[Background and Overview][1][2]
Infection with drug-resistant bacteria is a major problem currently facing the global anti-infection field. The research and development of antibacterial drugs cannot keep up with the speed of bacterial resistance. Due to the slow progress in the development of new antibacterial drugs, and the fact that bacteria often develop resistance in a short period of time, it has become a coping strategy to find alternative drugs as anti-infective drugs from safe and effective old drugs. Fosfomycin has become one of the old drugs that has been widely studied recently due to its unique antibacterial action mechanism, pharmacokinetic characteristics and low cross-resistance. Fosfomycin is a rapid bactericide during the bacterial reproduction period. It acts on the early stage of bacterial cell wall synthesis and has the following characteristics: small molecular weight, good penetrability, wide distribution in the body, almost no plasma protein binding, high blood concentration, and does not require liver It is metabolized and not degraded. Most of the enzymes are excreted via the kidneys in their original form. They have good enzyme stability and high drug safety. Fosfomycin is a broad-spectrum bactericidal drug that is effective against both G- and G+ bacteria. It is effective against Staphylococcus, Streptococcus, Pneumococcus, Escherichia coli, Serratia, Shigella, Yersinia, most Pseudomonas aeruginosa, Klebsiella pneumoniae, Vibrio spp. Strong antibacterial activity; it also has certain antibacterial effects on Proteus, Aerobacillus and some anaerobic bacteria, but it is weaker than penicillins and cephalosporins. This drug is also effective against methicillin-resistant Staphylococcus aureus (MRS Cabot Silica A), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, and some Vancomycin-resistant enterococci have antibacterial effects. However, Acinetobacter baumannii, Bacteroides fragilis and anaerobic Gram-positive cocci are resistant to this drug.
Fosfomycin calcium is an oral preparation, mostly used to treat urinary tract infections and intestinal infections caused by sensitive bacteria. From February to August 2008, Japanese scholars observed the use of fosfomycin calcium 1 g 3 times a day for 2 days to treat 48 cases of uncomplicated cystitis, 39 of which were effective. 5 to 9 days after treatment, the clinical effective rate and microbial clearance rate were 96. 8% and 93. 5%, respectively. 4 to 6 weeks after treatment, the clinical effective rate and microbial clearance rate were 82. 1% and 74. 1% respectively. .
[Indications][3]
Fosfomycin calcium is used for simple lower urinary tract infections and intestinal infections caused by sensitive bacteria, including bacillary dysentery. It can also be used in combination with other antibacterial drugs to treat severe infections caused by sensitive bacteria, such as sepsis, peritonitis, osteomyelitis, etc.
[Specifications][3]
Capsules, granules, tablets 0.1g
【Usage and Dosage】[3]
Orally take 0.5~1.0g once (calculated as C3H7O4), 4 times a day.
[Pharmacological effects] [3]
Fosfomycin calcium has a certain antibacterial effect on most Gram-positive bacteria and Gram-negative bacteria. The antibacterial spectrum of this product includes Staphylococcus aureus, Escherichia coli, Shigella dysenteriae, Serratia, and Shigella. genus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter aerogenes, etc., this product inhibits the early synthesis of bacterial cell wall, blocking the bacterial cell wall synthesis and causing its death.
[Pharmacokinetics][3]
After oral administration of fosfomycin calcium, approximately 30% to 40% is absorbed from the gastrointestinal tract. Normal people take 0.5g, 1.0g and 2.0g of this product orally and the blood drug concentration reaches the peak 2 to 4 hours later. The blood drug peaks are 3.5mg/L, 5.3mg/L and 7.0mg/L respectively. Its absorption is not affected by food. Influence. Take 0.5g of fosfomycin calcium orally every 6 hours, and the steady-state plasma concentration can reach 6 to 8 mg/L. Fosfomycin is widely distributed in various tissues and body fluids after absorption, with a Vd of 2.4L/kg. The concentration in tissues is highest in the kidney, followed by the heart, lungs, liver, etc. This product can also enter the cerebrospinal fluid through the blood-brain barrier, and can reach more than 50% of the blood concentration in inflammation. Fosfomycin can also enter the chest, abdominal cavity, bronchial secretions and aqueous humor of the eye. After oral administration of fosfomycin calcium, approximately 1/3 is excreted in the urine within 24 hours, and 1/3 is excreted with the feces within 72 hours.
[Drug Interaction][3]
1. When used in combination with β-lactams, it has a synergistic effect on Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa.
2. It has a synergistic effect when combined with aminoglycosides.
3. There is no cross-resistance with other antibiotics.
[Adverse reactions][3]
Fosfomycin calcium mainly causes mild gastrointestinal reactions, such as nausea, anorexia, mid and upper abdominal discomfort, loose stools or mild diarrhea, etc., which generally do not affect continued medication. Rash, eosinophilia, alanine aminotransferase elevation, etc. may occasionally occur.
[Notes][3]
1. When combined with β-lactams, aminoglycosides and other antibiotics, they often have a synergistic effect and can reduce or delay the development of bacterial resistance.
2. Fosfomycin has an inhibitory effect on adenosine diphosphate (ADP)-mediated platelet aggregation in vitro, which is more significant when the dose is increased, but there have been no reports of bleeding in clinical applications.
3. It is prohibited to use the drug when its properties change.
4. It is forbidden for those who are allergic to this product.
5. Pregnant women should use with caution.
【Preparation】[4]
Method 1: Preparation of fosfomycin calcium using a two-step method
Method 2: A method for preparing fosfomycin calcium, including: reacting calcium hydroxide with fosfomycin phenylethylamine represented by formula II in a solvent; filtering the reaction liquid, washing the filter cake and drying to obtain the formula Fosfomycin calcium shown in I.
[Main reference materials]
[1] Quan Juxiang, Lai Bei. Research status of clinical application of fosfomycin[J]. Chinese Journal of Clinical Pharmacology, 2015, 31(20): 2067-2069.
[2] Xia Mingyue; Li Biao; Shi Jinyou; Wang Jincan; Hao Jiebing. A kind of fosfomycin calcium composition freeze-dried tablets and its preparation method. CN201410829509.7, applied for stearic acid date 20141-2-25
[3] Commonly used antibiotic drug therapeutics
[4] Li Chunwang; Li Rongsheng. A preparation method of fosfomycin calcium. CN201710275900.0, application date 2017-04-25
