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1.
Front Cell Infect Microbiol ; 11: 778808, 2021.
Article in English | MEDLINE | ID: covidwho-1789350

ABSTRACT

Objectives: Overuse of antibiotics and antibiotic resistance are global healthcare problems. In pediatric patients with respiratory infections, viral and bacterial etiologies are challenging to distinguish, leading to irrational antibiotic use. Rapid and accurate molecular diagnostic testing methods for respiratory pathogens has been shown to facilitate effective clinical decision-making and guide antibiotic stewardship interventions in the developed regions, but its impacts on pediatric patient care in the developing countries remain unclear. Methods: In this single-center, retrospective case-control study, we compared demographics, clinical characteristics, especially microbiological findings, and antibiotic usage between pediatric patients with respiratory infection receiving FilmArray Respiratory Panel (FilmArray RP) testing and a matched routine testing control group. Our primary outcome was the duration of intravenous antibiotics treatment (DOT) during hospitalization. Results: Each group consisted of 346 children with a respiratory infection. In the FilmArray RP testing group, the DOT was shorter than that in the routine testing group (6.41 ± 3.67 days versus 7.23 ± 4.27 days; p = 0.006). More patients in the FilmArray RP testing group de-escalated antibiotic treatments within 72 hours of hospitalization (7.80%, 27/346 versus 2.60%, 9/346; p = 0.002). By contrast, fewer patients in the FilmArray RP testing group had escalated antibiotic treatments between 72 hours and seven days (7.80% versus 14.16%; p = 0.007). The cost of hospitalization was significantly lower in the FilmArray RP testing group ($ 1413.51 ± 1438.01 versus $ 1759.37 ± 1929.22; p = 0.008). Notably, the subgroup analyses revealed that the FilmArray RP test could shorten the DOT, improve early de-escalation of intravenous antibiotics within 72 hours of hospitalization, decline the escalation of intravenous antibiotics between 72 hours and seven days, and reduce the cost of hospitalization for both patient populations with or without underlying diseases. Conclusions: Molecular point-of-care testing for respiratory pathogens could help to reduce intravenous antibiotic use and health care costs of pediatric patients with respiratory infections in developing countries.


Subject(s)
Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Child , Humans , Molecular Diagnostic Techniques , Point-of-Care Testing , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Retrospective Studies
2.
Molecules ; 27(7)2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1785839

ABSTRACT

Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: ribavirin (approved in a limited number of countries due to side effects) and palivizumab (Synagis), which is intended only for the prevention, but not the treatment, of infection. Currently, various research groups are searching for new drugs against RSV, with three main areas of research: small molecules, polymeric drugs (proteins and peptides), and plant extracts. This review is devoted to currently developed protein and peptide anti-RSV drugs.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Tract Infections , Aged , Antiviral Agents/therapeutic use , Humans , Infant , Palivizumab/therapeutic use , Peptides/pharmacology , Peptides/therapeutic use , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Tract Infections/drug therapy
3.
Nutrients ; 14(6)2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1763050

ABSTRACT

BACKGROUND: Recent randomized controlled trials (RCTs) have reported inconsistent findings regarding the efficacy of vitamin D supplementation in the treatment of acute respiratory infections (ARIs). This study aimed to investigate the efficacy of vitamin D supplementation in the treatment of ARIs using a meta-analysis of RCTs. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for relevant articles in June 2021. Two of the authors independently assessed the eligibility of the trials. RESULTS: Out of 390 articles retrieved from the databases, we included 18 RCTs, which involved 3648 participants, with 1838 in an intervention group and 1810 in a control group in the final analysis. In the meta-analysis of all the trials, vitamin D supplements had a beneficial effect in the treatment of ARIs (relative risk (RR) = 1.07; 95% confidence interval (CI), 1.01-1.13; I2 = 66.9%). Publication bias was observed in the funnel plot. In the subgroup meta-analysis of high-quality RCTs, no significant efficacy of vitamin D supplements was found (RR = 1.02; 95% CI, 0.98-1.06; I2 = 24.0%). Although statistically significant changes of 7% in the treatment effects were observed, they are not considered as clinically substantial ones. CONCLUSIONS: The current meta-analysis suggests that vitamin D supplements are not clinically effective in the treatment of ARIs.


