And again, fosfomycin: from evidence of efficacy to implementation in treatment protocols for infections caused by multidrug-resistant pathogens.
25.07.2016
And again, fosfomycin: from evidence of efficacy to implementation in treatment protocols for infections caused by multidrug-resistant pathogens.
The solution to the problem of microbial resistance to antibacterial drugs, which is recognized by the WHO as one of the three global threats to humanity, is inconceivable without the development and introduction of new antibiotics into clinical practice. However, significant progress in this area is not expected: the colossal costs required for breakthrough research may only be partially recouped, and there is a high likelihood of producing an ordinary drug that will soon be relegated to reserve use.
But are there currently available tools in the physician's arsenal to overcome resistance? Publications in medical journals repeatedly draw specialists' attention to fosfomycin, with ongoing studies opening new horizons in effective antibiotic therapy (1,2,3). Furthermore, parenteral fosfomycin, not registered in the USA, has found supporters among American physicians, as evidenced by the use of extended protocols for intravenous forms of the drug (5).
Recently, data have emerged proving the effectiveness of fosfomycin in infections caused by carbapenem-resistant Enterobacteriaceae, with the activity of the drug being evaluated in comparison with leading developments currently in various stages of preclinical and clinical trials—meropenem + vaborbactam, imipenem + relebactam, plazomicin, and eravacycline. Researchers have evaluated fosfomycin as a promising drug with clear potential against polymicrobial resistant bacteria (1). It is important to understand that while polymyxins are no longer as safe and require a “benefit/risk” evaluation when necessary, fosfomycin, with its very broad therapeutic window and minimal risk of adverse reactions, can be used in patients from high-risk categories, and for achieving synergistic and additive effects, combinations of the drug with antibiotics from other groups are encouraged (2, 4).
Fosfomycin's unique ability to penetrate biofilms formed by bacteria on catheter surfaces and mucous membranes of the urinary tract works excellently in the treatment of catheter-associated bloodstream infections. When used in combination with anti-MRSA antibiotics, fosfomycin shows significantly higher microbiological effectiveness compared to standard regimens. According to D. Chai et al. (2016), the results of in-vivo studies should serve as the basis for revising the routine therapy protocols for systemic infections caused by methicillin-resistant Staphylococcus aureus (3).
References:
1. Thaden JT, Pogue JM, Kaye KS. Role of Newer and Re-emerging Older Agents in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae. Virulence. 2016 Jul 6:0. [Epub ahead of print]
2. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods. Front Microbiol. 2016 Jun 13;7:895.
3. Chai D, Liu X, Wang R, Bai Y, Cai Y. Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus. Biomed Res Int. 2016;2016:6413982.
4. Gómez-Garcés JL, Gil-Romero Y, Vazquez O, Merino F. Synergistic activity and clinical efficacy of fosfomycin and ciprofloxacin combination treatment for soft tissue infection caused by carbapenemase-producing Enterobacter cloacae. Enferm Infecc Microbiol Clin. 2016 Jun 27. [Epub ahead of print]
5. Frederick CM, Burnette J, Aragon L, Gauthier TP. Obtaining i.v. fosfomycin through an expanded-access protocol. Am J Health Syst Pharm. 2016 Jun 28. [Epub ahead of print]
But are there currently available tools in the physician's arsenal to overcome resistance? Publications in medical journals repeatedly draw specialists' attention to fosfomycin, with ongoing studies opening new horizons in effective antibiotic therapy (1,2,3). Furthermore, parenteral fosfomycin, not registered in the USA, has found supporters among American physicians, as evidenced by the use of extended protocols for intravenous forms of the drug (5).
Recently, data have emerged proving the effectiveness of fosfomycin in infections caused by carbapenem-resistant Enterobacteriaceae, with the activity of the drug being evaluated in comparison with leading developments currently in various stages of preclinical and clinical trials—meropenem + vaborbactam, imipenem + relebactam, plazomicin, and eravacycline. Researchers have evaluated fosfomycin as a promising drug with clear potential against polymicrobial resistant bacteria (1). It is important to understand that while polymyxins are no longer as safe and require a “benefit/risk” evaluation when necessary, fosfomycin, with its very broad therapeutic window and minimal risk of adverse reactions, can be used in patients from high-risk categories, and for achieving synergistic and additive effects, combinations of the drug with antibiotics from other groups are encouraged (2, 4).
Fosfomycin's unique ability to penetrate biofilms formed by bacteria on catheter surfaces and mucous membranes of the urinary tract works excellently in the treatment of catheter-associated bloodstream infections. When used in combination with anti-MRSA antibiotics, fosfomycin shows significantly higher microbiological effectiveness compared to standard regimens. According to D. Chai et al. (2016), the results of in-vivo studies should serve as the basis for revising the routine therapy protocols for systemic infections caused by methicillin-resistant Staphylococcus aureus (3).
References:
1. Thaden JT, Pogue JM, Kaye KS. Role of Newer and Re-emerging Older Agents in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae. Virulence. 2016 Jul 6:0. [Epub ahead of print]
2. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods. Front Microbiol. 2016 Jun 13;7:895.
3. Chai D, Liu X, Wang R, Bai Y, Cai Y. Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus. Biomed Res Int. 2016;2016:6413982.
4. Gómez-Garcés JL, Gil-Romero Y, Vazquez O, Merino F. Synergistic activity and clinical efficacy of fosfomycin and ciprofloxacin combination treatment for soft tissue infection caused by carbapenemase-producing Enterobacter cloacae. Enferm Infecc Microbiol Clin. 2016 Jun 27. [Epub ahead of print]
5. Frederick CM, Burnette J, Aragon L, Gauthier TP. Obtaining i.v. fosfomycin through an expanded-access protocol. Am J Health Syst Pharm. 2016 Jun 28. [Epub ahead of print]
