Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study

ObjectiveDiscriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses.MethodsChildren with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls.ResultsMxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 μg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78–99%) sensitivity and 100% (95% CI: 51–100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 μg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 μg/l, interquartile range: 679 to 2489).DiscussionMxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.     

Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy

BackgroundHuman rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood.ObjectivesThis study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients.Study designFrom April 2012–March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression.ResultsOne hundred and ten HM patients presented with HRV URTI (n = 78) and HRV LRTI (n = 32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0–9.2; p = 0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter.ConclusionsHRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.     

Time to resolution of respiratory and systemic coronavirus disease 2019 symptoms in community setting

ObjectivesTo assess the time to resolution of respiratory and systemic symptoms and their associated factors in outpatients during the coronavirus disease 2019 (COVID-19) pandemic.MethodsCohort study including adult outpatients, managed with Covidom, a telesurveillance solution, with RT-PCR-confirmed diagnosis, from 9 March 2020 until 23 February 2021. Follow up was 30 days after symptom onset.ResultsAmong the 9667 patients included, mean age was 43.2 ± 14.0 years, and 67.5% were female (n = 6522). Median body mass index (BMI) was 25.0 kg/m² (interquartile range 22.1–28.8 kg/m²). Main co-morbidities were: hypertension (12.9%; n = 1247), asthma (11.0%; n = 1063) and diabetes mellitus (5.5%; n = 527). The most frequent symptom during follow up was dyspnoea (65.1%; n = 6296), followed by tachypnoea (49.9%; n = 4821), shivers (45.6%; n = 4410) and fever (36.7%; n = 3550). Median times to resolution of systemic and respiratory symptoms were 3 days (95% CI 2−4 days) and 7 days (95% CI 6−8 days), respectively. Ultimately, 17.2% (95% CI 15.7%−18.8%) still presented respiratory symptoms at day 30. Longer time to respiratory symptom resolution was associated with older age, increased BMI, chronic obstructive pulmonary disease, coronary artery disease, asthma and heart failure. Regarding systemic symptoms, coronary artery disease, asthma, age above 40 years and elevated BMI were associated with longer time to resolution.ConclusionsTime to symptom resolution among outpatients with COVID-19 seemed shorter for systemic than respiratory symptoms. Prolonged respiratory symptoms were common at day 30. Risk factors associated with later resolution included age, and cardiovascular and pulmonary diseases.     

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries

ObjectivesTo describe the role of bacteria (including bacterial resistance), viruses (including those recently described) and mixed bacterial–viral infections in adults presenting to primary care with lower respiratory tract infection (LRTI).MethodsIn all, 3104 adults with LRTI were enrolled, of whom 141 (4.5%) had community-acquired pneumonia (CAP), and 2985 matched controls in a prospective study in 16 primary care networks in Europe, and followed patients up at 28–35 days. We detected Streptococcus pneumoniae and Haemophilus influenzae and assessed susceptibility, atypical bacteria and viruses.ResultsA potential pathogen was detected in 1844 (59%) (in 350 (11%) bacterial pathogens only, in 1190 (38%) viral pathogens only, and in 304 (10%) both bacterial and viral pathogens). The most common bacterial pathogens isolated were S. pneumoniae (5.5% overall, 9.2% in CAP patients) and H. influenzae (5.4% overall, 14.2% in CAP patients). Less than 1% of S. pneumoniae were highly resistant to penicillin and 12.6% of H. influenzae were β-lactamase positive. The most common viral pathogens detected were human rhinovirus (20.1%), influenza viruses (9.9%), and human coronavirus (7.4%). Influenza virus, human parainfluenza viruses and human respiratory syncytial virus as well as human rhinovirus, human coronavirus and human metapneumovirus were detected significantly more frequently in LRTI patients than in controls.ConclusionsA bacterial pathogen is identified in approximately one in five adult patients with LRTI in primary care, and a viral pathogen in just under half, with mixed infections in one in ten. Penicillin-resistant pneumococci and β-lactamase-producing H. influenzae are uncommon. These new findings support a restrictive approach to antibiotic prescribing for LRTI and the use of first-line, narrow-spectrum agents in primary care.     