Subject(s)
Respiratory Tract Infections , Vitamin D , Dietary Supplements , Humans , Randomized Controlled Trials as Topic , Respiratory Tract Infections/drug therapy , Vitamin D/therapeutic use , Vitamins/therapeutic use
4.
Front Public Health ; 10: 814669, 2022.
Article in English | MEDLINE | ID: covidwho-1731868

ABSTRACT

Background: This meta-analysis aimed to investigate the efficacy and safety of flavonoids in treating viral acute respiratory tract infections (ARTIs). Methods: Randomized controlled trials (RCTs) were entered into meta-analyses performed separately for each indication. Efficacy analyses were based on changes in disease-specific symptom scores. Safety was analyzed based on the pooled data from all eligible trials, by comparing the incidence of adverse events between flavonoids and the control. Results: In this study, thirty RCTs (n = 5,166) were included. In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group. In influenza, the flavonoids group improved the visual analog scores for symptoms. In COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for SARS-CoV-2 RT-PCR clearance, the RT-PCR positive subjects at day 7, time to achievement of the normal status of symptoms, patients needed oxygen, patients hospitalized and requiring mechanical ventilation, patients in ICU, days of hospitalization, and mortality vs. the control group. In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the tonsillitis severity score (TSS) on day 7. In acute rhinosinusitis, the flavonoids group decreased the sinusitis severity score (SSS) on day 7, days off work, and duration of illness. In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness. In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms. Furthermore, the results of the incidence of adverse reactions did not differ between the flavonoids and the control group. Conclusion: Results from this systematic review and meta-analysis suggested that flavonoids were efficacious and safe in treating viral ARTIs including the common cold, influenza, COVID-19, acute non-streptococcal tonsillopharyngitis, acute rhinosinusitis, acute bronchitis, bronchial pneumonia, and upper respiratory tract infections. However, uncertainty remains because there were few RCTs per type of ARTI and many of the RCTs were small and of low quality with a substantial risk of bias. Given the limitations, we suggest that the conclusions need to be confirmed on a larger scale with more detailed instructions in future studies.Systematic Review Registration: inplasy.com/inplasy-2021-8-0107/, identifier: INPLASY20218010.


Subject(s)
COVID-19 , Respiratory Tract Infections , COVID-19/drug therapy , Flavonoids/therapeutic use , Humans , Randomized Controlled Trials as Topic , Respiratory Tract Infections/drug therapy , SARS-CoV-2
5.
Pharmacol Res Perspect ; 10(2): e00925, 2022 04.
Article in English | MEDLINE | ID: covidwho-1712174

ABSTRACT

In this systematic review, we aimed to assess the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating respiratory tract infections in adults and children. PubMed, Scopus, Web of Science, Cochrane, and Embase databases were searched. A total of 34 randomized clinical trials were included in this systematic review. We assessed the risk of bias of all included studies using the Cochrane tool for risk of bias assessment. The evidence on ibuprofen, naproxen, aspirin, diclofenac, and other NSAIDs were rated for degree of uncertainty for each of the study outcomes and summarized using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Our findings suggest that high-quality evidence supports the use of NSAIDs to reduce fever in both adults and children. However, the evidence was uncertain for the use of NSAIDs to reduce cough. Most studies showed that NSAIDs significantly relieved sore throat. The evidence for mortality and oxygenation is limited. Regarding the adverse events, gastrointestinal discomfort was more frequently reported in children. For adults, our overall certainty in effect estimates was low and the increase in gastrointestinal adverse events was not clinically significant. In conclusion, NSAIDs seem to be beneficial in the outpatient management of fever and sore throat in adults and children. Although the evidence does not support their use to decrease mortality nor improve oxygenation in inpatient settings, the use of NSAIDs did not increase the rate of death or the need for ventilation in patients with respiratory tract infections. Further studies with a robust methodology and larger sample sizes are recommended.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Ambulatory Care , COVID-19/drug therapy , Hospitalization , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2
7.
Microbiol Spectr ; 10(1): e0155021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1685499

