In Vitro Antibacterial Activity of NB-003 against Propionibacterium acnes

Abstract

NB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections. In vitro susceptibility of Propionibacterium acnes to NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against all P. acnes isolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC 90 s/minimum bactericidal concentrations (MBC 90 s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 g/ml, respectively. In the presence of 50% sebum, the MIC 90 s/MBC 90 s of NB003 and BPOs increased to 128/1,024 and 400/1,600 g/ml, respectively. The MIC 90 s/MBC 90 s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC 90 s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC 90 s/MBC 90 s of 128/256 g/ml for NB003 and 214/428 g/ml for BPO. The addition of EDTA enhanced the in vitro efficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16-and >256-fold decrease in MIC 90 and MBC 90 , yielding a more potent MIC 90 /MBC 90 of <1/<1 g/ml. The kinetics of bactericidal activity of NB-003 against P. acnes were compared to those of a commercially available product of BPO. Electron micrographs of P. acnes treated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance of P. acnes revealed no stably resistant mutant strains.

Antibacterial Activity of Long-Chain Polyunsaturated Fatty Acids against Propionibacterium acnes and Staphylococcus aureus

“…Despite LC-PUFAs lacking bactericidal action against P. acnes , these compounds did exert similar antibacterial potency as BPO and SA indicating that potency should not prevent LC-PUFAs being considered as alternative agents in acne therapy. The antimicrobial potency of BPO against P. acnes in this present study is similar to previous reports, but the lack of bactericidal activity, such as has been reported previously, may stem from methodological differences in quantifying antimicrobial action and the preparation of the inoculum, as well as the use of different growth conditions and bacterial strains [27,28,29]. Despite no indication of P. acnes resistance to LC-PUFAs, the probability to select for strains with resistance to the action of these compounds warrants investigation, particularly as a large difference was observed between MIC and MBC values that may increase the opportunity for mutant selection [30].…”

The potential of bacteriocin AS-48 in the control of Propionibacterium acnes

“…4 logs of CFU/cm 2 and incubated under anaerobic conditions for 1 h to allow absorption and adherence of bacteria to the skin surface, Then, four different formulations containing 10 µg/ml of AS-48 plus lysozyme (4 mg/ml) were applied to the skin samples (cream, hydro-alcoholic solution, gel and cream plus urea). The treated skin formulation were incubated under anaerobic conditions and samples removed every hour to make a count of the survivors, rinsing with 1 ml cold saline twice to collect any viable bacteria still existing on the skin, diluting in saline solution to be plated onto Wilkins-Chalgren medium, and incubating anaerobically at 37°C (Pannu et al, 2011). A control without treatment was also carried out.…”

“…The synergy between these compounds highlights once again the importance of combining antimicrobial agents that act on different targets ("hurdle technology"): the simultaneous application of multiple barriers acting on different targets is more effective than just one, and allows the application of the active principles in more moderate doses (Leistner 2000). Besides, these active principles have the advantage of avoiding the development of resistance by pathogens that colonize and infect the skin (Bowe et al, 2006;Lee et al, 2008;Kang et al, 2009;Pannu et al, 2011). In summary, this study supports that AS-48 exhibits propierties that make it particularly promising in light of emerging antibiotic resistance across bacteria involved in treatment of dermatological disease as acne vulgaris.…”

Two important novelties in etiopathogenesis and therapy of acne

“…An antiproliferative action has also been demonstrated: Myrtacine® inhibits keratinocyte proliferation by 27% and 76% at 1 and 3 μg/mL, respectively . At concentrations ranging from 0.0001% to 0.03%, Myrtacine® inhibits the proliferation of planktonic and non‐planktonic P. acnes strains which are sensitive or resistant to erythromycin . This inhibition occurs at much lower concentrations than with benzoyl peroxide.…”

“…5 At concentrations ranging from 0.0001% to 0.03%, Myrtacineâ inhibits the proliferation of planktonic and non-planktonic P. acnes strains which are sensitive or resistant to erythromycin. [5][6][7] This inhibition occurs at much lower concentrations than with benzoyl peroxide. On P. acnes biofilm, 0.1% Myrtacineâ has two complementary actions: (i) very rapid inhibitory action on biofilm formation, after 5 h of contact, and (ii) destruction of biofilm, after 1 min of contact.…”