Retrospective cohort study investigating extent of pertussis transmission during a boarding school outbreak, England, December 2017 to June 2018.

On 1 May 2018, a pertussis outbreak was declared and widespread vaccination recommended at an all-female secondary boarding school in southern England. We conducted a retrospective cohort study to determine the extent of pertussis transmission and identify risk factors in this semi-closed population. Of 504 students and staff assessed before post-exposure vaccination, 48% (n = 240) had evidence of pertussis. A sub-analysis of 409 students found that both residential dormitory (p = 0.05) and school year (p = 0.03) were associated with pertussis, with odds decreasing by 11% for each increase in school year (95% confidence interval: 0.7-20.2). Odds of pertussis were 1.7 times higher in those assumed to have received acellular vaccines for their primary course compared with those assumed to have received whole-cell vaccines (based on date of birth), although this difference was not significant (p = 0.12). Our findings support the need for timely, widespread vaccination following identification of cases among adolescents in a semi-closed United Kingdom (UK) setting and to review the evidence for the introduction of an adolescent pertussis booster to the UK routine vaccination programme.

Cryptic resistance in Staphylococcus aureus: a risk for the treatment of skin infection?

PURPOSE OF REVIEW: The purpose of this review is to explore major challenges that face routine diagnostic laboratories in detecting cryptic (hidden) antibiotic resistances in Staphylococcus aureus and the impact of these covert resistances in the management of skin and soft tissue infections. RECENT FINDINGS: The review covers recent literature and works regarding a number of evolving mechanisms and forms of antibiotic resistances in S. aureus, including novel oxacillin-susceptible-mecA-positive meticillin-resistant S. aureus (OS-MRSA) strains and MRSA isolates that harbour a divergent mecA homologue termed mecC within the novel staphylococcal cassette chromosome mec XI element. SUMMARY: S. aureus strains causing skin and soft tissue infections are evolving with regard to virulence as well as antimicrobial resistance. Cryptic resistances continue to escape routine diagnostic tests. This means that there are still many unknowns regarding their global dissemination, virulence, threats in clinical practice and optimal treatment strategies. Larger studies are needed to further understand the pathogenic consequences of cryptic resistances in S. aureus in skin and soft tissue infections, which may ultimately provide novel preventive or treatment approaches for this significant human pathogen.

Diagnostic accuracy of loop-mediated isothermal amplification coupled to nanopore sequencing (LamPORE) for the detection of SARS-CoV-2 infection at scale in symptomatic and asymptomatic populations.

OBJECTIVES: Rapid, high throughput diagnostics are a valuable tool, allowing the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations so as to identify and isolate people with asymptomatic and symptomatic infections. Reagent shortages and restricted access to high throughput testing solutions have limited the effectiveness of conventional assays such as quantitative RT-PCR (RT-qPCR), particularly throughout the first months of the coronavirus disease 2019 pandemic. We investigated the use of LamPORE, where loop-mediated isothermal amplification (LAMP) is coupled to nanopore sequencing technology, for the detection of SARS-CoV-2 in symptomatic and asymptomatic populations. METHODS: In an asymptomatic prospective cohort, for 3 weeks in September 2020, health-care workers across four sites (Birmingham, Southampton, Basingstoke and Manchester) self-swabbed with nasopharyngeal swabs weekly and supplied a saliva specimen daily. These samples were tested for SARS-CoV-2 RNA using the Oxford Nanopore LamPORE system and a reference RT-qPCR assay on extracted sample RNA. A second retrospective cohort of 848 patients with influenza-like illness from March 2020 to June 2020 were similarly tested from nasopharyngeal swabs. RESULTS: In the asymptomatic cohort a total of 1200 participants supplied 23 427 samples (3966 swab, 19 461 saliva) over a 3-week period. The incidence of SARS-CoV-2 detection using LamPORE was 0.95%. Diagnostic sensitivity and specificity of LamPORE was >99.5% (decreasing to approximately 98% when clustered estimation was used) in both swab and saliva asymptomatic samples when compared with the reference RT-qPCR test. In the retrospective symptomatic cohort, the incidence was 13.4% and the sensitivity and specificity were 100%. CONCLUSIONS: LamPORE is a highly accurate methodology for the detection of SARS-CoV-2 in both symptomatic and asymptomatic population settings and can be used as an alternative to RT-qPCR.

Duration of intravenous antibiotic therapy for children with acute osteomyelitis or septic arthritis: a feasibility study.