ABSTRACT

Mycoplasma pneumoniae is a common pathogen causing respiratory disease in children. We sought to investigate the epidemiology of M. pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the coronavirus disease 2019 (COVID-19) pandemic. Eligible patients were prospectively enrolled from January 2020 to June 2021. Throat swabs were tested for M. pneumoniae RNA. M. pneumoniae IgM was tested by a colloidal gold assay. Macrolide resistance and the effect of the COVID-19 countermeasures on M. pneumoniae prevalence were assessed. Symptom scores, treatments, and outcomes were evaluated. Eight hundred sixty-two eligible children at 15 centers in China were enrolled. M. pneumoniae was detected in 78 (9.0%) patients. Seasonally, M. pneumoniae peaked in the first spring and dropped dramatically to extremely low levels over time until the next summer. Decreases in COVID-19 prevalence were significantly associated with decreases in M. pneumoniae prevalence (r = 0.76, P = 0.001). The macrolide resistance rate was 7.7%. The overall sensitivity and specificity of the colloidal gold assay used in determining M. pneumoniae infection were 32.1% and 77.9%, respectively. No more benefits for improving the severity of symptoms and outcomes were observed in M. pneumoniae-infected patients treated with a macrolide than in those not treated with a macrolide during follow-up. The prevalences of M. pneumoniae and macrolide resistance in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs. IMPORTANCE This is the first and largest prospective, multicenter, active, population-based surveillance study of the epidemiology of Mycoplasma pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the COVID-19 pandemic. Nationwide measures like strict face mask wearing and restrictions on population movement implemented to prevent the spread of COVID-19 might also effectively prevent the spread of M. pneumoniae. The prevalence of M. pneumoniae and the proportion of drug-resistant M. pneumoniae isolates in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for screening and diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs.


Subject(s)
Mycoplasma pneumoniae/isolation & purification , Pneumonia, Mycoplasma/microbiology , Respiratory Tract Infections/microbiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Drug Resistance, Bacterial , Female , Humans , Infant , Macrolides/therapeutic use , Male , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/physiology , Outpatients/statistics & numerical data , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/epidemiology , Prospective Studies , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Young Adult
8.
BMC Public Health ; 22(1): 252, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1677503

ABSTRACT

BACKGROUND: Sweden has seen an accelerated decline in the number of dispensed antibiotic prescriptions from an already low level during the Covid-19 pandemic. This prompted us to explore whether the decrease in antibiotic prescriptions has reached a critically low level and resulted in an increase in treatment of severe complications from common infections. The aim was to study if the accelerated decrease in antibiotic sales has led to an increase in complications in outpatients with common infections. METHOD: A population-based nationwide registry study based on the Swedish Prescribed Drug Register and the National Patient Register. RESULTS: The total number of dispensed antibiotic prescriptions decreased by 17% during 2020 compared to 2019. The decrease was most pronounced in younger age groups and for antibiotics targeting respiratory tract infections. The number of hospital admissions and visits to open specialist care due to pneumonia or complications related to otitis, tonsillitis, or sinusitis decreased by 4-44%. Prescriptions and numbers of visits or admissions due to urinary tract infections and skin infections remained largely unchanged compared to previous years. CONCLUSION: No increase in complications due to common bacterial infections could be detected despite an unprecedented decline in dispensed antibiotic prescriptions in outpatient care in 2020. The decrease in dispensed antibiotic prescriptions from pharmacies was probably primarily related to a general decrease in the incidence of respiratory infections due to the recommendations and restrictions implemented to mitigate the Covid-19 pandemic in Sweden. This in return led to fewer doctors' visits and consequently to fewer occasions to prescribe antibiotics, be they warranted or not.


Subject(s)
COVID-19 , Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , Drug Prescriptions , Humans , Pandemics , Practice Patterns, Physicians' , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , SARS-CoV-2
9.
BMJ Open ; 12(1): e046490, 2022 01 31.
Article in English | MEDLINE | ID: covidwho-1662313

