Efficacy of a cationic polymer as an adjunct to antibiotics with different target site against Pseudomonas aeruginosa

ROMERO, VERÓNICA L; ROSSET, CLARISA I.; MANZO, RUBEN H.; ALOVERO, FABIANA L.

Congreso; 3rd International Meeting on Pharmaceutical / 3ª Reunión Internacional de Ciencias Farmacéuticas-; 2014

UNIVERSIDAD NACIONAL DE CORDOBA Y UNIVERSIDAD NACIONAL DE ROSARIO

Emerging drug resistance, along with the few antibiotic discovery programs in the pharmaceutical industry has forced the scientific community to seek new alternatives. Numerous reports describe the antimicrobial properties of cationic polymers for pharmaceutical use. However, Eudragit E100® (Eu) has not been characterized in this sense. Recently, we described that Eu causes alterations in the bacterial envelopes of P.aeruginosa, but the polymer itself is not bactericidal. In this study we evaluate the effects, if any, of Eu on the antibacterial action of antibiotics with different site and spectrum of action: Ciprofloxacin (CIP) and Vancomycin (VAN) against P.aeruginosa. It is known that P.aeruginosa is outside of spectrum of action of VAN. In contrast, CIP is an effective antimicrobial against P.aeruginosa but growing resistance in clinical isolates has limited its use. Bactericidal activity of drug-containing Eu dispersions (Eu-CIP and Eu-VAN) was determined by time-kill assay against a fluoroquinolone-resistant P.aeruginosa clinical isolate (PaFQ-R1; MICCIP: 64µg/mL). Several concentrations and treatment times were tested. Simultaneously, drug solutions (CIP and VAN) and Eu dispersions were evaluated. Eu-ClP tended to kill Pa FQ-R1 rapidly, exhibiting bactericidal effect (3log10 reduction) after 1 h at 8µg/mL CIP, whereas 8-fold higher concentration was required from CIP. Initial inoculums eradication was observed after 6 h with 16µg/mL of drug in Eu-CIP, requiring 128µg/mL of CIP to achieve this effect. Eu-VAN also exhibited time- and concentration-dependent bactericidal activity against PaFQ-R1, achieving ≥ 3log10 reduction at low concentrations and short exposure times, and eradicating after 24 h in the whole range of VAN concentrations tested (128-1024 ug/ml). Furthermore, as expected, no effect was shown by VAN in any of the conditions assayed. Drug-free Eu exhibited bacteriostatic or slightly bactericidal action with regrowth seen at longer exposure times. The improved bactericidal effect observed using this cationic polymer in combination with two antibiotics against P.aeruginosa provides a useful tool to broaden the spectrum of antibiotics whose clinical use is limited by intrinsic resistance and/or have an alternative to prolong the usefulness of conventional antibiotics against multidrug resistant bacteria.