Oral antibiotics used in the treatment of chronic rhinosinusitis have limited penetration into the sinonasal mucosa: a randomized trial

Siu, Joey; Klingler, Lilian; Wang, Yi; Hung, C.T.; Jeong, Soo Hee; Smith, Susan E.; Tingle, Malcolm D.; Mackenzie, Brett Wagner; Biswas, Kristi; Douglas, Richard

doi:10.1080/00498254.2020.1814973

Cited by 8 publications

(14 citation statements)

References 43 publications

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“…Methods are detailed in a previous report. 13 These results were analyzed in relation to bacterial community data and clinical outcome scores.…”

Section: Determination Of Antibiotic Concentrations By Liquid Chromatography-tandem Mass Spectrometrymentioning

confidence: 99%

“…Antibiotic concentrations and mucus-to-tissue and mucusto-serum penetration ratios are detailed in a previous report 13 and summarized in Table S1. Significant correlations between antibiotic concentration with bacterial community data and bacterial load are shown in Table 3.…”

Section: Relationships Between Antibiotic Concentrations With Bacterial Community Datamentioning

confidence: 99%

“…[9][10][11] The required concentration at the target site of infection remains unknown because in vitro microorganism susceptibility testing does not take into account the tissue pharmacokinetics of the antimicrobial agent and the variability in drug distribution within the body. 12 A recent randomized study published by our group 13 measured the concentrations of two commonly prescribed antibiotics, roxithromycin and doxycycline, with once-daily dosing, in sinonasal tissue, mucus, and serum of CRS patients. Antibiotic concentrations in the mucus were on average 6.25× and 2.70× lower compared to that in the serum for doxycycline and roxithromycin, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…14,15,19,20 The non-target and cumulative effects of broad-spectrum antibiotics for the treatment of CRS have been understudied. In this randomized study, we aimed to provide further data to our initial study 13 demonstrating the effects of antibiotics taken once-daily on sinus and gut bacterial community compositions and abundances in CRS patients over a week. Second, we investigated relationships between microbiological data, clinical outcomes (nasal endoscopy scores and gastrointestinal symptoms), and antibiotic concentrations published in the initial report.…”

Section: Introductionmentioning

confidence: 99%

“…Second, we investigated relationships between microbiological data, clinical outcomes (nasal endoscopy scores and gastrointestinal symptoms), and antibiotic concentrations published in the initial report. 13…”

Section: Introductionmentioning

confidence: 99%

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Sinonasal and gastrointestinal bacterial composition and abundance are stable after 1 week of once‐daily oral antibiotic treatment for chronic rhinosinusitis

Siu

Mackenzie

Klingler³

et al. 2021

Int Forum Allergy Rhinol

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Background: Despite the widespread prescription of antibiotics for the treatment of chronic rhinosinusitis (CRS), their efficacy remains uncertain. Limited penetration of systemic antibiotics into the sinonasal mucosa has been reported previously by this group. This study aimed to investigate the short-term effects of antibiotics on the sinus and gut microbiota as well as any relationships these had with drug distribution.Methods: Thirty subjects undergoing functional endoscopic sinus surgery for CRS were randomized to one of three groups: (1) doxycycline (100 mg daily for 7 days); (2) roxithromycin (300 mg daily for 7 days); and (3) control (no antibiotics given). Sinonasal and stool samples collected before and after treatment were analyzed using 16S ribosomal RNA (rRNA) gene-targeted amplicon sequencing and Droplet Digital polymerase chain reaction (PCR) for bacterial community composition and the quantification of bacterial DNA, respectively.Results: There were no significant major bacterial community shifts or changes to bacterial diversity and load following the treatment period in all patient groups. Non-significant trend reductions were observed in gut microbial diversity with antibiotics. For the roxithromycin group, sinonasal bacterial diversity was negatively correlated with serum drug levels and reduced overall compared to controls (p < 0.05). The relative abundance of Staphylococcus ASV129 in sinonasal samples reduced with increasing mucus doxycycline levels (p = 0.01). Conclusion:Antibiotic prescription for CRS should be further investigated because of preliminary evidence of poor sinonasal drug penetration, unproven efficacy, and the potential impact of dysbiosis in the sinuses and off-target sites. Further studies should consider distinguishing the presence of DNA from viable and nonviable bacteria.

