Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2013

Efficacy and pharmacodynamic effects of five novel antimicrobials against methicillin-resistant Staphylococci (#221)

Elizabeth E Hickey 1 , Darren J Trott 1
  1. University of Adelaide, Roseworthy, SA, Australia

Staphylococcal skin infections are a common occurrence in both humans and animals and can vary from abscesses to widespread tissue necrosis. Treatment options for these types of infections have become severely limited in recent years by the increasing prevalence of methicillin-resistance and the emergence of multidrug resistance in a number of Staphylococcus species.

The efficacies of the five new antimicrobial compounds being developed as potential topical agents were assessed using CLSI recommended minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) testing against 21 strains of methicillin-sensitive staphylococci and 21 strains of methicillin-resistant staphylococci. Efficacy testing showed that four of these compounds were effective against methicillin-resistant staphylococciat low concentrations (MIC90≤ 4 µg/mL) while the fifth (LP 9666) exhibited antibacterial activity against resistant strains at higher concentrations (MIC90 = 64µg/mL). Following the results of efficacy testing, time-kill kinetic analyses were performed using two compounds (LP 1369 and 6315), which were selected based on favourable MBC data. The resulting data showed that these compounds were effective at reducing the number of bacteria over 24 hours at 1x, 4x and 8x the MIC50,suggesting that bactericidal activity may be occurring in a concentration-dependent manner. Finally, red cell lysis assays for all five compounds were performed using 2% sheep erythrocytes, which showed that four compounds did not demonstrate any toxicity while one compound (LP 1369) resulted in low level lysis at concentrations that greatly exceeded the MIC.

The results from this study indicate that four of these compounds are effective antimicrobials against methicillin-resistant staphylococci and with further development, including finding suitable formulations for in vivo efficacy testing in a murine model of cutaneous infection, could become potential topical treatments for methicillin-resistant staphylococci skin infections.