, Volume 64, Issue 15, pp 1621–1642 | Cite as

Newer Treatment Options for Skin and Soft Tissue Infections

Leading Article


In recent years, serious skin and soft tissue infections (SSTIs) caused by multidrug resistant pathogens have become more common. While the majority of SSTIs are caused by Staphylococcus aureus or β-haemolytic streptococci that are methicillin/oxacillin susceptible, the emergence of methicillin-resistant and vancomycin-resistant community-acquired and nosocomial Gram-positive pathogens has created a need for different therapeutic agents, such as linezolid, quinupristin/dalfopristin, daptomycin, and newer generation carbapenems and fluoroquinolones. This review focuses on agents presently in clinical development for the treatment of SSTIs caused by Gram-positive pathogens such as staphylococci, streptococci and enterococci including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Newer-generation carbapenems, such as meropenem and ertapenem, are characterised by a broad-spectrum of activity against Gram-positive and -negative aerobes and anaerobes, and are resistant to hydrolysis by many β-lactamases. Current-generation fluoroquinolones, such as levofloxacin, moxifloxacin and gatifloxacin, have demonstrated better eradication rates for S. aureus than conventional penicillin and cephalosporins. These antimicrobial agents can be used to treat methicillin-susceptible staphylococcal and streptococcal strains.

Oxazolidinones, streptogramin combinations and cyclic lipopeptides have novel mechanisms of action and have been studied in several multinational phase III clinical trials in the treatment of complicated and uncomplicated SSTIs. They possess a broad spectrum of activity against multidrug-resistant pathogens, including MRSA and VRE. Linezolid has been shown to be active against a wide variety of community-acquired and nosocomial antimicrobial-resistant pathogens with comparability to vancomycin, as well as resulting in reduced lengths of hospital stay. Cyclic lipopeptides such as daptomycin have a unique mechanism of action by disruption of bacterial membrane electric potentials with less likelihood for development of cross-resistance. Daptomycin has recently been US FDA approved for the treatment of complicated SSTI. However, rapid development of resistance to some of these newer agents has already been reported and this trend magnifies the importance of further need for effective antimicrobial agents.

Several investigational agents, such as dalbavancin, oritavancin and tige-cycline, are in advanced stages of development and are likely to proceed to licensing in the next few years. With their long half-lives, these agents have an advantage of less frequent dose administration with more rapid bactericidal activity and less likelihood for development of resistance. However, because of their proven activity against highly resistant organisms, these antibacterial agents should be reserved only for life-threatening situations and/or when resistant pathogens are suspected.

Rational antimicrobial use coupled with awareness of infection control measures is paramount to avert the emergence of multidrug-resistant organisms.


Linezolid Moxifloxacin Teicoplanin Daptomycin Tigecycline 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dr Linden is affiliated with Cubist Pharmaceuticals (speaker, consultant), Intermune (consultant) and King Pharmaceuticals (consultant). Dr Raghavan has received no funding and has no conflicts of interest directly relevant to the content of this review.


  1. 1.
    Nichols RL. Optimal treatment of complicated skin and skin structure infections. J Antimicrob Chemother 1999; 44 Suppl. A: 19–23PubMedCrossRefGoogle Scholar
  2. 2.
    Ploy MC, Grelaud C, Martin C, et al. First clinical isolate of vancomycin-intermediate Staphylococcus aureus in a French hospital. Lancet 1998; 351: 1212PubMedCrossRefGoogle Scholar
  3. 3.
    Fung HB, Chang JY, Kuczynski SA. Practical guide to the treatment of complicated skin and soft tissue infections. Drugs 2003; 63(14): 1459–80PubMedCrossRefGoogle Scholar
  4. 4.
    Panlilio AL, Culver DH, Gaynes RP, et al. Methicillin-resistant Staphylococcus aureus in US hospitals, 1975–1991. Infect Control Hosp Epidemiol 1992; 13: 582–6PubMedCrossRefGoogle Scholar
  5. 5.
