Exacerbations of Chronic Rhinosinusitis—Microbiology and Perspectives of Phage Therapy

Abstract

The chronically inflamed mucosa in patients with chronic rhinosinusitis (CRS) can additionally be infected by bacteria, which results in an acute exacerbation of the disease (AECRS). Currently, AECRS is universally treated with antibiotics following the guidelines for acute bacterial rhinosinusitis (ABRS), as our understanding of its microbiology is insufficient to establish specific treatment recommendations. Unfortunately, antibiotics frequently fail to control the symptoms of AECRS due to biofilm formation, disruption of the natural microbiota, and arising antibiotic resistance. These issues can potentially be addressed by phage therapy. In this study, the endoscopically-guided cultures were postoperatively obtained from 50 patients in order to explore the microbiology of AECRS, evaluate options for antibiotic treatment, and, most importantly, assess a possibility of efficient phage therapy. Staphylococcus aureus and coagulase-negative staphylococci were the most frequently isolated bacteria, followed by Haemophilus influenzae, Pseudomonas aeruginosa, and Enterobacteriaceae. Alarmingly, mechanisms of antibiotic resistance were detected in the isolates from 46% of the patients. Bacteria not sensitive to amoxicillin were carried by 28% of the patients. The lowest rates of resistance were noted for fluoroquinolones and aminoglycosides. Fortunately, 60% of the patients carried bacterial strains that were sensitive to bacteriophages from the Biophage Pharma collection and 81% of the antibiotic-resistant strains turned out to be sensitive to bacteriophages. The results showed that microbiology of AECRS is distinct from ABRS and amoxicillin should not be the antibiotic of first choice. Currently available bacteriophages could be used instead of antibiotics or as an adjunct to antibiotics in the majority of patients with AECRS.

Isolation, Characterization, and Comparison of Efficiencies of Bacteriophages to Reduce Planktonic and Biofilm-Associated Staphylococcus aureus

“…Recent studies on use of S. aureus phages have focused on the need for the ability of phages to disperse biofilms. [7][8][9][10][11][12][13][14] Studies that have looked at deciphering the reasons for phage therapy failure in experimental animals, wherein in vitro results were very promising and have suggested that absence of depolymerase may result in inability of phages to disrupt biofilms. 29 In the present study, planktonic cells of S. aureus were sensitive to phages PD1, PE1, and PE2.…”

“…The ability of phages and phage-derived proteins to remove S. aureus in clinical models has been lower compared with planktonic forms as tested in vitro. [8][9][10][11][12][13][14] More than 80% human infections caused by bacteria, infections are manifested by growth of the organism in biofilms. 15 The physiology of an organism in biofilm differs from those that are planktonic, 16 hence there is a need to evaluate the activity of phages both on planktonic forms, as well as on biofilms to select candidate therapeutic phages.…”

Anti-biofilm activity of bacteriophages and lysins in chronic rhinosinusitis

“…Notably, Corynebacterium and Lactobacillus sakei may prevent Staphylococcus colonization in the nose and sinuses (Drilling et al, 2016). According to the latest report, in 50 patients with acute exacerbation of chronic rhinosinusitis disease (AECRS), S. aureus, S. epidermidis and other coagulase-negative staphylococci were the most frequently occurring bacteria followed by H. influenzae, P. aeruginosa and Enterobacteriaceae (Szaleniec et al, 2019). Studies performed on pediatric patients revealed that the most abundant organism associated with chronic rhinosinusitis was Moraxella (Stapleton et al, 2020).…”

“…Mucosal inflammation in the paranasal sinuses is correlated with decreased microbial diversity and increased bacterial load (Drilling et al, 2016;Sivasubramaniam et al, 2018;Szaleniec et al, 2017). Increasing resistance to available antibiotics (up to 28% of some sinus bacterial isolates from CRS patients) may cause a problem in CRS treatment (Fong et al, 2017;Szaleniec et al 2019). The examined bacterial isolates, that is, S. aureus, S. epidermidis, other coagulase-negative staphylococci and P. aeruginosa from CRS patients, were the most resistant to antibiotics.…”

Modern approaches to the treatment of chronic polypous rhinosinusitis

“…• mucosecretolytic -to reduce the viscosity of secret due to the break of disulfide bonds, an increase in the frequency of oscillation of cilia of ciliated epithelium, which facilitates the outflow of secretions from the paranasal sinuses; • anti-inflammatory, due to the neutralization of oxygen OH-radicals, and a reduced synthesis of ethylene and histamine level; • antibacterial, manifested in bacteriostatic action on the main pathogens (Szaleniec et al 2019).…”