Pharmacological properties
Pharmacodynamics. Cefuroxime is a bactericidal cephalosporin antibiotic with high activity against a wide range of gram-positive and gram-negative bacteria, including strains that produce β-lactamases. Cefuroxime is resistant to the action of β-lactamases and therefore, accordingly, is active against many ampicillin- or amoxicillin-resistant strains. The main mechanism of bactericidal action is the disruption of bacterial cell wall synthesis.
Cefuroxime is effective in vitro against microorganisms such as:
gram-negative aerobes: Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus rettgeri, Providencia spp., Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae (including ampicillin-resistant strains), Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae (including strains that produce penicillinase), Neisseria meningitidis, Salmonella spp.; gram-positive aerobes: Staphylococcus aureus, Staphylococcus epidermidis (including strains that produce penicillinase, but excluding methicillin-resistant strains), Streptococcus pyogenes (as well as other β-hemolytic streptococci), Streptococcus pneumoniae, Streptococcus group B (Streptococcus agalactiae), Streptococcus mitis (viridans group), Bordetella pertussis; anaerobes: gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus species); Gram-positive bacteria (including most Clostridium spp.) and Gram-negative bacteria (including Bacteroides spp. and Fusobacterium spp.), Propionibacterium spp.; other microorganisms: Borrelia burgdorferi.
Microorganisms not susceptible to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin strains of Staphylococcus aureus, methicillin strains of Staphylococcus epidermidis, Legionella spp.
Some strains of microorganisms that are not sensitive to cefuroxime: Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., Bacteroides fragilis.
In vitro studies have shown that when cefuroxime is combined with aminoglycoside antibiotics, an additive effect is observed, in some cases synergism is detected.
Pharmacokinetics. C max cefuroxime in serum is observed 30-45 min after i / m administration. T ½ cefuroxime with i / v and i / m administration is approximately 70 min. Simultaneous administration of probenecid slows down the elimination of cefuroxime and causes an increase in its concentration in the blood plasma. Binding to plasma proteins ranges from 33 to 50%. Within 24 hours from the moment of administration, the drug is almost completely (85-90%) excreted unchanged in the urine, most of the drug is excreted in the first 6 hours. Cefuroxime is not metabolized and is excreted by glomerular filtration and tubular secretion. The level of cefuroxime in the blood plasma is reduced by dialysis. Cefuroxime concentrations exceeding the MIC for most common pathogenic microorganisms are achieved in bone tissue, synovial and intraocular fluids. Cefuroxime penetrates the blood-brain barrier in inflammation of the meninges.
A 750 mg vial of cefuroxime contains 42 mg (1.8 mEq) of sodium.
Indication
Treatment of infections caused by microorganisms sensitive to cefuroxime, or until the pathogen that caused the infectious disease is identified. Respiratory tract infections: acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess, postoperative chest infections. Ear, throat, nose infections: sinusitis, tonsillitis, pharyngitis and otitis media. Urinary tract infections: acute and chronic pyelonephritis, cystitis, asymptomatic bacteriuria. Soft tissue infections: cellulitis, erysipelas, wound infection. Bone and joint infections: osteomyelitis, septic arthritis. Obstetrics and gynecology: pelvic inflammatory disease. Gonorrhea, especially in cases where penicillin is contraindicated. Other infections, including septicemia, meningitis, peritonitis.
Prevention of infections: with an increased risk of infectious complications after operations on the chest and abdominal cavity, operations on the pelvic organs, during cardiovascular and orthopedic operations.
In most cases, Axetin monotherapy is effective. However, if necessary, the drug can be used in combination with aminoglycoside antibiotics or metronidazole (oral, suppository or injectable), especially for prophylaxis in gastrointestinal and gynecological surgery.
Application
Axetin injections are intended for intravenous or intramuscular administration only. Before using the drug, it is recommended to perform a skin test for tolerance.
general recommendations
Adults. For many infections, 750 mg 3 times a day i.m. or i.v. is sufficient. For more severe infections, the dose is increased to 1.5 g 3 times a day i.v. If necessary, the frequency of administration can be increased to 6 hours, the total daily dose will increase to 3-6 g. If necessary, some infections can be treated according to the following scheme: 750 mg or 1.5 g 2 times a day (i.v. or i.m.) followed by oral cefuroxime.
Infants and children. 30-100 mg/kg body weight per day, divided into 3-4 injections. For most infections, the optimal dose is 60 mg/kg/day.
