Novel antimicrobial agents against multi-drug-resistant gram-positive bacteria: An overview

Recent Patents on Anti-Infective Drug Discovery

Volumn 7, Issue 3, 2012, Pages 182-188

  Giannakaki, Venetia ^a   Miyakis, Spiros ^a,b,c  

^a ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^b UNIVERSITY OF WOLLONGONG   (Australia)

^c WOLLONGONG HOSPITAL   (Australia)

Author keywords

Antimicrobials; Clinical trial; Methicillin resistant Staphylococcus aureus; Multidrug resistance; Penicillin resistant Streptococcus pneumoniae; Vancomycin resistant enterococcus

Indexed keywords

AMOXICILLIN; ANTIINFECTIVE AGENT; CARBAPENEM DERIVATIVE; CEFAZOLIN; CEFTAZIDIME; CEFTOBIPROLE MEDOCARIL; CETHROMYCIN; DALBAVANCIN; ERAVACYCLINE; GE 2270 A; GSK 1322322; IMIPENEM; LINEZOLID; M 131; M 478; ME 1036; MEROPENEM; MODITHROMYCIN; NXL 103; OMADACYCLINE; ORITAVANCIN; PEPTIDE DEFORMYLASE INHIBITOR; RADEZOLID; RAZUPENEM; STREPTOGRAMIN DERIVATIVE; TEDIZOLID; TIGECYCLINE; TOMOPENEM; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN;

ABDOMINAL INFECTION; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; BINDING AFFINITY; CATHETER INFECTION; COMMUNICABLE DISEASE; COMMUNITY ACQUIRED PNEUMONIA; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; GASTROINTESTINAL DISEASE; GRAM POSITIVE BACTERIUM; GRAM POSITIVE INFECTION; HUMAN; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS INFECTION; MINIMUM INHIBITORY CONCENTRATION; MULTIDRUG RESISTANCE; NONHUMAN; OSTEOMYELITIS; PATENT; PNEUMONIA; PRIORITY JOURNAL; RESPIRATORY TRACT INFECTION; REVIEW; SKIN INFECTION; SOFT TISSUE INFECTION;

ANIMALS; ANTI-INFECTIVE AGENTS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, MULTIPLE, BACTERIAL; GRAM-POSITIVE BACTERIA; GRAM-POSITIVE BACTERIAL INFECTIONS; HUMANS;

EID: 84870196562     PISSN: 1574891X     EISSN: None     Source Type: Journal    
DOI: 10.2174/157489112803521959     Document Type: Review

References (82)