    Swartz MN. Subcutaneous tissue infections and abscesses. In: Mandell G, Douglas R, Bennett J, editors. Principles and practice of infectious disease. New York: Churchill Livingstone Inc., 1990: 808–18Google Scholar
  6. 6.
    Centers for Disease Control and Prevention. Staphylococcus aureus with reduced susceptibility to vancomycin in United States. MMWR Morb Mortal Wkly Rep 1997; 46: 765–6Google Scholar
  7. 7.
    Centers for Disease Control and Prevention. Notifiable diseases/ deaths in selected cities weekly information. MMWR Morb Mortal Wkly Rep 2001; 49(51): 1167–74Google Scholar
  8. 8.
    Centers for Disease Control and Prevention. Summary of provisonal cases of selected notifiable diseases United States cumulative week ending 2001 Dec 29. MMWR Morb Mortal Wkly Rep 2002 Jan; 50: 1169Google Scholar
  9. 9.
    Abbanat D, Macielag M, Bush K. Novel antibacterial agents for the treatment of serious gram-positive infections. Expert Opin Investig Drugs 2003; 12: 379–99PubMedCrossRefGoogle Scholar
  10. 10.
    Rennie RP, Jones RN, Mutnick AH. Occurrence and antimicrobial susceptibility patterns of pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 2000). Diagn Microbiol Infect Dis 2003; 45: 287–93PubMedCrossRefGoogle Scholar
  11. 11.
    Rybak MJ, Akins RL. Emergence of methicillin-resistant Staphylococcus aureus with intermediate glycopeptide resistance: clinical significance and treatment options. Drugs 2001; 61(1): 1–7PubMedCrossRefGoogle Scholar
  12. 12.
    Jones ME, Schmitz FJ, Fluit AC, et al. Frequency of occurrence and antimicrobial susceptibility of bacterial pathogens associated with skin and soft tissue infections during 1997 from an International Surveillance Programme: SENTRY Participants Group. Eur J Clin Microbiol Infect Dis 1999; 18: 403–8PubMedCrossRefGoogle Scholar
  13. 13.
    Bell JM, Turnidge JD. High prevalence of oxacillin-resistant Staphylococcus aureus isolates from hospitalized patients in Asia-Pacific and South Africa: results from SENTRY antimicrobial surveillance program, 1998–1999. Antimicrob Agents Chemother 2002; 46: 879–81PubMedCrossRefGoogle Scholar
  14. 14.
    Bukharie HA, Abdelhadi MS, Saeed IA, et al. Emergence of methicillin-resistant Staphylococcus aureus as a community pathogen. Diagn Microbiol Infect Dis 2001; 40: 1–4PubMedCrossRefGoogle Scholar
  15. 15.
    Groom AV, Wolsey DH, Naimi TS, et al. Community-acquired methicillin-resistant Staphylococcus aureus in a rural American Indian Community. JAMA 2001; 286: 1201–5PubMedCrossRefGoogle Scholar
  16. 16.
    Gupta N, Prakash SK, Malik VK, et al. Community acquired methicillin resistant Staphylococcus aureus: a new threat for hospital outbreaks? Indian J Pathol Microbiol 1999; 42: 421–6PubMedGoogle Scholar
  17. 17.
    Naimi TS, LeDell KH, Boxrud DJ, et al. Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota, 1996–1998. Clin Infect Dis 2001; 33: 990–6PubMedCrossRefGoogle Scholar
  18. 18.
    Bertrand X, Hocquet D, Thouverez M, et al. Characterisation of methicillin-resistant Staphylococcus aureus with reduced susceptibility to teicoplanin in Eastern France. Eur J Clin Microbiol Infect Dis 2003; 22: 504–6PubMedCrossRefGoogle Scholar
  19. 19.
    Cepeda J, Hayman S, Whitehouse T, et al. Teicoplanin resistance in methicillin-resistant Staphylococcus aureus in an intensive care unit. J Antimicrob Chemother 2003; 52: 533–4PubMedCrossRefGoogle Scholar
  20. 20.
    Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997; 40: 135–6PubMedCrossRefGoogle Scholar
  21. 21.
