Antimicrobial activity of daptomycin tested against Gram-positive pathogens collected in Europe, Latin America, and selected countries in the Asia-Pacific Region (2011)

Abstract

We report the results of the international daptomycin surveillance programs for Europe, Latin America, and selected Asia-Pacific nations. A total of 7948 consecutive Gram-positive organisms of clinical significance were collected in 2011 and susceptibility tested against daptomycin and various comparator agents by Clinical and Laboratory Standards Institute (Clinical and Laboratory Standards Institute. M07-A9. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard: ninth edition Wayne, PA: CLSI. 2012.; Cubicin Package Insert 2012. Cubist Pharmaceuticals, Inc, Lexington, MA. Available at http://www.cubicin.com/pdf/PrescribingInformation.pdf. Accessed January 1, 2012.) broth microdilution methods. The test medium was adjusted to contain physiological levels of calcium (50 mg/L) when testing daptomycin. Daptomycin exhibited potent activity against methicillin-susceptible and -resistant Staphylococcus aureus overall and for each region (MIC_50/90, 0.25–0.5/0.5 μg/mL), with susceptibility rates at 100.0% in Latin America, Australia/New Zealand, and India, and at 99.9% in Europe. The daptomycin MIC_50/90 for coagulase-negative staphylococci was also at 0.25–0.5/0.5 μg/mL, and only 1 isolate was considered nonsusceptible with a MIC value at 2 μg/mL. Daptomycin was also highly active against Enterococcus faecalis (MIC_50/90, 1/1–2 μg/mL) and E. faecium (MIC_50/90, 2/2 μg/mL for both vancomycin-susceptible and -resistant isolates). All enterococcal isolates were susceptible to daptomycin (MIC, ≤4 μg/mL) and tigecycline. Susceptibility to linezolid for E. faecalis was at 100.0%, while for E. faecium regional susceptibility rates were at 100.0% except in Europe (99.0%). Viridans group streptococci (MIC_50/90, 0.25/1 μg/mL) and β-haemolytic streptococci (MIC_50/90, ≤0.06/0.25 μg/mL) continue to be very susceptible to daptomycin. In summary, the results of this investigation document the high potency and wide spectrum of daptomycin when tested against a large resistance-surveillance collection of Gram-positive pathogens and indicate that daptomycin nonsusceptibility remains rare among indicated species after many years of clinical use worldwide.

Introduction

Vancomycin, linezolid, and, more recently, daptomycin have continued to be the dominant agents used for serious infections caused by Gram-positive pathogens (Sader et al., 2009, Sader et al., 2011a, Sader et al., 2011b), especially for methicillin-resistant Staphylococcus aureus (MRSA) and enterococci. As resistance to vancomycin has emerged, daptomycin with its documented bactericidal action has evolved as a key agent for persisting MRSA and vancomycin-resistant enterococci (VRE) infections. Potent daptomycin activity against MRSA having elevated vancomycin MIC values (2 μg/mL) has been documented in vitro (Sader et al., 2010) and in vivo via a retrospective case-controlled study where a higher probability of survival was achieved (Moore et al., 2012). Other post-approval clinical investigations of daptomycin across Europe (Falcone et al., 2012, Gonzalez-Ruiz et al., 2011) and in Taiwan (Lai et al., 2012) demonstrated that daptomycin therapy had high clinical success, reduced hospital length of stay, and was safe and well tolerated (patients receiving drug during 2006–2009). Daptomycin has also been found to be active against linezolid-resistant strains by Mendes et al. (2009) using 142 isolates of staphylococci and Enterococcus spp. worldwide.

However, daptomycin nonsusceptible isolates have been rarely detected worldwide with the mechanism being attributed to various gene mutations (mprF, YycFG, RNA polymerase subunits), changes in membrane fluidity and cell wall thickness, and alterations in membrane charge (Bertsche et al., 2011, Humphries et al., 2012, Mishra et al., 2012). To address these threats of elevated daptomycin MIC values, studies of various drug combinations have been promising, e.g., combinations of daptomycin and penicillins (ampicillin, nafcillin, or oxacillin), and trimethoprim/sulfamethoxazole, and ceftaroline (Avery et al., 2012, Mehta et al., 2012, Mishra et al., 2012, Rose et al., 2012, Sakoulas et al., 2012, Steed et al., 2012). Such strategies can also minimize the development of daptomycin resistance (Berti et al., 2012, Dhand et al., 2011).

To assist in the understanding of the level of contemporary daptomycin nonsusceptibility in staphylococcal species (MIC, ≥2 μg/mL), enterococci (MIC, ≥8 μg/mL), and streptococci (MIC, ≥2 μg/mL), we present the analysis of the international daptomycin surveillance programs for Europe, Latin America, and selected Asia-Pacific nations collected in 2011. This network of 69 medical centers provided 7948 clinical isolates for reference testing against daptomycin (CLSI, 2012).