ABSTRACT

OBJECTIVE: To evaluate the trajectories of acute upper respiratory tract infections (URTIs), COVID-19, and the use of antibiotics in Finland during the COVID-19 epidemic. DESIGN: Population-based cohort study. SETTING: Electronic medical records from a nationwide healthcare chain in Finland. PARTICIPANTS: 833 444 patients from a cohort of 1 970 013 Finns who had used medical services between 2017 and 2020. MAIN OUTCOME MEASURES: Number of weekly patients of acute URTIs, COVID-19, and the prescribed number of antibiotics in Finland between 6 January 2020 and 21 June 2020. We estimated the respective expected numbers from 1 March 2020 onward using autoregressive integrated moving average model from 1 January 2017 to 1 March 2020. We assessed the public interest in COVID-19 by collecting Google search trend frequencies. RESULTS: There was a rapid increase in COVID-related internet searches between weeks 10 and 12. At the same time, there was a 106% increase in diagnoses of acute URTIs, from 410 per 100 000 inhabitants to 845 per 100 000. The first COVID-19 cases were diagnosed on week 11. Prescriptions for URTI-related antibiotics declined by 71% (403 per 100 000 to 117 per 100 000) between weeks 11 and 15 while no relevant change took place in prescriptions of antibiotics for urinary tract infections. CONCLUSIONS: At the beginning of the epidemic, many people contacted healthcare professionals with relatively mild symptoms, as indicated by the reduced rate of URTI-antibiotics prescriptions. Our findings indicate that health service providers should be prepared for rapid variations in service demand. Securing access of true COVID-19 patients to proper diagnostics, care and isolation measures may help in preventing the spread of the disease.


Subject(s)
COVID-19 , Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Finland/epidemiology , Humans , Incidence , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , Time Factors
10.
Pharm Res ; 39(1): 57-73, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1615473

ABSTRACT

PURPOSE: Chloroquine and hydroxychloroquine are effective against respiratory viruses in vitro. However, they lack antiviral efficacy upon oral administration. Translation of in vitro to in vivo exposure is necessary for understanding the disconnect between the two to develop effective therapeutic strategies. METHODS: We employed an in vitro ion-trapping kinetic model to predict the changes in the cytosolic and lysosomal concentrations of chloroquine and hydroxychloroquine in cell lines and primary human airway cultures. A physiologically based pharmacokinetic model with detailed respiratory physiology was used to predict regional airway exposure and optimize dosing regimens. RESULTS: At their reported in vitro effective concentrations in cell lines, chloroquine and hydroxychloroquine cause a significant increase in their cytosolic and lysosomal concentrations by altering the lysosomal pH. Higher concentrations of the compounds are required to achieve similar levels of cytosolic and lysosomal changes in primary human airway cells in vitro. The predicted cellular and lysosomal concentrations in the respiratory tract for in vivo oral doses are lower than the in vitro effective levels. Pulmonary administration of aerosolized chloroquine or hydroxychloroquine is predicted to achieve high bound in vitro-effective concentrations in the respiratory tract, with low systemic exposure. Achieving effective cytosolic concentrations for activating immunomodulatory effects and adequate lysosomal levels for inhibiting viral replication could be key drivers for treating viral respiratory infections. CONCLUSION: Our analysis provides a framework for extrapolating in vitro effective concentrations of chloroquine and hydroxychloroquine to in vivo dosing regimens for treating viral respiratory infections.


Subject(s)
Chloroquine/administration & dosage , Chloroquine/pharmacokinetics , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/pharmacokinetics , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Administration, Inhalation , Aerosols , Algorithms , COVID-19 , Cell Line , Cytosol/metabolism , Humans , Hydrogen-Ion Concentration , Lysosomes/metabolism , Primary Cell Culture
11.
BMJ Open ; 12(1): e048267, 2022 01 03.
Article in English | MEDLINE | ID: covidwho-1604369

ABSTRACT

INTRODUCTION: Up to 80% of patients with respiratory tract infections (RTI) attending healthcare facilities in rural areas of China are prescribed antibiotics, many of which are unnecessary. Since 2009, China has implemented several policies to try to reduce inappropriate antibiotic use; however, antibiotic prescribing remains high in rural health facilities. METHODS AND ANALYSIS: A cluster randomised controlled trial will be carried out to estimate the effectiveness and cost effectiveness of a complex intervention in reducing antibiotic prescribing at township health centres in Anhui Province, China. 40 Township health centres will be randomised at a 1:1 ratio to the intervention or usual care arms. In the intervention group, practitioners will receive an intervention comprising: (1) training to support appropriate antibiotic prescribing for RTI, (2) a computer-based treatment decision support system, (3) virtual peer support, (4) a leaflet for patients and (5) a letter of commitment to optimise antibiotic use to display in their clinic. The primary outcome is the percentage of antibiotics (intravenous and oral) prescribed for RTI patients. Secondary outcomes include patient symptom severity and duration, recovery status, satisfaction, antibiotic consumption. A full economic evaluation will be conducted within the trial period. Costs and savings for both clinics and patients will be considered and quality of life will be measured by EuroQoL (EQ-5D-5L). A qualitative process evaluation will explore practitioner and patient views and experiences of trial processes, intervention fidelity and acceptability, and barriers and facilitators to implementation. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Biomedical Research Ethics Committee of Anhui Medical University (Ref: 20180259); the study has undergone due diligence checks and is registered at the University of Bristol (Ref: 2020-3137). Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals in China, the UK and internationally. TRIAL REGISTRATION NUMBER: ISRCTN30652037.