    Parenti F, Schito GC, Courvalin P. Teicoplanin chemistry and microbiology. J Chemother 2000; 12 Suppl. 5: 5–14Google Scholar
  22. 22.
    Ohno A, Ishii Y, Yamaguchi K. Regulation mechanism of glycopeptide resistance expression [in Japanese]. Nippon Rinsho 1997; 55(5): 1206–12PubMedGoogle Scholar
  23. 23.
    Cormican MG, Jones RN. Emerging resistance to antimicrobial agents in gram-positive bacteria: enterococci, staphylococci and nonpneumococcal streptococci. Drugs 1996; 51 Suppl. 1: 6–12CrossRefGoogle Scholar
  24. 24.
    Jones RN. Resistance patterns among nosocomial pathogens: trends over the past few years. Chest 2001; 119 (2 Suppl.): 397S–404SPubMedCrossRefGoogle Scholar
  25. 25.
    Centers for Disease Control and Prevention. Vancomycin-resistant Staphylococcus aureus: Pennsylvania, 2002, MMWR Morb Mortal Wkly Rep 2002; 51(40): 902Google Scholar
  26. 26.
    Weigel LM, Clewell DB, Gill SR, et al. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 2003; 302: 1569–71PubMedCrossRefGoogle Scholar
  27. 27.
    Boyce JM. Vancomycin-resistant Enterococcus: detection, epidemiology, and control measures. Infect Dis Clin North Am 1997; 11: 367–84PubMedCrossRefGoogle Scholar
  28. 28.
    Linden PK, Miller CB. Vancomycin-resistant enterococci: the clinical effect of a common nosocomial pathogen. Diagn Microbiol Infect Dis 1999; 33: 113–20PubMedCrossRefGoogle Scholar
  29. 29.
    Moellering RC. Linezolid: the first oxazolidinone antimicrobial. Ann Intern Med 2003; 138: 135–42PubMedGoogle Scholar
  30. 30.
    Guay DR. Treatment of bacterial skin and skin structure infections. Expert Opin Pharmacother 2003; 4: 1259–75PubMedCrossRefGoogle Scholar
  31. 31.
    Pharmacia Corporation. Zyvox (Linezolid tablets and for suspension and injection) [package insert]. Kalamazoo (MI): Pharmacia Corporation, 2003Google Scholar
  32. 32.
    Shinabarger DL, Marotti KR, Murray RW, et al. Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother 1997; 41: 2132–6PubMedGoogle Scholar
  33. 33.
    Edlund C, Oh H, Nord CE. In vitro activity of linezolid and eperezolid against anaerobic bacteria. Clin Microbiol Infect 1999; 5: 51–3PubMedCrossRefGoogle Scholar
  34. 34.
    Cammarata SK, McConnell-Martin MA, Oliphant TH, et al. Efficacy of linezolid in gram positive infections: results from two phase II trials. Pharmacotherapy 2000; 20: 349CrossRefGoogle Scholar
  35. 35.
    Duvall SE, Bruss JB, McConnell-Martin MA, et al. Comparison of linezolid to oral clarithromycin in the treatment of uncomplicated skin infections: results from multinational phase III trial [poster]. 9th International Congress of Infectious Diseases; 2000 Apr 10–13; Buenos AiresGoogle Scholar
  36. 36.
    Stevens DL, Smith LG, Bruss JB, et al. Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2000; 44: 3408–13PubMedCrossRefGoogle Scholar
  37. 37.
    Stevens DL, Herr D, Lampiris H, et al. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2002; 34: 1481–90PubMedCrossRefGoogle Scholar
  38. 38.
    Li JZ, Willke RJ, Rittenhouse BE, et al. Effect of linezolid versus vancomycin on length of hospital stay in patients with complicated skin and soft tissue infections caused by known or suspected methicillin-resistant staphylococci: results from a randomized clinical trial. Surg Infect (Larchmt) 2003; 4: 57–70CrossRefGoogle Scholar
  39. 39.
