High Concentrations of Divalent Cations in Extracellular Environments Reduce in vitro Antibiotic Activity of Tigecycline

Jeongwoo Jo; Sunju Kim; Kwan Soo Ko

doi:10.4167/jbv.2021.51.2.074

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2021 Vol.51, Issue 2 Preview Page Next Page

Original Article

High Concentrations of Divalent Cations in Extracellular Environments Reduce in vitro Antibiotic Activity of Tigecycline

30 June 2021. pp. 74-78

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Abstract

Tigecycline is known to form a complex with divalent cations such as Mg²⁺ and Ca²⁺, which is essential for a mode of action of tigecycline. In this study, we investigated the effects of levels of divalent cations on the in vitro antibacterial activity of tigecycline against two strains each of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. When Mg²⁺ or Ca²⁺ was added to be tantamount to criteria levels of severe hypermagnesemia or hypercalcemia in Mueller-Hinton II broth, minimum inhibitory concentrations were increased 2- to 4-fold in all strains. In media containing high concentrations of Mg²⁺ or Ca²⁺, bacterial survival rates increased significantly after 24-hour exposure to tigecycline for all strains except one K. pneumoniae strain. Thus, levels of divalent cations in extracellular condition might affect tigecycline activity. While testing on humans is still required, our results suggest that caution should be exercised when using tigecycline to treat infected patients with hypermagnesemia and hypercalcemia.

Keywords

Tigecycline

Divalent cation

Hypermagnesemia

Hypercalcemia

References

Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature 2017;543:15.

10.1038/nature.2017.2155028252092

Doi Y. Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections. Clin Infect Dis 2019;69:S565-75.

10.1093/cid/ciz83031724043PMC6853760

Stein GE, Craig WA. Tigecycline: A Critical Analysis. Clin Infect Dis 2006;43:518-24.

10.1086/50549416838243

D'Amato R, Thornsberry C. Calcium and magnesium in Mueller-Hinton agar and their influence on disk diffusion susceptibility results. Curr Microbiol 1979;2:135-8.

10.1007/BF02605869

Sun Y, Cai Y, Liu X, Bai N, Liang B, Wang R. The emergence of clinical resistance to tigecycline. Int J Antimicrob Agents 2013;41:110-6.

10.1016/j.ijantimicag.2012.09.00523127485

Wessels JM, Ford WE, Szymczak W, Schneider S. The Complexation of Tetracycline and Anhydrotetracycline with Mg2+ and Ca2+: A Spectroscopic Study. J Phys Chem B 1998;102:9323-31.

10.1021/jp9824050

Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing: 29th informational supplement, M100-S29. Wayne, PA: CLSI, 2019.

Navarro-González J, Mora-Fernández C, García-Pérez J. Clinical Implications of Disordered Magnesium Homeostasis in Chronic Renal Failure and Dialysis. Semin Dial 2009;22:37-44.

10.1111/j.1525-139X.2008.00530.x19250445

Pankey GA. Tigecycline. J Antimicrob Chemother 2005;56:470-80.

10.1093/jac/dki24816040625

Stewart AF. Clinical practice. Hypercalcemia Associated with Cancer. N Engl J Med 2005;352:373-9.

10.1056/NEJMcp04280615673803

Chopra I, Roberts M. Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance. Microbiol Mol Biol Rev 2001;65:232-60.

10.1128/MMBR.65.2.232-260.200111381101PMC99026

Thanassi DG, Suh GS, Nikaido H. Role of outer membrane barrier in efflux-mediated tetracycline resistance of Escherichia coli. J Bacteriol 1995;177:998-1007.

10.1128/jb.177.4.998-1007.19957860612PMC176695

Hope R, Warner M, Mushtaq S, Ward ME, Parsons T, Livermore DM. Effect of medium type, age and aeration on the MICs of tigecycline and classical tetracyclines. J Antimicrob Chemother 2005;56:1042-6.

10.1093/jac/dki38616286361

Torrico M, González N, Giménez MJ, Alou L, Sevillano D, Navarro D, et al. Influence of Media and Testing Methodology on Susceptibility to Tigecycline of Enterobacteriaceae with Reported High Tigecycline MIC. J Clin Microbiol 2010;48:2243-6.

10.1128/JCM.00119-1020351208PMC2884517

Deitchman AN, Singh RSP, Rand KH, Derendorf H. Enhanced in vitro activity of tigecycline in the presence of chelating agents. Int J Antimicrob Agents 2018;51:799-802.

10.1016/j.ijantimicag.2017.12.02729305959PMC5940551

Groisman EA, Hollands K, Kriner MA, Lee EJ, Park SY, Pontes MH. Bacterial Mg²⁺ Homeostasis, Transport, and Virulence. Annu Rev Genet 2013;47:625-46.

10.1146/annurev-genet-051313-05102524079267PMC4059682

Dominguez DC. Calcium signalling in bacteria. Mol Microbiol 2004;54:291-7.

10.1111/j.1365-2958.2004.04276.x15469503

Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol 2010;7:653-60.

10.1038/nrurol.2010.19021139641

Information

Publisher :The Korean Society for Microbiology and The Korean Society of Virology
Publisher(Ko) :대한미생물학회‧대한바이러스학회
Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
Volume : 51
No :2
Pages :74-78
Received Date : 2021-05-12
Revised Date : 2021-06-14
Accepted Date : 2021-06-15
DOI :https://doi.org/10.4167/jbv.2021.51.2.074

JOURNAL OF BACTERIOLOGY AND VIROLOGY ISSN:1598-2467(Print) 2093-0429(Online)

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