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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 -
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 -
Otolaryngology--head and Neck Surgery :... Apr 2017Objective To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM... (Review)
Review
Objective To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources PubMed database of the National Library of Science. Review Methods We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.
Topics: Antigens, Bacterial; Antigens, Viral; Congresses as Topic; Haemophilus influenzae; Humans; Moraxella catarrhalis; Otitis Media; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate; Viral Vaccines
PubMed: 28372533
DOI: 10.1177/0194599816632178 -
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 -
The EMBO Journal Mar 2023Moraxella catarrhalis is an important human respiratory pathogen and a major causative agent of otitis media and chronic obstructive pulmonary disease. Toll-like...
Moraxella catarrhalis is an important human respiratory pathogen and a major causative agent of otitis media and chronic obstructive pulmonary disease. Toll-like receptors contribute to, but cannot fully account for, the complexity of the immune response seen in M. catarrhalis infection. Using primary mouse bone marrow-derived macrophages to examine the host response to M. catarrhalis infection, our global transcriptomic and targeted cytokine analyses revealed activation of immune signalling pathways by both membrane-bound and cytosolic pattern-recognition receptors. We show that M. catarrhalis and its outer membrane vesicles or lipooligosaccharide (LOS) can activate the cytosolic innate immune sensor caspase-4/11, gasdermin-D-dependent pyroptosis, and the NLRP3 inflammasome in human and mouse macrophages. This pathway is initiated by type I interferon signalling and guanylate-binding proteins (GBPs). We also show that inflammasomes and GBPs, particularly GBP2, are required for the host defence against M. catarrhalis in mice. Overall, our results reveal an essential role for the interferon-inflammasome axis in cytosolic recognition and immunity against M. catarrhalis, providing new molecular targets that may be used to mitigate pathological inflammation triggered by this pathogen.
Topics: Mice; Humans; Animals; Inflammasomes; Caspases; NLR Family, Pyrin Domain-Containing 3 Protein; Moraxella catarrhalis; Carrier Proteins; Immunity, Innate
PubMed: 36762431
DOI: 10.15252/embj.2022112558 -
Expert Opinion on Therapeutic Targets 2016Moraxella catarrhalis is a prominent pathogen that causes acute otitis media in children and lower respiratory tract infections in adults, resulting in a significant... (Review)
Review
INTRODUCTION
Moraxella catarrhalis is a prominent pathogen that causes acute otitis media in children and lower respiratory tract infections in adults, resulting in a significant socioeconomic burden on healthcare systems globally. No vaccine is currently available for M. catarrhalis. Promising M. catarrhalis target antigens have been characterized in animal models and should soon enter human clinical trials.
AREAS COVERED
This review discusses the detailed features and research status of current candidate target antigens for an M. catarrhalis vaccine. The approaches for assessing M. catarrhalis vaccine efficacy are also discussed.
EXPERT OPINION
Targeting the key molecules contributing to serum resistance may be a viable strategy to identify effective vaccine targets among M. catarrhalis antigens. Elucidating the role and mechanisms of the serum and mucosal immune responses to M. catarrhalis is significant for vaccine target selection, testing and evaluation. Developing animal models closely simulating M. catarrhalis-caused human respiratory diseases is of great benefit in better understanding pathogenesis and evaluating vaccine efficacy. Carrying out clinical trials will be a landmark in the progress of M. catarrhalis vaccine research. Combined multicomponent vaccines will be a focus of future M. catarrhalis vaccine studies.
Topics: Adult; Animals; Bacterial Vaccines; Child; Disease Models, Animal; Drug Design; Humans; Molecular Targeted Therapy; Moraxella catarrhalis; Moraxellaceae Infections; Otitis Media; Respiratory Tract Infections
PubMed: 26565427
DOI: 10.1517/14728222.2015.1081686 -
Journal of Applied Microbiology Feb 2019This study aimed to verify the formation of biofilms by Moraxella bovis, Moraxella ovis and Moraxella bovoculi isolates from ruminants. In addition, the lysozyme...
AIMS
This study aimed to verify the formation of biofilms by Moraxella bovis, Moraxella ovis and Moraxella bovoculi isolates from ruminants. In addition, the lysozyme activity against the isolates of M. bovis, M. ovis and M. bovoculi in free form and in biofilms was determined.