1. Carmeli Y, Eliopoulos G, Mozaffari E, Samore M. Health and economic outcomes of vancomycin-resistant enterococci. Arch Intern Med 2002; 162: 2223-8.
2. Lodise TP, McKinnon PS. Clinical and economic impact of methicillin resistance in patients with Staphylococcus aureus bacteremia. Diagn Microbiol Infect Dis 2005; 52: 113-22.
3. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000; 118: 146-55.
4. Saravolatz LD, Pawlak J, Johnson LB. In vitro susceptibilities and molecular analysis of vancomycin-intermediate and vancomycinresistant Staphylococcus aureus isolates. Clin Infect Dis 2012
5. Van Bambeke F, Reinert RR, Appelbaum PC, Tulkens PM, Peetermans WE. Multidrug-resistant Streptococcus pneumoniae infections: Current and future therapeutic options. Drugs 2007; 67: 2355-82.
6. Peleg AY, Miyakis S, Ward DV, Earl AM, Rubio A, Cameron DR, et al. Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus. PLoS One 2012; 7: e28316.
7. Kelesidis T, Humphries R, Uslan DZ, Pegues DA. Daptomycin nonsusceptible enterococci: An emerging challenge for clinicians. Clin Infect Dis 2011; 52: 228-34.
8. Witte W, Cuny C. Emergence and spread of cfr-mediated multiresistance in staphylococci: An interdisciplinary challenge. Future Microbiol 2011; 6: 925-31.
9. Sanchez Garcia M, De la Torre MA, Morales G, Pelaez B, Tolon MJ, Domingo S, et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA 2010; 303: 2260-4.
10. Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008; 46 (Suppl 5): S344-9.
11. Saravolatz LD, Pawlak, J., Johnson, L., Bonilla, H, Saravolatz, LD, 2ND, Fakih, M. G., Fugelli, A. & Olsen, W. M. In vitro activity of LTX-109 a synthetic antimicrobial peptide against MRSA, VISA, VRSA, Daptomycin-non-susceptible Staphylococcus aureus (DNSSA) and Linezolid-non-susceptible SA (LNSSA). Antimicrob Agents Chemother 2012a; 56: 4478-82.
12. European antimicrobial resistance surveillance system. Annual Report 2009 14 December 2010]; Available from: http://www.ecdc.europa.eu/en/publications/Publications/1011_SUR_annual_EARS_Net_2009.pdf.
13. Klein E, Smith DL, Laxminarayan R. Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005. Emerg Infect Dis 2007; 13: 1840-6.
14. Nori US, Manoharan A, Thornby JI, Yee J, Parasuraman R, Ramanathan V. Mortality risk factors in chronic haemodialysis patients with infective endocarditis. Nephrol Dial Transplant 2006; 21: 2184-90.
15. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 1-12.
16. Hooper CY, Smith WJ. Telavancin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Ther Clin Risk Manag 2012; 8: 131-7.
17. Ciabatti R, Malabarba A. Semisynthetic glycopeptides: Chemistry, structure-activity relationships and prospects. Farmaco 1997; 52: 313-21.
18. Streit JM, Fritsche TR, Sader HS, Jones RN. Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates. Diagn Microbiol Infect Dis 2004; 48: 137-43.
19. Chen AY, Zervos MJ, Vazquez JA. Dalbavancin: A novel antimicrobial. Int J Clin Pract 2007; 61: 853-63.
20. Seltzer E, Dorr MB, Goldstein BP, Perry M, Dowell JA, Henkel T. Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. Clin Infect Dis 2003; 37: 1298-303.
21. Jauregui LE, Babazadeh S, Seltzer E, Goldberg L, Krievins D, Frederick M, et al. Randomized, double-blind comparison of onceweekly dalbavancin versus twice-daily linezolid therapy for the treatment of complicated skin and skin structure infections. Clin Infect Dis 2005; 41: 1407-15.
22. Raad I, Darouiche R, Vazquez J, Lentnek A, Hachem R, Hanna H, et al. Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis 2005; 40: 374-80.
23. Zhanel GG, Schweizer F, Karlowsky JA. Oritavancin: Mechanism of action. Clin Infect Dis 2012; 54 Suppl 3: S214-9.
24. Bouza E, Burillo A. Oritavancin: A novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains. Int J Antimicrob Agents 2010; 36: 401-7.