    Hartman CS, Leach TS, Kaja RW, et al. Linezolid in the treatment of vancomycin-resistant Enterococcus: a dose comparative, multicenter phase III trial [abstract no. 40]. Proceedings of 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; TorontoGoogle Scholar
  40. 40.
    Cubist Pharmaceuticals Inc. Cubist Pharmaceuticals presents additional phase III clinical results on Cidecin®. Media release, 26 October 2001 [online]. Available from URL: [Accessed 2004 Apr 15]
  41. 41.
    Nichols RL, Graham DR, Barriere SL, et al. Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin. Synercid Skin and Skin Structure Infection Group. J Antimicrob Chemother 1999; 44: 263–73Google Scholar
  42. 42.
    Rehm SJ, Graham DR, Srinath L, et al. Successful administration of quinupristin/dalfopristin in the outpatient setting. J Antimicrob Chemother 2001; 47: 639–45PubMedCrossRefGoogle Scholar
  43. 43.
    Moellering RC, Linden PK, Reinhardt J, et al. The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium: Synercid Emergency-Use Study Group. J Antimicrob Chemother 1999; 44: 251–61PubMedCrossRefGoogle Scholar
  44. 44.
    Graham DR, Lucasti C, Malafaia O, et al. Ertapenem once daily versus piperacillin-tazobactam 4 times per day for treatment of complicated skin and skin-structure infections in adults: results of a prospective, randomized, double-blind multicenter study. Clin Infect Dis 2002; 34: 1460–8PubMedCrossRefGoogle Scholar
  45. 45.
    Nicodemo AC, Robledo JA, Jasovich A, et al. A multicentre, double-blind, randomised study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int J Clin Pract 1998; 52: 69–74PubMedGoogle Scholar
  46. 46.
    Graham DR, Talan DA, Nichols RL, et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial. Clin Infect Dis 2002; 35: 381–9PubMedCrossRefGoogle Scholar
  47. 47.
    Tarshis GA, Miskin BM, Jones TM, et al. Once-daily oral gatifloxacin versus oral levofloxacin in treatment of uncomplicated skin and soft tissue infections: double-blind, multicenter, randomized study. Antimicrob Agents Chemother 2001; 45(8): 2358–62PubMedCrossRefGoogle Scholar
  48. 48.
    Parish LC, Routh HB, Miskin B, et al. Moxifloxacin versus cephalexin in the treatment of uncomplicated skin infections. Int J Clin Pract 2000; 54: 497–503PubMedGoogle Scholar
  49. 49.
    Seltzer E, Dorr MB, Goldstein BP, et al. Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. Clin Infect Dis 2003; 37: 1298–303PubMedCrossRefGoogle Scholar
  50. 50.
    Giamerellou H. Phase III trail comparing 3–7 days of oritavancin vs 10–14 days of vancomycin/cephalexin in the treatment of patients with complicated skin and skin structure infections (cSSSI) [poster L-739a]. 43rd International Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2003 Sep 14–17; Chicago, S75Google Scholar
  51. 51.
    Postier RG, Green SL, Klein SR, et al. Results of a mutlicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients. Clin Ther 2004; 6(5): 704–14CrossRefGoogle Scholar
  52. 52.
    Linden PK. Treatment options for vancomycin-resistant enterococcal infections. Drugs 2002; 62(3): 425–41PubMedCrossRefGoogle Scholar
  53. 53.
    Livermore DM, Mushtaq S, Warner M. Susceptibility testing with linezolid by different methods, in relation to published ‘general breakpoints’. J Antimicrob Chemother 2001; 48: 452–4PubMedCrossRefGoogle Scholar
  54. 54.
    Wise R, Andrews JM, Boswell FJ, et al. The in-vitro activity of linezolid (U-100766) and tentative breakpoints. J Antimicrob Chemother 1998; 42: 721–8PubMedCrossRefGoogle Scholar
  55. 55.
    Wienkers LC, Wynalda MA, Feenstra KL, et al. In vitro metabolism of linezolid (PNU-100766); lack of induction or inhibition of cytochrome P450 enzymes and studies on the mechanism of formation of the major human metabolite, PNU-142586 [poster]. Proceedings of the 39th Interscience Conference on Antimicrobial Therapy and Chemotherapy; American Society for Microbiology; 1999 Sep 26–29; San FranciscoGoogle Scholar
  56. 56.
