that remdesivir is able to suppress SARS-CoV-2 replication in vivo but that its efficacy may be compromised by factors reducing penetration into the lung. Based on data from influenza and Mycobacterium tuberculosis lung infections we conclude that early use of remdesivir combined with other agents should now be evaluated.Summary SentenceDeep sequencing of longitudinal samples from SARS-CoV-2 infected paediatric patients identifies evidence of remdesivir-associated inhibition of viral replication in vivo and uncovers evidence of within host evolution of distinct viral genotypes.

IntroductionSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) specific antibodies have been shown to neutralize the virus in-vitro. Understanding antibody dynamics following SARS-CoV-2 infection is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies is also vital for large seroprevalence surveys which inform government policies and public health interventions. However, rapidly waning antibodies following SARS-CoV-2 infection could jeopardize the sensitivity of serological testing on which these surveys depend.MethodsThis prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody titers were quantified to the SARS-CoV-2 nucleoprotein (N), spike (S-)protein and the receptor-binding-domain (RBD) of the S-protein. Titers were log-transformed and a multivariate log-linear model with time-since-infection and clinical variables was fitted by Bayesian methods.ResultsThe mean estimated half-life of the N-antibody was 52 days (95% CI 42-65). The S- and RBD-antibody had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD-antibody titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N-antibody test for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236).DiscussionAfter SARS-CoV-2 infection, the predicted half-life of N-antibody was 52 days with 50% of seropositive participants becoming seronegative to this antibody at 195 days. Widely used serological tests that depend on the N-antibody will therefore significantly underestimate the prevalence of infection following the majority of infections.Significance statementWe believe that our study has significant and urgent public health and translational impact. Firstly, our findings demonstrate that the half-life of the SARS-CoV-2 nucleoprotein antibody is only 52 days. This has immediate and important implications for large-scale seroprevalence surveys, government policy and mathematical modelling predictions which rely on serological tests that target this antibody. Secondly, the slower decay of the SARS-CoV-2 spike protein antibody identified in this study makes assays to the spike protein a more reliable target for serological assays in the longer term. We demonstrate a strong positive linear correlation between spike/RBD antibody and ACE-2 receptor binding in vitro. Our findings are therefore likely to reflect the time to loss of a functional antibody response in SARS-CoV-2.FundingGOSH charity, Wellcome Trust (201470/Z/16/Z and 220565/Z/20/Z). GOSH NIHR Funded Biomedical Research Centre.Trial registration numberNCT04380896.

Summary Background Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. Methods We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). Findings There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8–96·9]) and specificity (99 of 100; 99·0% [94·6–100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3–96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6–93·1]) and specificity (94 of 100; 94·0% [87·4–97·8]) and agreement (254 of 300; 84·7% [80·6–88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6–13·6) in asymptomatic health-care workers and 44·7% (42·0–47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0–18·9). Interpretation Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. Funding None.

Background: Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been shown to neutralize the virus in-vitro and prevent disease in animal challenge models upon re-exposure. However, current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. Methods: The Co-Stars study prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike (S), receptor-binding-domain (RBD) and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for maximum 7 months with the Mesoscale Discovery Assay. Survival analysis determined the proportion of sero-reversion while two hierarchical Gamma models predicted the upper- and lower-bounds of long-term antibody trajectory. Results: A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days post-symptoms, 99% of participants had detectable S-antibodies compared to 75% with detectable N-antibodies. S-antibody was predicted to remain detectable in 95% of participants until 465 days [95%CI 370-575] using a ‘continuous-decay’ model and indefinitely using a ‘decay-to-plateau’ model to account for antibody secretion by long-lived plasma cells. S-antibody titers correlated strongly with surrogate neutralization in-vitro (R2=0.72). N-antibodies, however, decayed rapidly with a half-life of 60 days [95%CI 52-68]. Conclusions: The Co-STAR's study data presented here provides evidence for long-term persistence of neutralizing S-antibodies. This has important implications for the duration of functional immunity following SARS-CoV-2 infection. In contrast, the rapid decay of N-antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics following SARS-CoV-2 infection. Trial Registration: NCT04380896. Funding Statement: GOSH charity, Wellcome Trust (201470/Z/16/Z and 220565/Z/20/Z). GOSH NIHR Funded Biomedical Research Centre. Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: This study was approved by the UK Health Research Authority (www.hra.nhs.uk). Written informed consent was obtained from all participants before recruitment to the study.

Adult-onset measles is rare in the UK, particularly in patients with a complete vaccination history.We present a case of a UK-born patient who received all childhood vaccinations, had no history of recent travel or unwell contacts who was diagnosed with measles complicated by pneumomediastinum. This case highlights the need to consider measles in any patient presenting with a constellation of a macular rash, fever and conjunctivitis, regardless of vaccination status. The nature of the rash can provide an important clue to the diagnosis. Liaison with infection specialists facilitates early diagnosis, allowing for appropriate initial investigations, improving clinical management and early infection control precautions being instituted.