Neonates. 30-100 mg/kg/day, divided into 2-3 injections. It should be noted that T½ of cefuroxime in the first weeks of life may be 3-5 times higher than in adults.
Gonorrhea. One injection of 1.5 g or two injections of 750 mg into both buttocks.
Meningitis. Axetine is used as monotherapy for bacterial meningitis if it is caused by sensitive strains.
Adults: 3 g IV every 8 hours.
Infants and children: 150-250 mg/kg/day IV, divided into 3 or 4 doses.
Prophylaxis. The usual dose is 1.5 g IV during induction of anesthesia for abdominal, pelvic, and orthopedic surgery. This may be supplemented by 750 mg IM 8 and 16 hours later.
For operations on the heart, lungs, esophagus, and blood vessels, the usual dose is 1.5 g intravenously, which is administered at the stage of induction of anesthesia, and then supplemented with an intramuscular injection of 750 mg 3 times a day for the next 24-48 hours.
For total joint replacement, 1.5 g of cefuroxime powder is mixed with one packet of methyl methacrylate polymer cement before adding the liquid monomer.
sequential therapy
Pneumonia: 1.5 g of cefuroxime 2-3 times a day (in / m or in / in) for 48-72 hours, then cefuroxime is used orally, the dose is 500 mg 2 times a day for 7-10 days.
Exacerbation of chronic bronchitis: 750 mg of cefuroxime 2-3 times a day (in / m or in / in) for 48-72 hours, then cefuroxime is used orally, the dose is 500 mg 2 times a day for 5-10 days.
The duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical condition of the patient.
Renal impairment. Cefuroxime is excreted by the kidneys. Therefore, as with other similar antibiotics, patients with impaired renal function are recommended to reduce the dose of cefuroxime to compensate for the slower excretion of the drug. There is no need to reduce the standard dose (750 mg-1.5 g 3 times a day) if the creatinine clearance level is 20 ml/min. Adults with severe renal impairment (creatinine clearance 10-20 ml/min) are recommended a dose of 750 mg 2 times a day, in more severe cases (creatinine clearance 10 ml/min) - 750 mg 1 time a day.
In hemodialysis, 750 mg should be administered intravenously or intramuscularly at the end of each dialysis session. In addition to parenteral administration, cefuroxime can be added to the peritoneal dialysis fluid (usually 250 mg for every 2 liters of dialysis fluid). For patients undergoing long-term arteriovenous hemodialysis or rapid hemofiltration in intensive care units, the recommended dose is 750 mg 2 times a day. Patients undergoing slow hemofiltration should follow the dosage regimen for treatment of impaired renal function.
Features of drug administration. For i/m administration, add 3 ml of water for injection to 750 mg of cefuroxime. Shake gently until an opaque suspension is formed.
For intravenous administration, dissolve 750 mg of cefuroxime in not less than 6 ml of water for injections, 1.5 g in 15 ml. For infusions lasting no more than 30 minutes, 1.5 g of cefuroxime can be dissolved in 50-100 ml of water for injections. The resulting solutions can be administered directly into a vein or into a drip tube for infusion therapy.
During storage of already diluted solutions, changes in color saturation may occur.
Contraindication
Hypersensitivity to cephalosporin antibiotics.
Side effects
Side effects are mainly isolated and generally mild and reversible in nature. In addition, the frequency of adverse reactions varies depending on the indication.
Infections and infestations: overgrowth of non-susceptible microorganisms, e.g. Candida, with prolonged use.
From the blood and lymphatic system: neutropenia, eosinophilia, leukopenia, decreased hemoglobin level, positive Coombs test, thrombocytopenia, hemolytic anemia.
Cephalosporins have the property of being absorbed on the surface of the red blood cell membrane and interacting with antibodies, causing a positive Coombs test result, which can affect blood group determination and very rarely - hemolytic anemia.
Immune system disorders: hypersensitivity reactions including skin rash, urticaria and pruritus; drug fever, interstitial nephritis, anaphylactic shock, angioedema, cutaneous vasculitis.
Gastrointestinal disorders: gastrointestinal discomfort: nausea, vomiting and diarrhea; pseudomembranous colitis.
Hepatobiliary reactions: transient elevations of liver enzymes, transient elevations of bilirubin. Transient elevations of liver enzymes or bilirubin occurred mainly in patients with pre-existing liver disease, but there is no evidence of adverse effects on the liver.