25. Mendes RE, Woosley LN, Farrell DJ, Sader HS, Jones RN. Oritavancin activity against vancomycin-susceptible and vancomycin-resistant Enterococci with molecularly characterized glycopeptide resistance genes recovered from bacteremic patients, 2009-2010. Antimicrob Agents Chemother 2012; 56: 1639-42.
26. Zhanel GG, Calic D, Schweizer F, Zelenitsky S, Adam H, Lagace-Wiens PR, et al. New lipoglycopeptides: A comparative review of dalbavancin, oritavancin and telavancin. Drugs 2010; 70: 859-86.
27. Yun HC, Ellis MW, Jorgensen JH. Activity of ceftobiprole against community-associated methicillin-resistant Staphylococcus aureus isolates recently recovered from US military trainees. Diagn Microbiol Infect Dis 2007; 59: 463-6.
28. Widmer AF. Ceftobiprole: A new option for treatment of skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008; 46: 656-8.
29. Lim D, Strynadka NC. Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat Struct Biol 2002; 9: 870-6.
30. Livermore DM. Can beta-lactams be re-engineered to beat MRSA? Clin Microbiol Infect 2006; 12 Suppl 2: 11-6.
31. Noel GJ, Bush K, Bagchi P, Ianus J, Strauss RS. A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections. Clin Infect Dis 2008; 46: 647-55.
32. Sumita Y, Nouda H, Kanazawa K, Fukasawa M. Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 1995; 39: 910-6.
33. Shinagawa H, Yamaga H, Houchigai H, Sumita Y, Sunagawa M. Synthesis and biological properties of a new series of anti-MRSA beta-lactams; 2-(thiazol-2-ylthio)carbapenems. Bioorg Med Chem 1997; 5: 601-21.
34. Sunagawa M, Itoh M, Kubota K, Sasaki A, Ueda Y, Angehrn P, et al. New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems. J Antibiot (Tokyo) 2002; 55: 722-57.
35. Livermore DM, Warner M. Effects of low temperature and high salt on the activity of the novel carbapenem PZ-601 (SMP-601) against methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 2009; 63: 411-3.
36. Koga T, Masuda N, Kakuta M, Namba E, Sugihara C, Fukuoka T. Potent in vitro activity of tomopenem (CS-023) against methicillinresistant Staphylococcus aureus and Pseudomonas aeruginosa. Antimicrob Agents Chemother 2008; 52: 2849-54.
37. Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T. Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Antimicrob Agents Chemother 2009; 53: 1238-41.
38. Sahm D, Draghi D, Thornsberry C. Activity of ME1036, a novel anti-MRSA carbapenem, against Gram-positive and Gram-negative pathogens. Forty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy 2006; 201, Abstract F1-236.
39. Fenoll A, Aguilar L, Robledo O, Gimenez MJ, Granizo JJ, Biek D, et al. In vitro activity of ME1036 versus other beta-lactams against penicillin-resistant Streptococcus pneumoniae serotypes exhibiting higher amoxicillin than penicillin MIC. J Antimicrob Chemother 2008; 62: 1156-8.
40. Sader HS, Fritsche TR, Jones RN. Antimicrobial activities of Ceftaroline and ME1036 tested against clinical strains of community-acquired methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2008; 52: 1153-5.
41. Morrissey I, Biek D, Janes R. ME1036, a novel carbapenem, with enhanced activity against clinical isolates causing bacteraemic community-acquired pneumonia. J Antimicrob Chemother 2009; 64: 209-10.
42. Sutcliffe JA. Antibiotics in development targeting protein synthesis. Ann N Y Acad Sci 2011; 1241: 122-52.
43. Luna VA, Xu ZQ, Eiznhamer DA, Cannons AC, Cattani J. Susceptibility of 170 isolates of the USA300 clone of MRSA to macrolides, clindamycin and the novel ketolide cethromycin. J Antimicrob Chemother 2008; 62: 639-40.
44. English ML, Fredericks CE, Milanesio NA, Rohowsky N, Xu ZQ, Jenta TR, et al. Cethromycin versus clarithromycin for communityacquired pneumonia: Comparative efficacy and safety outcomes from two double-blinded, randomized, parallel-group, multicenter, multinational noninferiority studies. Antimicrob Agents Chemother 2012; 56: 2037-47.
