Fosfomycin Information & Fosfomycin Links at HealthHaven.com

Fosfomycin
Systematic (IUPAC) name
	[(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
Identifiers
CAS number	23155-02-4 78964-85-9 (tromethamine)
ATC code	J01XX01
PubChem	446987
DrugBank	APRD00987
Chemical data
Formula	C3H7O4P
Mol. mass	138.059 g/mol
Pharmacokinetic data
Bioavailability	30–37% (oral, fosfomycin tromethamine); varies with food intake
Protein binding	Nil
Metabolism	Nil
Half life	5.7 hours (mean)
Excretion	Renal and fecal, unchanged
Therapeutic considerations
Pregnancy cat.	B(US)
Legal status	℞-only(US)
Routes	Oral
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Fosfomycin (also known as phosphomycin and phosphonomycin) is a broad-spectrum antibiotic^[1] produced by certain Streptomyces species.

[edit] Uses

Fosfomycin is indicated in the treatment of urinary tract infections, where it is usually administered as a single oral megadose.^[2]

The drug is well tolerated and has a low incidence of harmful side-effects. ^[2] However, development of bacterial resistance under therapy is a frequent occurrence and makes fosfomycin unsuitable for sustained therapy of severe infections.

Additional uses have been proposed.^[3] The global problem of advancing antimicrobial resistance has led to a renewed interest in its use more recently.^[4]

[edit] Mechanism of action

Fosfomycin is an antimetabolite of phosphoenolpyruvate in the enzymatic synthesis of N-acetylmuramic acid via enolpyruvate transferase, a component of the bacterial cell wall glycopeptide murein.^[5] The epoxide ring of fosfomycin covalently reacts with a cysteine residue in the enzyme's active site, which results in the enzyme's irreversible inactivation.

Fosfomycin enters the bacterial cell through the glycerophosphate transporter.

[edit] Resistance

Mutations that inactivate the non-essential glycerophosphate transporter render bacteria resistant to fosfomycin. Three groups of fosfomycin resistance enzymes have also been identified: FosA, FosB and FosX. FosA adds a glutathione molecule to fosfomycin, whereas FosB and FosX add cysteine or water, respectively, to fosfomycin. All three enzymes attack carbon 1 of fosfomycin, which opens the epoxide ring and renders the drug ineffective. ^[6]

[edit] Biosynthetic gene cluster

The complete fosfomycin biosynthetic gene cluster from Streptomyces fradiae has been cloned and sequenced and the heterologous production of fosfomycin in Streptomyces lividans has been achieved by Ryan Woodyer of the Huimin Zhao and Wilfred van der Donk research groups.^[7]

[edit] See also

Fosmidomycin

[edit] References

^ Grif K, Dierich MP, Pfaller K, Miglioli PA, Allerberger F (August 2001). "In vitro activity of fosfomycin in combination with various antistaphylococcal substances". The Journal of antimicrobial chemotherapy 48 (2): 209–17. PMID 11481290. http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11481290.
^ ^a ^b Patel SS, Balfour, JA (1997). "Fosfomycin tromethamine: A review of its antibacterial activity, pharmakinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections". Drugs 53: 637-656. PMID 9098664.
^ Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI (April 2008). "Fosfomycin: use beyond urinary tract and gastrointestinal infections". Clin. Infect. Dis. 46 (7): 1069–77. doi:10.1086/527442. PMID 18444827. http://www.journals.uchicago.edu/doi/abs/10.1086/527442?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov.
^ Falagas ME, Grammatikos AP, Michalopoulos A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther. 2008; 6(5):593-600 [PMID:18847400]
^ "Cell Envelope.1995". http://www.micro.siu.edu/micr425/425Notes/02-CellEnv.html. Retrieved 2008-11-08.
^ Fillgrove, K. L., Pakhomova, S., Newcomer, M. E., and Armstrong, R. N. (2003) Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms, J Am Chem Soc 125, 15730-15731
^ Woodyer RD, Shao Z, Thomas PM, et al (November 2006). "Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster". Chemistry & biology 13 (11): 1171–82. doi:10.1016/j.chembiol.2006.09.007. PMID 17113999. http://linkinghub.elsevier.com/retrieve/pii/S1074-5521(06)00340-1.

[edit] External links

Fosfomycin information at RxList

[pmid11481290-0] Grif K, Dierich MP, Pfaller K, Miglioli PA, Allerberger F (August 2001). "In vitro activity of fosfomycin in combination with various antistaphylococcal substances". The Journal of antimicrobial chemotherapy 48 (2): 209–17. PMID 11481290. http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11481290.

[pmid9098664-1] Patel SS, Balfour, JA (1997). "Fosfomycin tromethamine: A review of its antibacterial activity, pharmakinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections". Drugs 53: 637-656. PMID 9098664.

[pmid18444827-2] Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI (April 2008). "Fosfomycin: use beyond urinary tract and gastrointestinal infections". Clin. Infect. Dis. 46 (7): 1069–77. doi:10.1086/527442. PMID 18444827. http://www.journals.uchicago.edu/doi/abs/10.1086/527442?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov.

[3] Falagas ME, Grammatikos AP, Michalopoulos A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther. 2008; 6(5):593-600 [PMID:18847400]

[urlCell_Envelope.1995-4] "Cell Envelope.1995". http://www.micro.siu.edu/micr425/425Notes/02-CellEnv.html. Retrieved 2008-11-08.

[5] Fillgrove, K. L., Pakhomova, S., Newcomer, M. E., and Armstrong, R. N. (2003) Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms, J Am Chem Soc 125, 15730-15731

[pmid17113999-6] Woodyer RD, Shao Z, Thomas PM, et al (November 2006). "Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster". Chemistry & biology 13 (11): 1171–82. doi:10.1016/j.chembiol.2006.09.007. PMID 17113999. http://linkinghub.elsevier.com/retrieve/pii/S1074-5521(06)00340-1.

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