Bacterial biofilms in the upper airway - evidence for role in pathology and implications for treatment of otitis media

Bakaletz, Lauren O.

doi:10.1016/j.prrv.2012.03.001

Cited by 98 publications

(68 citation statements)

References 57 publications

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“…They found that biofilm-producing pathogens were more frequently isolated from the nasopharynx in the recurrent AOM group than in the control group, and H. influenzae was confirmed to be the main pathogen in the recurrent group (11). In addition, Bakaletz reported that biofilms contribute to both chronic otitis media and recurrent AOM (12). In the current study, nearly all of the H. influenzae isolates (94.6%) had the ability to form biofilms.…”

Section: Discussionsupporting

confidence: 54%

“…Treatment failures and relapses of AOM in children are influenced not only by microbiological factors, such as antibiotic resistance (10), viral coinfection (16,17), biofilm formation (11,12), and invasion of epithelial cells (18), but also by host factors, including immaturity of the immune system (17), lack of breastfeeding (19), tubal dysfunction (20), recent antibiotic usage (21), and multiple episodes of AOM. In addition, environmental factors such as attending a day care center (2) and the presence of siblings (22) influence treatment failure and relapse of AOM.…”

Section: Discussionmentioning

confidence: 99%

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Improvement Rate of Acute Otitis Media Caused by Haemophilus influenzae at 1 Week Is Significantly Associated with Time to Recovery

et al. 2013

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The susceptibilities of the isolates to ampicillin were determined, and microtiter biofilm assays and invasion assays using BEAS-2B cells were performed. The association between these bacterial characteristics and clinical relapses of AOM and treatment failures was evaluated. Seventy-four children (39 boys and 35 girls) with a median age of 1 year (interquartile range [IQR], 0.25 to 2 years) were enrolled. Among 74 H. influenzae isolates, 37 showed intermediate resistance or resistance to ampicillin (MIC, >2 g/ml). In the microtiter biofilm assay, the median optical density at 600 nm (OD 600 ) was 0.68 (IQR, 0.24 to 1.02), and 70 isolates formed biofilms. The median invasion rate was 15% (IQR, 0 to 10%), and 46 isolates invaded BEAS-2B cells. Relapses and treatment failures occurred in 19 and 6 children, respectively. There was no significant difference in the invasion rates between patients with and those without relapses or treatment failures. Also, there was no significant association between biofilm formation and relapse or treatment failure. The improvements in the severity scores after 1 week were significantly associated with the recovery time (P < 0.0001). We did not identify any significant association between relapse or treatment failure and bacterial factors. AOM has a multifactorial etiology, and this may explain why we could not find a significant association. An improvement in the severity score after 1 week of treatment may be a useful predictor of the outcome of AOM.A cute otitis media (AOM) is the most common disease of the upper respiratory tract in childhood, and treatment of AOM is the most frequent reason that children in the United States take antibiotics (1). In Japan, the incidence of AOM has increased recently, and many children now need hospitalization to receive intravenous antibiotics for the treatment of intractable AOM with persistent purulent otorrhea (2).We previously reported that Haemophilus influenzae can form a biofilm both in vitro (3) and in vivo (4). Bacterial biofilms are recognized as having an important role in various human infections, and the bacteria in a biofilm are more resistant to antibiotic therapy than are planktonic microorganisms, suggesting that biofilms might play an important role in the pathogenesis and chronicity of otitis media (3). In addition, an investigation of the mechanism of airway epithelium invasion by H. influenzae revealed that the bacteria are internalized by the adenoid cells of children (5). We also previously demonstrated that H. influenzae isolated from clinical samples can invade and destroy human bronchial epithelial cells (BEAS-2B cells) (6), suggesting that such activity might delay the resolution of AOM. However, the association between biofilm formation or invasion of bronchial epithelial cells and the clinical course and outcome of AOM due to H. influenzae has been unclear.Accordingly, we measured the biofilm formation and invasion of bronchial epithelial cells by H. influenzae isolated from children with AOM, and we evaluated the ...

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Improvement Rate of Acute Otitis Media Caused by Haemophilus influenzae at 1 Week Is Significantly Associated with Time to Recovery

et al. 2013

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“…Readers are referred to reviews of H. influenzae and infections of the respiratory tract for more information (237)(238)(239)(240)(241)(242)(243).…”

Section: Haemophilus Influenzae In the Post-hib-vaccine Eramentioning

confidence: 99%

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

2014

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SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described ( Haemophilus pittmaniae and Haemophilus sputorum ), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species ( Aggregatibacter aphrophilus , Aggregatibacter segnis , and Aggregatibacter actinomycetemcomitans ). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus . Due to the limited pathogenicity of H. haemolyticus , the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology practice. However, identification of some strains will still be problematic, necessitating DNA sequencing of multiple housekeeping gene fragments or full-length 16S rRNA genes.

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“…The illnesses caused by this transition from carriage to disease result in a mortality rate of ∼15-20% in adults with an even higher rate in elderly patients (2)(3)(4). Pediatric cases include >20 million yearly occurrences, primarily middle ear infections, in the United States and account for the majority of emergency room admissions and associated antibiotic prescriptions, accruing billions of dollars in annual socioeconomic costs (6,7). Invasive disease has a more devastating impact in resource-limited countries, with an estimated 1 million children (11% of all deaths below age 5 y) succumbing to pneumococcal infection annually (8)(9)(10)(11).…”

mentioning

confidence: 99%

Directed vaccination against pneumococcal disease

Hill

Beitelshees

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a “smart” vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens.

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Bacterial biofilms in the upper airway - evidence for role in pathology and implications for treatment of otitis media

Cited by 98 publications

References 57 publications

Improvement Rate of Acute Otitis Media Caused by Haemophilus influenzae at 1 Week Is Significantly Associated with Time to Recovery

Improvement Rate of Acute Otitis Media Caused by Haemophilus influenzae at 1 Week Is Significantly Associated with Time to Recovery

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

Directed vaccination against pneumococcal disease

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