Subject(s)
Anti-Bacterial Agents , Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , China , Humans , Inappropriate Prescribing/prevention & control , Primary Health Care , Quality of Life , Randomized Controlled Trials as Topic , Respiratory Tract Infections/drug therapy
12.
Br J Gen Pract ; 72(716): e217-e224, 2022 03.
Article in English | MEDLINE | ID: covidwho-1608429

ABSTRACT

BACKGROUND: There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. AIM: To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. DESIGN AND SETTING: Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. METHOD: Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. RESULTS: Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. CONCLUSION: Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-and-see policy in most of these patients with flu-like illness seems the best option.


Subject(s)
COVID-19 , Respiratory Tract Infections , Virus Diseases , Adult , Child , Humans , Pandemics , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , SARS-CoV-2 , Virus Diseases/complications , Virus Diseases/diagnosis , Virus Diseases/epidemiology
13.
J Antimicrob Chemother ; 77(3): 799-802, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1569708

ABSTRACT

BACKGROUND: Antibacterial prescribing for respiratory tract infections (RTIs) accounts for almost half of all prescribing in primary care. Nearly a quarter of antibacterial prescribing in primary care is estimated to be inappropriate, the greatest being for RTIs. The COVID-19 pandemic has changed the provision of healthcare services and impacted the levels of antibacterials prescribed. OBJECTIVES: To describe the changes in community antibacterial prescribing for RTIs in winter 2020-21 in England. METHODS: RTI antibacterial prescribing was measured in prescription items/1000 population for primary care from January 2014 and in DDDs/1000 population/day for the totality of RTI prescribing [combined with Accident & Emergency (A&E) in secondary care], from January 2016 to February 2021. Trends were assessed using negative binomial regression and seasonally adjusted interrupted time-series analysis. RESULTS: Antibacterials prescribed for RTIs reduced by a further 12.4% per season compared with pre-COVID (P < 0.001). In winter 2020-21, RTI prescriptions almost halved compared with the previous winter in 2019-20 (P < 0.001). The trend observed for total RTI prescribing (primary care with A&E) was similar to that observed in the community alone. CONCLUSIONS: During COVID-19, RTI prescribing reduced in the community and the expected rise in winter was not seen in 2020-21. We found no evidence that RTI prescribing shifted from primary care to A&E in secondary care. The most likely explanation is a decrease in RTIs and presentations to primary care associated with national prevention measures for COVID-19.


Subject(s)
COVID-19 , Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , England/epidemiology , Humans , Inappropriate Prescribing/prevention & control , Pandemics , Practice Patterns, Physicians' , Primary Health Care , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , Seasons
14.
Clin Microbiol Infect ; 28(4): 491-501, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1540547

