Ceftriaxone, 1 g

Ceftriaxone – cephalosporin antibiotic of III generation for parenteral use, has bactericidal action, inhibits cell membrane synthesis, in vitro suppresses the growth of most Gram-positive and Gram-negative microorganisms. Ceftriaxone is resistant to beta-lactamase enzymes (both penicillinase and cephalosporinase produced by most Gram-positive and Gram-negative bacteria). In vitro and in clinical practice ceftriaxone is generally effective against the following microorganisms:

Gram-positive:
Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus V (Str. agalactiae), Streptococcus viridans, Streptococcus bovis.

Note: Staphylococcus spp. resistant to methicillin is also resistant to cephalosporins, including ceftriaxone. Most strains of enterococci (e.g., Streptococcus faecalis) are also resistant to ceftriaxone.

Gram-negative:
Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp, Enterobacter spp. (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including Kl. pneumoniae), Moraxella spp, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are resistant), Salmonella spp. (including S. typhi), Serratia spp, Vibrio spp. (including V. cholerae), Yersinia spp. (including Y. enterocolitica)

Note: Many strains of the listed microorganisms, which in the presence of other antibiotics, such as penicillins, first generation cephalosporins and aminoglycosides multiply steadily, are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone both in vitro and in animal experiments. According to clinical data in primary and secondary syphilis good effectiveness of ceftriaxone is noted.

Anaerobic pathogens:
Bacteroides spp. (including some strains of B. fragilis), Clostridium spp. (including CI. difficile), Fusobacterium spp. (except F. mostiferum. F. varium), Peptococcus spp., Peptostreptococcus spp.

Note: Some strains of many Bacteroides spp. (for example, B. fragilis), producing beta-lactamase, are resistant to ceftriaxone. To determine the sensitivity of microorganisms it is necessary to use disks containing ceftriaxone, because it has been shown that in vitro certain strains of pathogens may be resistant to classical cephalosporins.

Pharmacokinetics:

When administered parenterally, ceftriaxone penetrates well into tissues and body fluids. In healthy adult subjects, ceftriaxone is characterized by a long, about 8 hours, half-life. The areas under the concentration-time curve in blood serum when administered intravenously and intramuscularly coincide. This means that bioavailability of ceftriaxone with intramuscular administration is 100%. When administered intravenously, ceftriaxone rapidly diffuses into the interstitial fluid, where it retains its bactericidal effect against pathogens sensitive to it for 24 hours.

The half-life in healthy adult subjects is about 8 hours. In newborns under 8 days and in older adults over 75 years of age, the average half-life is about twice as long. In adults, 50-60% of ceftriaxone is excreted unchanged in the urine and 40-50% is also excreted unchanged in the bile. Under the influence of intestinal flora ceftriaxone is converted into an inactive metabolite. In infants about 70% of the administered dose is excreted by the kidneys. In adults with renal insufficiency or liver pathology pharmacokinetics of ceftriaxone is almost unchanged, the elimination half-period is lengthened slightly. If renal function is impaired, excretion with bile increases, and if there is hepatic pathology, renal excretion of ceftriaxone increases.

Ceftriaxone reversibly binds to albumin and this binding is inversely proportional to the concentration: for example, at a drug concentration in serum of less than 100 mg/l the binding of ceftriaxone to proteins is 95%, and at a concentration of 300 mg/l – only 85%. Due to the lower content of albumin in interstitial fluid, the concentration of ceftriaxone in it is higher than in blood serum.

Perfusion into the cerebrospinal fluid: In infants and children with cerebral membrane inflammation, ceftriaxone penetrates into the cerebrospinal fluid, with an average of 17% of the drug concentration in serum diffusing into the cerebrospinal fluid in bacterial meningitis, which is about 4 times greater than in aseptic meningitis.

