Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care.

BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+.

Standardised treatment protocol for necrotizing otitis externa: retrospective case series and systematic literature review.

OBJECTIVES: There is currently no consensus on the most effective treatment protocol for necrotizing otitis externa (NOE). This article aims to produce a NOE treatment protocol from the literature and clinical experience. METHODS: A total of 26 case series from the literature were reviewed in combination with a retrospective case series of inpatients from Hull University Teaching Hospitals NHS Trust from 2013-2018. Over 5 years, 40 patients were identified, with only 29 being analysed due to unavailable or incomplete case notes. RESULTS: In the literature review, the most common bacterial species causing NOE was Pseudomonas aeruginosa. Resistance to ciprofloxacin was prevalent, however multidrug resistance was rare. Ciprofloxacin and ceftazidime were the most widely used antibiotics. No ceftazidime resistance was reported in the literature or in our cohort. The average age of the patients in our cohort was 80 years. Moreover, 62% had either diabetes mellitus or were immunosuppressed. One patient died directly due to NOE-related sepsis. Intravenous ceftazidime monotherapy was mostly used. The duration of treatment was 6-7 weeks, with no relapses documented. CONCLUSION: Ceftazidime monotherapy was an effective empirical treatment in our cohort, and a total duration of 6-7 weeks of antibiotics was sufficient. We have created a standardised treatment protocol based on our findings that will need to be validated in a larger cohort of patients.

Sixty-eight consecutive patients assessed for COVID-19 infection: Experience from a UK Regional infectious diseases Unit.

BACKGROUND: Assessment of possible infection with SARS-CoV-2, the novel coronavirus responsible for COVID-19 illness, has been a major activity of infection services since the first reports of cases in December 2019. OBJECTIVES: We report a series of 68 patients assessed at a Regional Infection Unit in the UK. METHODS: Between 29 January 2020 and 24 February 2020, demographic, clinical, epidemiological and laboratory data were collected. We compared clinical features between patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment. RESULTS: Patients assessed were aged from 0 to 76 years; 36/68 were female. Peaks of clinical assessments coincided with updates to the case definition for suspected COVID-19. Microbiological diagnoses included SARS-CoV-2, mycoplasma pneumonia, influenza A, non-SARS/MERS coronaviruses and rhinovirus/enterovirus. Nine of sixty-eight received antimicrobials, 15/68 were admitted, 5 due to inability to self-isolate. Patients requiring admission on clinical grounds or antimicrobials (14/68) were more likely to have fever or raised respiratory rate compared to those not requiring admission or antimicrobials. CONCLUSIONS: The majority of patients had mild illness, which did not require clinical intervention. This finding supports a community testing approach, supported by clinicians able to review more unwell patients. Extensions of the epidemiological criteria for the case definition of suspected COVID-19 lead to increased screening intensity; strategies must be in place to accommodate this in time for forthcoming changes as the epidemic develops.

Positron emission tomography and reframing vasculitis as a spectrum of disease when investigating a patient with a fever of unknown origin.

A retired businessman presented to the infectious diseases department with a history of ongoing fevers and myalgia and raised inflammatory markers. This continued despite adequate antibiotic treatment of an epididymo-orchitis. Extensive investigations, including bone marrow and liver biopsies and a positron emission tomography, did not reveal a cause but showed reactive change in the bone marrow. Later, he developed a vasculitic rash and vision loss due to non-arteritic anterior ischaemic optic neuropathy. High-dose steroids were immediately initiated. A temporal artery biopsy was performed, which confirmed a healing large vessel vasculitis, possibly giant cell arteritis. He has responded very well to therapy. We must better appreciate the limitations of positron emission tomography in investigating a fever of unknown origin. The case also encourages awareness of autoimmune disorders as the leading category of causative diseases for this in older age groups.

Spontaneous Bacterial Peritonitis due to Actinomyces Mimicking a Perforation of the Proximal Jejunum.

BACKGROUND Pelvic-abdominal actinomycosis is a rare chronic condition caused by an anaerobic, gram-negative rod-shaped commensal bacterium of the Actinomyces species. When Actinomyces becomes pathogenic, it frequently causes a chronic infection with granulomatous abscess formation with pus. Due to diversity in clinical and radiological presentation, actinomycosis can easily be mistaken for several other conditions. Peritonitis without preceding abscess formation caused by Actinomyces species has been described in only few cases before in literature. CASE REPORT We report a case of spontaneous pelvic-abdominal peritonitis with presence of pneumoperitoneum and absence of preceding abscesses due to acute actinomycosis mimicking a perforation of the proximal jejunum in a 42-year-old female with an intra-uterine contraceptive device in place. Explorative laparotomy revealed 2 liters of odorless pus but no etiological explanation for the peritonitis. The intra-uterine contraceptive device was removed. Cultivation showed growth of Actinomyces turicensis. The patient was successfully treated with penicillin. CONCLUSIONS In the case of primary bacterial peritonitis or lower abdominal pain without focus in a patient with an intra-uterine device in situ, Actinomyces should be considered as a pathogen.