New antimicrobial agents for the treatment of Gram-positive bacterial infections

Clinical Microbiology and Infection

Volumn 14, Issue 5, 2008, Pages 411-420

  Aksoy, D Y ^a,b   Unal, S ^a  

^a HACETTEPE UNIVERSITY   (Turkey)

^b NONE   (Turkey)

Author keywords

Ceftobiprole; Daptomycin; Linezolid; Quinupristin dalfopristin; Review; Tigecycline

Indexed keywords

ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; AZTREONAM; BETA LACTAM ANTIBIOTIC; CEFALEXIN; CEFTAROLINE; CEFTOBIPROLE; CILASTATIN PLUS IMIPENEM; CYCLOSPORIN; DALBAVANCIN; DALFOPRISTIN PLUS QUINUPRISTIN; DAPTOMYCIN; DICLOXACILLIN; DORIPENEM; ERYTHROMYCIN; ICLAPRIM; LINEZOLID; METICILLIN; ORITAVANCIN; OXACILLIN; PENICILLIN G; POLYPEPTIDE ANTIBIOTIC AGENT; RANBEZOLIDE; SEROTONIN AGONIST; SEROTONIN UPTAKE INHIBITOR; TELAVANCIN; TIGECYCLINE; UNCLASSIFIED DRUG; VANCOMYCIN;

ANEMIA; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTHRALGIA; BACTERIAL ENDOCARDITIS; BACTERIAL INFECTION; BACTERIAL PNEUMONIA; BACTERICIDAL ACTIVITY; BACTERIOSTASIS; BONE MARROW SUPPRESSION; CENTRAL NERVOUS SYSTEM INFECTION; CLINICAL TRIAL; CONSTIPATION; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DOSE RESPONSE; DRUG ACCUMULATION; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG COMPETITION; DRUG COST; DRUG DOSE COMPARISON; DRUG ELIMINATION; DRUG FEVER; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDICATION; DRUG INDUCED HEADACHE; DRUG PENETRATION; DRUG SAFETY; DRUG SYNTHESIS; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ENTEROCOCCAL INFECTION; GRAM POSITIVE BACTERIUM; HOSPITAL INFECTION; HUMAN; HYPERBILIRUBINEMIA; INFECTIOUS ARTHRITIS; INJECTION SITE INFLAMMATION; INJECTION SITE PAIN; LACTIC ACIDOSIS; LEUKOPENIA; LIVER TOXICITY; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MONOTHERAPY; MULTIDRUG RESISTANCE; MUSCLE DISEASE; MYALGIA; NAUSEA; NEPHROTOXICITY; NEUROPATHY; NONHUMAN; OPTIC NERVE DISEASE; OPTIMAL DRUG DOSE; PANCYTOPENIA; PATIENT COMPLIANCE; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; RHABDOMYOLYSIS; SEROTONIN SYNDROME; SKIN INFECTION; SOFT TISSUE INFECTION; STAPHYLOCOCCUS INFECTION; STREPTOCOCCUS INFECTION; STREPTOCOCCUS PNEUMONIAE; THROMBOCYTOPENIA; THRUSH; UNSPECIFIED SIDE EFFECT; VANCOMYCIN RESISTANT ENTEROCOCCUS; VEIN DISEASE; VOMITING;

BACTERIA (MICROORGANISMS); POSIBACTERIA; STAPHYLOCOCCUS; STREPTOCOCCUS PNEUMONIAE;

EID: 41949129811     PISSN: 1198743X     EISSN: 14690691     Source Type: Journal    
DOI: 10.1111/j.1469-0691.2007.01933.x     Document Type: Review

References (96)

