Acute lower respiratory tract infection in infancy: a seven year follow-up study

Seven years after hospitalisation for acute lower respiratory tract infection in infancy, 200 children and their case -controls were assessed for respiratory status and epidemiological characteristics. The index group comprised 100 cases where respiratory syncytial virus had been responsible for the index illness (RSV +) and 100 cases in whom this organism had not been found (RSV -).No differences were noted between index and control children with respect to birth weight and gestational age, although breast feeding was more frequently observed in control children. Index children reported more respiratory symptoms and asthma as well as other indices of respiratory illhealth. Although index children appeared to be a socially disadvantaged group, parental respiratory symptoms and smoking habits were comparable in both groups of children. The atopic background was similar in index and control populations. At follow -up, index children were shorter than controls, although their weights were comparable. Tests of respiratory function were diminished in index children, who also had evidence of bronchial hyperreactivity.RSV+ and RSV- index children showed similar clinical characteristics and atopic background. No significant differences were found in the age at which the index illness occurred, or in the proportion who were breast -fed. The results of tests of respiratory function and exercise test were comparable in RSV+ and RSV- children.Children who had suffered bronchitis, bronchiolitis or pneumonia had similar clinical characteristics compared to their controls, with the exception that fewer children who had bronchiolitis were breast -fed, and children who suffered pneumonia were of lower birth weight. All three sub -groups of index children reported more respiratory symptoms and ill health than their controls. Social and family factors were less favourable when compared to control children. The atopic background was similar between the three disease categories, and also between index and control children. Tests of respiratory function were significantly reduced only in children who had bronchiolitis, although the trend in the bronchitis and pneumonia children was also towards poorer function. A one -way analysis of variance between disease categories on the differences between case and control for each respiratory function measurement showed that differences within a disease category was geater than the differences between disease categories.Following the index illness, children were reported to cough, wheeze or remain asymptomatic. Those with symptoms were almost identical in terms of clinical, social and family characteristics, as well as atopic background; but differed from their controls. Tests of respiratory function were diminished in both groups of symptomatic children, with evidence of bronchial hyper- reactivity. The asymptomatic index children did not differ from the symptomatic children with respect to social factors, suggesting that these contribute little to the occurrence of respiratory symptoms. Asymptomatic children were of similar height to their controls. Respiratory function was also comparable although there was a slight trend to hyper- reactive airways.Children whose index illness was attributed solely to acute infections (RSV +, non -atopic) reported similar occurrences of respiratory symptoms to their controls. Respiratory function was also comparable. When there was a background history of atopy, children reported more respiratory symptoms and had significantly lower tests of respiratory function as well as evidence of bronchial hyperreactivity when compared with controls. The results suggest that atopy is a determinant of poor respiratory function, but they may have also been influenced by the discrepancy in numbers. Bronchial reactivity was present in excess in atopic and non -atopic index cases, despite being significant only in the atopic children.Index children with bronchial reactivity showed similar clinical, atopic, social and family characteristics to those without evidence of hyperreactive airways, but these two groups differed clinically and in social and family background from control children. Those with bronchial reactivity wheezed more, and there was a greater percentage of asthmatics. Respiratory function was significantly diminished compared to controls. There was no excess of atopic disorders in the index children with hyperreactive airways.Children without evidence of hyperreactive airways also reported more respiratory symptoms, but bronchitis rather than asthma was diagnosed in these children. Except for a lower PEFR, all other tests of respiratory function were similar between index and control children.Ventilatory dysfunction paralleled bronchial reactivity. It is not clear which is of primary importance, or if there is any relationship between the two. Acute respiratory infection may have caused both these abnormalities, or they could have predated the event, rendering children more susceptible to infection

Risk of bloodstream infection in children admitted to paediatric intensive care units in England and Wales following emergency inter-hospital transfer.

PURPOSE: Adherence to full sterile procedures may be compromised when central venous catheters are inserted as part of emergency resuscitation and stabilisation, particularly outside the intensive care unit. Half of emergency admissions to paediatric intensive care units (PICU) in the UK occur after stabilisation at other hospitals. We determined whether bloodstream infection (BSI) occurred more frequently in children admitted to PICU after inter-hospital transfer compared to within-hospital admissions. METHODS: Data on emergency admissions to 20 PICUs in England and Wales for children <16 years between 2003-2012 were linked from the national PICU audit database (PICANet) and national infection surveillance (LabBase2). PICU-acquired BSI was defined as any positive blood culture sampled between 2 days after admission and 2 days following discharge from PICU. RESULTS: A total of 32,861/62,515 (53%) admissions were inter-hospital transfers. Multivariable regression showed no significant difference in rates of PICU-acquired BSI by source of admission (incidence-rate ratio for inter-hospital transfer versus within-hospital admission = 0.97; 95% CI 0.87-1.07) after adjusting for other risk-factors. Rates decreased more rapidly between 2003 and 2012 for inter-hospital transfers: 17.0% (95% CI 14.9-19.0% per year) compared with 12.4% (95% CI 9.9-14.9% per year) for within-hospital admissions. The median time to first PICU-acquired BSI did not differ significantly between inter-hospital transfers (7 days; IQR 4-13) and within-hospital admissions (8 days; IQR 4-15). CONCLUSIONS: Nationally, inter-hospital transfer is no longer a significant risk factor for PICU-acquired BSI. Given the large proportion of infection occurring in the second week of admission, initiatives to further reduce PICU-acquired BSI should focus on maintaining sterile procedures after admission

Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.