45. Wierzbowski AK, Karlowsky JA, Hoban DJ, Zhanel GG. In vitro activity of the investigational ketolide cethromycin against macrolide-and penicillin-resistant Streptococcus pneumoniae: Review of the 1998 to 2006 Canadian Respiratory Organism Susceptibility Study (CROSS). J Antimicrob Chemother 2009; 63: 620-2.
46. Nelson ML, Levy SB. The history of the tetracyclines. Ann N Y Acad Sci 2011; 1241: 17-32.
47. Grossman TH, Starosta AL, Fyfe C, O'Brien W, Rothstein DM, Mikolajka A, et al. Target-and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother 2012; 56: 2559-64.
48. Fyfe C, T. G, O'Brien W, Achorn C, Sutcliffe J. The novel broad spectrum fluorocycline TP-434 is active against MDR Gramnegative pathogens. 21st European Congress of Clinical Microbiology and Infectious Diseases 2011; abstr. P1149.
49. Sutcliffe J, O'Brien W, Achorn C, Appelbaum P, Pillar C, Zurenko G. In vitro activity of fluorocycline TP-434 against panels of recent bacterial clinical isolates. 50th Intersci. Conf. Antimicrob. Agents Chemother 2010; abstr. F1-2158.
50. Politano AD, Sawyer RG. NXL-103, a combination of flopristin and linopristin, for the potential treatment of bacterial infections including community-acquired pneumonia and MRSA. Curr Opin Investig Drugs 2010; 11: 225-36.
51. Vidaillac C, Parra-Ruiz J, Winterfield P, Rybak MJ. In vitro pharmacokinetic/pharmacodynamic activity of NXL103 versus clindamycin and linezolid against clinical Staphylococcus aureus and Streptococcus pyogenes isolates. Int J Antimicrob Agents 2011; 38: 301-6.
52. Bouchillon SK, Hackel M, Hoban DJ, Zalazain M, Butler D. In vitro activity of GSK1322322, a novel peptide deformylase inhibitor, against 4,836 pathogens from skin and soft tissue infections and respiratory tract infections. 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2010.
53. Lewandowski T, Demarsh P, Peters T, Kulkarni S. Potent activity of GSK1322322, a novel peptide deformylase inhibitor, after oral dosing in a murine multi-drug resistant Staphylococcus aureus infection model. 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2010
54. Ross JE, Scangarella-Oman NE, Miller LA, Sader HS, Jones RN. Determination of disk diffusion and MIC quality control ranges for GSK1322322, a novel peptide deformylase inhibitor. J Clin Microbiol 2011; 49: 3928-30.
55. Shinabarger D. Mechanism of action of the oxazolidinone antibacterial agents. Expert Opin Investig Drugs 1999; 8: 1195-202.
56. Jones RN, Ross JE, Bell JM, Utsuki U, Fumiaki I, Kobayashi I, et al. Zyvox Annual Appraisal of Potency and Spectrum program: linezolid surveillance program results for 2008. Diagn Microbiol Infect Dis 2009; 65: 404-13.
57. Long KS, Vester B. Resistance to linezolid caused by modifications at its binding site on the ribosome. Antimicrob Agents Chemother 2012; 56: 603-12.
58. Brown SD, Traczewski MM. Comparative in vitro antimicrobial activities of torezolid (TR-700), the active moiety of a new oxazolidinone, torezolid phosphate (TR-701), determination of tentative disk diffusion interpretive criteria, and quality control ranges. Antimicrob Agents Chemother 2010; 54: 2063-9.
59. Shaw KJ, Poppe S, Schaadt R, Brown-Driver V, Finn J, Pillar CM, et al. In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains. Antimicrob Agents Chemother 2008; 52: 4442-7.
60. Lemaire S, Tulkens PM, Van Bambeke F. Cellular pharmacokinetics of the novel biaryloxazolidinone radezolid in phagocytic cells: Studies with macrophages and polymorphonuclear neutrophils. Antimicrob Agents Chemother 2010; 54: 2540-8.
61. Locke JB, Finn J, Hilgers M, Morales G, Rahawi S, Kedar GC, et al. Structure-activity relationships of diverse oxazolidinones for linezolid-resistant Staphylococcus aureus strains possessing the cfr methyltransferase gene or ribosomal mutations. Antimicrob Agents Chemother 2010; 54: 5337-43.
