Susceptibility Pattern of Gram-positive Organisms Isolated in Australian Medical Centers (2004, 2006-2007): Results from a Multi-center Prospective Surveillance Program

Daptomycin is a cyclic lipopeptide with potent bactericidal activity against most Gram-positive organisms including multidrug-resistant (MDR) organisms. The unique structure of daptomycin confers a novel mechanism of action, which involves insertion of the lipophilic daptomycin tail into the bacterial cell membrane, causing rapid membrane depolarization and a potassium ion efflux, resulting in rapid bacterial death. Furthermore, daptomycin remains bactericidal against stationary-phase cultures of both oxacillin (methicillin)-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) present at high density (10 9 cfu) in a simulated endocarditis vegetation model. Daptomycin has been used for the treatment of complicated skin and skin structure infections (cSSSI) since 2003 (USA), and was later approved for the treatment of right sided infective endocarditis (RIE) due to S. aureus and for S. aureus bacteraemia when associated with RIE or cSSSI. Daptomycin has also been used in many European countries and, has more recently been licensed in other nations. We evaluated the in vitro activity of daptomycin and comparators against contemporary clinical isolates collected in eight hospitals across Australia. Background: Antimicrobial susceptibility (S) patterns of Gram-positive (GP) organisms most commonly associated with hospital- and community-acquired infections in Australia were evaluated. Methods: Bacterial isolates were consecutively collected from patients in 8 Australian medical centers in the 2004- 2007 period and tested for S by CLSI broth microdilution methods with appropriate supplements. Results: 1,603 organisms were tested, most from bacteremia and skin/skin structure infections. Resistance (R) to erythromycin, levofloxacin (LEV), trimethoprim/sulfamethoxazole (TMP/SMX) and tetracycline (TET; 39.6%) were high among MRSA (24.4% of S. aureus). Vancomycin (VAN), linezolid (LZD) and daptomycin (DAP) were very active against MRSA and DAP was 4-fold more potent than VAN or LZD (Table). TMP/SMX-R was also elevated among CoNS (37.8%). CoNS strains with decreased S to teicoplanin (TEI; 98.0% S) and quinupristin/dalfopristin (Q/D; 99.0% S) were observed. E. faecium showed very low S to ampicillin (14.3%) and Q/D (71.4%), and elevated high-level R to gentamicin (50.0%); in contrast, all strains were S to DAP (MIC range, 1-4 µg/ml) and TEI. Among viridans gr. strep., 75.4 and 92.8% were S to penicillin and ceftriaxone, respectively. All GP tested were S to DAP except for 1 MRSA (VISA) with DAP MIC of 2 µg/ml (1 log 2 dilution above S breakpoint). Only 58.4% of β- haemolytic strep. were S to TET.