    Fenstra KL, Slatter JG, Stalker DJ, et al. Metabolism and excretion of the oxazolidinone antibiotic linezolid (PNU-100-766) following oral administration of [14C]PNU-100766 to healthy volunteers [abstract no. A-53; poster]. Proceedings of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; American Society for Microbiology; 1998 Sep 24–27; San DiegoGoogle Scholar
  57. 57.
    Brier ME, Stalker DJ, Aronoff GR, et al. Pharmacokinetics of linezolid in subjects with renal dysfunction. Antimicrob Agents Chemother 2003 Sep; 47(9): 2775–80PubMedCrossRefGoogle Scholar
  58. 58.
    Cammarata SK, Hafkin B, Demke DM, et al. Efficacy of linezolid in skin and soft tissue infections [abstract no. 133]. 9th European Conference on Clinical Microbiology and Infectious Diseases; 1999 Mar 21–24; BerlinGoogle Scholar
  59. 59.
    Noskin GA, Siddiqui F, Stosor V, et al. Iitn vititro activities of linezolid against important gram-positive bacterial pathogens including vancomycin-resistant enterococci. Antimicrob Agents Chemother 1999; 43: 2059–62PubMedGoogle Scholar
  60. 60.
    Patel R, Rouse MS, Piper KE, et al. Iitn vititro activity of linezolid against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Diagn Microbiol Infect Dis 1999; 34: 119–22PubMedCrossRefGoogle Scholar
  61. 61.
    Rybak MJ, Cappelletty DM, Moldovan T, et al. Comparative iitn vititro activities and postantibiotic effects of the oxazolidinone compounds eperezolid (PNU-100592) and linezolid (PNU-100766) versus vancomycin against Sittaphylococcus aitureus, coagulase-negative staphylococci, Enterococcus fitaecalis, and Eitnterococcus fitaecium. Antimicrob Agents Chemother 1998; 42: 721–4PubMedCrossRefGoogle Scholar
  62. 62.
    Bernard L, Stern R, Lew D, et al. Serotonin syndrome after concomitant treatment with linezolid and citalopram. Clin Infect Dis 2003; 36: 1197PubMedCrossRefGoogle Scholar
  63. 63.
    Hachem RY, Hicks K, Huen A, et al. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis 2003; 37: e8–11PubMedCrossRefGoogle Scholar
  64. 64.
    Green SL, Maddox JC, Huttenbach ED. Linezolid and reversible myelosuppression [letter]. JAMA 2001; 285: 1291PubMedCrossRefGoogle Scholar
  65. 65.
    Kuter DJ, Tillotson GS. Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid. Pharmacotherapy 2001; 21: 1010–3PubMedCrossRefGoogle Scholar
  66. 66.
    Apodaca AA, Rakita RM. Linezolid-induced lactic acidosis. N Engl J Med 2003; 348: 86–7PubMedCrossRefGoogle Scholar
  67. 67.
    Corallo CE, Pauli AE. Linezolid-induced neuropathy [letter]. Med J Aust 2002; 177: 332PubMedGoogle Scholar
  68. 68.
    Lee E, Burger S, Shah J, et al. Linezolid-associated toxic optic neuropathy: a report of 2 cases. Clin Infect Dis 2003; 37: 1389–91PubMedCrossRefGoogle Scholar
  69. 69.
    Matson KL, Miller SE. Tooth discoloration after treatment with linezolid. Pharmacotherapy 2003; 23: 682–5PubMedCrossRefGoogle Scholar
  70. 70.
    Jones RN, Della-Latta P, Lee LV, et al. Linezolid-resistant Eitnterococcus fitaecium isolated from a patient without prior exposure to an oxazolidinone: report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis 2002; 42: 137–9PubMedCrossRefGoogle Scholar
  71. 71.
