METHODS AND ANALYSIS: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are 'clinical cure' at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.
ETHICS AND DISSEMINATION: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children's and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.
TRIAL REGISTRATION: ACTRN12616000046404.
MATERIALS AND METHODS: A two-arm prospective cohort study was conducted among adult patients with COVID-19 categories 2 and 3 treated with Paxlovid® and a matched control group. A standard risk-stratified scoring system was used to establish Paxlovid® eligibility. All patients who were prescribed Paxlovid® and took at least one dose of Paxlovid® were included in the study. The control patients were selected from a centralised COVID-19 patient registry and matched based on age, gender and COVID-19 stage severity.
RESULTS: A total of 552 subjects were included in the study and evenly allocated to the treatment and control groups. There was no statistically significant difference in 28-day hospitalisation after diagnosis [Paxlovid®: 26 (9.4%), Control: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or all-cause death [Paxlovid®: 2 (0.7%), Control: 3 (1.1%), OR 1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant reduction in hospitalisation duration, intensive care unit admission events or supplementary oxygen requirement in the treatment arm. Ethnicity, COVID-19 severity at diagnosis, comorbidities and vaccination status were predictors of hospitalisation events.
CONCLUSION: In this two-arm study, Paxlovid® did not significantly lower the incidence of hospitalisation, all-cause death and the need for supplemental oxygen. Adverse effects were frequent but not severe. Paxlovid® efficacy varied across settings and populations, warranting further real-world investigations.
OBJECTIVE: To determine the clinical characteristics, culprit drugs and outcome of patients with AGEP.
METHODS: A retrospective note review of all AGEP patients seen from 2001-2015.
RESULTS: Among 21 AGEP patients, 76% were Malays, 9.5% Chinese, 9.5% Indians, and 5% Iban. Sixteen were females and 5 were males. Median age of patients was 40 years (IQR: 26). The main culprit drug was amoxicillin (10 cases), followed by cloxacillin (three cases), phenytoin (two cases) and one case each of carbamazepine, sulphasalazine, allopurinol, cephalexin, ceftriaxone, celecoxib and herbal product. The median time from drug initiation to onset of AGEP was 3 days (IQR: 5.5). Fever was documented in 52.4 %, mucosal involvement 9.5%, purpura 4.7% and blisters 4.7%. Neutrophilia was observed in 63.6% of patients and eosinophilia in 28.5%. While most patients required admission (67%), all achieved complete recovery within 15 days without any sequela.
CONCLUSIONS: AGEP predominantly affects Malay females in this study. The most common culprit drug was amoxicillin. Our patients exhibited the classic clinical manifestations of AGEP and confirmed the generally benign nature of this reaction upon drug withdrawal. Although the overall prognosis is good, prompt diagnosis of AGEP is important because drug withdrawal is the mainstay therapy.
METHODS: This is a retrospective case-control study (ratio 1:1) where a patient with CRE infection or colonisation was matched with a control. The control was an individual who tested negative for CRE but was a close contact of a patient testing positive and was admitted at the same time and place. Univariate and multivariate statistical analyses were done.
RESULTS: The study included 154 patients. The majority of the CRE was Klebsiella species (83%). From univariate analysis, the significant risk factors were having a history of indwelling devices (OR: 2.791; 95% CI: 1.384-5.629), concomitant other MDRO (OR: 2.556; 95% CI: 1.144-5.707) and hospitalisation for more than three weeks (OR: 2.331; 95% CI: 1.163-4.673). Multivariate analysis showed that being unable to ambulate on admission (adjusted OR: 2.345; 95% CI: 1.170-4.699) and antibiotic exposure (adjusted OR: 3.515; 95% CI: 1.377-8.972) were independent predictors. The in-hospital mortality rate of CRE infection was high (64.5%). CRE acquisition resulted in prolonged hospitalisation (median=35 days; P<0.001).
CONCLUSION: CRE infection results in high morbidity and mortality. On top of the common risk factors, patients with mobility restriction, prior antibiotic exposures and hospitalisation for more than three weeks should be prioritised in the screening strategy to control the spread of CRE.