Fosfomycin injection

fosfomycin

1. FOSFOMYCIN : RESURGENCE OF OLD COMPANION

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. 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.

5. Treatment options Fluoroquinolones , Trimethoprim‑ sulfamethoxazole , Nitrofurantoin , Second and third‑generation cephalosporins .

6. 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.

7. 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)

8. Injectable Formulation Each vial contains: Fosfomycin Sodium BP equivalent to Fosfomycin ……………..4 gm DOSAGE FORM Powder for solution for infusion

9. 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.

10. Antimicrobial spectrum of fosfomycin

11. Antimicrobial spectrum of fosfomycin

12. 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.

13. 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.

14. Adult dosage recommendation

15. Paediatric dosage recommendation

16. Dosage for patients with renal impairment

17. 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 .

18. 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 .

19. 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.

20. 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.

21. 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.

22. 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 .

23. 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 .

24. Can it be useful in surgical prophylaxis?

25. Why it is useful in transplant patients? The prevalence of UTI among KT recipients varies widely from 23% to 75%.

26. 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

27. 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