Tigecycline: pharmacological concerns and resistance
Keywords:Tigecycline, Multidrug resistant bacteria, Resistance
Tigecycline, a semisynthetic derivative of minocycline, has a broad spectrum of activity against both gram positive and gram negative multidrug resistant bacteria. The drug acts on 30S ribosomal subunit and inhibits protein synthesis. Since the drug has excellent tissue distribution, it is very useful for treatment of skin infections, intra-abdominal infections and pneumonia. Side effects of the drug are usually mild. The common side effects include nausea and vomiting. The exact mechanism of resistance remains unclear. However, resistance mediated by enhanced expression of resistance nodulation cell division (RND) type efflux pumps is one of the most frequently reported mechanisms. Resistance has been observed worldwide. However, the rate of resistance is low.
Beauduy CE, Winston LG. Chapter 44: Tetracyclines, Macrolides, Clindamycin, Chloramphenicol, Streptogramins, and Oxazolidinones. In: Katzung BG, editor. Basic and Clinical Pharmacology, 14e. New York, NY: McGraw-Hill; 2018. Available at http://accessmedicine.mhmedical.com/content.aspx?bookid=2249§ionid=175215158. Accessed on 10 May 2020.
Stein GE, Craig WA. Tigecycline: A Critical Analysis. Clin Infect Dis. 2006;43:518-24.
Sum PE, Petersen P. Synthesis and structure-activity relationship of novel glycylcycline derivatives leading to the discovery of GAR-936. Bioorg Med Chem Lett. 1999;9:1459-62.
Petersen PJ, Jacobus NV, Weiss WJ, Sum PE, Testa RT. In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Anti-microb Agents Chemother. 1999;43:738-44.
Wang Q, Zhang P, Zhao D, Jiang Y, Zhao F, Wang Y, et al. Emergence of tigecycline resistance in Escherichia coli co-producing MCR-1 and NDM-5 during tigecycline salvage treatment. Infect Drug Resist. 2018;11:2241-8.
Kasbekar N. Tigecycline: a new glycylcycline antimicrobial agent. Am J Health Syst Pharm. 2006;63:1235-43.
Letter to Wyeth Pharmaceuticals, Inc. Department of Health and Human Services; 2009. Available at https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/021821s013,021821s017,021821s018ltr.pdf. Accessed on 10 May 2020.
Pournaras S, Koumari V, Spanakis N, Gennimata V, Tsakris A. Current perspectives on tigecycline resistance in Enterobacteriaceae: susceptibility testing issues and mechanisms of resistance. Int J Antimicrob Agents. 2016;48:11-8.
Jenner L, Starosta AL, Terry DS, Mikolajka A, Filonava L, Yusupov M, et al. Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis. Proc Natl Acad Sci. 2013;110(1):3812-6.
Seputiene V, Povilonis J, Armalyte J, Suziedelis K, Pavilonis A, Suziedeliene E. Tigecycline how powerful is it in the fight against antibiotic-resistant bacteria. Medicina (Kaunas). 2010;46:240-8.
Stein GE, Babinchak T. Tigecycline: an update. Diagn Microbiol Infect Dis. 2013;75:331-6.
Satlin MJ, Kubin CJ, Blumenthal JS, Cohen AB, Furuya EY, Wilson SJ, et al. Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine. Anti-microb Agents Chemother. 2011;55:5893-9.
Cunha BA, McDermott B, Nausheen S. Single daily high-dose tigecycline therapy of a multidrug-resistant (MDR) Klebsiella pneumoniae and Enterobacter aerogenes nosocomial urinary tract infection. J Chemother. 2007;19:753-4.
Geerlings SE, Donselaar VD, Pant KA, Keur I. Successful treatment with tigecycline of two patients with complicated urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli. J Anti-microb Chemother. 2010;65:2048-9.
Tigecycline (Rx). Available at https://reference.medscape.com/drug/tygacil-tigecy-cline-342527#0. Accessed on 10 May 2020.