    Gonzales RD, Schreckenberger PC, Graham MB, et al. Infections due to vancomycin-resistant enterococcus faecium resistant to linezolid [letter]. Lancet 2001; 357: 1179PubMedCrossRefGoogle Scholar
  72. 72.
    Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid resistance in a clinical isolate of Sittaphylococcus aitureus. Lancet 2001 Jul 21; 358: 207–8PubMedCrossRefGoogle Scholar
  73. 73.
    Mutnick AH, Enne V, Jones RN. Linezolid resistance since 2001: SENTRY antimicrobial surveillance program. Ann Pharmacother 2003; 37: 769–74PubMedCrossRefGoogle Scholar
  74. 74.
    Pai MP, Rodvold KA, Schreckenberger PC, et al. Risk factors associated with the development of infection with linezolid- and vancomycin-resistant Enterococcus fitaecium. Clin Infect Dis 2002; 35: 1269–72PubMedCrossRefGoogle Scholar
  75. 75.
    Rahim S, Pillai SK, Gold HS, et al. Linezolid-resistant, vancomycin-resistant Eitnterococcus fitaecium infection in patients without prior exposure to linezolid. Clin Infect Dis 2003; 36: E146–8PubMedCrossRefGoogle Scholar
  76. 76.
    Herrero IA, Issa NC, Patel R. Nosocomial spread of linezolid-resistant, vancomycin-resistant Enterococcus faecium. N Engl J Med 2002; 346: 867–9PubMedCrossRefGoogle Scholar
  77. 77.
    Wilke RJ, Li ZJ Rittenhouse BE, et al. Linezolid’s effects on early hospital discharge in hospitalized patients with complicated skin and soft tissue infections under varying rates of methicillin resistant Staphyiococcus infection: analysis of results from two randomized clinical trials [abstract no. 112]. Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; TorontoGoogle Scholar
  78. 78.
    Snydman DR, Jacobus NV, McDermott LA, et al. Comparative iitn vititro activities of daptomycin and vancomycin against resistant gram-positive pathogens. Antimicrob Agents Chemother 2000; 44: 3447–50PubMedCrossRefGoogle Scholar
  79. 79.
    Barry AL, Fuchs PC, Brown SD. Iitn vititro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrob Agents Chemother 2001; 45: 1919–22PubMedCrossRefGoogle Scholar
  80. 80.
    Laganas V, Alder J, Silverman JA. Iitn vititro bactericidal activities of daptomycin against Staphyiococcus aureus and Enterococcus faecalis are not mediated by inhibition of lipoteichoic acid biosynthesis. Antimicrob Agents Chemother 2003; 47: 2682–4PubMedCrossRefGoogle Scholar
  81. 81.
    Silverman JA, Perlmutter NG, Shapiro HM. Correlation of daptomycin bactericidal activity and membrane depolarization in Staphyiococcus aureus. Antimicrob Agents Chemother 2003; 47: 2538–44PubMedCrossRefGoogle Scholar
  82. 82.
    Cubist Pharmaceuticals Inc. Cubist Pharmaceuticals presents phase III clinical results on Cidecin™ at 11th ECCMID in Istanbul, Turkey. Media release, 3 April 2001 [online]. Available from URL: [Accessed 2004 Apr15]
  83. 83.
    Snydman DR. Daptomycin [abstract no. 1125]. Proceedings of 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; Sep 17–20; Toronto. Washington, DC: American Society for Microbiology, 2000Google Scholar
  84. 84.
    Daptomycin: Cidecin, Dapcin, LY 146032. Drugs RD 2002; 3: 33–39Google Scholar
  85. 85.
    Dowzicky M, Nadler HL, Feger C, et al. Evaluation of in vitro activity of quinupristin/dalfopristin and comparator antimicrobial agents against worldwide clinical trial and other laboratory isolates. Am J Med 1998; 104: 34S-42SCrossRefGoogle Scholar
  86. 86.
    Jones RN, Ballow CH, Biedenbach DJ, et al. Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada. Diagn Microbiol Infect Dis 1998; 31: 437–51PubMedCrossRefGoogle Scholar
  87. 87.
