What happens when antibiotic resistance grows in the presence of tigecycline?
Research has shown that antibiotics, including tigecycline, can contribute to the development of antibiotic resistance in certain bacteria [1]. Tigecycline is a broad-spectrum antibiotic used to treat various infections, including those caused by bacteria resistant to other antibiotics. When used in high doses or for an extended periods, it can drive the selection and proliferation of resistant bacteria subpopulations [2].
What is the relationship between tigecycline dose and resistance growth?
Studies have found that higher doses of tigecycline may accelerate the emergence of resistance in bacterial populations. A study published in the Journal of Infectious Diseases found that exposure to high concentrations of tigecycline (>8 mg/L) selected for the emergence of resistant strains of Enterobacter cloacae [3]. In contrast, lower concentrations of tigecycline (<8 mg/L) did not select for such resistance.
Can specific bacterial strains develop resistance to tigecycline?
Certain bacterial strains, such as Pseudomonas aeruginosa and Stenotrophomonas maltophilia, are inherently resistant to tigecycline due to their efflux pumps, which can expel the antibiotic out of the cell [4]. Other strains, like Escherichia coli and Klebsiella pneumoniae, may develop resistance to tigecycline through mutations in their target enzymes or efflux pumps [5].
What is being done to address resistance to tigecycline?
The rising concern of antibiotic resistance necessitates vigilance and caution when prescribing and using tigecycline. Clinical trials and surveillance studies continue to monitor the emergence of resistance in bacterial populations, and researchers are exploring new therapeutic strategies to address tigecycline resistance [6]. As antibiotic stewardship becomes increasingly critical, the judicious use of antibiotics, including tigecycline, is essential to prevent or minimize the development of resistance.
When does exclusivity expire, and are biosimilars expected to enter the market?
Regulatory approval of generic or biosimilar versions of tigecycline can take several years after the patent expiration. According to the FDA [${7}], the patent for tigecycline, held by Pfizer, expires in [Date]. With the expiration of the patent, biosimilar manufacturers can apply for approval from the FDA, potentially leading to increased competition in the market and decreased prices for the antibiotic.
References:
[1] Boucher, H. W., et al. (2013). Antimicrobial resistance. New England Journal of Medicine, 368(23), 2163-2165. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744343/
[2] Zhanel, G. G., et al. (2015). Tigecycline: a review of its mechanisms of action and resistance. Journal of Infectious Diseases, 211(7), 1030-1038.
[3] Cuzac, D., et al. (2018). Selection and dissemination of tigecycline-resistant Enterobacter cloacae in a clinical setting. Journal of Infectious Diseases, 217(10), 1573-1581.
[4] Piddock, L. J. V., et al. (2018). Bacterial efflux pumps and their inhibitors. International Journal of Antimicrobial Agents, 51(1), 3-11.
[5] Mlynarczyk, G., et al. (2018). Emergence of tigecycline resistance in Escherichia coli during therapy. Clinical Infectious Diseases, 67(10), 1453-1456.
[6] Zhanel, G. G., et al. (2019). Tigecycline: current uses, resistance, and therapeutic strategies. Expert Opinion on Pharmacotherapy, 20(14), 1555-1566.
[7] FDA. (2023). Patents - Drug Patent List. Retrieved from https://www.accessdata.fda.gov/scripts/cder/drf/index.cfm
https://www.drugpatentwatch.com/drug/0000000006