In Vitro Activities of Dalbavancin and 12 Other Agents against 329 Aerobic and Anaerobic Gram-Positive Isolates Recovered from Diabetic Foot Infections

Abstract

Tests of dalbavancin's in vitro activity against 209 aerobic and 120 anaerobic isolates from pretreatment diabetic foot infections showed an MIC 90 of <0.125 g/ml against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and 120 anaerobes (Clostridium perfringens, other clostridia, Peptoniphilus asaccharolyticus, Finegoldia magna, and Anaerococcus prevotii), compared to respective MIC 90 s for MSSA and MRSA of 0.5 and 1 g/ml for vancomycin, 4 and 4 g/ml for linezolid, 0.5 and 0.5 g/ml for daptomycin, and 0.25 and >8 g/ml for clindamycin.Diabetes will affect ϳ14.5 million Americans by 2010 (8), and diabetic foot infections (DFIs) account for 20% of all hospitalizations of diabetic patients (1). DFIs are often multibacterial with aerobic and anaerobic bacteria. Recently, community-acquired methicillin-resistant Staphylococcus aureus (MRSA) (2,3,14) has accounted for 50% of all S. aureus skin and skin structure infection (SSTI) isolates (2,3,14). Previously, we noted (6) that MRSA was isolated from 20% of DFIs. As a reference lab for a DFI study, we received 473 pretreatment specimens, of which 91.3% grew aerobic bacteria, including 48% that grew S. aureus as one of the isolates (one-quarter of which were MRSA), and 41.6% grew anaerobes, with anaerobic gram-positive cocci the most common isolates.Dalbavancin (BI397) is new glycopeptide (4, 10) with good activity against gram-positive organisms, including MRSA, but none against gram-negative organisms (13,19). Dalbavancin has a long elimination half-life (ϳ8.5 days) and has been effective in treating gram-positive SSTIs (9, 18) with a two-dose regimen. For DFIs, an antimicrobial agent with a long half-life, especially one administered once weekly, seems to be advantageous.Specimens were obtained from patients with clinical infection who had not received antimicrobials within 48 h and after wound debridement. To avoid bias, 329 consecutively isolated gram-positive aerobic and anaerobic organisms were selected for this study. Isolates were identified by standard criteria (12, 15) and stored in skim milk at Ϫ70°C. Frozen anaerobic cultures were subcultured twice onto brucella agar supplemented with hemin, vitamin K 1 , and 5% sheep blood (Anaerobe Systems, Morgan Hill, CA) to ensure purity and good growth. Aerobic strains were subcultured to Trypticase soy blood agar. Susceptibility testing was performed according to CLSI (formerly NCCLS) standards M11-A6 (17) and M7-A6 (16).The types and numbers of strains tested are shown in Table 1. Laboratory-standard reference powders were either obtained from their manufacturers or purchased from Sigma Chemicals (St. Louis, MO).The MICs for anaerobes were determined by the agar dilution method using brucella agar supplemented with hemin, vitamin K 1 , and 5% laked sheep blood. Antimicrobial agents were reconstituted according to the manufacturers' instructions. Serial twofold dilutions of dalbavancin were prepared at 100-fold the final concentration in dimethyl sulfoxide on the day of t...

Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review

“…Dalbavancin demonstrates activity against most grampositive anaerobic pathogens although it remains inactive against most gram-negative anaerobic rods Goldstein et al 2006b). When compared to vancomycin, dalbavancin was found overall to be one to three dilutions more active in vitro against gram-positive anaerobes .…”

“…Although no susceptibility breakpoints have been established, dalbavancin appears to demonstrate excellent activity against staphylococci. MICs for MSSA, MRSA, and Coagulase negative Staphylococcus (CoNS) range from 0.06 to 0.5 µg/mL in most reports (Candiani et al 1999;Woodford 2003;Flamm et al 2004;Streit et al 2004;Jones et al 2005;Lin et al 2005;Goldstein et al 2006b). Dalbavancin displays generally lower MICs against staphylococci when compared to other agents (Candiani et al 1999;Malabarba and Ciabatti 2001;Woodford 2003;Streit et al 2004;Lin et al 2005).…”

“…When compared to vancomycin, dalbavancin was found overall to be one to three dilutions more active in vitro against gram-positive anaerobes . Similarly, in a study evaluating the effectiveness of dalbavancin against pre-treatment clinical isolates from diabetic foot infections, it was noted to be active against 120 anaerobic isolates with MICs ranging from less than 0.125 µg/mL to 0.5 µg/ml (Goldstein et al 2006b). Dalbavancin has no clinically relevant activity against gramnegative bacteria (Jones et al 2001).…”

“…Dalbavancin has no clinically relevant activity against gramnegative bacteria (Jones et al 2001). Dalbavancin's activity against gram-positive anaerobes may impart signifi cant clinical benefi t in the management of polymicrobial cSSTIs (Goldstein et al 2006b).…”

Activity of Dalbavancin Tested against Staphylococcus spp. and β-Hemolytic Streptococcus spp. Isolated from 52 Geographically Diverse Medical Centers in the United States

“…␤-Hemolytic streptococci, however, are evolving towards reduced antimicrobial susceptibility profiles which include resistance to MLS B agents and tetracyclines, and they have developed tolerance or resistance to some beta-lactam agents, vancomycin, and fluoroquinolones, although this is rarely seen at present (3,8,11,25). Dalbavancin has proven activity against nonindicated strains, which include gram-positive anaerobes isolated from diabetic foot ulcers and many other important gram-positive aerobes, including some antimicrobial-resistant strains (10). The U.S. Food and Drug Administration (FDA) has recently issued dalbavancin a marketable letter.…”