J Korean Med Assoc.  2014 Oct;57(10):837-844. 10.5124/jkma.2014.57.10.837.

Treatment of drug resistant bacteria: new bugs, old drugs, and new therapeutic approaches

• Choi YH

• KMID: 1958383
• DOI: http://doi.org/10.5124/jkma.2014.57.10.837

Abstract

Rapidly increasing antimicrobial resistance and lack of effective antibiotics are dilemma in the treatment of infectious diseases. Clinicians are now considering the use of old antibiotics such as colistin, fosfomycin because of limitation of therapeutic options. The unique pharmacokinetic and pharmacodynamics properties of these antibiotics have led the new therapeutic approaches, such as the combination of agents and newer dosing regimens. Colistin has become the last drug of the treatment of multidrug resistant gram-negative bacteria and the loading dose and high dose maintenance has been suggested. Tigecycline is licensed for the treatment of complicated skin and intra-abdominal infections and has broad activity against gram-positive and gram-negative pathogens but cautious use in the treatment of bloodstream infection and pneumonia is recommended. Oral and intravenous fosfomycin may be effective treatment options in the case of resistant gram-negative infections but clinical studies are limited.

Keyword

Antimicrobial resistance; Colistin; Tigecycline; Fosfomycin

MeSH Terms

Anti-Bacterial Agents
Bacteria*
Colistin
Communicable Diseases
Fosfomycin
Gram-Negative Bacteria
Intraabdominal Infections
Pneumonia
Skin
Anti-Bacterial Agents
Colistin
Fosfomycin

Reference

1. Song JH. Current status and future strategies of antimicrobial resistance in Korea. Korean J Med. 2009; 77:143–151.

2. Bergen PJ, Landersdorfer CB, Zhang J, Zhao M, Lee HJ, Nation RL, Li J. Pharmacokinetics and pharmacodynamics of 'old' polymyxins: what is new? Diagn Microbiol Infect Dis. 2012; 74:213–223.

3. Bergen PJ, Li J, Rayner CR, Nation RL. Colistin methanesulfonate is an inactive prodrug of colistin against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2006; 50:1953–1958.

4. Plachouras D, Karvanen M, Friberg LE, Papadomichelakis E, Antoniadou A, Tsangaris I, Karaiskos I, Poulakou G, Kontopidou F, Armaganidis A, Cars O, Giamarellou H. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother. 2009; 53:3430–3436.

5. Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, Nation RL. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother. 2011; 55:3284–3294.

6. Dudhani RV, Turnidge JD, Nation RL, Li J. fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models. J Antimicrob Chemother. 2010; 65:1984–1990.

7. Owen RJ, Li J, Nation RL, Spelman D. In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. J Antimicrob Chemother. 2007; 59:473–477.

8. Mohamed AF, Karaiskos I, Plachouras D, Karvanen M, Pontikis K, Jansson B, Papadomichelakis E, Antoniadou A, Giamarellou H, Armaganidis A, Cars O, Friberg LE. Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill. Antimicrob Agents Chemother. 2012; 56:4241–4249.

9. Florescu DF, Qiu F, McCartan MA, Mindru C, Fey PD, Kalil AC. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis. 2012; 54:670–680.

10. Gu WJ, Wang F, Tang L, Bakker J, Liu JC. Colistin for the treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: a systematic review and meta-analysis. Int J Antimicrob Agents. 2014; 08. 10. [Epub]. http://dx.doi.org/10.1016/j.ijantimicag.2014.07.004.

11. Lopez-Cortes LE, Cisneros JM, Fernandez-Cuenca F, Bou G, Tomas M, Garnacho-Montero J, Pascual A, Martinez-Martinez L, Vila J, Pachon J, Rodriguez Bano J. on behalf of the GEIH/REIPIAb2010 Group. Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort. J Antimicrob Chemother. 2014; 06. 25. [Epub]. http://dx.doi.org/10.1093/jac/dku233.

12. Liapikou A, Rosales-Mayor E, Torres A. Pharmacotherapy for hospital-acquired pneumonia. Expert Opin Pharmacother. 2014; 15:775–786.

13. Giua R, Pedone C, Cortese L, Antonelli Incalzi R. Colistin bladder instillation, an alternative way of treating multi-resistant Acinetobacter urinary tract infection: a case series and review of literature. Infection. 2014; 42:199–202.