An essential resource for practitioners in infectious diseases and microbiology, studying for the new FRCPath Part 1 infection examination accredited by the Royal College of Pathologists, and trainees sitting the membership exams of the Royal College of Physicians. Including over 300 multiple choice questions in an exam-style Q&A format, this guide provides an invaluable revision platform for domestic and international trainees alike, with scope to present infection-based support for other medical specialties, where infection forms a core component, including intensive care. Authored by leading specialists in infectious diseases and microbiology, this invaluable training guide is the first of its kind to cover both undergraduate and postgraduate material in infectious diseases. Mapping directly from the FRCPath and RCP infection curricula, students are able to explore areas of curriculum to gain knowledge and optimise decision-making skills, under pressure.

Neonatal Legionella pneumophila infection is rare and mortality is high. There has been limited success with the use of extracorporeal membrane oxygenation, with reported mortality in infants of 88%. We present the case of a 5 day old infant with neonatal legionellosis who had been exposed to cold mist humidifiers in the home, filled from a domestic water supply contaminated with legionella. The infant was treated with veno-arterial extracorporeal membrane oxygenation and survived with subsequently normal neurodevelopmental follow-up. In view of the rapid growth of the worldwide humidifier market, the association between neonatal legionella and use of cold mist humidification may be important. Consideration of legionellosis should be given for any neonate presenting with severe sepsis or respiratory compromise who has been exposed to aerosol generating home humidifiers. In spite of previously reported high mortality in infants, this case demonstrates that excellent outcome is possible with early escalation to VA ECMO.

Outpatient parenteral antibiotic therapy (OPAT) is an established antimicrobial delivery method in the UK. OPAT services differ nationwide, with a paucity of high-quality outcome data to enable benchmarking. A retrospective review of clinical outcomes and adverse events (AEs) of all patients treated during 2008-2017 was performed to identify factors associated with success and failure. Regression models were used to identify factors associated with OPAT success, and AEs were described for the study population using definitions recommended by BSAC. In the 10-year period, 2870 patient episodes resulted in 69 610 days of treatment, with a 91.7% rate of successful therapy completion and 92.0% of infections cured or improved. We encountered 196 AEs, including 1 case of Clostridium difficile-associated diarrhoea. AEs occurred in 10.9% of patient episodes. Adverse drug and line events occurred at a rate of 3.3 and 1.78 per 1000 treatment days, respectively. Rashes, blood dyscrasias and hepatitis were the most common drug AEs. The odds of OPAT success was greater for patients who spent more time (14 days) on OPAT therapy (OR = 2.32; P0.01), utilised a peripheral line (OR = 1.83; P0.01), were treated in the clinic compared with self-administration (OR = 2.1; P0.02) and did not experience an AE (OR = 0.23; P0.01). In our setting, the odds of a successful OPAT episode were associated with longer treatment course, OPAT delivered via a peripheral line, administration in an OPAT clinic setting, and no adverse line or drug events.

Antimicrobial resistance (AMR) in populations experiencing war has yet to be addressed, despite the abundance of contemporary conflicts and the protracted nature of twenty-first century wars, in combination with growing global concern over conflict-associated bacterial pathogens. The example of the Syrian conflict is used to explore the feasibility of using existing global policies on AMR in conditions of extreme conflict. The available literature on AMR and prescribing behaviour in Syria before and since the onset of the conflict in March 2011 was identified. Overall, there is a paucity of rigorous data before and since the onset of conflict in Syria to contextualize the burden of AMR. However, post onset of the conflict, an increasing number of studies conducted in neighbouring countries and Europe have reported AMR in Syrian refugees. High rates of multidrug resistance, particularly Gram-negative organisms, have been noted amongst Syrian refugees when compared with local populations. Conflict impedes many of the safeguards against AMR, creates new drivers, and exacerbates existing ones. Given the apparently high rates of AMR in Syria, in neighbouring countries hosting refugees, and in European countries providing asylum, this requires the World Health Organization and other global health institutions to address the causes, costs, and future considerations of conflict-related AMR as an issue of global governance. (c) 2018 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Current evidence describing antimicrobial resistance (AMR) in the context of the Syrian conflict is of poor quality and sparse in nature. This paper explores and reports the major drivers of AMR that were present in Syria pre-conflict and those that have emerged since its onset in March 2011. Drivers that existed before the conflict included a lack of enforcement of existing legislation to regulate over-the-counter antibiotics and notification of communicable diseases. This contributed to a number of drivers of AMR after the onset of conflict, and these were also compounded by the exodus of trained staff, the increase in overcrowding and unsanitary conditions, the increase in injuries, and economic sanctions limiting the availability of required laboratory medical materials and equipment. Addressing AMR in this context requires pragmatic, multifaceted action at the local, regional, and international levels to detect and manage potentially high rates of multidrug-resistant infections. Priorities are (1) the development of a competent surveillance system for hospital-acquired infections, (2) antimicrobial stewardship, and (3) the creation of cost-effective and implementable infection control policies. However, it is only by addressing the conflict and immediate cessation of the targeting of health facilities that the rehabilitation of the health system, which is key to addressing AMR in this context, can progress.

