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Seminars in Immunopathology Feb 2020Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with... (Review)
Review
Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with genetic predisposition, and shaping the lung microbiome especially during birth and in very early life. The healthy lung microbial composition is characterized by a prevalence of bacteria belonging to the phyla Bacteroidetes, Actinobacteria, and Firmicutes. However, viral respiratory infections are associated with an abundance of Proteobacteria with genera Haemophilus and Moraxella in young children and adult asthmatics. This dysbiosis supports the activation of inflammatory pathways and contributes to bronchoconstriction and bronchial hyperresponsiveness. Exogenous factors can affect the natural lung microbiota composition positively (farming environment) or negatively (allergens, air pollutants). It is evident that also gut microbiota dysbiosis has a high influence on asthma pathogenesis. Antibiotics, antiulcer medications, and other drugs severely impair gut as well as lung microbiota. Resulting dysbiosis and reduced microbial diversity dysregulate the bidirectional crosstalk across the gut-lung axis, resulting in hypersensitivity and hyperreactivity to respiratory and food allergens. Efforts are undertaken to reconstitute the microbiota and immune balance by probiotics and engineered bacteria, but results from human studies do not yet support their efficacy in asthma prevention or treatment. Overall, dysbiosis of gut and lung seem to be critical causes of the increased emergence of asthma.
Topics: Adult; Asthma; Child; Child, Preschool; Dysbiosis; Gastrointestinal Microbiome; Humans; Lung; Microbiota
PubMed: 32072252
DOI: 10.1007/s00281-019-00775-y -
Clinical Microbiology Reviews Dec 2022All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues... (Review)
Review
All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, , Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized ("typical") bacterial pathogens as well as a role for commensal bacteria ("normal respiratory flora"). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.
Topics: Adult; Humans; Bacteriology; Pneumonia, Bacterial; Streptococcus pneumoniae; Pneumonia, Viral; Bacteria; Community-Acquired Infections
PubMed: 36165783
DOI: 10.1128/cmr.00015-22 -
JAMA Jul 2023The large overlap between symptoms of acute sinusitis and viral upper respiratory tract infection suggests that certain subgroups of children being diagnosed with acute... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The large overlap between symptoms of acute sinusitis and viral upper respiratory tract infection suggests that certain subgroups of children being diagnosed with acute sinusitis, and subsequently treated with antibiotics, derive little benefit from antibiotic use.
OBJECTIVE
To assess if antibiotic therapy could be appropriately withheld in prespecified subgroups.
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial including 515 children aged 2 to 11 years diagnosed with acute sinusitis based on clinical criteria. The trial was conducted between February 2016 and April 2022 at primary care offices affiliated with 6 US institutions and was designed to evaluate whether symptom burden differed in subgroups defined by nasopharyngeal Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis on bacterial culture and by the presence of colored nasal discharge.
INTERVENTIONS
Oral amoxicillin (90 mg/kg/d) and clavulanate (6.4 mg/kg/d) (n = 254) or placebo (n = 256) for 10 days.
MAIN OUTCOMES AND MEASURES
The primary outcome was symptom burden based on daily symptom scores on a validated scale (range, 0-40) during the 10 days after diagnosis. Secondary outcomes included treatment failure, adverse events including clinically significant diarrhea, and resource use by families.
RESULTS
Most of the 510 included children were aged 2 to 5 years (64%), male (54%), White (52%), and not Hispanic (89%). The mean symptom scores were significantly lower in children in the amoxicillin and clavulanate group (9.04 [95% CI, 8.71 to 9.37]) compared with those in the placebo group (10.60 [95% CI, 10.27 to 10.93]) (between-group difference, -1.69 [95% CI, -2.07 to -1.31]). The length of time to symptom resolution was significantly lower for children in the antibiotic group (7.0 days) than in the placebo group (9.0 days) (P = .003). Children without nasopharyngeal pathogens detected did not benefit from antibiotic treatment as much as those with pathogens detected; the between-group difference in mean symptom scores was -0.88 (95% CI, -1.63 to -0.12) in those without pathogens detected compared with -1.95 (95% CI, -2.40 to -1.51) in those with pathogens detected. Efficacy did not differ significantly according to whether colored nasal discharge was present (the between-group difference was -1.62 [95% CI, -2.09 to -1.16] for colored nasal discharge vs -1.70 [95% CI, -2.38 to -1.03] for clear nasal discharge; P = .52 for the interaction between treatment group and the presence of colored nasal discharge).