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“…Methods are detailed in a previous report. 13 These results were analyzed in relation to bacterial community data and clinical outcome scores.…”

Section: Determination Of Antibiotic Concentrations By Liquid Chromatography-tandem Mass Spectrometrymentioning

confidence: 99%

Section: Relationships Between Antibiotic Concentrations With Bacterial Community Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sinonasal and gastrointestinal bacterial composition and abundance are stable after 1 week of once‐daily oral antibiotic treatment for chronic rhinosinusitis

Siu

Mackenzie

Klingler³

et al. 2021

Int Forum Allergy Rhinol

Self Cite

View full text Add to dashboard Cite

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Is there a role for antibiotics in the treatment of chronic rhinosinusitis?

Smith

Kim

Douglas

2022

Journal of Allergy and Clinical Immunology

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Novel strategies for inhibition of bacterial biofilm in chronic rhinosinusitis

Shariati

Vesal

Khoshbayan

et al. 2022

Journal of Applied Microbiology

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An important role has been recently reported for bacterial biofilm in the pathophysiology of chronic diseases, such as chronic rhinosinusitis (CRS). CRS, affecting sinonasal mucosa, is a persistent inflammatory condition with a high prevalence around the world. Although the exact pathological mechanism of this disease has not been elicited yet, biofilm formation is known to lead to a more significant symptom burden and major objective clinical indicators. The high prevalence of multidrugresistant bacteria has severely restricted the application of antibiotics in recent years.Furthermore, systemic antibiotic therapy, on top of its insufficient concentration to eradicate bacteria in the sinonasal biofilm, often causes toxicity, antibiotic resistance, and an effect on the natural microbiota, in patients. Thus, coming up with alternative therapeutic options instead of systemic antibiotic therapy is emphasized in the treatment of bacterial biofilm in CRS patients. The use of topical antibiotic therapy and antibiotic eluting sinus stents that induce higher antibiotic concentration, and decrease side effects could be helpful. Besides, recent research recognized that various natural products, nitric oxide, and bacteriophage therapy, in addition to the hindered biofilm formation, could degrade the established bacterial biofilm.However, despite these improvements, new antibacterial agents and CRS biofilm interactions are complicated and need extensive research. Finally, most studies were performed in vitro, and more preclinical animal models and human studies are required to confirm the collected data. The present review is specifically discussing potential therapeutic strategies for the treatment of bacterial biofilm in CRS patients. K E Y W O R D S antibiofilm agents, bacterial biofilm, chronic rhinosinusitis, multi-drug resistant bacteria, new therapeutic approaches Phospholipid liposomes Reducing the liposome size and formulating liposomes as positively charged increased the penetration and inhibition of bacterial biofilms Dong et al. (2015) 2017 S. epidermidis Gentamicin with laser generated shockwaves (LGS) LGS increases the efficacy of topical antibiotics in an in vitro model Yao et al. (2017) 2017 S. aureus Silk fibroin-nano silver The Nanoparticle solution was an effective topical agent against S. aureus biofilms in the rabbit model of sinusitis Jia et al. (2017) 2018 Prospective blinded comparative study Spray cryotherapy Spray cryotherapy removed multi-species biofilm from the mucosa surface Vlad et al. (2018) 2018 S. aureus Chitogel combined with deferiprone and gallium protoporphyrin (CG-DG) CG-DG was effective against S. aureus biofilms in a sheep sinusitis model Ooi et al. (2018) 2020 Haemophilus influenzae (CIs) Antibodies against the DNABII protein integration host factor This treatment was highly effective in preventing the formation H. influenzae biofilms Martyn et al. (2020) 2020 S. aureus Isosorbide mononitrate (ISMN) loaded nanoparticles conjugated with an anti-S. aureus alpha-toxin antibody This trea...

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Oral antibiotics used in the treatment of chronic rhinosinusitis have limited penetration into the sinonasal mucosa: a randomized trial

Cited by 8 publications

References 43 publications

Sinonasal and gastrointestinal bacterial composition and abundance are stable after 1 week of once‐daily oral antibiotic treatment for chronic rhinosinusitis

Sinonasal and gastrointestinal bacterial composition and abundance are stable after 1 week of once‐daily oral antibiotic treatment for chronic rhinosinusitis

Is there a role for antibiotics in the treatment of chronic rhinosinusitis?

Novel strategies for inhibition of bacterial biofilm in chronic rhinosinusitis

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