2. Why there is a need to
reconsider old option ?
• The continuously increasing problem of
antibacterial resistance and its potential
consequences are major challenge for
physicians.
• Clinicians often face problems in choosing
appropriate antibiotic therapy for treating
infections caused by gram-positive and
gram-negative bacteria, because these
pathogens are often resistant to several
classes of antibiotics.
3. Why there is a need to
reconsider old option ?
• Drug-resistant bacteria, such as methicillin-resistant Staphylococcus
aureus and multidrug-resistant Pseudomonas, Acinetobacter, and
Klebsiella species, have been frequently isolated from patients with
serious infections and are associated with a considerable mortality rate.
• These facts created the need to discover new effective treatment
solutions or even re-evaluate and reintroduce already existing
therapeutic agents for treating infections caused by drug-resistant
bacteria.
4.
5. Urinary tract infection
• Urinary tract infections (UTI) may be defined by their location (lower vs. upper)
or whether they are complicated or uncomplicated.
• Typical symptoms of lower urinary tract infections include dysuria, frequency,
urgency, suprapubic pain/tenderness, and/or hematuria usually in
combination with pyuria and bacteriuria.
• Symptoms of upper urinary tract infections include fever, chills, nausea,
vomiting, and flank pain or tenderness.
• Infections of the urinary tract can be categorized in 3 ways as well:
uncomplicated, complicated, and pyelonephritis.
8. What is the problem with
current treatment options?
• With rampant overuse and abuse of these drugs, particularly in the
developing countries like India with availability of over the counter
drugs, Gram-negative organisms have become overwhelmingly
resistant to all or most of these agents, making outpatient oral therapy
increasingly difficult.
• Hence older molecules like fosfomycin need to be reconsider for
management of UTIs, particularly those caused by E. coli and
Enterococcus faecalis, and in combination with other antibiotics in the
treatment of nosocomial infections due to resistant Gram-positive and
Gram-negative bacteria.
9. What is fosfomycin?
• Fosfomycin, a phosphonic acid derivative, was initially described
and isolated in 1969 from cultures of Streptomyces species.
• Today, fosfomycin tromethamine, a soluble salt with improved
bioavailability over fosfomycin, is being synthetically prepared
and is approved for the treatment of uncomplicated urinary
tract infections (UTIs) caused by Escherichia coli and
Enterococcus faecalis. (sachet formulation)
10. Injectable Formulation
Each vial contains:
• Fosfomycin Sodium BP equivalent to
• Fosfomycin……………..4 gm
DOSAGE FORM
• Powder for solution for infusion
11. How fosfomycin acts?
• Fosfomycin is a bactericidal antibiotic that interferes with cell wall
synthesis in both Gram-positive and Gram-negative bacteria by
inhibiting the initial step involving phosphoenolpyruvate
synthetase.
• Fosfomycin enters the cells of fosfomycin-susceptible bacteria
• It inhibits the synthesis of peptidoglycan by blocking the formation
of N-acetylmuramic acid.
15. Approved indications
• Fosfomycin is indicated for the treatment of the following infections
in adults and children including neonates:
• - Acute osteomyelitis
• - Complicated urinary tract infections
• - Nosocomial lower respiratory tract infections
• - Bacterial meningitis
• - Bacteremia that occurs in association with, or is suspected to be
associated with, any of the infections listed above.
16. Fosfomycin should be used only when it is considered inappropriate to
use antibacterial agents that are commonly recommended for the
initial treatment of the infections listed above, or when these
alternative antibacterial agents have failed to demonstrate efficacy.
20. Warning and precautions
• Caution is advised when fosfomycin is used in patients with cardiac insufficiency,
hypertension, hyperaldosteronism, hypernatraemia or pulmonary oedema. One
vial with 4 g of fosfomycin contains 56 mmol (1280 mg) sodium.
• A high sodium load associated with the use of fosfomycin may result in
decreased levels of potassium in serum or plasma.
• A low-sodium diet is recommended during fosfomycin treatment. The
substitution of potassium may be necessary in some cases.
• Serum electrolyte levels and water balance must be monitored during therapy
with fosfomycin.
21. Warning and precautions
• Antibacterial agent-associated colitis and pseudo-membranous
colitis have been reported with nearly all antibacterial agents
including fosfomycin, and may range in severity from mild to life-
threatening.
• Therefore, it is important to consider this diagnosis in patients who
present with diarrhea during or subsequent to the administration of
fosfomycin.
22. Can I use with other
antibiotics?
• Combination of fosfomycin with a β-lactam antibiotic such as
penicillin, ampicillin, cefazolin or the class of carbapenems,
usually shows an additive to synergistic effect.
• The same applies to the combination of fosfomycin with most
anti-staphylococcal (linezolid, quinupristin/dalfopristin,
moxifloxacin) agents in the treatment of staphylococcal
infections.
23. Can I use it in pregnancy?
• For fosfomycin, no clinical data on
pregnancies are available. Animal
studies do not indicate direct or
indirect harmful effects with respect to
pregnancy, embryonal/foetal
development, parturition or postnatal
development.
• Fosfomycin should therefore not be
prescribed to pregnant women unless
the benefit outweighs the risk.
24. Can I use it in lactating
women?
• After the administration of
fosfomycin, low quantities of
fosfomycin were found in human
milk.
• Fosfomycin should therefore not be
administered during lactation,
unless the benefit outweighs the
risk.
25. Where it can be used in
critical care settings?
• Useful in critically ill patients with sepsis
or nosocomial-acquired infections due to
MRSA, vancomycin-resistant
Enterococcus, and MDR Gram negative
bacteria, especially carbapenem-resistant
K. pneumoniae, in combination with other
antibiotics, due to its unique mechanism
of action and its protective effect against
nephrotoxicity induced by
aminoglycosides or colistin.
26. Where it can be used in
combination?
• Fosfomycin may be considered an alternative for the treatment of
infections due to carbapenem-resistant K. pneumoniae in adult
patients, especially in combination with other antibiotics.
• One rationale for combining fosfomycin with a second
antimicrobial agent is to prevent the emergence of fosfomycin
resistant strains.
28. Why it is useful in
transplant patients?
• The prevalence of UTI among KT recipients varies widely from 23% to 75%.
29. Points to remember
• Fosfomycin is a broad-spectrum bactericidal antibiotic which is active
against both Gram-positive and Gram-negative bacteria.
• Its unique mechanism of action may provide a synergistic effect to
other antibiotics including beta-lactams, aminoglycosides, and
fluoroquinolones
• High susceptibility against E.coli
• Optimum urinary concentration allows once daily dosing
30. Points to remember
• Lower resistance rates even after long-term usage
• Established efficacy and safety with single-dose therapy
• Better patient compliance
• Useful in critically ill patients and for surgical prophylaxis and
transplant infections
