CIPROFLOXACIN-CONTAINING EUDRAGIT E100 AQUEOUS DISPERSIONS EXHIBIT IMPROVED IN VITRO ACTIVITY RESPECT TO FREE-DRUG AGAINST FLUOROQUINOLONE- AND METHICILLIN-RESISTANT Staphylococcus aureus (FQ-R MRSA)

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

Rosario

Congreso; 2° REUNION INTERNACIONAL DE CIENCIAS FARMACÉUTICAS- RICIFA 2012; 2012

UNIVERSIDAD NACIONAL DE ROSARIO

Introduction Staphylococcus aureus is a known etiologic agent of eye and skin infections (1). The increasing incidence of strains that are less susceptible to a variety of antibiotics, including fluoroquinolones, limits the therapeutic alternatives. (2). Previously, was described the improved bactericidal action of ofloxacin loaded in Eudragit E100 aqueous dispersions against Fluoroquinolone-resistant P.aeruginosa clinical isolates, attributed to an outer membrane disorganizing effect of Gram negative bacteria (FEMS). In this study, the same cationic polymer was used to prepare ciprofloxacin-containing Eudragit E100 aqueous dispersions (Eu-CIP) and was evaluated the effect on bactericidal activity of CIP against Gram positive bacteria, in particular a fluroquinolone- and methicillin-resistant S. aureus (FQ-R MRSA). Materials and methods Killing-curve studies were performed in saline due to the partial precipitation of Eudragit E100 in the culture medium during long incubation period. Overnight cultures in Mueller?Hinton agar were adjusted in saline to a bacterial concentration of approximately 108 cells/mL-1 and incubated in presence of CIP in Eu-CIP or free solution, assessing a wide range of concentrations. The cultures were incubated at 37 °C and sampled periodically up to 24 h. The number of viable cells was determined by subculturing the cells on Mueller?Hinton agar plates in duplicate for 24 h. Each time-dependent killing experiment was performed on three independent occasions and the data presented are the average of all values obtained. In addition, bacterial cultures were evaluated by scanning electronic microscopy (SEM) after 3 h of exposure to each treatment. Results killing curve assays results were expressed as the change in the initial inoculum after exposure to each treatment (Table 1). The highlighted portion in the Table is indicating times and concentrations in which 3 log reduction of inoculum was exhibited by Eu-CIP and bold values correspond to conditions required to achieve bacterial eradication. Ciprofloxacin free solution did not yield bacterial eradication in the entire range of drug concentrations evaluated up to 24h. Drug-free Eu exhibited bacteriostatic or slightly bactericidal effect depending on the concentration or time considered with regrowth seen at longer exposure times. Morphological alterations in the bacterial envelopes of S. aureus treated with Eu-CIP were observed by SEM. Conclusions: The bactericidal action of CIP against MRSA was enhanced in Eu-CIP. After short exposure to Eu-CIP notorious morphological changes were observed. Further studies are necessary in order to assess the mechanisms involved in the enhanced bactericidal action of CIP observed against Gram positive bacteria. The observed effect would contribute to prolong the usefulness life of fluoroquinolones, antimicrobial whose therapeutic utility is limited by the constant emergence of resistant strains. References 1-Kanafani Z, Fowler Jr VG. Staphylococcus aureus Infections: New Challenges from an Old Pathogen. Enferm Infecc Microbiol Clin 2006; 24(3):182-93. 2-Schito SC. The importance of the development of antibiotic resistance in Staphylococcus aureus. Clinical Microbiology and Infection 2006; 12(1): 3-8. 3-Romero V, Pons, P, Bocco, JL, Manzo R, Alovero F. Eudragit E100® potentiates the bactericidal action of ofloxacin against fluoroquinolone-resistant Pseudomonas aeruginosa. FEMS Microbiology Letters. 2012; 334: 102-110.