ABSTRACT

BACKGROUND: The prevalence of bacterial infection in patients with COVID-19 is low, however, empiric antibiotic use is high. Risk stratification may be needed to minimize unnecessary empiric antibiotic use. OBJECTIVE: To identify risk factors and microbiology associated with respiratory and bloodstream bacterial infection in patients with COVID-19. DATA SOURCES: We searched MEDLINE, OVID Epub and EMBASE for published literature up to 5 February 2021. STUDY ELIGIBILITY CRITERIA: Studies including at least 50 patients with COVID-19 in any healthcare setting. METHODS: We used a validated ten-item risk of bias tool for disease prevalence. The main outcome of interest was the proportion of COVID-19 patients with bloodstream and/or respiratory bacterial co-infection and secondary infection. We performed meta-regression to identify study population factors associated with bacterial infection including healthcare setting, age, comorbidities and COVID-19 medication. RESULTS: Out of 33 345 studies screened, 171 were included in the final analysis. Bacterial infection data were available from 171 262 patients. The prevalence of co-infection was 5.1% (95% CI 3.6-7.1%) and secondary infection was 13.1% (95% CI 9.8-17.2%). There was a higher odds of bacterial infection in studies with a higher proportion of patients in the intensive care unit (ICU) (adjusted OR 18.8, 95% CI 6.5-54.8). Female sex was associated with a lower odds of secondary infection (adjusted OR 0.73, 95% CI 0.55-0.97) but not co-infection (adjusted OR 1.05, 95% CI 0.80-1.37). The most common organisms isolated included Staphylococcus aureus, coagulase-negative staphylococci and Klebsiella species. CONCLUSIONS: While the odds of respiratory and bloodstream bacterial infection are low in patients with COVID-19, meta-regression revealed potential risk factors for infection, including ICU setting and mechanical ventilation. The risk for secondary infection is substantially greater than the risk for co-infection in patients with COVID-19. Understanding predictors of co-infection and secondary infection may help to support improved antibiotic stewardship in patients with COVID-19.


Subject(s)
Antimicrobial Stewardship , Bacterial Infections , COVID-19 , Respiratory Tract Infections , Bacteria , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , COVID-19/epidemiology , Female , Humans , Respiratory Tract Infections/drug therapy
15.
Int J Environ Res Public Health ; 18(22)2021 11 16.
Article in English | MEDLINE | ID: covidwho-1523957

ABSTRACT

With the growing spread of COVID-19 worldwide, the appeal to alternative and nutritional therapies in conjunction with medical therapies has been heightened. This article aims to review studies assessing the roles of Chinese traditional medicine and nutrition in upper respiratory infections, including COVID-19. Various Chinese herbal protocols have been shown to fight respiratory infections, with several having been tested on the novel coronavirus. Additionally, promising findings have been reported when medical treatments were complemented with nutritional interventions. Supplementation with vitamins C and D, Zinc and Selenium are discussed, in addition to certain phytochemicals and food that also possess immunoregulatory and antiviral properties. Further clinical studies are needed to establish these alternative treatments as part of the management of emerging respiratory infections.


Subject(s)
COVID-19 , Respiratory Tract Infections , Humans , Micronutrients , Respiratory Tract Infections/drug therapy , SARS-CoV-2 , Vitamins
16.
BMJ Glob Health ; 6(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1504055

ABSTRACT

INTRODUCTION: Despite acute respiratory infections (ARIs) being the single largest reason for antibiotic use in under-5 children in Bangladesh, the prevalence of antibiotic use in the community for an ARI episode and factors associated with antibiotic use in this age group are unknown. METHODS: We analysed nationally representative, population-based, household survey data from the Bangladesh Demographic and Health Survey 2014 to determine the prevalence of antibiotic use in the community for ARI in under-5 children. Using a causal graph and multivariable logistical regression, we then identified and determined the sociodemographic and antibiotic source factors significantly associated with the use of antibiotics for an episode of ARI. RESULTS: We analysed data for 2 144 children aged <5 years with symptoms of ARI from 17 300 households. In our sample, 829 children (39%) received antibiotics for their ARI episode (95% CI 35.4% to 42.0%). Under-5 children from rural households were 60% (adjusted OR (aOR): 1.6; 95% CI 1.2 to 2.1) more likely to receive antibiotics compared with those from urban households, largely driven by prescriptions from unqualified or traditional practitioners. Private health facilities were 50% (aOR: 0.5; 95% CI 0.3 to 0.7) less likely to be sources of antibiotics compared with public health facilities and non-governmental organisations. Age of children, sex of children or household wealth had no impact on use of antibiotics. CONCLUSION: In this first nationally representative analysis of antibiotic use in under-5 children in Bangladesh, we found almost 40% of children received antibiotics for an ARI episode. The significant prevalence of antibiotic exposure in under-5 children supports the need for coordinated policy interventions and implementation of clinical practice guidelines at point of care to minimise the adverse effects attributed to antibiotic overuse.