Skin and subcutaneous tissue disorders: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the urinary system: increased plasma creatinine levels, blood urea nitrogen and decreased creatinine clearance.
General disorders and administration site conditions: Injection site reactions, which may include pain and thrombophlebitis. The likelihood of pain at the IM injection site increases with higher doses, but this is unlikely to be a reason for discontinuation of treatment.
Special instructions
It is prescribed with extreme caution to patients who have had allergic reactions to penicillins or other β-lactam antibiotics.
As with other meningitis treatment regimens, cases of partial hearing loss have been reported in a few sick children treated with cefuroxime.
As with antibiotic treatment, Haemophilus influenzae cultures have been detected in the cerebrospinal fluid 18 to 36 hours after cefuroxime injection. However, the clinical significance of this finding is unknown.
As with other antibiotics, prolonged use of cefuroxime may result in overgrowth of non-susceptible organisms (e.g. Candida, Enterococci, Clostridium difficile), which may necessitate discontinuation of treatment.
Ability to influence the reaction rate when driving vehicles or operating other mechanisms. There are no reports of the effect of cefuroxime on the reaction rate when driving vehicles or operating other mechanisms.
Use during pregnancy or breastfeeding. The drug is prescribed with caution in the first months of pregnancy. Cefuroxime is excreted in breast milk. If necessary, use of the drug should be discontinued.
Children. The drug is used in pediatric practice.
Interactions
Like other antibiotics, cefuroxime may affect the intestinal flora, leading to reduced estrogen reabsorption and reduced efficacy of combined oral contraceptives.
During treatment with Axetin, it is recommended to determine blood and plasma glucose levels using the glucose oxidase or hexosokinase method.
Axetine does not affect the results of enzymatic methods for determining glycosuria.
The drug may slightly affect the results of studies using methods based on copper reduction (Benedict, Fehling, Clinitest), but this does not lead to false-positive results, as is the case with some other cephalosporins.
Cefuroxime does not affect the alkaline picrate creatinine test result.
Incompatibility: Cefuroxime should not be mixed in the same syringe with aminoglycoside antibiotics.
The pH of 2.74% sodium bicarbonate solution for injection significantly affects the color of the solution, so this solution is not recommended for diluting cefuroxime. However, if necessary, if the patient is receiving sodium bicarbonate solution intravenously by infusion, Axetin can be administered directly into the dropper tube.
1.5 g of Axetin dissolved in 15 ml of water for injection can be used together with metronidazole injection (500 mg/100 ml), both drugs retain their activity for 24 hours at temperatures below 25 °C.
1.5 g of Axetin are compatible with 1 g of azlocillin (in 15 ml of solvent) or with 5 g (in 50 ml of solvent) for 24 hours at a temperature of 4 °C and 6 hours at a temperature not exceeding 25 °C.
Axetine (5 mg/ml) can be stored for 24 hours at 25°C in 5% or 10% p-rexylitol for injection.
Axetine is compatible with solutions containing up to 1% lidocaine hydrochloride.
Axetine is compatible with most commonly used solutions for intravenous injections. It retains its properties for 24 hours at room temperature in the following solutions:
0.9% sodium chloride solution for injection; 5% glucose solution for injection; 0.18% sodium chloride solution with 4% glucose solution for injection; 5% glucose solution with 0.9% sodium chloride solution for injection; 5% glucose solution with 0.45% sodium chloride solution for injection; 5% glucose solution with 0.225% sodium chloride solution for injection; 10% glucose solution for injection; 10% inverted glucose solution in water for injection; Ringer's solution; Ringer-lactate solution; M / 6 sodium lactate solution; Hartmann's solution.
The stability of Axetin in 0.9% sodium chloride solution for injection with 5% glucose solution is not altered in the presence of hydrocortisone sodium phosphate.
Axetine is also compatible for 24 hours at room temperature when diluted in an infusion solution:
with heparin (10 or 50 units/ml) in 0.9% sodium chloride solution for injection; with potassium chloride solution (10 or 40 mEq/l) in 0.9% sodium chloride solution for injection.
Overdose
Overdose of cephalosporin antibiotics can lead to symptoms of brain irritation, which can lead to convulsions. Cefuroxime levels can be reduced by hemodialysis or peritoneal dialysis. Treatment is symptomatic.
Storage conditions
At a temperature not exceeding 25 °C in the original packaging out of the reach of children. In case of emergency, the prepared solution or suspension is stored in the refrigerator for 24 hours at a temperature of 2-8 °C.