BACKGROUND: There is little current consensus regarding the route or duration of antibiotic treatment for acute osteomyelitis (OM) and septic arthritis (SA) in children. OBJECTIVE: To assess the overall feasibility and inform the design of a future randomised controlled trial (RCT) to reduce the duration of intravenous (i.v.) antibiotic use in paediatric OM and SA. DESIGN: (1) A prospective service evaluation (cohort study) to determine the current disease spectrum and UK clinical practice in paediatric OM/SA; (2) a prospective cohort substudy to assess the use of targeted polymerase chain reaction (PCR) in diagnosing paediatric OM/SA; (3) a qualitative study to explore families' views and experiences of OM/SA; and (4) the development of a core outcome set via a systematic review of literature, Delphi clinician survey and stakeholder consensus meeting. SETTING: Forty-four UK secondary and tertiary UK centres (service evaluation). PARTICIPANTS: Children with OM/SA. INTERVENTIONS: PCR diagnostics were compared with culture as standard of care. Semistructured interviews were used in the qualitative study. RESULTS: Data were obtained on 313 cases of OM/SA, of which 218 (61.2%) were defined as simple disease and 95 (26.7%) were defined as complex disease. The epidemiology of paediatric OM/SA in this study was consistent with existing European data. Children who met oral switch criteria less than 7 days from starting i.v. antibiotics were less likely to experience treatment failure (9.6%) than children who met oral switch criteria after 7 days of i.v. therapy (16.1% when switch was between 1 and 2 weeks; 18.2% when switch was > 2 weeks). In 24 out of 32 simple cases (75%) and 8 out of 12 complex cases (67%) in which the targeted PCR was used, a pathogen was detected. The qualitative study demonstrated the importance to parents and children of consideration of short- and long-term outcomes meaningful to families themselves. The consensus meeting agreed on the following outcomes: rehospitalisation or recurrence of symptoms while on oral antibiotics, recurrence of infection, disability at follow-up, symptom free at 1 year, limb shortening or deformity, chronic OM or arthritis, amputation or fasciotomy, death, need for paediatric intensive care, and line infection. Oral switch criteria were identified, including resolution of fever for ≥ 48 hours, tolerating oral food and medicines, and pain improvement. LIMITATIONS: Data were collected in a 6-month period, which might not have been representative, and follow-up data for long-term complications are limited. CONCLUSIONS: A future RCT would need to recruit from all tertiary and most secondary UK hospitals. Clinicians have implemented early oral switch for selected patients with simple disease without formal clinical trial evidence of safety. However, the current criteria by which decisions to make the oral switch are made are not clearly established or evidence based. FUTURE WORK: A RCT in simple OM and SA comparing shorter- or longer-course i.v. therapy is feasible in children randomised after oral switch criteria are met after 7 days of i.v. therapy, excluding children meeting oral switch criteria in the first week of i.v. therapy. This study design meets clinician preferences and addresses parental concerns not to randomise prior to oral switch criteria being met. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The value of procalcitonin measurement in localized skin and skin structure infection, diabetic foot infections, septic arthritis and osteomyelitis.

Serum procalcitonin (PCT) is an established diagnostic marker for severe or systemic bacterial infections such as pneumonia, sepsis and septic shock. Data regarding the role of PCT in localized infections without systemic inflammatory response syndrome are scarce. The aim of this review is to assess the value of PCT measurements in localized infections such as skin and skin structure infections, diabetic foot infections, septic arthritis (SA) and osteomyelitis. It appears that serum PCT is unlikely to change the clinical practice in skin and skin structure infection. However, serum PCT could have a role in diagnosis and monitoring of diabetic foot infections in hospitalized settings. There are conflicting reports regarding the ability of serum PCT to distinguish SA from non-SA; synovial PCT may be more appropriate in these settings, including in implant-related infections. Better designed studies are needed to evaluate the usefulness of PCT with or without other biomarkers in localized infections.

Nasal self-swabbing for estimating the prevalence of Staphylococcus aureus in the community.

Staphylococcus aureus remains a significant cause of morbidity and mortality and, therefore, a burden on healthcare systems. Our aim was to estimate the current rate of nasal S. aureus carriage in the general population and to determine the feasibility of nasal self-swabbing as a means of detection. Two thousand people (1200 adults and 800 children) from a single NHS general practice in Southampton, UK, were randomly selected from a general practice age sex register, stratified by age and sex, and invited to undertake nasal self-swabbing in their own home. Overall, 362 (32.5%) swabs from adults and 168 (22%) from children were returned. Responses were greater for adults and those of increased age, female gender and decreasing socio-economic deprivation. The overall estimated practice carriage rate of S. aureus directly standardized for age sex was 28% [95% confidence interval (CI) 26.1-30.2%]. Carriage of meticillin-susceptible S. aureus was 27% (95% CI 26.1-30.2%), whilst that of meticillin-resistant S. aureus was 1.9% (95% CI 0.7-3.1%). Although nasal self-swabbing rates were relatively low, they are comparable to other studies and may allow large population-based carriage studies to be undertaken at relatively low cost. Importantly, this study updates prevalence data for S. aureus carriage in the community.