Dong Z, Abbas MN, Kausar S, Yang J, Li L, Tan L, et al. Biological Functions and Molecular mechanisms of antibiotic tigecycline in the treatment of cancers. Int J Mol Sci. 2019;20:3577.
Sahu R, Walker LA, Tekwani BL. In vitro and in vivo anti-malarial activity of tigecycline, a glycylcycline antibiotic, in combination with chloroquine. Malaria J. 2014;13:414.
US Food and Drug Administration. FDA drug safety communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new boxed warning. Silver Spring (MD): FDA; 2013.
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;11:834-44.
Prasad P, Sun J, Danner RL, Natanson C. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis. 2012;54:1699-709.
Du X, He F, Shi Q, Zhao F, Xu J, Fu Y, et al. The rapid emergence of tigecycline resistance in blakpc-2 harboring Klebsiella pneumoniae, as mediated in vivo by mutation in TET a during tigecycline treatment. Front Microbiol. 2018;9:648.
Sekyere OJ, Govinden U, Bester LA, Essack SY. Colistin and tigecycline resistance in carbapenemase producing gram-negative bacteria: emerging resistance mechanisms and detection methods. J Appl Microbiol. 2016;121:601-17.
Ruzin A, Immermann FW, Bradford PA. Real-time PCR and statistical analyses of acrAB and ramA expression in clinical isolates of Klebsiella pneumoniae. Anti-microb Agents Chemother. 2008;52:3430-2.
Bratu S, Landman D, George A, Salvani J, Quale J. Correlation of the expression of acrB and the regulatory genes marA, soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York City. J Anti-microb Chemother. 2009;64:278-83.
Veleba M, Higgins PG, Gonzalez G, Seifert H, Schneiders T. Characterization of RarA, a novel AraC family multidrug resistance regulator in Klebsiella pneumoniae. Anti-microb Agents Chemother. 2012;56:4450-8.
Veleba M, Schneiders T. Tigecycline resistance can occur independently of the ramA gene in Klebsiella pneumoniae. Anti-microb Agents Chemother. 2012;56:4466-7.
Nielsen LE, Snesrud EC, Leone OF, Kwak YI, Aviles R, Steele ED, et al. IS5 element integration, a novel mechanism for rapid in vivo emergence of tigecycline nonsusceptibility in Klebsiella pneumoniae. Anti-microb Agents Chemother. 2014;58:6151-6.
Cannatelli A, Giani T, D’andrea MM, Pilato DV, Arena F, Conte V, et al. MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. Anti-microb Agents Chemother. 2014;58:5696-703.
Beabout K, Hammerstrom TG, Perez AM, Magalhaes BF, Prater AG, Clements TP, et al. The ribosomal S10 protein is a general target for decreased tigecycline susceptibility. Anti-microb Agents Chemother. 2015;59:5561-6.
Sader HS, Flamm RK, Jones RN. Tigecycline activity tested against antimicrobial resistant surveillance subsets of clinical bacteria collected worldwide (2011). Diagn Microbiol Infect Dis. 2013;76:217-21.
Bertrand X, Dowzicky MJ. Anti-microbial susceptibility among Gram-negative isolates collected from intensive care units in North America, Europe, the Asia-Pacific Rim, Latin America, the Middle East, and Africa between 2004 and 2009 as part of the Tigecycline Evaluation and Surveillance Trial. Clin Ther. 2012;34:124-37.
Sader HS, Jones RN, Stilwell MG, Dowzicky MJ, Fritsche TR. Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents. Diagn Microbiol Infect Dis. 2005;52:181-6.
Garrison MW, Mutters R, Dowzicky MJ. In vitro activity of tigecycline and comparator agents against a global collection of gram-negative and gram-positive organisms: Tigecycline Evaluation and Surveillance Trial 2004 to 2007. Diagn Microbiol Infect Dis. 2009;65:288-99.