Antibiotics for lower respiratory tract infection in children presenting in primary care (ARTIC-PC): the predictive value of molecular testing

ObjectivesThis study aimed to assess whether the presence of bacteria or viruses in the upper airway of children presenting with uncomplicated lower respiratory tract infection (LRTI) predicts the benefit of antibiotics.MethodsChildren between 6 months and 12 years presenting to UK general practices with an acute LRTI were randomized to receive amoxicillin 50 mg/kg/d for 7 days or placebo. Children not randomized (ineligible or clinician/parental choice) could participate in a parallel observational study. The primary outcome was the duration of symptoms rated moderately bad or worse. Throat swabs were taken and analyzed for the presence of bacteria and viruses by multiplex PCR.ResultsSwab results were available for most participants in the trial (306 of 432; 71%) and in the observational (182 of 326; 59%) studies. Bacterial pathogens potentially sensitive to amoxicillin (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae) were detected among 51% of the trial placebo group and 49% of the trial antibiotic group. The median difference in the duration of symptoms rated moderately bad or worse between antibiotic and placebo was similar when potentially antibiotic-susceptible bacteria were present (median: –1 day; 99% CI, –12.3 to 10.3) or not present (median: –1 day; 99% CI, –4.5 to 2.5). Furthermore, bacterial genome copy number did not predict benefit. There were similar findings for all secondary outcomes and when including the data from the observational study.DiscussionThere was no clear evidence that antibiotics improved clinical outcomes conditional on the presence or concentration of bacteria or viruses in the upper airway. Before deploying microbiologic point-of-care tests for children with uncomplicated LRTI in primary care, rigorous validating trials are needed.     

Viral etiologies of acute respiratory tract infections among hospitalized children – A comparison between single and multiple viral infections

BackgroundAcute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed.MethodsWe retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared.ResultsA total of 442 patients were enrolled. Patients with positive viral detection (N = 311) had a significantly lower rate of leukocytosis (p = 0.03), less evidence of bacterial infection (p = 0.004), and shorter duration of hospitalization (p = 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups.The most commonly identified virus was human rhinovirus. About 27% (n = 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was independently associated with multiple viral infections (p = 0.022), respiratory syncytial virus (RSV) infection (p = 0.001) and longer hospitalization duration (p = 0.011).ConclusionMultiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.     

Lower respiratory tract infection in the community: associations between viral aetiology and illness course

ObjectivesThis study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection.MethodsA prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed.ResultsThe PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07–2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50–11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07–0.25 points or 2.3–8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65–0.96) and hMPV infections (AHR 0.77, 95% CI 0.62–0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06–0.16 per 10 cycles decrease in Ct value), but not with symptom duration.ConclusionsIn healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.     

Epidemiologic,clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults: Rhinovirus among adults and children

Backgroundhuman rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults.Objectivesto characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding.Study designobservational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding.Resultseighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18 years. Fifty-four were HRV-A, 11HRV-B, and 19HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P < 0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P = 0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (P trend = 0.01).Conclusionsamong otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.     

Infectious meningitis and encephalitis in adults in Denmark: a prospective nationwide observational cohort study (DASGIB)