METHODS AND RESULTS
In this study, 54 isolates of Moraxella sp. obtained from bovine and ovine clinical samples were evaluated in vitro for capacity of biofilm formation and lysozyme susceptibility in planktonic and sessile cells. In addition, biofilms produced by four Moraxella sp. isolates were visualized under scanning electron microscope (SEM). It was possible to demonstrate, for the first time, the ability to form biofilms by M. ovis and M. bovoculi. The isolates of Moraxella sp. have the capacity to form biofilms in different intensities, varying among weak, moderate and strong. It was verified that the lysozyme shows activity on Moraxella sp. in planktonic form. However, on biofilms there was a reduction in the production, but without impairing its formation, and on consolidated biofilms the lysozyme did not have the capacity to eradicate the preformed biofilms.
CONCLUSIONS
This work shows the capacity of biofilm formation by Moraxella sp. of veterinary importance. The lysozyme susceptibility of Moraxella sp. in planktonic form shows that this enzyme has bacteriostatic activity on this micro-organism and it reduced the production of biofilms.
SIGNIFICANCE AND IMPACT OF THE STUDY
Based on the results, it is possible to infer that the biofilm formation capacity by Moraxella sp. and the resistance to lysozyme concentrations equal to or greater than the physiological levels of the ruminant tear may be linked not only to the capacity to colonize the conjunctiva, but also to remain in this place even after healing of the lesions, being a reservoir of Moraxella sp. in a herd.
Topics: Animals; Biofilms; Cattle; Cattle Diseases; Keratoconjunctivitis, Infectious; Moraxella; Moraxella bovis; Moraxellaceae Infections; Muramidase; Sheep
PubMed: 30142702
DOI: 10.1111/jam.14086 -
Journal of Clinical Medicine Mar 2022is the most clinically relevant species among spp. For decades, it was considered to be part of the normal human flora in the upper respiratory tract. However, since... (Review)
Review
is the most clinically relevant species among spp. For decades, it was considered to be part of the normal human flora in the upper respiratory tract. However, since the late 1970s, considerable evidence has proposed that is an important pathogen in the human respiratory tract. Even though Infective Endocarditis (IE) is rarely caused by spp., these infections can be problematic due to the lack of experience in their management. The aim of this study was to systematically review all published cases of IE by spp. A systematic review of PubMed, Scopus and Cochrane library (through 8 December 2021) for studies providing epidemiological, clinical, microbiological data as well as treatment data and outcomes of IE by spp. was performed. A total of 27 studies, containing data for 31 patients, were included. A prosthetic valve was present in 25.8%. Mitral valve was the most commonly infected site. Fever, sepsis and embolic phenomena were the most common clinical presentations. Cephalosporins, aminoglycosides, aminopenicillins and penicillin were the most commonly used antimicrobials. Overall mortality was 12.9%.
PubMed: 35407461
DOI: 10.3390/jcm11071854 -
Frontiers in Cellular and Infection... 2022Otitis media (OM) is an inflammatory disorder in the middle ear. It is mainly caused by viruses or bacteria associated with the airways. and are the three main... (Review)
Review
Otitis media (OM) is an inflammatory disorder in the middle ear. It is mainly caused by viruses or bacteria associated with the airways. and are the three main pathogens in infection-related OM, especially in younger children. In this review, we will focus upon the multifaceted gene regulation mechanisms that are well-orchestrated in , and during the course of infection in the middle ear either in experimental OM or in clinical settings. The sophisticated findings from the past 10 years on how the othopathogens govern their virulence phenotypes for survival and host adaptation phase variation- and quorum sensing-dependent gene regulation, will be systematically discussed. Comprehensive understanding of gene expression regulation mechanisms employed by pathogens during the onset of OM may provide new insights for the design of a new generation of antimicrobial agents in the fight against bacterial pathogens while combating the serious emergence of antimicrobial resistance.
Topics: Gene Expression Regulation; Haemophilus influenzae; Humans; Moraxella catarrhalis; Otitis Media; Streptococcus pneumoniae
PubMed: 35252035
DOI: 10.3389/fcimb.2022.826018