    Aventis Pharmaceuticals. Synercid (Quinupristin/dalfopristin for injection) [package insert]. Kansas City (MO): Aventis Pharmaceuticals, 1999Google Scholar
  88. 88.
    Beyer D, Pepper K. The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs 1998; 7: 591–9PubMedCrossRefGoogle Scholar
  89. 89.
    Aumercier M, Bouhallab S, Capmau ML, et al. RP 59500: a proposed mechanism for its bactericidal activity. J Antimicrob Chemother 1992; 30 Suppl. A: 9–14PubMedCrossRefGoogle Scholar
  90. 90.
    Drew RH, Perfect JR, Srinath L, et al., for the Synercid Emergency-Use Study Group. Treatment of methicillin-resistant Staphylococcus aureus infections with quinupristin-dalfopristin in patients intolerant of or failing prior therapy. J Antimicrob Chemother 2000; 46(5): 775–84PubMedCrossRefGoogle Scholar
  91. 91.
    Olsen KM, Rebuck JA, Rupp ME. Arthralgias and myalgias related to quinupristin-dalfopristin administration. Clin Infect Dis 2001; 32: e83–6PubMedCrossRefGoogle Scholar
  92. 92.
    Carver PL, Whang E, VandenBussche HL, et al. Risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin therapy. Pharmacotherapy 2003; 23: 159–64PubMedCrossRefGoogle Scholar
  93. 93.
    Linden PK, Moellering Jr RC, Wood CA, et al. Treatment of vancomycin-resistant Eitnterococcus fitaecium infections with quinupristin/dalfopristin. Clin Infect Dis 2001; 33: 1816–23PubMedCrossRefGoogle Scholar
  94. 94.
    Chow JW, Donahedian SM, Zervos MJ. Emergence of increased resistance to quinupristin/dalfopristin during therapy for Enterococcus fitaecium bacteremia. Clin Infect Dis 1997; 24: 90–1PubMedCrossRefGoogle Scholar
  95. 95.
    Winston DJ, Emmanouilides C, Kroeber A, et al. Quinupristin/ dalfopristin therapy for infections due to vancomycin-resistant Eitnterococcus fitaecium. Clin Infect Dis 2000; 30: 790–7PubMedCrossRefGoogle Scholar
  96. 96.
    Rehm SJ. Two new treatment options for infections due to drug-resistant gram-positive cocci. Cleve Clin J Med 2002; 69: 397–13PubMedCrossRefGoogle Scholar
  97. 97.
    Basker MJ, Boon RJ, Hunter PA. Comparative antibacterial properties in vititro of seven olivanic acid derivatives: MM 4550, MM 13902, MM 17880, MM 22380, MM 22381, MM 22382 and MM 22383. J Antibiot (Tokyo) 1980; 33: 878–84CrossRefGoogle Scholar
  98. 98.
    Nichols RL, Smith JW, Geckler RW, et al. Meropenem versus imipenem/cilastatin in the treatment of hospitalized patients with skin and soft tissue infections. South Med J 1995; 88: 397–404PubMedCrossRefGoogle Scholar
  99. 99.
    Fuchs PC, Barry AL, Brown SD. Iitn-vitro antimicrobial activity of a carbapenem, MK-0826 (L-749,345) and provisional interpretive criteria for disc tests. J Antimicrob Chemother 1999; 43: 703–6PubMedCrossRefGoogle Scholar
  100. 100.
    Kohler J, Young K, Painter RE, et al. Ertapenem resistance selection in Pseudomonas aeruginosa [abstract no. 1518]. Program and abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; ChicagoGoogle Scholar
  101. 101.
    Gentry LO. Review of quinolones in the treatment of infections of the skin and skin structure. J Antimicrob Chemother 1991; 28 Suppl. C: 97–110PubMedCrossRefGoogle Scholar
  102. 102.
    Chow AT, Chen A, Lattime H, et al. Penetration of levofloxacin into skin tissue after oral administration of multiple 750mg once-daily doses. J Clin Pharm Ther 2002; 27: 143–50PubMedCrossRefGoogle Scholar
  103. 103.