1. Johnson AP, Livermore DM, Tillotson GS. Antimicrobial susceptibility of Gram-positive bacteria: What's current, what's anticipated ? J Hosp Infect 2001; 49 (suppl A): S3-S11.
2. Leclercq R, Derlot E, Duval J, Courvalin P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med 1988; 319: 157-160.
3. Uttley AH, Collins CH, Naidoo J, George RC. Vancomycin-resistant enterococci. Lancet 1988; i: 57-58.
4. Aksoy DY, Tanriover MD, Unal S. Antimicrobial resistance: Preventable or inevitable. Problem of the era from two perspectives. In: Gould I, van der Meer J, eds, Antibiotic policies: Fighting resistance, 1st edn. New York: Springer, 2007: 113-133.
5. Anonymous. CDC National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1990 to May 1999. Am J Infect Control 1999; 27: 520-532.
6. Kobayashi K, Rao M, Keis S, Reiney FA, Smith JM, Cook GM. Enterococci with reduced susceptibility to vancomycin in New Zealand. J Antimicrob Chemother 2000; 46: 405-410.
7. Appelbaum PC. MRSA - the tip of the iceberg. Clin Microbiol Infect 2006; 12 (suppl 2): 3-10.
8. Chen CY, Tang JL, Hsueh PR et al. Trends and antimicrobial resistance of pathogens causing bloodstream infections among febrile neutropenic adults with hematological malignancy. J Formos Med Assoc 2004; 103: 526-532.
9. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Steering Committee. EUCAST technical note on linezolid. Clin Microbiol Infect 2006; 12: 1243-1245.
10. Deshpande LM, Fritsche TR, Moet GJ, Biedenbach DJ, Jones RN. Antimicrobial resistance and molecular epidemiology of vancomycin-resistant enterococci from North America and Europe: A report from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis 2007; 58: 163-170.
11. Gonzales RD, Schreckenberger PC, Graham MB, Kelkar S, DenBesten K, Quinn JP. Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid. Lancet 2001; 357: 1179.
12. Toh SM, Xiong L, Arias CA et al. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol Microbiol 2007; 64: 1506-1514.
13. Ross JE, Fritsche TR, Sader HS, Jones RN. Oxazolidinone susceptibility patterns for 2005: International report from Zyvox Annual Appraisal of Potency and Spectrum study. Int J Antimicrob Agents 2007; 29: 295-301.
14. Mylona E, Fanourgiakis P, Vryonis E et al. Linezolid-based therapy in Staphylococcus epidermidis endocarditis. Int J Antimicrob Agents 2007; 29: 597-598.
15. Munoz P, Rodrigues-Creixems M, Moreno M et al. Linezolid therapy for infective endocarditis. Clin Microbiol Infect 2007; 13: 211-215.
16. Moitra RK, Auckland C, Cawley MI, Jones G, Cooper C. Systemic nocardiosis in a splenectomized patient with systemic lupus erythematosus. Successful treatment using linezolid. J Clin Rheumatol 2003; 9: 47-50.
17. Sood R, Bhadauriya T, Rao M et al. Antimycobacterial acitivities of oxazolidinones: A review. Infect Disord Drug Targets 2006; 6: 343-354.
18. Ntziora F, Falagas ME. Linezolid for the treatment of patients with central nervous system infection. Ann Pharmacother 2007; 41: 296-308.
19. Falagas ME, Siempos II, Papagelopoulos PJ, Vardakas KZ. Linezolid for the treatment of adults with bone and joint infections. Int J Antimicrob Agents 2007; 29: 233-239.
20. Kutscha-Lissberg F, Hebler U, Muhr G, Koller M. Linezolid penetration into bone and joint tissues infected with methicillin-resistant staphylococci. Antimicrob Agents Chemother 2003; 47: 3964-3966.
21. Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH. Linezolid vs vancomycin, analysis of two double blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 2003; 124: 1789-1797.
22. Wilson SE. Clinical trial results with linezolid, an oxazolidinone, in the treatment of soft tissue and post-operative Gram positive infections. Surg Infec (Larchmt) 2001; 2: 25-35.
23. Hau T. Efficacy and safety of linezolid in the treatment of skin and soft tissue infections. Eur J Clin Microbiol Infect Dis 2002; 21: 491-498.
24. Maclayton DO, Hall RG. Pharmacologic treatment options for nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus. Ann Pharmacother 2007; 41: 235-244.
25. Ruiz ME, Guerrero IC, Tuazon CU. Endocarditis caused by methicillin-resistant Staphylococcus aureus: Treatment failure with linezolid. Clin Infect Dis 2002; 35: 1018-1020.
