Excipients can improve antibiotic activity in Pseudomonas aeruginosa biofilms

L-alanine, succinic acid, and N-acetyl-D-glucosaminitol may be useful as antibiotic adjuvants in anti-biofilm formulations

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A new study screened 190 potential excipients alone, and in combination with tobramycin against Pseudomonas aeruginosa grown in planktonic or biofilm form. Forty-eight materials tested caused a reduction of P. aeruginosa proliferation either alone or combined with tobramycin. Among them, L-alanine, D-alanine, and N-acetyl-D-glucosaminitol enhanced the activity of tobramycin. In addition, L-alanine and succinic acid significantly reduced the survival of P. aeruginosa biofilms.

Molecules acting as carbon nutrient sources for bacteria are able to stimulate bacterial dispersion from a biofilm and/or reverse the persister state of a subpopulation of bacteria within the biofilms, making bacteria more susceptible to antibiotics. This work highlights the importance of evaluating the excipients of the pharmaceutical preparations regarding their drug activities or drug inhibitions.

Abstract

Purpose: It is unknown if inactive pharmaceutical ingredients influence the activity of antibiotics they are co-formulated with. Recently it was found that materials acting as carbon nutrient sources for bacteria can promote bacterial dispersion from a biofilm and/or reverse the persister state of a subpopulation of bacteria within the biofilms. Both can make bacteria more susceptible to antibiotics. Thus, the aim was to identify potential excipients to improve antibiotic activity in Pseudomonas aeruginosa biofilms.

Methods: We screened 190 potential excipients alone, and in combination with tobramycin sulfate against P. aeruginosa (strain PAO1) grown planktonically or as biofilms. After the excipient screening stage, we investigated the effect of 10 selected excipients against a more virulent strain (luminescent strain UCBPP-PA14). Temporal changes in luminescence, as an indicator of bacterial proliferation, and surviving colony forming units (CFUs) from the treated PA14 biofilms were quantified.

Results: Forty-eight materials tested caused a reduction of PAO1 proliferation either alone or combined with tobramycin. L-alanine (p < 0.05), D-alanine (p > 0.05), and N-acetyl-D-glucosaminitol (p > 0.05) improved the activity of tobramycin measured by PA14 luminometry. Additionally, L-alanine and succinic acid significantly reduced the survival of PA14 biofilms (p < 0.05).

Conclusions: L-alanine, succinic acid, and N-acetyl-D-glucosaminitol may be useful as antibiotic adjuvants in future tobramycin anti-biofilm formulations.

Reference: Bahamondez-Canas T, Smyth HDC. Influence of Excipients on the Antimicrobial Activity of Tobramycin Against Pseudomonas aeruginosa Biofilms. Pharm Res. 2018 Jan 2;35(1):10. doi: 10.1007/s11095-017-2301-5.

https://link.springer.com/article/10.1007%2Fs11095-017-2301-5

Go to the profile of Celia Fortuna Rodrigues

Celia Fortuna Rodrigues

PharmD, PhD Candidate, University of Minho

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