ObjectivesTo monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.MethodsNationwide prospective observational study of all cases of proven community-acquired infectious meningitis and encephalitis in adults treated in all infectious diseases departments in Denmark from 1 January 2015 to 30 June 2016. We included data on symptoms, aetiology, treatment and outcome assessed by the Glasgow Outcome Scale (GOS) 30 days after discharge. GOS 1–4 was categorized as unfavourable outcome.ResultsDuring 18 months of observation, we identified 252 cases of viral meningitis (3.6/100 000/year), 214 cases of bacterial meningitis (3.1/100 000/year) and 96 cases of infectious encephalitis (1.4/100 000/year). In bacterial meningitis, Streptococcus pneumoniae was the most frequent infectious agent (n = 101) followed by Staphylococcus aureus (n = 24) and β-haemolytic streptococci (n = 14). Meningococcal meningitis was rare (n = 11). In encephalitis, herpes simplex virus type 1 was most common (n = 37) followed by varicella zoster virus (n = 20), whereas varicella zoster virus (n = 61) was most common in viral meningitis followed by enterovirus (n = 50) and herpes simplex virus type 2 (n = 46). Case fatality and unfavourable outcome occurred in 31/214 (15%) and 96/214 (45%) with bacterial meningitis and in 5/96 (5%) and 55/89 (62%) with encephalitis. For viral meningitis, unfavourable outcome occurred in 41/252 (17%).ConclusionsThe epidemiology and clinical presentation of the examined central nervous system infections differed considerably and bacterial meningitis was more frequent than previously estimated. Overall prognosis remains poor for bacterial meningitis and encephalitis. Prospective nationwide clinical databases of central nervous system infections may be superior to epidemiological monitoring based on notifications or laboratory systems.     

Comparison of phenoxymethylpenicillin,amoxicillin, and doxycycline for erythema migrans in general practice. A randomized controlled trial with a 1-year follow-up

ObjectivesTo compare the three most commonly used antibiotics for erythema migrans (EM) in Norwegian primary care.MethodsA randomized, parallel, controlled trial was carried out. Treatments were open to the patients, but blinded for the GPs and investigators. Patients eligible for inclusion were aged ≥18 years and clinically diagnosed with EM. Block randomization was processed in blocks of six. Patients were assigned to receive one of three antibiotic treatments for 14 days: phenoxymethylpenicillin (PCV), amoxicillin, or doxycycline. The primary outcome was the duration of EM in days in the three treatment groups. Patients kept a diary for the 14 days of treatment, in which they registered concomitant symptoms and side effects. The patients consulted their GP after 14 days of treatment and had a 1-year follow-up to monitor any development of disseminated Lyme borreliosis (LB). EMs with a duration of more than 14 days were followed until resolution. ClinicalTrials.gov NCT01368341 and EU Clinical Trials Register 2010-023747-15.ResultsOne hundred and eighty eight patients (PCV: n = 56, amoxicillin: n = 64, doxycycline: n = 68) were included by 44 Norwegian general practitioners (GPs) from June 2011 to November 2013. Follow-up was completed by December 2014. The median duration of EM was altogether 14 days (range 3–293). For the PCV group median duration was 14 days (range 5–91), for amoxicillin 13 days (range 4–179) and for doxycycline 14 days (range 3–293). The duration of EM did not differ significantly between the three antibiotic groups (p 0.277). None of the patients developed disseminated LB within the 1-year follow-up.ConclusionsWe did not find 14 days of PCV, doxycycline, and amoxicillin treatments to differ in effectiveness or safety in the treatment of clinically diagnosed EM in primary care.     

Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis

ObjectivesDespite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown.MethodsA cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013–2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control.ResultsA total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4⁺ and CD8⁺ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17–6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02–3.57) and MN (3.33, 1.26–9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08–2.63), underlying medical conditions (1.94, 95% CI 1.09–3.46) and lack of antiviral therapy (2.08, 95% CI 1.04–4.17) were predictors for higher T-cell responses.ConclusionsSurvivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.     

Efficacy of favipiravir in adults with mild COVID-19: a randomized,double-blind,multicentre, placebo-controlled clinical trial

ObjectiveTo evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo.MethodsIn this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality.ResultsTwo hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32–44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6–12 days) in the favipiravir group and 8 days (IQR: 6–12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571–1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4–11 days) in the favipiravir group and 7 days (IQR: 5–10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events.ConclusionIn this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.     

Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial

ObjectiveWe explored whether initial treatment with the herbal drug uva ursi (UU) reduces antibiotic use in women with uncomplicated urinary tract infection (UTI) without increasing symptom burden and complication frequency compared with antibiotic treatment.MethodsA double-blind randomized controlled trial was conducted in 42 family practices in Germany. The participants were adult women with suspected uncomplicated UTIs receiving either UU 105 mg 3 × 2 tablets for 5 days (intervention) or fosfomycin a 3-g single dose (control), and their respective placebos. Participants and investigators were blinded. The primary outcome included (1) antibiotic courses day 0–28 as superiority, and (2) symptom burden (sum of daily symptom scores) day 0–7, as non-inferiority outcome (margin 125%). Clinicaltrials.gov: NCT03151603.ResultsOverall, 398 patients were randomly allocated to groups receiving UU (n = 207) and fosfomycin (n = 191). The number of antibiotic courses was 63.6% lower (95% CI 53.6%–71.4%; p < 0.0001) in the UU group than in the fosfomycin group. The ratio of total symptom burden in the UU group compared with control was 136.5% (95% CI 122.7–151.9; p 0.95), failing non-inferiority. Eight women developed pyelonephritis in the UU group compared with two in the fosfomycin group (mean difference 2.8; 95% CI 0.2–5.9; p 0.067). Adverse events were similar between the groups.DiscussionIn women with uncomplicated UTIs, initial treatment with UU reduced antibiotic use but led to a higher symptom burden and more safety concerns than fosfomycin.     

Relationship of secondhand smoke and infant lower respiratory tract infection severity by familial atopy status

BackgroundIndividuals with atopy have more severe complications of infectious diseases. We hypothesized that the importance of secondhand smoke (SHS) on lower respiratory tract infection (LRTI) severity would be greater in infants with a familial atopic predisposition.ObjectiveTo determine whether infants with a familial atopic predisposition are more susceptible to adverse effects of SHS, resulting in more severe LRTI.MethodsWe conducted cross-sectional analyses of mother-infant dyads enrolled during 2004 to 2008 during an infant LRTI. Predictor variables were SHS and 2 measures of a familial atopic predisposition (maternal atopic disease with allergen sensitization or familial atopy). LRTI severity was determined by bronchiolitis severity score (BSS) and hospital length of stay (LOS). We conducted multivariable regression analysis to test for a differential relationship between SHS and LRTI severity by measures of familial atopic predisposition.ResultsIn 451 dyads, 57% of infants had SHS exposure, 36% had a mother with atopic disease, and 68% had familial atopy. We did not detect differences in BSS or LOS by SHS exposure stratified by history of maternal atopic disease. In bivariate analysis, there was a significant difference in LOS by SHS in those with familial atopy (P = .006) but not in those without (P = .66). In multivariable analysis, among infants with familial atopy, there was a 23% increased LOS in infants with SHS exposure (P = .03), whereas no statistical significance was detected in those without familial atopy (P = .07).ConclusionIn infants with familial atopy, SHS was associated with longer hospital LOS for LRTI but not BSS. Because the effect was seen only among hospitalized infants, confirmation is required.     

Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis

BackgroundAcute rhinosinusitis (ARS) is triggered by viral or, uncommonly, bacterial infection, causing inflammatory symptoms for ≤12 weeks.ObjectiveTo investigate effects of mometasone furoate nasal spray (MFNS) vs amoxicillin and placebo on minimal-symptom days.MethodsA double-blind, parallel-group, placebo- and active-controlled 15-day study randomly assigned patients 12 years of age or older to MFNS 200 μg twice daily, MFNS 200 μg once daily, amoxicillin 500 mg 3 times daily, or placebo.Patients had baseline rhinosinusitis major symptom score (MSS; combined rhinorrhea, postnasal drip, congestion, sinus headache, facial pain) of ≥5 and ≤12 (maximum: 15) for 7 to 28 days; scores were similar among groups. Minimal-symptom days and minimal-congestion days were defined post hoc by average am/pm MSS ≤4 and average am/pm congestion ≤1.ResultsMFNS twice daily (n = 234) showed more minimal-symptom days vs placebo (n = 246) (62.69% vs 50.33%; P < .0001) or amoxicillin (n = 248) (54.35%; P = .0040). The MFNS QD was associated with numerically more minimal-symptom days than amoxicillin or placebo (54.72%; P ≤ .8982). MFNS was associated with more minimal-congestion days than placebo (72.97%, 67.73%, and 56.67% for twice daily, once daily, and placebo; P < .0001, each vs placebo) and MFNS BID with more minimal-congestion days than amoxicillin (72.97% vs 64.15%; P = .0007). Median time to first minimal-symptom day sustained until study end was 8.5 days for MFNS BID vs. 11 for placebo (P = .0085).ConclusionMFNS 200 μg twice daily significantly increased minimal-symptom days vs amoxicillin or placebo in patients with ARS. Results of this intranasal corticosteroids (INS) therapy indicate it can improve outcomes and potentially reduce inappropriate antibiotic use.     