Streptococcus pneumoniae infections arising in hospitalized patients are often assumed to be sporadic and linked to community acquisition. Here, whole-genome sequencing was used to demonstrate nosocomial acquisition of antimicrobial-resistant sequence type 156 (ST156) serotype 9V S. pneumoniae in 3 respiratory patients that resulted in two bacteremias and one lower respiratory tract infection. Two of the cases arose in patients who had recently been discharged from the hospital and were readmitted from the community. Nosocomial spread was suspected solely because of the highly unusual resistance pattern and case presentations within 24 h of one another. The outbreak highlights the potential for rapid transmission and the short incubation period in the respiratory ward setting.

Antibiotic resistance is increasingly recognised as a major threat to global health, with few new antimicrobial agents in development. The intensive care unit provides a unique environment for the growth and spread of drug-resistant organisms. Knowledge of the pathogenesis and mechanisms of resistance of drug-resistant organisms provides a conceptual framework which underpins the clinical manifestation of infections caused by these organisms, and is crucial for the intensivist to understand. Particular importance lies in the prevention of infection and the control of drug-resistant pathogens. The major resistance mechanisms of these organisms will be highlighted, focusing on specific gram-positive (meticillin-resistant Staphylococcus aureus and glycopeptide-resistant Enterococci), gram-negative ( Pseudomonas aeruginosa, Acinetobacter baumannii and multi-drug resistant Enterobacteriaceae) organisms, and then placed in historical and clinical context.

Since 2013, wounded and ill children from Syria have received treatment in Israel. Screening cultures indicated that multidrug-resistant (MDR) pathogens colonized 89 (83%) of 107 children. For 58% of MDR infections, the pathogen was similar to that identified during screening. MDR screening of these children is valuable for purposes of isolation and treatment.

Pseudomonas aeruginosa infection in cystic fibrosis (CF) is common and is associated with significant morbidity and mortality. Antibiotics aimed at Pseudomonas are used to eradicate early infection, suppress chronic infection, and treat acute exacerbations. Treatment options are limited due to increasing resistance and in vitro susceptibility information does not always correlate with in vivo outcomes. A case is presented with chronic Pseudomonas infection and the management and antibiotic choices for the patient during an acute hospital admission discussed, including the role of inhaled antibiotics such as tobramycin.

A 66-year-old woman with a history of tissue aortic valve replacement and chronic back pain presented to the emergency department with a suspected right leg deep vein thrombosis. A recent outpatient MRI had revealed discitis. A ventricular fibrillation cardiac arrest occurred in the emergency department. Cardiac output was restored on the fifth defibrillation. A transthoracic echocardiogram showed large aortic valve vegetations. Clinical impression was of infective endocarditis with cardiac arrest secondary to coronary artery embolisation. Peripheral blood cultures grew Cardiobacterium hominis, and appropriate intravenous antibiotic therapy was administered. The infected prosthetic valve was excised. The patient experienced postoperative complete heart block and a right hemisphere cerebrovascular accident, however she is now recovering well. This case describes an unusual case of infective endocarditis secondary to C. hominis, with disc, leg, coronary artery and brain septic embolisation. Infective endocarditis is an important differential diagnosis in multisystem presentations.

A 61-year-old patient presented with drowsiness, decreased appetite and weight loss. On examination he had several splinter haemorrhages and a tender mass over the right temporal region. Respiratory and abdominal examinations were unremarkable and heart sounds were normal with no clinically audible murmurs. He spiked regular temperatures and consequently had several blood cultures taken. Transthoracic and transoeseophageal echocardiogram showed a 3 cm mitral valve vegetation. MRI confirmed suspicions of septic emboli in the brain. Blood cultures grew Rothia aeria and he was started on benzylpenicillin, rifampicin and gentamicin. After a period of observation he deteriorated clinically and biochemically, surgical intervention therefore ensued with an urgent metallic mitral valve replacement. Nineteen days postsurgery the patient was successfully discharged on outpatient antibiotic therapy and warfarin. In view of complications such as embolisation and cerebral infarction, R aeria endocarditis should be managed aggressively and with a high index of clinical suspicion.