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.