26. Schweiger ES, Weinberg JM. Novel antibacterial agents for skin and skin structrure infections. J Am Acad Dermatol 2004; 50: 331-340.
27. Bishop E, Melvani S, Howden BP, Charles PG, Grayson ML. Good clinical outcomes but high rates of adverse reactions during linezolid therapy for serious infections: A proposed protocol for monitoring therapy in complex patients. Antimicrob Agents Chemother 2006; 50: 1599-1602.
28. Bryson HM, Spencer CM. Quinupristin-dalfopristin: Antibacterial activity, pharmacokinetic profile, therapeutic trials and tolerability and current status. Drugs 1996; 52: 406-415.
29. Cocito C, Di Giambattista M, Nyssen E, Vannuffel P. Inhibition of protein synthesis by streptogramins and related antibiotics. J Antimicrob Chemother 1997; 39 (suppl A): 7-13.
30. Johnson AP, Livermore DM. Quinupritin/dalfopristin: A new addition to antimicrobial arsenal. Lancet 1999; 354: 2012-2013.
31. 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: 263-273.
32. Eliopoulos G. Antimicrobial agents for treatment of serious infections caused by resistant Staphylococcus aureus and enterococci. Eur J Clin Microbiol Infect Dis 2005; 24: 826-831.
33. Moellering RC, Linden PK, Reinhardt J, Blumberg EA, Bompart F, Talbot GH. 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: 251-261.
34. Stamatakis MK, Richards JG. Interaction between quinupristin/ dalfopristin and cyclosporine. Ann Pharmacother 1997; 31: 576-578.
35. Torres-Viera C, Dembry LM. Approaches to vancomycin-resistant enterococci. Curr Opin Infect Dis 2004; 17: 541-547.
36. Ginsburg I. The role of bacteriolysis in the pathophysiology of inflammation, infection and post infectious sequelas. APMIS 2002; 110: 753-770.
37. Akins RL, Rybak MJ. Bactericidal activities of two daptomycin regimens against clinical strains of glycopeptide intermediate-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus isolates in an in.vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 2001; 45: 454-459.
38. Rybak MJ, Hershberger E, Moldovan T, Grucz RG. In vitro activities of daptomycin, vancomycin, linezolid and quinupristin/dalfopristin against staphylococci and enterococci including vancomycin-intermediate and resistant strains. Antimicrob Agents Chemother 2000; 44: 1062-1066.
39. Cha R, Grucz RG, Rybak MJ. Daptomycin dose-effect relationship against resistant gram-positive organisms. Antimicrob Agents Chemother 2003; 47: 1598-1603.
40. Arbeit RD, Maki D, Tally FP et al. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 2004; 38: 1673-1661.
41. Martone WJ, Lamp KC. Efficacy of daptomycin in complicated skin and skin-structure infections due to methicillin-sensitive and -resistant Staphylococcus aureus: Results from the CORE registry. Curr Med Res Opin 2006; 22: 2337-2343.
42. Fowler VG, Boucher HW, Corey GR et al. S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006; 355: 653-665.
43. Segreti JA, Crank CW, Finney MS. Daptomycin for the treatment of gram-positive bacteremia and infective endocarditis. A retrospective case series of 31 patients. Pharmacotherapy 2006; 26: 347-352.
44. Vouillamoz J, Moreillon P, Giddey M, Entenza JM. Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multi-drug resistant enterococci. J Antimicrob Chemother 2006; 58: 1208-1214.
45. Silverman JA, Mortin LI, Vanpraagh AD, Li T, Alder J. Inhibition of daptomycin by pulmonary surfactant: In vitro modeling and clinical impact. J Infect Dis 2005; 191: 2149-2152.
46. Falagas ME, Giannopoulou KP, Ntziora F, Vardakas KZ. Daptomycin for endocarditis and/or bacteraemia: A systematic review of the experimental and clinical evidence. J Antimicrob Chemother 2007; 60: 7-19.
47. Mangili A, Bica I, Snydman DR, Hamer DH. Daptomycin-resistant methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 2005; 40: 1058-1060.
48. Skiest DJ. Treatment failure resulting from resistance of Staphylococcus aureus to daptomycin. J Clin Microbiol 2006; 44: 655-656.
49. Hoban DJ, Bouchillon SK, Johnson BM et al. In vitro activities of tigecycline against 6792 gram-negative and gram-positive clinical isolates from the global Tigecyline Evaluation and Surveillance Trial (TEST Program, 2004). Diagn Microbiol Infect Dis 2005; 52: 215-227.
