FOSFOMYCINE The First Line Antimicrobial in Urinary Tract Infection 2022 (PART II) Dr. Sharda Jain , Dr Jyoti Agarwal

1. The First Line Antimicrobial
in Urinary Tract Infection 2022
Dr Sharda Jain
Dr Jyoti Agarwal
FOSFOMYCINE

2. 2
• Discovered in 1969 in Spain
• A phosphonic acid derivative
• Broad spectrum bactericidal antibiotic with
activity against both Gram +ve and Gram –ve
uropathogens
• Features in the WHO list of essential medicines
Basics of Fosfomycin

3. 3
Mode of action of Fosfomycin

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Mode of action of Fosfomycin
 Fosfomycin inhibits the cell wall synthesis of bacteria.
1. Fosfomycin interferes with the first committed step in
peptidoglycan biosynthesis.
2. It inactivates enzyme UDP-N Acetyl Glucosamine
Enolpyruvyl transferase (MurA)
 Fosfomycin also reduces adherence of bacteria to
uroepithelial cells

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• Absorption
Rapidly absorbed following oral administration and converted to the
free acid, fosfomycin.
Absolute oral bioavailability under fasting conditions is 40%
• Distribution
Not bound to plasma proteins. Distributed in the kidneys, bladder
wall, prostate and seminal vesicles
• Excretion
Unchanged in both urine and faeces
• Half-life
5.7 (+_2.8) hours. Urinary concentrations equal to or greater than
100 µg/mL were maintained for 26-48 hours.
Pharmacokinetics

6.  Gram Negative uropathogens
Escherichia coli (E.coli)
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
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Spectrum of Coverage
 Gram Positive uropathogens
Enterococcus faecalis
Staphylococcus saprophyticus

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• High susceptibility against E.coli
• Optimum urinary concentration allows once daily dosing
• Lowest resistance rates compared to other
antimicrobials
• Established efficacy and safety with single dose therapy
• Better patient compliance
Salient features

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Highest efficacy against
E.coli
J Clin Diagn Res. 2017 Feb

9. Shows least resistance
Ind J of Med Res 2019, 149

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• Unique antibiotic that is chemically unrelated to any other known
antibiotic
• No cross resistance with other antibiotics because of its unique
structure and mechanism
• Ability to penetrate into biofilms. Not only eradicates clinically
significant bacteria but also modify biofilm structure
• Low rates of drug interactions with other agents
Why fosfomycin shows least
resistance ?

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International
recommendations

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The forgotten antibiotic
for MDR Gram negative
bacteria
A first line oral therapy
for Acute Uncomplicated
Cystitis
Testimonials from leading
journals
Brazilian Journal of
Infectious Disease
2015

13. Dosage

14. Take Home Points
Canadian Journal of Infectious disease & Medical Microbiology, 2016

15. Summary
• UTI is the common infection occurring in young women.
• The most common pathogen causing UTI is E.coli.
• The most common presentation in young non pregnant women is acute
uncomplicated cystitis.
• The recommended treatment for acute uncomplicated cystitis is short
course with antimicrobials like Fosfomycin, nitrofurantoin, and quinolones.
• Fosfomycin is a broad spectrum bactericidal antibiotic which is active
against both gram positive and gram negative bacteria.

16. Summary
• Fosfomycin should be considered as first line treatment of acute
uncomplicated cystitis due to the following unique features:
 High susceptibility against E.coli.
 Optimal urinary concentration
 Least resistance even after long term use
 Established efficacy and safety
 Single dose therapy with better patient compliance
• Single dose Fosfomycin had similar clinical and bacteriological efficacy to 3-7
day regimens of quinolones, nitrofurantoin, co-trimoxazole and amoxicillin
in women with uncomplicated lower UTIs.
• The recommended dose of Fosfomycin is single 3 g dose.

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Dr. Sharda Jain
Fosfomycin