CONCLUSIONS
In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens on presentation, and its effects did not depend on the color of nasal discharge. Testing for specific bacteria on presentation may represent a strategy to reduce antibiotic use in this condition.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02554383.
Topics: Child; Humans; Male; Acute Disease; Amoxicillin; Anti-Bacterial Agents; Clavulanic Acid; Common Cold; Sinusitis; Female; Child, Preschool; Nasopharynx; Streptococcus pneumoniae; Haemophilus influenzae; Moraxella catarrhalis
PubMed: 37490085
DOI: 10.1001/jama.2023.10854 -
Drugs in Context 2020In the pediatric age group, approximately 7.5% of upper respiratory tract infections (URIs) are complicated by acute bacterial sinusitis (ABS). Despite its prevalence,... (Review)
Review
BACKGROUND
In the pediatric age group, approximately 7.5% of upper respiratory tract infections (URIs) are complicated by acute bacterial sinusitis (ABS). Despite its prevalence, ABS is often overlooked in young children. The diagnosis and management present unique challenges in primary care. This is an updated narrative review on the evaluation, diagnosis, and management of ABS.
METHODS
A PubMed search was performed using the key term 'acute sinusitis'. The search strategy included clinical trials, meta-analyses, randomized controlled trials, observational studies, and reviews. The search was restricted to the English literature and children.
RESULTS
(non-typeable), , and are the major pathogens in uncomplicated ABS in otherwise healthy children. In complicated ABS, polymicrobial infections are common. The diagnosis of acute sinusitis is mainly clinical and based on stringent criteria, including persistent symptoms and signs of a URI beyond 10 days, without appreciable improvement; a URI with high fever and purulent nasal discharge at onset lasting for at least 3 consecutive days; and biphasic or worsening symptoms.
CONCLUSION
Data from high-quality studies on the management of ABS are limited. The present consensus is that amoxicillin-clavulanate, at a standard dose of 45 mg/kg/day orally, is the drug of choice for most cases of uncomplicated ABS in children in whom antibacterial resistance is not suspected. Alternatively, oral amoxicillin 90 mg/kg/day can be administered. For those with severe ABS or uncomplicated acute sinusitis who are at risk for severe disease or antibiotic resistance, oral high-dose amoxicillin-clavulanate (90 mg/kg/day) is the drug of choice.
PubMed: 33281908
DOI: 10.7573/dic.2020-9-3 -
Microbiology Spectrum Dec 2021The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial...
The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteria; COVID-19; Child; China; Communicable Diseases; Drug Resistance, Bacterial; Escherichia coli; Humans; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Moraxella catarrhalis; Pseudomonas aeruginosa; SARS-CoV-2; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae; Streptococcus pyogenes
PubMed: 34730410
DOI: 10.1128/Spectrum.00283-21 -
Cureus Jun 2022Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to... (Review)
Review
Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to its therapeutic benefits. This study aims to discuss the mechanism of development of infections, prevention, and timely treatment to prevent complications such as septic shock and mortality. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and reporting guidelines for systematic review. Inclusion and exclusion criteria were determined. A total of 10 research papers were extracted after exploring Pubmed and Google Scholar from 2001 to 2021. The New Castle Ottawa Questionnaire for non-randomized clinical trials and the National Institutes of Health (NIH) quality assessment tool for case reports and case series were used to assess the risk of bias. The studies included in this systematic review describe infections with , , unusual species, , and . The main goal of this review is to impress upon the seriousness of the infectious complications associated with eculizumab. Health care providers should maintain a high index of suspicion for early identification and treatment.
