Activity of Retapamulin against Streptococcus pyogenes and Staphylococcus aureus Evaluated by Agar Dilution, Microdilution, E-Test, and Disk Diffusion Methodologies

Abstract

The in vitro activity of retapamulin against 106 Staphylococcus aureus isolates and 109 Streptococcus pyogenes isolates was evaluated by the agar dilution, broth microdilution, E-test, and disk diffusion methodologies. Where possible, the tests were performed by using the CLSI methodology. The results of agar dilution, broth microdilution, and E-test (all with incubation in ambient air) for S. aureus yielded similar MICs, in the range of 0.03 to 0.25 g/ml. These values corresponded to zone diameters between 25 and 33 mm by the use of a 2-g retapamulin disk. Overall, 99% of the agar dilution results and 95% of E-test results for S. aureus were within ؎1 dilution of the microdilution results. For S. pyogenes, the MICs obtained by the agar and broth microdilution methods (both after incubation in ambient air) were in the range of 0.008 to 0.03 g/ml, and E-test MICs (with incubation in ambient air) were 0.016 to 0.06 g/ml. For S. pyogenes, 100% of the agar dilution MIC results were within ؎1 dilution of the broth microdilution results. E-test MICs (after incubation in ambient air) were within ؎1 and ؎2 dilutions of the broth microdilution results for 76% and 99% of the isolates, respectively. E-test MICs for S. pyogenes strains in CO 2 were up to 4 dilutions higher than those in ambient air. Therefore, it is recommended that when retapamulin MICs are determined by E-test, incubation be done in ambient air and not in CO 2 , due to the adverse effect of CO 2 on the activity of this compound. Diffusion zones (with incubation in CO 2 ) for S. pyogenes were 18 to 24 mm. Retapamulin MICs for all strains by all methods (with incubation in ambient air) were <0.25 g/ml. These results demonstrate that S. pyogenes (including macrolide-resistant strains) and S. aureus (including methicillin-resistant and vancomycin-nonsusceptible strains) are inhibited by very low concentrations of retapamulin and that all four testing methods are satisfactory for use for susceptibility testing.

Retapamulin Inhibition of Translation and 50S Ribosomal Subunit Formation in Staphylococcus aureus Cells

“…Others have also shown equivalent inhibitory effects of retapamulin against both sensitive and resistant S. aureus strains (19,20). It is thus a promising antimicrobial agent which should be useful against a variety of drug-resistant microorganisms.…”

“…Semisynthetic derivatives of the mutilins which show enhanced antibacterial activity against a variety of pathogens have been made. Retapamulin (SB 275833) is especially effective against gram-positive cocci (13,15,19). Inhibition of peptide bond formation is FIG.…”

Establishing Molecular Tools for Genetic Manipulation of the Pleuromutilin-Producing FungusClitopilus passeckerianus

“…A novel semisynthetic pleuromutilin, retapamulin {mutilin 14-(exo-8-methyl-8-azabicyclo [3.2.1]oct-3-yl-sulfanyl)-acetate}, is active against Staphylococcus aureus and Streptococcus pyogenes (39,47) and is the first pleuromutilin derivative which has been formulated as a topical antibacterial agent for treating human skin infections (14,38,41). In 2007, the Food and Drug Administration and the European Commission approved a new topical retapamulin ointment for the treatment of impetigo and infected small lacerations, abrasions, or sutured wounds.…”

In Vitro Activity of Tigecycline against Gram-Positive and Gram-Negative Pathogens as Evaluated by Broth Microdilution and Etest

“…Surveillance programs can be accomplished in a variety of fashions (distributed, local network reporting, and centralized) and can use a variety of testing methodologies (broth microdilution, Etest, disk diffusion, and automated systems). As the reference standard, broth microdilution testing serves as the method of comparison for the development and evaluation of alternative susceptibility testing methodologies (12,15).…”