Neomycin Sulfate Improves the Antimicrobial Activity of Mupirocin-Based Antibacterial Ointments

Abstract

In the midst of the current antimicrobial pipeline void, alternative approaches are needed to reduce the incidence of infection and decrease reliance on last-resort antibiotics for the therapeutic intervention of bacterial pathogens. In that regard, mupirocin ointment-based decolonization and wound maintenance practices have proven effective in reducing Staphylococcus aureus transmission and mitigating invasive disease. However, the emergence of mupirocin-resistant strains has compromised the agent's efficacy, necessitating new strategies for the prevention of staphylococcal infections. Herein, we set out to improve the performance of mupirocin-based ointments. A screen of a Food and Drug Administration (FDA)-approved drug library revealed that the antibiotic neomycin sulfate potentiates the antimicrobial activity of mupirocin, whereas other library antibiotics did not. Preliminary mechanism of action studies indicate that neomycin's potentiating activity may be mediated by inhibition of the organism's RNase P function, an enzyme that is believed to participate in the tRNA processing pathway immediately upstream of the primary target of mupirocin. The improved antimicrobial activity of neomycin and mupirocin was maintained in ointment formulations and reduced S. aureus bacterial burden in murine models of nasal colonization and wound site infections. Combination therapy improved upon the effects of either agent alone and was effective in the treatment of contemporary methicillin-susceptible, methicillin-resistant, and high-level mupirocin-resistant S. aureus strains. From these perspectives, combination mupirocin-and-neomycin ointments appear to be superior to that of mupirocin alone and warrant further development.

Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment

“…To evaluate whether ZnPT and SSD were compatible in ointment format, both agents were formulated alone and in combination in standard polyethylene glycol (PEG)-based vehicle and assessed for activity in antimicrobial plate assays, as previously described ( 28 ). To perform the assessment, P. aeruginosa , S. aureus , or A. baumannii cells were spread on agar plates, PEG-based ointment containing 1% dimethyl sulfoxide (DMSO) (vehicle) or 1% SSD or 0.25% ZnPT or the SSD-ZnPT combination (1% SSD–0.25% ZnPT) was applied to the center of the plate, and the resulting zone of growth inhibition was measured following overnight incubation.…”

“…Antimicrobial zones of inhibition were measured for PEG ointment compilations using the indicated bacterial strains, as previously described ( 28 ). To do so, 100 µl of 1 × 10 8 CFU ml −1 of A. baumannii , S. aureus , or P. aeruginosa was spread on MH plates using a sterile glass hockey stick.…”

Identification of Small Molecule Inhibitors of Staphylococcus aureus RnpA

“…As a means to efficiently screen compound libraries for members with on-target antimicrobial effects, we previously developed a whole cell-based mupirocin synergy assay to enrich for agents that are capable of inhibiting cellular RnpA [17]. The premise for the assay was that RNase P (RnpA + rnpB ) and tRNA synthetases work in a sequential manner to generate charged tRNA molecules needed for translation.…”

Coconut Oil as a Therapeutic agent in Medication Induced Contact Dermatitis

“…Interestingly, theories suggesting that neomycin-containing ointments sensitize the skin more than creams, lotions, or powders. 13 For therapeutic purposes, based on the severity of various skin diseases, neomycin would be used as a single medication or can be given in combination with other topical agents like bacitracin, polymyxin, antifungals and corticosteroids. 14,15 Natural plant oils, due to their easy availability, accessibility and low cost they are most commonly used globally for treating various skin ailments.…”