Polymyxin B and ethylenediaminetetraacetic acid act synergistically against Pseudomonas aeruginosa and Staphylococcus aureus.

Polymyxin B and ethylenediaminetetraacetic acid are antimicrobials possessing antibiofilm activity. They act by displacement and chelation, respectively, of divalent cations in bacterial membranes and may therefore act synergistically when applied in combination. If so, this combination of agents may be useful for the treatment of diseases like cystic fibrosis (CF), in which biofilms are present on the respiratory epithelium. We used checkerboard assays to investigate the synergy between these agents using reference strains Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 6538 in planktonic form. We then determined the efficacy of each agent against biofilms of both species grown on 96-pin lids and proceeded to combination testing against the P. aeruginosa reference strain and 10 clinical isolates from patients with CF. Synergism was observed for planktonic forms of both species and for biofilms of P. aeruginosa. The susceptibility of biofilms of P. aeruginosa clinical isolates to these agents was variable compared to the laboratory reference strain. This combination of agents may be useful in the management of biofilm-associated conditions, particularly those amenable to topical therapies. These results provide a basis upon which the antimicrobial and antibiofilm efficacy of preparations containing these agents may be enhanced.IMPORTANCEBacteria living in biofilms produce a protective matrix which makes them difficult to kill. Patients with severe respiratory disease often have biofilms. Polymyxin B is an antibiotic commonly used in topical medications, such as eye drops and nasal sprays. Ethylenediaminetetraacetic acid (EDTA) is used widely as a preservative in medication but also has antimicrobial properties. It has been hypothesized that Polymyxin B and EDTA could have a synergistic relationship: when used in combination their antimicrobial effect is enhanced. Here, we evaluated the levels at which Polymyxin B and EDTA work together to kill common pathogens Pseudomonas aeruginosa and Staphylococcus aureus. We found that Polymyxin B and EDTA were synergistic. This synergy may be useful in the management of planktonic infection with P. aeruginosa and S. aureus, or biofilm infection with P. aeruginosa. This synergy may be beneficial in the treatment of respiratory biofilms, in which P. aeruginosa biofilms are common.

In vitro Nasodine Can be an Effective Antibiofilm Agent for Biofilms that May Cause CRS.

OBJECTIVES: Bacterial biofilms on the sinonasal mucosa, especially biofilms of Staphylococcus aureus, are associated with greater severity and recalcitrance of chronic rhinosinusitis (CRS). There are few, if any, antibiofilm agents suitable for sinonasal application available for the management of this problem. Nasodine® Nasal Spray (Nasodine) is a 0.5% povidone-iodine-based formulation that has been developed for sinonasal application. We investigated the antibiofilm efficacy of Nasodine to determine whether it may be a candidate for the treatment of biofilm-associated CRS. METHODS: Biofilms of S. aureus ATCC 6538 were grown in vitro using the Centers for Disease Control biofilm reactor. Intact biofilms were treated by immersion in 0.9% saline (control), half concentration Nasodine, or full concentration Nasodine for between 5 min and 6 h. Further biofilm cells were dispersed into suspension then treated for between 30 s and 5 min. Surviving bacteria were then enumerated by culture and counting colonies, and the log10 reduction in viable bacteria was compared with control. RESULTS: Nasodine demonstrated time and concentration-dependent bacterial killing against intact biofilm. Statistically significant reductions in viable bacteria from intact biofilms were seen with exposures as brief as 5 min. Nasodine consistently eradicated dispersed biofilm within 1 min. CONCLUSION: Nasodine is highly active against biofilms of S. aureus ATCC 6538 in vitro. Biofilm killing is impeded by the presence of the intact biofilm structure. LAY SUMMARY: In chronic rhinosinusitis (CRS), bacterial communities called biofilms are associated with more severe inflammation. An iodine-based nasal spray called Nasodine almost completely eradicates bacterial biofilms after 6 h of exposure. Nasodine may be useful for treating CRS. Laryngoscope, 133:2490-2495, 2023.

Topical Antibiofilm Agents With Potential Utility in the Treatment of Chronic Rhinosinusitis: A Narrative Review.

The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.

A reappraisal of adult thoracic surface anatomy.

Accurate surface anatomy is essential for safe clinical practice. Numerous inconsistencies in clinically important surface markings exist between and within anatomical reference texts. The aim of this study was to investigate key thoracic surface anatomical landmarks in vivo using computed tomographic (CT) imaging. High-resolution thoracic CT scans from 153 supine adults (mean age 63, range 19-89 years; 53% female) taken at end tidal inspiration were analyzed by dual consensus reporting to determine the surface anatomy of the sternal angle, central veins, heart, lungs, and diaphragm. Patients with kyphosis/scoliosis, distorting space-occupying lesions, or visceromegaly were excluded. The position of the cardiac apex, formation of the brachiocephalic veins, and vertebral levels of the sternal angle, xiphisternal joint, and aortic hiatus were consistent with commonly accepted surface markings although there was a wide range of normal variation. In contrast, common surface markings were markedly inaccurate for the following: the position of the tracheal bifurcation, aortic arch, and azygos vein termination (below the plane of the sternal angle at T5-T6 vertebral level in most individuals); the superior vena cava/right atrial junction (most often behind the fourth costal cartilage); the lower border of the lung (adjacent to T12 vertebra posteriorly); and the level at which the inferior vena cava and esophagus traverse the diaphragm (T11 in most). Surface anatomy must be reappraised using modern imaging in vivo if it is to be evidence based and fit for purpose. The effects of gender, age, posture, respiration, build, and ethnicity also deserve greater emphasis.

Inconsistencies in surface anatomy: The need for an evidence-based reappraisal.

Accurate surface anatomy is a key component of safe clinical practice. But how consistent are modern clinical and surface anatomy texts in their reporting of common surface anatomy landmarks? Thirteen popular texts in common use were analyzed in detail: one clinical and anatomical reference text; seven clinical anatomy texts; two surface anatomy texts; and three clinical examination texts. Content relating to surface anatomy was reviewed, summarized, and assessed for consistency. Four main findings emerged: (i) there are numerous inconsistencies in clinically important surface markings (e.g., the femoral artery in the groin, superficial and deep inguinal rings, and accessory nerve in the posterior triangle), including inconsistencies within some texts; (ii) there is a consensus on many surface markings, e.g., the spleen and termination of the spinal cord; (iii) few texts address variation in surface anatomy related to age, sex, body mass, posture, respiration, and ethnicity; and (iv) the three standard clinical examination texts included in this review contain comparatively little surface anatomy. Seven surface anatomy landmarks were redefined within an evidence-based framework: termination of the spinal cord, supracristal plane, base of the appendix, renal length, the deep inguinal ring, the femoral artery in the groin, and the accessory nerve in the posterior triangle of the neck. An evidence-based framework is essential if surface anatomy is to be accurate and clinically relevant.