Increased Systemic Cytokine/Chemokine Expression in Asthmatic and Non‐asthmatic Patients with Bacterial,Viral or Mixed Lung Infection

This study was aimed to determine the profiles of serum cytokines (IL‐1β, TNF‐α, IL‐4, IL‐5) and chemokines (MCP‐1: monocyte chemoattract protein‐1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non‐asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non‐asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non‐asthmatic patients was observed. However, higher concentrations of chemokines (MCP‐1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non‐asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non‐asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status.     

The impact of Helicobacter pylori on EGF,EGF receptor,and the c-erb-B2 expression

PurposeIncreased expression of epidermal growth factor (EGF), its receptor (EGFR), and c-erb-B2 protein, which is homological with the EGF receptor, in gastric mucosa, may play a role in gastric carcinogenesis. We assessed if the infection and eradication of Helicobacter pylori (H. pylori) affects the gastric expression of growth factors and serum gastrin concentrations.Patients/methodsWe examined immunohistochemically gastric EGF and both receptors’ expression in: gastric cancer (GC; n = 29), chronic gastritis with H. pylori infection (GHp+; n = 40) before and after eradication and in patients without H. pylori infection (GHp−; n = 42).ResultsBefore the eradication therapy, gastric mucosal EGF and both receptor's expressions in GHp+ patients were increased compared to GHp− (p < 0.05), but were similar to GC. After eradication, EGF and the receptor's expression significantly decreased in the gastric body. Both EGFR and c-erb-B2 expression in the antrum were still higher than in GHp− (p < 0.05), and remained comparable to GC.ConclusionsIn patients with H. pylori infection the gastric mucosal EGF, EGFR, and c-erb-B2 expressions are similar to those observed in gastric cancer. The persistence of the antral expression of receptors after eradication, at a level comparable to the gastric cancer group, suggests their eventual role in the progression of changes initiated by H. pylori toward carcinogenesis.     

Maternal colonization and early-onset neonatal bacterial sepsis in the Gambia,West Africa: a genomic analysis of vertical transmission

ObjectivesTo define bacterial aetiology of neonatal sepsis and estimate the prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs.MethodsWe carried out a cross-sectional study of newborns with clinical sepsis admitted to three hospitals in the Gambia neonatal wards. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically-matched paired neonatal blood cultures and maternal genital tract bacterial isolates.ResultsWe enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0–6 after birth) of which 26% (36/137) were because of a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis because of Staphylococcus aureus (n = 5), Klebsiella pneumonia (n = 2), and Enterococcus faecalis (n = 1), phenotypically matched their maternal genital tract isolates. Pairwise single-nucleotide variants comparisons showed differences of 12 to 52 single-nucleotide variants only between maternal and newborn S. aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36).ConclusionsWe found a low prevalence of vertical transmission of maternal genital tract colonization in maternal-newborn pairs for early-onset neonatal sepsis in the West African context. Identifying infection acquisition pathways among newborns is essential to prioritize preventive interventions, which could be targeted at the mother or infection control in the hospital environment, depending on the major pathways of transmission.     

Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting

ObjectivesTo investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19).MethodsA retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed.ResultsA total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low.ConclusionsWe found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.