PubMed: 35784997
DOI: 10.7759/cureus.25640 -
International Journal of Pediatric... Mar 2020To review and highlight significant advances made towards vaccine development and understanding of the immunology of otitis media (OM) since the 19th International... (Review)
Review
OBJECTIVE
To review and highlight significant advances made towards vaccine development and understanding of the immunology of otitis media (OM) since the 19th International Symposium on Recent Advances in Otitis Media (ISOM) in 2015, as well as identify future research directions and knowledge gaps.
DATA SOURCES
PubMed database, National Library of Medicine.
REVIEW METHODS
Key topics were assigned to each panel member for detailed review. Draft reviews were collated, circulated, and thoroughly discussed when the panel met at the 20th ISOM in June 2019. The final manuscript was prepared with input from all panel members.
CONCLUSIONS
Since 2015 there have been a number of studies assessing the impact of licensed pneumococcal vaccines on OM. While these studies have confirmed that these vaccines are effective in preventing carriage and/or disease caused by vaccine serotypes, OM caused by non-vaccine serotype pneumococci and other otopathogens remains a significant health care burden globally. Development of multi-species vaccines is challenging but essential to reducing the global burden of OM. Influenza vaccination has been shown to prevent acute OM, and with novel vaccines against nontypeable Haemophilus influenzae (NTHi), Moraxella catarrhalis and Respiratory Syncytial Virus (RSV) in clinical trials, the potential to significantly prevent OM is within reach. Research into alternative vaccine delivery strategies has demonstrated the power of maternal and mucosal vaccination for OM prevention. Future OM vaccine trials must include molecular diagnostics of middle ear effusion, for detection of viruses and bacteria that are persisting in biofilms and to enable accurate assessment of vaccine impact on OM etiology. Understanding population differences in natural and vaccine-induced immune responses to otopathogens is also important for development of the most effective OM vaccines. Improved understanding of the interaction between otopathogens will also advance development of effective therapies and encourage the assessment of the indirect benefits of vaccination.
IMPLICATIONS FOR PRACTICE
While NTHi and M. catarrhalis are the predominant otopathogens, funding opportunities to drive vaccine development for these species are limited due to a focus on prevention of childhood mortality rather than morbidity. Delivery of a comprehensive report on the high financial and social costs of OM, including the potential for OM vaccines to reduce antibiotic use and subsequent development of antimicrobial resistance (AMR), would likely assist in engaging stakeholders to recognize the value of prevention of OM and increase support for efforts on OM vaccine development. Vaccine trials with OM prevention as a clinical end-point are challenging, however a focus on developing assays that measure functional correlates of protection would facilitate OM vaccine development.
Topics: Biofilms; Haemophilus Vaccines; Humans; Influenza Vaccines; Microbial Interactions; Moraxellaceae Infections; Otitis Media; Otitis Media with Effusion; Pneumococcal Vaccines; Respiratory Syncytial Virus Vaccines; Serogroup; Vaccination; Vaccines
PubMed: 31948716
DOI: 10.1016/j.ijporl.2019.109839 -
IDCases 2020An 81-year-old man with lung cancer with bone metastases, interstitial pneumonia, and emphysema, was hospitalized for pain control. He developed fever and chills during...
An 81-year-old man with lung cancer with bone metastases, interstitial pneumonia, and emphysema, was hospitalized for pain control. He developed fever and chills during hospitalization. Physical examination revealed a fever of 39.1 °C, but there were no findings on history or physical examination to suggest the source of the infection. Gram-negative cocci were detected in the blood culture (Fig. 1) and in a Gram stained sputum smear (Figs. 3 and 4). and were ruled out based on history and an absence of suggestive symptoms. The cause of his fever was diagnosed as bacteremic pneumonia based on the blood culture and the sputum smear results, and he was treated with intravenous ceftriaxone. This case illustrates the importance of Gram staining of sputum and blood culture. should be considered in the differential diagnosis when gram-negative cocci are detected in the blood and the sputum.
PubMed: 32082989
DOI: 10.1016/j.idcr.2020.e00712