REVIEW ON CLINICALLY DEVELOPING ANTIBIOTICS
The world is running out of antibiotics. Between 1940 and 1962, more than 20 new classes of antibiotics were marketed. Since then, only two new classes of antibiotics were marketed. Now, not enough analogues are reaching the market to stem the tide of antibiotic resistance, particularly among gram-negative bacteria which indicates the need of novel antibiotics for their effective action. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund the discovery of new antibiotics are described.
2. Infectious Diseases Society of America. Bad drugs, No Drugs. Alexandria, Virginia. Infectious Diseases Society of America; 2004.
3. Sabiha I, Twinkle G, Aarti A, Nilanjan D. A comparative study of an antimicrobial profile having broad-spectrum bacteriocins against antibiotics. Asian J Pharm Clin Res 2017;10:44-7.
4. Antibiotics research: problems and perspectives Statement. Academy of Sciences and Humanities in Hamburg German National Academy of Sciences Leopoldina; 2013.
5. Hellen G, Molly MP, Suraj P, Sumanth G, Jordan L, Devra B, et al. State of the Worldâ€™s Antibiotics: CDDEP; 2015.
6. Sadiya Z, Syed B, Shym N, Tanveer A, Faaiza Q. Synergistic combinations of broad-spectrum antibiotics against acinetobacterspp. Int J Pharm Pharm Sci 2015;7:214-7.
7. Conly JM, Johnston BL. Where are all the new antibiotics? The new antibiotic paradox. Can J Infect Dis Med Microbiol 2005;16:159-60.
8. Dalhoff A. Resistance surveillance studies: a multifaceted problem-the fluoroquinolone example. Infection 2012;40:239â€“62.
9. LÃ¼bbert C, Becker RD, Rodloff AC, Laudi S, Busch T, Bartels M, et al. Colonization of liver transplant recipients with KPC-producing Klebsiellapneumoniaeis associated with high infection rates and excess mortality: a caseâ€“control analysis. Infection 2014;42:309â€“16.
10. Anthony RM, Gerry H, Yanmin H. Novel classes of antibiotics or more of the same? Br J Pharmacol 2011;163:184â€“94.
11. Draenert R, Seybold U, Grutzner E, Bogner JR. Novel antibiotics: are we still in the preâ€“postâ€‘antibiotic era? Infection 2015;43:145â€“51.
12. Fischbach MA, Walsh CT. Antibiotics for emerging pathogens. Science 2009;325:1089-93.
13. Ivan DB, Xian Jin, Ricardo V, Daniel P, Sacha J, Bee Ha Gan, et al. Chemical space guided discovery of antimicrobial bridged bicyclic peptides against pseudomonas aeruginosa and its biofilms. Chem Sci 2016;7:1-812.
14. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, et al. New antibiotic kills pathogens without detectable resistance. Nature 2015;517:455â€“9.
15. Mima T, Brian HK, Drew AR, Malcolm GPP, Eric D, Herbert P, et al. In vitro activity of BAL30072 against Burkholderia pseudomallei. Int J Antimicrob Agents 2011;38:157â€“9.
16. New antibiotics acting against resistant microorganisms. Available from: https:/www.google.co.in.novelantibioticsdiagram. [Last accessed on 09 Jul 2017]
17. Infectious Diseases Society of America (IDSA), Promoting Antimicrobial Stewardship in Human Medicine. Available from: https://www.idsociety.org/Stewardship_Policy/. [Last accessed on 08 Jul 2017]
18. Lambert PA. Bacterial resistance to antibiotics: modified target sites. Adv Drug Delivery Rev 2005;57:1471â€“85.
19. Singh SB, Barrett JF. Empirical antibacterial drug discoveryâ€“foundation in natural products. Biochem Pharmacol 2006; 71:1006-15.
20. Zhanel GG, Schweizer F, Karlowsky JA. Oritavancin: mechanism of action. Clin Infect Dis 2012;54:214â€“9.
21. Rubino CM, Van Wart SA, Sujata MB, Paul GA, Jill SM, Alan F. Oritavancin population pharmacokinetics in healthy subjects and patients with complicated skin and skin structure infections or bacteremia. Antimicrob Agents Chemother 2009;53:4422-8.
22. Belley A, Francis FA, Sarmiento I, Hong D, Warren R, Greg M, et al. Pharmacodynamics of a simulated single 1,200-milligram dose of oritavancin in an in vitro pharmacokinetic/pharmacodynamic model of methicillin-resistant Staphylococcus aureusinfection. J Antimicrob Chemother 2013;57:205â€“11.
23. Seltzer E. Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. Clin Infect Dis 2003;37:1298â€“303.
24. Jauregui LE, Simon B, Elyse S, Lisa G, Dainis K, Mark F, 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;41:1407â€“15.
25. Dorr MB, Daniela J, Marco C, James D, Giorgio M, Adriano M, et al. Human pharmacokinetics and rationale for once-weekly dosing of dalbavancin, a semi-synthetic glycopeptide. J Antimicrob Chemother 2005;55:25â€“30.
26. Helen WB, Mark W, George HT, Sailaja P, Anita FD, Michael W, et al. Once-weekly dalbavancin versus daily conventionaltherapy for skin infection. N Engl J Med 2014;370:2169â€“79.
27. FDA. FDA approves new antibacterial drug Zerbaxa; 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427534.htm. [Last accessed on 08 Jul 2017]
28. Lemaire S, Tulkens PM, Van Bambeke F. Contrasting effects of acidic pH on the extracellular and intracellular activities of the anti-gram-positive fluoroquinolonesmoxifloxacin and delafloxacin against Staphylococcus aureus. Antimicrob Agents Chemother 2011;55:649â€“58.
29. Siala W, Marie P, Francoise V, Paul MT, Marie H, Oliver D, et al. Antibiotic activity against biofilms from Staphylococcus aureus clinical isolates: factors determining the activity of the investigational fluoroquinolone delafloxacin in comparison with daptomycin and vancomycin. Antimicrob Agents Chemother 2014;58:6385â€“97.
30. Citeline. Pharmaprojects; 2012. Available from: http://www. citeline.com/products/pharmaprojecs. [Last accessed on 08 Jul 2017].
31. Helen WB, George HT, Daniel KB, John B, Robert JG, et al. 10 x â€™20 progressâ€”development of new drugs active against gram-negative bacilli: an update from the infectious diseases society of America. Clin Infect Dis 2013;56:1685â€“94.