BACKGROUND: Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care. METHODS: We did a randomised controlled trial of children admitted to 14 English paediatric intensive care units. Children younger than 16 years were eligible if they were admitted or being prepared for admission to a participating paediatric intensive care unit and were expected to need a central venous catheter for 3 or more days. Children were randomly assigned (1:1:1) to receive a central venous catheter impregnated with antibiotics, a central venous catheter impregnated with heparin, or a standard central venous catheter with computer generated randomisation in blocks of three and six, stratified by method of consent, site, and envelope storage location within the site. The clinician responsible for inserting the central venous catheter was not masked to allocation, but allocation was concealed from patients, their parents, and the paediatric intensive care unit personnel responsible for their care. The primary outcome was time to first bloodstream infection between 48 h after randomisation and 48 h after central venous catheter removal with impregnated (antibiotic or heparin) versus standard central venous catheters, assessed in the intention-to-treat population. Safety analyses compared central venous catheter-related adverse events in the subset of children for whom central venous catheter insertion was attempted (per-protocol population). This trial is registered with ISRCTN number, ISRCTN34884569. FINDINGS: Between Nov 25, 2010, and Nov 30, 2012, 1485 children were recruited to this study. We randomly assigned 502 children to receive standard central venous catheters, 486 to receive antibiotic-impregnated catheters, and 497 to receive heparin-impregnated catheters. Bloodstream infection occurred in 18 (4%) of those in the standard catheters group, 7 (1%) in the antibiotic-impregnated group, and 17 (3%) assigned to heparin-impregnated catheters. Primary analyses showed no effect of impregnated (antibiotic or heparin) catheters compared with standard central venous catheters (hazard ratio [HR] for time to first bloodstream infection 0.71, 95% CI 0.37-1.34). Secondary analyses showed that antibiotic central venous catheters were better than standard central venous catheters (HR 0.43, 0.20-0.96) and heparin central venous catheters (HR 0.42, 0.19-0.93), but heparin did not differ from standard central venous catheters (HR 1.04, 0.53-2.03). Clinically important and statistically significant absolute risk differences were identified only for antibiotic-impregnated catheters versus standard catheters (-2.15%, 95% CI -4.09 to -0.20; number needed to treat [NNT] 47, 95% CI 25-500) and antibiotic-impregnated catheters versus heparin-impregnated catheters (-1.98%, -3.90 to -0.06, NNT 51, 26-1667). Nine children (2%) in the standard central venous catheter group, 14 (3%) in the antibiotic-impregnated group, and 8 (2%) in the heparin-impregnated group had catheter-related adverse events. 45 (8%) in the standard group, 35 (8%) antibiotic-impregnated group, and 29 (6%) in the heparin-impregnated group died during the study. INTERPRETATION: Antibiotic-impregnated central venous catheters significantly reduced the risk of bloodstream infections compared with standard and heparin central venous catheters. Widespread use of antibiotic-impregnated central venous catheters could help prevent bloodstream infections in paediatric intensive care units. FUNDING: National Institute for Health Research, UK

Generalisability and Cost-Impact of Antibiotic-Impregnated Central Venous Catheters for Reducing Risk of Bloodstream Infection in Paediatric Intensive Care Units in England

Background: We determined the generalisability and cost-impact of adopting antibiotic-impregnated CVCs in all paediatric intensive care units (PICUs) in England, based on results from a large randomised controlled trial (the CATCH trial; ISRCTN34884569). Methods: BSI rates using standard CVCs were estimated through linkage of national PICU audit data (PICANet) with laboratory surveillance data. We estimated the number of BSI averted if PICUs switched from standard to antibiotic-impregnated CVCs by applying the CATCH trial rate-ratio (0.40; 95% CI 0.17,0.97) to the BSI rate using standard CVCs. The value of healthcare resources made available by averting one BSI as estimated from the trial economic analysis was £10,975; 95% CI -£2,801,£24,751. Results: The BSI rate using standard CVCs was 4.58 (95% CI 4.42,4.74) per 1000 CVC-days in 2012. Applying the rate-ratio gave 232 BSI averted using antibiotic CVCs. The additional cost of purchasing antibiotic-impregnated compared with standard CVCs was £36 for each child, corresponding to additional costs of £317,916 for an estimated 8831 CVCs required in PICUs in 2012. Based on 2012 BSI rates, management of BSI in PICUs cost £2.5 million annually (95% uncertainty interval: -£160,986, £5,603,005). The additional cost of antibiotic CVCs would be less than the value of resources associated with managing BSI in PICUs with standard BSI rates >1.2 per 1000 CVC-days. Conclusions: The cost of introducing antibiotic-impregnated CVCs is less than the cost associated with managing BSIs occurring with standard CVCs. The long-term benefits of preventing BSI could mean that antibiotic CVCs are cost-effective even in PICUs with extremely low BSI rates

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study.

Background: Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods: This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results: Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation: NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding: National Institute for Health Research and Medical Research Council

Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill &amp; Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London

Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill &amp; Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London