Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections

Naoki Aikawa, Shinya Kusachi, Hiroshige Mikamo, Yoshio Takesue, Shinichi Watanabe, Yoshiyuki Tanaka, Akiko Morita, Keiko Tsumori, Yoshiaki Kato, Tomoko Yoshinari, Naoki Aikawa, Shinya Kusachi, Hiroshige Mikamo, Yoshio Takesue, Shinichi Watanabe, Yoshiyuki Tanaka, Akiko Morita, Keiko Tsumori, Yoshiaki Kato, Tomoko Yoshinari

Abstract

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.

Trial registration: ClinicalTrials.gov NCT00770341.

References

    1. Silverman JA, Perlmutter NG, Shapiro HM. Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother. 2003;47:2538–2544. doi: 10.1128/AAC.47.8.2538-2544.2003.
    1. Baltz RH. Daptomycin: mechanisms of action and resistance, and biosynthetic engineering. Curr Opin Chem Biol. 2009;13:144–151. doi: 10.1016/j.cbpa.2009.02.031.
    1. Dryden MS. Complicated skin and soft tissue infection. J Antimicrob Chemother 2010;65(suppl 3):iii35–44
    1. Stefani S, Goglio A. Methicillin-resistant Staphylococcus aureus: related infections and antibiotic resistance. Int J Infect Dis. 2010;14(suppl 4):S19–S22. doi: 10.1016/j.ijid.2010.05.009.
    1. Fuchs PC, Barry AL, Brown SD. In vitro bactericidal activity of daptomycin against staphylococci. J Antimicrob Chemother. 2002;49:467–470. doi: 10.1093/jac/49.3.467.
    1. Sader HS, Watters AA, Fritsche TR, Jones RN. Daptomycin antimicrobial activity tested against methicillin-resistant staphylococci and vancomycin-resistant enterococci isolated in European medical centers (2005) BMC Infect Dis. 2007;7:29. doi: 10.1186/1471-2334-7-29.
    1. Tsuji BT, Rybak MJ, Cheung CM, Amjad M, Kaatz GW. Community- and health care-associated methicillin-resistant Staphylococcus aureus: a comparison of molecular epidemiology and antimicrobial activities of various agents. Diagn Microbiol Infect Dis. 2007;58:41–47. doi: 10.1016/j.diagmicrobio.2006.10.021.
    1. Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis. 2004;38:1673–1681. doi: 10.1086/420818.
    1. Goto H, Shimada K, Ikemoto H, Oguri T. Antimicrobial susceptibility of pathogens isolated from more than 10,000 patients with infectious respiratory diseases: a 25-year longitudinal study. J Infect Chemother. 2009;15:347–360. doi: 10.1007/s10156-009-0719-3.
    1. Kunishima H, Yamamoto N, Kobayashi T, Minegishi M, Nakajima S, Chiba J, et al. Methicillin-resistant Staphylococcus aureus in a Japanese community hospital: 5-year experience. J Infect Chemother. 2010;16:414–417. doi: 10.1007/s10156-010-0076-2.
    1. Hasegawa S, Miki M, Wan K, Aoki I. A phase I study in Japanese healthy subjects with single and multiple intravenous dose of daptomycin (MK-3009) Antibiot Chemother. 2011;27:135–148.
    1. Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL. Relationship between initial vancomycin concentration–time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49:507–514. doi: 10.1086/600884.
    1. Minson Q, Gentry CA. Analysis of linezolid-associated hematologic toxicities in a large veterans affairs medical center. Pharmacotherapy. 2010;30:895–903. doi: 10.1592/phco.30.9.895.
    1. Fowler VG, Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355:653–665. doi: 10.1056/NEJMoa053783.
    1. Bhavnani SM, Rubino CM, Ambrose PG, Drusano GL. Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clin Infect Dis. 2010;50:1568–1574. doi: 10.1086/652767.
    1. Figueroa DA, Mangini E, Amodio-Groton M, Vardianos B, Melchert A, Fana C, et al. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis. 2009;49:177–180. doi: 10.1086/600039.
    1. Sader HS, Jones RN. Antimicrobial susceptibility of Gram-positive bacteria isolated from US medical centers: results of the Daptomycin Surveillance Program (2007–2008) Diagn Microbiol Infect Dis. 2009;65:158–162. doi: 10.1016/j.diagmicrobio.2009.06.016.
    1. Moise PA, Hershberger E, Amodio-Groton MI, Lamp KC. Safety and clinical outcomes when utilizing high-dose (≥8 mg/kg) daptomycin therapy. Ann Pharmacother. 2009;43:1211–1219. doi: 10.1345/aph.1M085.
    1. Mermel LA, Allon M, Bouza E, Craven AE, Flynn P, O’Grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;49:1–45. doi: 10.1086/599376.
    1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–e55. doi: 10.1093/cid/ciq146.

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