Subject(s)
Anti-Bacterial Agents , Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , Bangladesh/epidemiology , Child , Humans , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Rural Population
17.
BMJ Open ; 11(11): e047474, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501711

ABSTRACT

OBJECTIVE: To evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults. METHOD: Seventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD -1.20 points, 95% CI -0.66 to -1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD -0.15, 95% CI -0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality). CONCLUSIONS: In adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted. PROSPERO REGISTRATION NUMBER: CRD42020182044.


Subject(s)
COVID-19 , Respiratory Tract Infections , Adult , Humans , Randomized Controlled Trials as Topic , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/prevention & control , SARS-CoV-2 , Zinc/therapeutic use
19.
Int J Mol Sci ; 22(21)2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1488614

ABSTRACT

Human Ezrin Peptides (HEPs) are inhibitors of expression of IL-6 and other inflammatory cytokines, amplifiers of adaptive B cell and T cell immunity and enhancers of tissue repair. The mutation stable C-terminus of HIV gp120, mimics 69% of the "Hep-receptor", a zipped α-helical structure in the middle of the α domain of human ezrin protein. Synthetic peptides homologous to the Hep-receptor of ezrin of five to fourteen amino acids, activate anti-viral immunity against a wide range of viruses (HIV, HCV, herpes, HPV, influenza and other human respiratory viruses). Human Ezrin Peptide One (HEP1) TEKKRRETVEREKE (brand name Gepon, registered for human use in Russia from 2001) is a successful treatment for opportunistic infections in HIV-infected patients. That treats HEP1and prevents mucosal candidiasis, herpes zoster outbreaks and infection-induced chronic diarrhea. There are clinical publications in Russian on the successful treatments of chronic recurrent vaginal candidiasis, acute and chronic enterocolitis and dysbacteriosis, which are accompanied by normalization of the mucosal microbiome, and the decline or disappearance of inflammation. HEP1 is also an effective treatment and prevention for recurrent inflammation and ulceration in the stomach, duodenum and colon. HEP1 and RepG3 GEKKRRETVEREGG (a derivative of HEP1) have been used successfully as an inhaled spray peptide solution to treat a small number of human volunteers with mild-to-moderate COVID, resulting from SARS-CoV-2 infection, based on earlier successes in treating acute viral respiratory disease with inflammatory complications. Ezrin peptides seem to correct a dysregulation of innate immune responses to SARS-CoV-2. They are also adjuvants of B cell adaptive immunity and increase antibody titres, resulting in protection from lethal virus infection of mice. In a clinical study in Moscow, orally administered HEP1 was shown to enhance antibody-titres produced in response to hepatitis-B vaccination. These very preliminary but promising results with ezrin peptide treatment of COVID must be replicated in large-scale randomised placebo controlled clinical studies, to be verified.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Cytoskeletal Proteins/pharmacology , Cytoskeletal Proteins/therapeutic use , Adaptive Immunity/drug effects , Adjuvants, Immunologic/pharmacology , Animals , Antiviral Agents/therapeutic use , HIV Infections/drug therapy , Humans , Mice , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy
20.
Viruses ; 13(11)2021 10 25.
Article in English | MEDLINE | ID: covidwho-1481025

ABSTRACT

Solid organ transplantation is often lifesaving, but does carry an increased risk of infection. Respiratory viral infections are one of the most prevalent infections, and are a cause of significant morbidity and mortality, especially among lung transplant recipients. There is also data to suggest an association with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. Respiratory viral infections can appear at any time post-transplant and are usually acquired in the community. All respiratory viral infections share similar clinical manifestations and are all currently diagnosed using nucleic acid testing. Influenza has good treatment options and prevention strategies, although these are hampered by resistance to neuraminidase inhibitors and lower vaccine immunogenicity in the transplant population. Other respiratory viruses, unfortunately, have limited treatments and preventive methods. This review summarizes the epidemiology, clinical manifestations, therapies and preventive measures for clinically significant RNA and DNA respiratory viruses, with the exception of SARS-CoV-2. This area is fast evolving and hopefully the coming decades will bring us new antivirals, immunologic treatments and vaccines.


Subject(s)
Organ Transplantation , Respiratory Tract Infections , Transplant Recipients , Virus Diseases , Antiviral Agents/therapeutic use , Graft Rejection , Humans , Lung Transplantation , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Virus Diseases/diagnosis , Virus Diseases/drug therapy , Virus Diseases/epidemiology , Virus Diseases/prevention & control
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