Alicia Demirjian’s research while affiliated with The London College and other places

Objective Staphylococcus capitis , a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection of S. capitis versus other CoNS species. Methods In this retrospective case–control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed. Results We identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22–27 weeks) and with extremely low birth weight (400–999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species ( Staphylococcus epidermidis, S. capitis , Staphylococcus haemolyticus and Staphylococcus warneri ) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate. Conclusion Infants with S. capitis detected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species.

Objective We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks’ gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance. Design and setting Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE). Participants All live births ≥34 weeks’ gestation between September 2020 and August 2021. Outcome measures EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age . We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures. Results Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (<72 hours) was 0.64/1000 live births. The incidence of EOS identified >24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals. Conclusion There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life.

Introduction Reducing inappropriate antibiotic prescribing tempers the growing threat of antimicrobial resistance. We aimed to quantify the associated impact of COVID-19-related national restrictions in England on dental antibiotic dispensing and describe changes in appointments and modes of delivery of care. Methods Interrupted time series analyses were completed using NHS Business Service Authority (NHSBSA) ePACT2 data to measure the associated change in antibiotic dispensing in England following COVID-19-related restrictions (which began March 2020). For face-to-face dental consultations, NHS dental treatment plan (FP17) data were used. For remote consultations during the COVID-19 period, NHSBSA Compass system remote management data were used. Results Between January 2016 and February 2020, there was a decreasing trend in antibiotic dispensing (−0.02 per 1000 population per month, P < 0.05). In contrast, there was an increase of 0.98 per 1000 population (P < 0.05) in March. The peak in antibiotic use occurred between June 2020 and July 2020, once the restrictions were eased. At the end of the study period (July 2021), the elevated prescribing trend had not returned to pre-pandemic counterfactual levels, although exhibiting a declining trend. A stable trend in dental treatment plans was seen pre-COVID-19, with a sharp decline coinciding with the restrictions. Dental treatment plans had not yet returned to the higher pre-pandemic levels. Conclusions Dental antibiotic prescribing significantly increased with the national COVID-19 restrictions when service delivery was altered with the closure of dental practices and introduction of remote consultations. Teledentistry was likely associated with inappropriate antibiotic prescribing. Continued antimicrobial stewardship and prudent use of antibiotics in dentistry is important.

Background: The multi-drug resistant Staphylococcus capitis clone, NRCS-A is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. Aim: To investigate the potential for S. capitis to colonise surfaces within NICUs. Methods: Surface swabs were collected from four NICUs with and without known NRCS-A colonisations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. Findings: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whilst S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for 3 days with minimal losses in viability (< 0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. Conclusion: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

Objective: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. Methods: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. Results: We analysed WGS data of 838S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005-2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. Conclusions: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection.

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.

Objective Invasive bacterial infections account for an estimated 15% of infant deaths worldwide. We aimed to estimate the incidence and trends in invasive bacterial infections in infants caused by Gram-negative pathogens in England during 2011–2019. Methods Laboratory-confirmed invasive bacterial infections in infants (<1 year old) were identified in the UK Health Security Agency national laboratory surveillance data from April 2011 to March 2019. Polymicrobial infections were defined as two or more bacterial species from the same normally sterile sample site. Early-onset infections were defined as <7 days from birth and late-onset as ≥7 days (neonates 7–28 days; infants ≥29 days). Trend analyses were carried out using Poisson (for episodes/incidence) and beta (for proportions) regression. Results The annual incidence of invasive bacterial infections increased by 35.9%, from 189.8 to 258.0 cases per 100 000 live births (p<0.001). Late-onset infections in both neonates and infants increased substantially over the study period (p<0.001), whereas early-onset infections increased slightly (p=0.002). Escherichia coli was the most common Gram-negative pathogen isolated and accounted for 27.2% of the overall rise in Gram-negative infant disease incidence. Polymicrobial infections almost doubled, increasing from 29.2 to 57.7 per 100 000 live births (p<0.001), and mostly involved two species (81.3%, 1604/1974 episodes). Conclusions The incidence of Gram-negative invasive bacterial infections in infants increased between 2011/2012 and 2018/2019 in England, driven mainly by an increase in late-onset infections. Further work is required to elucidate the risk factors and drivers of this increased incidence so that opportunities for prevention can be identified.

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.

In June 2021, a national incident team was formed due to an increased detection of Staphylococcus capitis in samples from hospitalised infants. Staphylococcus capitis has been known to cause outbreaks in neonatal units across the globe, but the extent of the UK spread was unclear. A literature review was undertaken to support case identification, clinical management and environmental infection control. A literature search was undertaken on multiple databases from inception to 24 May 2021, using keywords such as “Staphylococcus capitis”, “NRCS-A”, “S. capitis”, “neonate”, “newborn” and “neonatal intensive care unit” (NICU). After screening, 223 articles of relevance were included. Results show incidences of S. capitis outbreaks have frequently been associated with the outbreak clone (NRCS-A) and environmental sources. The NRCS-A harbours a multidrug resistance profile that includes resistance to beta-lactam antibiotics and aminoglycosides, with several papers noting resistance or heteroresistance to vancomycin. The NRCS-A clone also harbours a novel SCCmec-SCCcad/ars/cop composite island and increased vancomycin resistance. The S. capitis NRCS-A clone has been detected for decades, but the reasons for the potentially increased frequency are unclear, as are the most effective interventions to manage outbreaks associated with this clone. This supports the need for improvements in environmental control and decontamination strategies to prevent transmission.