62. Zhang YM, Rock CO. Membrane lipid homeostasis in bacteria. Nat Rev Microbiol 2008; 6: 222-33.
63. Ji Y, Yin D, Fox B, Holmes DJ, Payne D, Rosenberg M. Validation of antibacterial mechanism of action using regulated antisense RNA expression in Staphylococcus aureus. FEMS Microbiol Lett 2004; 231: 177-84.
64. Zhang YM, White SW, Rock CO. Inhibiting bacterial fatty acid synthesis. J Biol Chem 2006; 281: 17541-4.
65. Massengo-Tiasse RP, Cronan JE. Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci 2009; 66: 1507-17.
66. Marrakchi H, Zhang YM, Rock CO. Mechanistic diversity and regulation of Type II fatty acid synthesis. Biochem Soc Trans 2002; 30: 1050-5.
67. Escaich S, Prouvensier L, Saccomani M, Durant L, Oxoby M, Gerusz V, et al. The MUT056399 inhibitor of FabI is a new antistaphylococcal compound. Antimicrob Agents Chemother 2011; 55: 4692-7.
68. Bogdanovich T, Clark C, Kosowska-Shick K, Dewasse B, McGhee P, Appelbaum PC. Antistaphylococcal activity of CG400549, a new experimental FabI inhibitor, compared with that of other agents. Antimicrob Agents Chemother 2007; 51: 4191-5.
69. Parsons JB, Frank MW, Subramanian C, Saenkham P, Rock CO. Metabolic basis for the differential susceptibility of Gram-positive pathogens to fatty acid synthesis inhibitors. Proc Natl Acad Sci USA 2011; 108: 15378-83.
70. Karlowsky JA, Kaplan N, Hafkin B, Hoban DJ, Zhanel GG. AFN-1252, a FabI inhibitor, demonstrates a Staphylococcus-specific spectrum of activity. Antimicrob Agents Chemother 2009; 53: 3544-8.
71. Therien AG. Inhibitors of SpsB as potentiators of-Lactam antibiotics in methicillin-resistant Staphylococcus aureus. in 51st Intersci. Conf. Antimicrob. Agents Chemother. 2011. Chicago, Il: American Society for Microbiology.
72. Donald R. A Novel lipoglycopeptide inhibitor of signal peptidase i synergizes with imipenem against MRSA: A new approach for developing an MRSA combination therapy. in 51st Intersci. Conf. Antimicrob. Agents Chemother. 2011. Chicago, Il: American Society for Microbiology.
73. Lamarche MJ. Lead Optimization of Thiopeptide GE2270 A: Identification of Clinical Compound LFF571. in 51st Intersci. Conf. Antimicrob. Agents Chemother. 2011. Chicago, Il.
74. Isaksson J, Brandsdal BO, Engqvist M, Flaten GE, Svendsen JS, Stensen W. A synthetic antimicrobial peptidomimetic (LTX 109): stereochemical impact on membrane disruption. J Med Chem 2011; 54: 5786-95.
75. Saravolatz LD, Pawlak J, Johnson L, Bonilla H, Saravolatz LD, 2nd, Fakih MG, et al. In vitro activity of LTX-109 a synthetic antimicrobial peptide against MRSA, VISA, VRSA, daptomycinnon-susceptible Staphylococcus aureus (DNSSA) and linezolidnon-susceptible SA (LNSSA). Antimicrob Agents Chemother 2012.
76. Ebright R.H. Target and method for inhibition of bacterial RNA polymerase. US8198021 (2012).
77. Mukhopadhyay J SE, Knight J, Levy RL, Ebright RH. Antibacterial peptide microcin J25 (MCCJ25) inhibits transcription by binding within, and obstructing, the RNA polymerase secondary channel. Mol Cell 2004; 14: 739-51.
78. Mackerell JR A, Zhang H, Osterman A, Kolhatkar R. Targeting NAD Biosynthesis in bacterial pathogens. US20120190708A1 (2012).
79. Wang LE, Morales DR, Lim J, Breaker RR. Riboswitches that Sense S-adenosylhomocysteine and activate genes involved in coenzyme recycling. Mol Cell 2008; 29: 691-702.
80. Batey, R., Edwards, A., Reyes, F. S-adenosyl-(L)-homocysteine (SAH) Riboswitches and compositions and uses thereof. WO2011160126A2 (2011).
81. Schmidtchen, A., Malmsten, M. Novel antimicrobials peptides. WO2012033450A1 (2012).
82. De Leeuw, E., Mackerell, J.R.A. Defensin-like molecules as novel antimicrobial agents. WO2012061767A2 (2012).