    Bayer Corporation. Avelox (moxifloxacin hydrochloride tablets and injection) [package insert]. West Haven (CT): Bayer Corporation, 2003Google Scholar
  104. 104.
    Perry CM, Ormrod D, Hurst M, et al. Gatifloxacin: a review of its use in the management of bacterial infections. Drugs 2002; 62(1): 169–207PubMedCrossRefGoogle Scholar
  105. 105.
    Lowe MN, Lamb HM. Gemifloxacin. Drugs 2000; 59: 1137–47PubMedCrossRefGoogle Scholar
  106. 106.
    Muijsers RB, Jarvis B. Moxifloxacin in uncomplicated skin and skin structure infections. Drugs 2002; 62(6): 967–73PubMedCrossRefGoogle Scholar
  107. 107.
    Tarshis GA, Miskin BM, Jones TM, et al. Once-daily oral gatifloxacin versus oral levofloxacin in treatment of uncomplicated skin and soft tissue infections: double-blind, multicenter, randomized study. Antimicrob Agents Chemother 2001; 45: 2358–62PubMedCrossRefGoogle Scholar
  108. 108.
    Nichols RL, Smith JW, Gentry LO, et al. Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections. South Med J 1997; 90: 1193–200PubMedCrossRefGoogle Scholar
  109. 109.
    Candiani G, Abbondi M, Borgonovi M, et al. litn-vitro and litn-vitivo antibacterial activity of bi 397, a new semi-synthetic glycopeptide antibiotic. J Antimicrob Chemother 1999; 44: 179–92PubMedCrossRefGoogle Scholar
  110. 110.
    Goldstein EJ, Citron DM, Merriam CV, et al. Iitn vititro activities of dalbavancin and nine comparator agents against anaerobic gram-positive species and corynebacteria. Antimicrob Agents Chemother 2003; 47: 1968–71PubMedCrossRefGoogle Scholar
  111. 111.
    Jones RN, Biedenbach DJ, Johnson DM, et al. Iitn vititro evaluation of bi 397, a novel glycopeptide antimicrobial agent. J Chemother 2001; 13: 244–54PubMedGoogle Scholar
  112. 112.
    Chambers HF. Daptomycin/LY333328/evernimicin [poster]. Presentation at the 37th Annual Meeting of the Infectious Disease Society of America; 1999 Nov 18–21; PhiladelphiaGoogle Scholar
  113. 113.
    Harland S, Tebbs SE, Elliott TS. Evaluation of the in-vitro activity of the glycopeptide antibiotic LY333328 in comparison with vancomycin and teicoplanin. J Antimicrob Chemother 1998; 41: 273–6PubMedCrossRefGoogle Scholar
  114. 114.
    Zeckel ML, Preston DA, Allen BS. Iitn vititro activities of ly333328 and comparative agents against nosocomial grampositive pathogens collected in a 1997 Global Surveillance Study. Antimicrob Agents Chemother 2000; 44: 1370–4PubMedCrossRefGoogle Scholar
  115. 115.
    Schwalbe RS, McIntosh AC, Qaiyumi S, et al. Iitn vititro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci. Antimicrob Agents Chemother 1996; 40: 2416–9PubMedGoogle Scholar
  116. 116.
    Moellering Jr RC. New narrow spectrum agents for the treatment of infections caused by gram-positives [abstract no. S80]. 38th Annual Meeting of the Infectious Diseases Society of America; 2000 Sep 7–10; New OrleansGoogle Scholar
  117. 117.
    Gales AC, Jones RN. Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1203 recent clinical bacterial isolates. Diagn Microbiol Infect Dis 2000; 36: 19–36PubMedCrossRefGoogle Scholar

Copyright information

© Adis data information BV 2004

Authors and Affiliations

  1. 1.Department of Internal MedicineConemaugh Memorial Medical Center HospitalJohnstownUSA
  2. 2.Department of Critical Care MedicineUniversity of Pittsburgh Medical CenterPittsburghUSA

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