Eradicating Chronic Ear, Nose, and Throat Infections

Smith, Angelia; Buchinsky, Farrel J.; Post, J. Christopher

doi:10.1177/0194599810391620

Cited by 49 publications

(20 citation statements)

References 46 publications

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“…The difficulties of treating biofilm infections, which can be up to 1,000 times more resistant to antibiotics [40], has prompted some physicians to propose a gradual move away from traditional antibiotic treatments and toward non-antibiotic therapies [41]. If antibiotics are to continue to be relevant for treating bacterial infections it is important that their effects on biofilms be explored.…”

Section: Introductionmentioning

confidence: 99%

Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

Li²,

Gunawardana

et al. 2014

PLoS ONE

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Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

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Section: Introductionmentioning

confidence: 99%

Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

Li²,

Gunawardana

et al. 2014

PLoS ONE

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“…Agents that are effective in treating upper respiratory tract biofilms, such as mupirocin and gentian violet (102), are difficult to deliver or potentially ototoxic within the middle ear. Proposed strategies focus on electromechanical and biochemical disruption of biofilm adherence and proliferation.…”

Section: The Importance Of Biofilm Phenotypes In Otitis Mediamentioning

confidence: 99%

New Paradigms in the Pathogenesis of Otitis Media in Children

et al. 2013

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Acute otitis media (AOM) is a multifactorial disease with a significant socioeconomic impact. The pathogenesis of AOM is attributed to a variety of well-established internal and extrinsic factors. Recent evidence strongly points to bacterial biofilm formation as an important contributor to this disease entity. The nasopharynx is a likely reservoir for infection with subsequent seeding of pathogens to the middle ear via planktonic shedding. Various modalities have been used to directly detect biofilm formation in the middle ear mucosa of children with AOM. Further insights into this disease may lead to new strategies for prevention and treatment.

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“…Because biofilm is usually resistant to conventional antibiotic treatment, eradication of biofilms is a promising treatment modality [25]. To evaluate the treatment modality, a robust and reliable model is needed.…”

Section: Discussionmentioning

confidence: 99%

“…In a clinical situation, most infections consist of mixed flora and synergy plays an important role among multiple organisms. Though complex biofilm composed of multiple species is frequently observed in the bacterial infection, little is known about the role of complex biofilm in OM [25]. Further studies are needed to elucidate these issues.…”

Section: Discussionmentioning

confidence: 99%

In VitroStreptococcus pneumoniaeBiofilm Formation andIn VivoMiddle Ear Mucosal Biofilm in a Rat Model of Acute Otitis Induced byS. pneumoniae

Yadav

Chae

Song

2012

Clin Exp Otorhinolaryngol

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ObjectivesStreptococcus pneumoniae is one of the most common pathogens of otitis media (OM) that exists in biofilm, which enhances the resistance of bacteria against antibiotic killing and diagnosis, compared to the free-floating (planktonic) form. This study evaluated biofilm formation by S. pneumoniae on an abiotic surface and in the middle ear cavity in a rat model of OM.MethodsIn vitro biofilm formation was evaluated by inoculation of a 1:100 diluted S. pneumoniae cell suspension in a 96-well microplate. Adherent cells were quantified spectrophotometrically following staining with crystal violet by measurement of optical density at 570 nm. The ultrastructure of pneumococcal biofilm was assessed by scanning electron microscopy (SEM). For in vitro biofilm study, S. pneumoniae cell suspensions containing 1×107 colony forming units were injected through transtympanic membrane into the middle ear cavity of Sprague Dawley rats. The ultrastructure of middle ear mucus was observed by SEM 1 and 2 weeks post-inoculation.ResultsThe in vitro study revealed robust biofilm formation by S. pneumoniae after 12-18 hours of incubation in high glucose medium, independent of exogenously supplied competence stimulating peptide and medium replacement. Adherent cells formed three-dimensional structures approximately 20-30 µm thick. The in vivo study revealed that ciliated epithelium was relatively resistant to biofilm formation and that biofilm formation occurred mainly on non-ciliated epithelium of the middle ear cavity. One week after inoculation, biofilm formation was high in 50% of the treated rats and low in 25% of the rats. After 2 weeks, biofilm formation was high and low in 25% and 37.5% of rats, respectively.ConclusionThe results imply that glucose level is important for the S. pneumoniae biofilm formation and S. pneumoniae biofilm formation may play important role in the pathophysiology of OM.

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Eradicating Chronic Ear, Nose, and Throat Infections

Abstract: Eradicating ENT biofilms is difficult when treating single-organism or mixed flora biofilms. Antibiotic therapy is often ineffective against biofilms, and clinical treatment may need to focus on nonantibiotic therapies that reduce, disrupt, or eradicate ENT biofilms.

Cited by 49 publications

References 46 publications

Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

New Paradigms in the Pathogenesis of Otitis Media in Children

In VitroStreptococcus pneumoniaeBiofilm Formation andIn VivoMiddle Ear Mucosal Biofilm in a Rat Model of Acute Otitis Induced byS. pneumoniae

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