{"id":193,"date":"2023-06-25T10:27:00","date_gmt":"2023-06-25T09:27:00","guid":{"rendered":"https:\/\/microregistrar.com\/?p=193"},"modified":"2023-06-25T10:27:00","modified_gmt":"2023-06-25T09:27:00","slug":"fosfomycin","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=193","title":{"rendered":"Fosfomycin"},"content":{"rendered":"\n

Nature:<\/strong><\/h3>\n\n\n\n

Small (Mol weight \u2013 138) phosphoenolpyruvate analogue manufactured synthetically but originally obtained from Streptomyces fradiae and some Pseudomonas sp.
A broad-spectrum, a bactericidal antibiotic.<\/p>\n\n\n\n

Mechanism of action:<\/strong><\/h3>\n\n\n\n

Inhibit bacterial cell wall formation at a very early stage by inactivating enol pyruvate transferase (MurA).<\/strong>
MurA catalyzes the transfer of enolpyruvate<\/em> from phosphoenolphyruvate to uridine diphospho-N-acetylglucosamine (UNAG), the first step of bacterial cell wall<\/em> synthesis. [Jin 2009]<\/p>\n\n\n\n

It also has immunomodulatory action.<\/strong><\/p>\n\n\n\n

Synergy:<\/strong> It shows the synergistic\/additive effect with many antibiotics against St. aureus, E coli, Pseudomonas aeruginosa, Proteus, Providencia etc.<\/p>\n\n\n\n

Mechanism of resistance:<\/strong><\/h3>\n\n\n\n

1. Reduced permeability<\/strong> \u2013 mutation in chromosomal GlpT, UhpT genes alters the transporter proteins responsible for uptake of fosfomycin \u2013 Glycerol 3-phosphate transporter and glucose 6-phosphate transporter. This mechanism is seen in gram positives (e.g. Staph aureus) and gram-negative bacteria.
2. Target modification<\/strong> \u2013 change in the fosfomycin target, the enzyme enolpyruvate transferase (MurA) can confer resistance \u2013 seen in gram-negative bacteria like E coli.
It is mediated by a mutation in the chromosomal gene murA, which encodes for enolpyruvate transferase.
3. Enzymatic inactivation of Fosfomycin \u2013<\/strong>
fosA gene-mediated glutathione transferase (this mechanism is seen in E coli and Pseudomonas).            fosB is a  transferase (Senn in Staphylococcus and Bacillus).
fosX are hydrolase (Seen in Listeria ).
These 3 are metalloenzymes, and the genes (fosA, fosB, fosX) could be located on chromosome or plasmid.
FomA or FomB are kinases that also inactivates fosfomycin (seen in some Pseudomonas sp).
The location of these two genes (fomA, fomB) is chromosomal. <\/p>\n\n\n\n

Spectrum:<\/strong><\/h3>\n\n\n\n

Gram-positive-<\/em><\/strong>
Staph aureus, including MRSA (GISA may be resistant), Enterococcus \u2013 Susceptible.<\/em>
Staph saprophyticus could be resistant.<\/em>
Streptococcus (including GAS\/GBS) \u2013 variable. Many alpha haemolytic Streptococcus are resistant.<\/em>
Gram-negative:<\/em><\/strong>
E coli, Citrobacter, Proteus mirabilis (including ESBL, MBL)- sensitive.<\/em>
Enterobacter, Proteus vulgaris, Providencia, Serratia may be resistant.<\/em>
Pseudomonas, Acinetobacter, Morganella \u2013 Resistant.<\/em>
Anaerobes:<\/em><\/strong>
Not active.<\/em><\/p>\n\n\n\n

PK\/PD:<\/strong><\/h3>\n\n\n\n

Metabolism:<\/strong> Excreted unchanged in urine and faeces.
Excretion<\/strong>: Mainly renal.
Bioavailability or oral preparation<\/strong>:  approx 40% (for tromethamine preparation), food reduces absorption.
Route:<\/strong> IV, PO.
PK\/PD index<\/strong> \u2013 Optimum PK\/PD index is not clear (Time>MIC or AUC\/MIC; however, it is most likely AUC\/MIC and C<\/em>max\/MIC).<\/p>\n\n\n\n

Common adverse effects:<\/strong><\/h3>\n\n\n\n

Gastrointestinal adverse effects, vaginitis, headache.<\/p>\n\n\n\n

Use:<\/strong><\/h3>\n\n\n\n

UTI
Often used in combination with another antibiotic for various indications.
Surgical prophylaxis.<\/p>\n\n\n\n

Potential questions:<\/h3>\n\n\n\n

Fosfomycin \u2013 Short answer.
Mechanism of fosfomycin resistance.
Which bacteria are intrinsically resistant to fosfomycin? (Leave your answer below)<\/p>\n","protected":false},"excerpt":{"rendered":"

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