Staphylococcus aureus, a major pyogenic pathogen responsible for community- and hospital-acquired infections, is commonly found in chronic rhinosinusitis (CRS) but its involvement in the development of nasal polyposis is still debated. Several studies have reported the asymptomatic, transient or permanent, carriage of S. aureus in the anterior nares of approximately 30-50% of the population, yet no link has been established between this observation and the incidence of staphylococcal rhinosinusitis. Persistent carriers have higher S. aureus loads and a higher risk of acquiring S. aureus infection in general. Neither prolonged courses of antibiotics nor nasal topical treatments as described by Müller et al., leads to high rates of permanent eradication of S. aureus carriage. While S. aureus was traditionally considered as an obligate extracellular pathogen colonizing many different types of host tissues and secreting various enzymes and toxins for tissue Aim: The prevalence of intracellular Staphylococcus aureus organisms in the nasal mucosa of patients with recurrent infectious rhinosinusitis episodes was studied. Method: Twenty-seven consecutive adult patients who failed medical management of chronic rhinosinusitis (CRS) of multiple origins, associated or not with nasal polyposis, were consecutively enrolled for endonasal sinus surgery (including partial middle turbinectomy, middle antrostomy, ethmoidectomy, sphenoidotomy) and followed for a 12-month post-operative period. Results: Seventeen of these patients showed the presence of intracellular S. aureus as detected by confocal laser scan immunofluorescence microscopy in epithelial cells of surgical intranasal biopsy specimens. Nine of the patients with and two without intracellular bacteria yielded S. aureus in endoscopically guided cultures of middle meatus secretions, despite the recent administration of prophylactic antibiotics. Eleven of the 17 patients with intracellular S. aureus relapsed for rhinosinusitis within the 12-month follow-up period. Molecular typing of sequential S. aureus isolates demonstrated the persistence of unique patient-specific S. aureus clonotypes in nine of the patients with intracellular bacteria during the 12-month follow- up. Conclusion: The presence of intracellular S. aureus in epithelial cells of the nasal mucosa is a significant risk factor for recurrent episodes of rhinosinusitis due to persistent bacterial clonotypes, which appear refractory to antimicrobial and surgical therapy. Keywords: Chronic rhinosinusitis, endoscopic sinus surgery, Staphylococcus aureus, recurrent infections, intracellular reservoir destruction, more recent in vitro studies indicate that S. aureus may also exhibit a facultative intracellular lifestyle. S. aureus has been shown to survive not only within neutrophils thus contributing to infection, but also in epithelial cells, fibroblasts, endothelial cells and cultured enterocytic or osteoblastic cells. One proposed mechanism for S. aureus intracellular persistence is the formation of small colony variants, which protect them from host immune reactions and extend their survival within non-professional phagocytes. We recently described the presence of intracellular S. aureus in middle meatus mucosal biopsies of a few CRS patients. This clinical study evaluates the frequency of intracellular residency and its impact on recurrent CRS episodes by S. aureus in a larger cohort of consecutively enrolled patients.
The most effective anti-staphylococcal agent against
intracellular infections is clearly rifampin, but its use in
monotherapy is compromized by rapid emergence of highlevel
resistance. To overcome this problem, a combined
regimen of rifampin with a fluoroquinolone might be suggested,
though the impact of this combined antimicrobial regimen
for eradicating intracellular S. aureus reservoirs has yet to be
established and warrants further studies. In the same line, the
development of more elaborated in vitro assays that could
monitor the impact of antimicrobial therapy against intracellular
S. aureus would be most useful. In addition to systemic
antibiotherapy, improved strategies of local therapy are currently
tested. Preliminary data suggest that bid nasal lavage
with 0.5% sodium hypochlorite in saline solution seems to
improve the clinical status.
However the beneficial effects of such regimen does not seem
to last over one month.