14. Karaiskos I, Galani L, Baziaka F, Giamarellou H. Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drugresistant Acinetobacter baumannii ventriculitis and meningitis: a literature review. Int J Antimicrob Agents. 2013; 41:499–508.

15. Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, Bassetti M, Malacarne P, Petrosillo N, Galdieri N, Mocavero P, Corcione A, Viscoli C, Zarrilli R, Gallo C, Utili R. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis. 2013; 57:349–358.

16. Liu B, Liu Y, Di X, Zhang X, Wang R, Bai Y, Wang J. Colistin and anti-Gram-positive bacterial agents against Acinetobacter baumannii. Rev Soc Bras Med Trop. 2014; 47:451–456.

17. Gaibani P, Lombardo D, Lewis RE, Mercuri M, Bonora S, Landini MP, Ambretti S. In vitro activity and post-antibiotic effects of colistin in combination with other antimicrobials against colistin-resistant KPC-producing Klebsiella pneumoniae bloodstream isolates. J Antimicrob Chemother. 2014; 69:1856–1865.

18. Paul M, Carmeli Y, Durante-Mangoni E, Mouton JW, Tacconelli E, Theuretzbacher U, Mussini C, Leibovici L. Combination therapy for carbapenem-resistant Gram-negative bacteria. J Antimicrob Chemother. 2014; 69:2305–2309.

19. Velkov T, Roberts KD, Nation RL, Thompson PE, Li J. Pharmacology of polymyxins: new insights into an 'old' class of antibiotics. Future Microbiol. 2013; 8:711–724.

20. Martis N, Leroy S, Blanc V. Colistin in multi-drug resistant Pseudomonas aeruginosa blood-stream infections: a narrative review for the clinician. J Infect. 2014; 69:1–12.

21. Townsend ML, Pound MW, Drew RH. Potential role of tigecycline in the treatment of community-acquired bacterial pneumonia. Infect Drug Resist. 2011; 4:77–86.

22. Giamarellou H, Poulakou G. Pharmacokinetic and pharmacodynamic evaluation of tigecycline. Expert Opin Drug Metab Toxicol. 2011; 7:1459–1470.

23. Tasina E, Haidich AB, Kokkali S, Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis. 2011; 11:834–844.

24. Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens ver-sus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013; 57:1756–1762.

25. Betts JW, Phee LM, Hornsey M, Woodford N, Wareham DW. In vitro and in vivo activities of tigecycline-colistin combination therapies against carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2014; 58:3541–3546.

26. Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence. Antimicrob Agents Chemother. 2014; 58:654–663.

27. Brust K, Evans A, Plemmons R. Tigecycline in treatment of multidrug-resistant gram-negative bacillus urinary tract infections: a systematic review. J Antimicrob Chemother. 2014; 69:2606–2610.

28. Roussos N, Karageorgopoulos DE, Samonis G, Falagas ME. Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections. Int J Antimicrob Agents. 2009; 34:506–515.

29. Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis. 2008; 46:1069–1077.

30. Seo MR, Kim SJ, Kim Y, Kim J, Choi TY, Kang JO, Wie SH, Ki M, Cho YK, Lim SK, Lee JS, Kwon KT, Lee H, Cheong HJ, Park DW, Ryu SY, Chung MH, Pai H. Susceptibility of Escherichia coli from community-acquired urinary tract infection to fosfomycin, nitrofurantoin, and temocillin in Korea. J Korean Med Sci. 2014; 29:1178–1181.

31. Karaiskos I, Giamarellou H. Multidrug-resistant and extensively drug-resistant gram-negative pathogens: current and emerging therapeutic approaches. Expert Opin Pharmacother. 2014; 15:1351–1370.

32. Samonis G, Maraki S, Karageorgopoulos DE, Vouloumanou EK, Falagas ME. Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur J Clin Microbiol Infect Dis. 2012; 31:695–701.

33. Neuner EA, Sekeres J, Hall GS, van Duin D. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother. 2012; 56:5744–5748.

34. Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M, Oikonomou A, Poulakou G, Roilides E, Giamarellou H. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrugresistant and extensively drug-resistant carbapenemase-producing gram-negative bacteria. Int J Antimicrob Agents. 2014; 43:52–59.