50. Pankey GA. Tigecyline. J Antimicrob Chemother 2005; 56: 470-480.
51. Projan SJ. Preclinical pharamcology of GAR-936, a novel glycylcyline antibacterial agent. Pharmacotherapy 2000; 20: 219S-223S.
52. Sum PE, Petersen P. Synthesis and structure-activity relationship of novel glycylcyline derivatives leading to the discovery of GAR-936. Bioorg Med Chem Lett 1999; 9: 1459-1462.
53. Al-Tatari H, Abdel-Haq N, Chearskul P, Asmar B. Antibiotics for treatment of resistant Gram-positive coccal infections. Ind J Pediatr 2006; 73: 323-334.
54. Sacchidanand S, Penn RL, Embil JM et al. Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a phase.3, randomized, double-blind trial. Int J Infect Dis 2005; 9: 251-261.
55. Ellis-Grosse EJ, Babichak T, Dartois N et al. The efficacy and safety of tigecycline in the treatment of skin and skin structure infections: results of 2 double-blind phase.3 comparison studies with vancomycin-aztreonam. Clin Infect Dis 2005; 41 (suppl 5): S341-S353.
56. Babinchak T, Ellis-Grosse E, Dartois N et al. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis 2005; 41 (suppl 5): S354-S367.
57. Oliva ME, Rekha A, Yellin A et al. A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections. BMC Infect Dis 2005; 5: 88.
58. Stein GE, Craig WA. Tigecycline: A critical analysis. Clin Infect Dis 2006; 43: 518-524.
59. Cooper RD, Snyder NJ, Zweifel MJ et al. Reductive alkylation of glycopeptide antibiotics: Synthesis and antibacterial activity. J Antibiot 1996; 49: 575-581.
60. Malabarba A, Ciabatti R. Glycopeptide derivatives. Curr Med Chem 2001; 8: 1759-1773.
61. Allen NE, Nicas TI. Mechanism of action of oritavancin and related glycopeptide antibiotics. FEMS Microbiol Rev 2003; 26: 511-532.
62. Guay DR. Oritavancin and tigecyline: Investigational antimicrobials for multi-drug resistant bacteria. Pharmacotherapy 2004; 24: 58-68.
63. Saleh-Mghir A, Lefort A, Petegnief Y et al. Activity and diffusion of LY333328 in experimental endocarditis due to vancomycin-resistant Enterococcus faecalis. Antimicrob Agents Chemother 1999; 43: 115-120.
64. Lefort A, Saleh-Mghir A, Garry L, Carbon C, Fantin B. Activity of LY333328 combined with gentamicin in vitro and in rabbit experimental endocarditis due to vancomycin-susceptible or -resistant Enterococcus faecalis. Antimicrob Agents Chemother 2000; 44: 3017-3021.
65. Rupp ME, Fey PD, Longo GM. Effect of LY333328 against vancomycin-resistant Enterococcus faecium in a rat central venous catheter-associated infection model. J Antimicrob Chemother 2001; 47: 705-707.
66. Kaatz GW, Seo SM, Aeschlimann JR, Houlihan HH, Mercier RC, Rybak MJ. Efficacy of LY3333328 against experimental methicillin-resistant Staphylococcus aureus endocarditis. Antimicrob Agents Chemother 1998; 42: 981-983.
67. Gerber J, Smirnov A, Wellmer A et al. Activity of LY333328 in experimental meningitis caused by a Streptococcus pneumoniae strain susceptible to penicillin. Antimicrob Agents Chemother 2001; 45: 2169-2172.
68. Boylan CJ, Campanale K, Iverson PW, Phillips DL, Zeckel ML, Parr TR. Pharmacodynamics of oritavancin (LY333328) in a neutropenic-mouse thigh model of Staphylococcus aureus infection. Antimicrob Agents Chemother 2003; 47: 1700-1706.
69. Mercier RC, Hrebickova L. Oritavancin: A new avenue for resistant Gram-positive bacteria. Expert Rev Anti-Infect Ther 2005; 3: 325-332.
70. Loutit JS, O'Riordan W, San Juan J et al. Phase.2 trial comparing four regimens of oritavancin vs. comparator in the treatment of patients with S. aureus bacteremia. Clin Microbiol Infect 2004; 10 (suppl 3): 122.
71. Van Bambeke F, Carryn S, Seral C et al. Cellular pharmacokinetics and pharmacodynamics of oritavancin (LY333328) glycopeptide in a model of J774 mouse macrophages. Antimicrob Agents Chemother 2004; 48: 2853-2860.
72. Judice JK, Pace JL. Semi-synthetic glycopeptide antibacterials. Bioorg Med Chem Lett 2003; 13: 4165-4168.
73. Van Bambeke F. Glycopeptides in clinical development: Pharmacological profile and clinical perspectives. Curr Opin Pharmacol 2004; 4: 471-478.
74. Pace JL, Yang G. Glycopeptides: Update on an old successful antibiotic class. Biochem Pharmacol 2006; 71: 968-980.