Canigia FL, Dowzicky MJ. Susceptibility of important Gram-negative pathogens to tigecycline and other antibiotics in Latin America between 2004 and 2010. Ann Clin Microbiol Anti-microb. 2012;11:29.
Sader HS, Farrell DJ, Jones RN. Tigecycline activity tested against multidrug resistant Enterobacteriaceae and Acinetobacter spp. isolated in US medical centers (2005-2009). Diagn Microbiol Infect Dis. 2011;69:223-7.
Dowzicky MJ, Park CH. Update on antimicrobial susceptibility rates among Gram-negative and Gram-positive organisms in the United States: results from the Tigecycline Evaluation and Surveillance Trial (TEST) 2005 to 2007. Clin Ther. 2008;30:2040-50.
Wiens LPR, Simner PJ, Forward KR, Tailor F, Adam HJ, Decorby M, et al. Analysis of 3789 in and outpatient Escherichia coli isolates from across Canada results of the CANWARD 2007-2009 study. Diagn Microbiol Infect Dis. 2011;69:314-19.
Sader HS, Farrell DJ, Flamm RK, Jones RN. Variation in potency and spectrum of tigecycline activity against bacterial strains from U.S. medical centers since its approval for clinical use (2006 to 2012). Anti-microb Agents Chemother. 2014;58:2274-80.
Persio DJR, Dowzicky MJ. Regional variations in multidrug resistance among Enterobacteriaceae in the USA and comparative activity of tigecycline, a new glycylcycline anti-microbial. Int J Anti-microb Agents. 2007;29:518-27.
Bouchillon SK, Iredell JR, Barkham T, Lee K, Dowzicky MJ. Comparative in vitro activity of tigecycline and other antimicrobials against gram-negative and gram-positive organisms collected from the Asia-Pacific Rim as part of the Tigecycline Evaluation and Surveillance Trial (TEST). Int J Antimicrob Agents. 2009;33:130-6.
Chen YH, Lu PL, Huang CH, Liao CH, Lu CT, Chuang YC, et al. Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010. Anti-microb Agents Chemother. 2012;56:1452-7.
Hsu MS, Liao CH, Liu CY, Yang CJ, Huang YT, Hsueh PR. In vitro susceptibilities of clinical isolates of ertapenem-non-susceptible Enterobacteriaceae to nemonoxacin, tigecycline, fosfomycin and other anti-microbial agents. Int J Anti-microb Agents. 2011;37:276-8.
Araj GF, Ibrahim GY. Tigecycline in vitro activity against commonly encountered multidrug-resistant Gram-negative pathogens in a Middle Eastern country. Diagn Microbiol Infect Dis. 2008;62:411-15.
Renteria MI, Biedenbach DJ, Bouchillon SK, Hoban DJ, Raghubir N, Sajben P, et al. In vitro activity of tigecycline against isolates collected from complicated skin and skin structure infections and intra-abdominal infections in Africa and Middle East countries: TEST 2007-2012. Diagn Microbiol Infect Dis. 2014;79:54-9.
Zarouni AM, Senok A, Zarooni AN, Nassay AF, Panigrahi D. Extended spectrum β-lactamase-producing Enterobacteriaceae: in vitro susceptibility to fosfomycin, nitrofurantoin and tigecycline. Med Princ Pract. 2012;21:543-7.
Lauritsen NN, Marchandin H, Dowzicky MJ. Anti-microbial susceptibility of tigecycline and comparators against bacterial isolates collected as part of the TEST study in Europe (2004-2007). Int J Antimicrob Agents. 2009;34:121-30.
Balode A, Polic PV, Dowzicky MJ. Anti-microbial susceptibility of Gram negative and Gram-positive bacteria collected from countries in Eastern Europe: results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2004-2010. Int J Anti-microb Agents. 2013;41:527-35.
Cattoir V, Dowzicky MJ. A longitudinal assessment of antimicrobial susceptibility among important pathogens collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) in France between 2004 and 2012. Anti-microb Resist Infect Control. 2014;3:36.