75. Gander S, Kinnaird A, Finch R. Telavancin: In vitro activity against staphylococci in a biofilm model. J Antimicrob Chemother 2005; 56: 337-343.
76. Reyes N, Skinner R, Benton BM et al. Efficacy of telavancin in a murine model of bacteraemia induced by methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 2006; 58: 462-465.
77. Stucki A, Gerber P, Acosta F, Cottagnoud M, Cottagnaud P. Efficacy of telavancin against penicillin-resistant pneumococci and Staphylococcus aureus in a rabbit meningitis model and determination of kinetic parameters. Antimicrob Agents Chemother 2006; 50: 770-773.
78. Madrigal AG, Basuino L, Chambers HF. Efficacy of telavancin in a rabbit model of aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus or vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 2005; 49: 3163-3165.
79. Sun HK, Duchin K, Nightingale CH, Shaw JP, Seroogy J, Nicolau DP. Tissue penetration of telavancin after intravenous administration in healthy subjects. Antimicrob Agents Chemother 2006; 50: 788-790.
80. Stryjewski ME, Chu VH, O'Riordan WD et al. Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram positive bacteria; FAST.2 study. Antimicrob Agents Chemother 2006; 50: 862-867.
81. Stryjewski ME, O'Riordan WD, Lau WK et al. Telavancin versus standard therapy for treatment of complicated skin and skin structure infections due to gram positive bacteria. Clin Infect Dis 2005; 40: 1601-1607.
82. Dorr MB, Jabes D, Cavaleri M et al. Human pharmacokinetics and rationale for once-weekly dosing of dalbavancin, a semisynthetic glycopeptide. J Antimicrob Chemother 2005; 55 (suppl 2): 25-30.
83. Jauregui LE, Babazadeh S, Seltzer E et al. Randomized, double-blind comparison of once weekly dalbavancin versus twice-daily linezolid therapy for the treatment of complicated skin and skin structure infections. Clin Infect Dis 2005; 41: 1407-1415.
84. Lefort A, Pavie J, Garry L, Chau F, Fantin B. Activities of dalbavancin in vitro and in a rabbit model of experimental endocarditis due to Staphylococcus aureus with or without reduced susceptibility to vancomycin and teicoplanin. Antimicrob Agents Chemother 2004; 48: 1061-1064.
85. Malabarba A, Goldstein BP. Origin, structure and activity in vitro and in vivo of dalbavancin. J Antimicrob Chemother 2005; 55 (suppl 2): 15-20.
86. Raad I, Darouiche R, Vazquez J et al. Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infections caused by Gram-positive pathogens. Clin Infect Dis 2005; 40: 374-380.
87. Hebeisen P, Heinze-Krauss I, Angehrn P, Hohl P, Page MG, Then RL. In vitro and in vivo properties of Ro-63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob Agents Chemother 2001; 45: 825-836.
88. Bogdanovich T, Ednie LM, Shapiro S, Appelbaum PC. Antistaphylococcal activity of ceftobipirole: A new broad spectrum cephalosporin. Antimicrob Agents Chemother 2005; 49: 4210-4219.
89. Chambers HF. Evaluation of ceftobiprole in a rabbit model of aortic valve endocarditis due to methicillin-resistant and vancomycin intermediate Staphylococcus aureus. Antimicrob Agents Chemother 2005; 49: 884-888.
90. Vaudaux P, Gjinovci A, Bento M, Li D, Schrenzel J, Lew DP. Intensive therapy with ceftobiprole medocaril of experimental foreign-body infection by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2005; 49: 3789-3793.
91. Noel GJ. Clinical profile of ceftobiprole, a novel beta-lactam antibiotic. Clin Microbiol Infect 2007; 13 (suppl 2): 25-29.
92. Chambers HF. Ceftobiprole: In vivo profile of a bactericidal cephalosporin. Clin Microbiol Infect 2006; 12 (suppl 2): 17-22.
93. Mushtaq S, Warner M, Ge Y, Kaniga K, Livermore DM. In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes. J Antimicrob Chemother 2007; 60: 300-311.
94. Poulakou G, Giamarellou H. Investigational treatments for postoperative surgical site infections. Expert Opin Investig Drugs 2007; 16: 137-155.
95. Hawser S, Lociuro S, Islam K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem Pharmacol 2006; 71: 941-948.
96. Mathur T, Bhateja P, Pandya M, Fatma T, Rattan A. In vitro activity of RBx 7644 (ranbezolid) on biofilm producing bacteria. Int J Antimicrob Agents 2004; 24: 369-373.