24 hours after intravenous administration of ceftriaxone at a dose of 50-100 mg/kg body weight, the concentration in the cerebrospinal fluid exceeds 1.4 mg/L. In adult meningitis patients, 2-25 hours after administration of ceftriaxone at a dose of 50 mg/kg body weight, the concentration of ceftriaxone was many times greater than the minimum suppressive dose necessary to suppress the pathogens that most frequently cause meningitis.

Indications

Infections caused by pathogens sensitive to ceftriaxone: Sepsis, meningitis, abdominal infections (peritonitis, inflammatory diseases of the gastrointestinal tract, biliary tract), infections of bones, joints, connective tissue, skin, infections in patients with reduced immune system function, kidney and urinary tract infections, respiratory tract infections, especially pneumonia, and ear, throat and nose infections, genital infections, including gonorrhea.

Preventing infections in the postoperative period.

Active ingredient

Composition

One bottle contains 1.0 g of Ceftriaxone sodium salt.

How to take, the dosage

In adults and in children over 12 years of age:The average daily dose is 1-2 g of ceftriaxone once daily (24 hours). In severe cases or in cases of infections caused by moderately sensitive pathogens, the single daily dose may be increased to 4 g.

For newborns, infants, and children under 12 years of age: The following regimen is recommended for a single daily dosage:
For newborns (up to two weeks of age): 20-50 mg/kg body weight per day (the dose of 50 mg/kg body weight should not be exceeded due to the immature enzyme system of newborns).

In infants and children under 12 years of age the daily dose is 20-75 mg/kg of body weight. In children with a body weight of 50 kg or more the dosage for adults should be followed. The dose more than 50 mg/kg of body weight should be administered as an intravenous infusion for at least 30 minutes.

The duration of therapy: depends on the course of the disease.

Combination therapy:

It has been shown in experiments that there is synergy between ceftriaxone and aminoglycosides for the effect on many Gram-negative bacteria. Although the potentiated effect of such combinations cannot be predicted in advance, in cases of severe and life-threatening infections (e.g., caused by Pseudomonas aeruginosa) their combined administration is justified.

Because of the physical incompatibility of ceftriaxone and aminoglycosides it is necessary to administer them separately in the recommended doses!

Gonorrhea:
For the treatment of gonorrhea caused by both penicillinase-forming and non-penicillinase-forming strains, the recommended dose is 250 mg once intramuscularly.

Prophylaxis in the pre- and postoperative period:
Before infected or suspected infected surgical procedures to prevent postoperative infections, a single injection of ceftriaxone at a dose of 1-2 g is recommended 30-90 minutes before surgery, depending on the risk of infection.

Inadequate renal and hepatic function:
In patients with impaired renal function, if liver function is normal, the dose of ceftriaxone does not need to be reduced. Only in preterminal renal insufficiency (creatinine clearance below 10 ml/min) it is necessary that the daily dose of ceftriaxone should not exceed 2 g.

In patients with impaired liver function, provided that renal function is maintained, the dose of ceftriaxone also does not need to be reduced.

In cases of concomitant severe hepatic and renal impairment the serum ceftriaxone concentration should be monitored regularly. In patients undergoing hemodialysis it is not necessary to change the drug dose after this procedure.

Intramuscular administration:
For intramuscular administration 1 g of the preparation should be diluted in 3.5 ml of 1% Lidocaine solution and injected deeply into the gluteal muscle; it is recommended to inject not more than 1 g of the preparation into one gluteus. Lidocaine solution should never be injected intravenously!

Intravenous injection:
For intravenous injection, 1g of the drug must be diluted in 10 ml of sterile distilled water and injected intravenously slowly over 2-4 minutes.

The duration of the intravenous infusion is at least 30 minutes. For intravenous infusion, 2 g of powder should be diluted in approximately 40 ml of calcium free solution, for example: in 0.9% sodium chloride solution, in 5% glucose solution, in 10% glucose solution, 5% levulose solution.

Special Instructions

Despite a detailed history, which is the rule for other cephalosporin antibiotics, we cannot rule out the possibility of anaphylactic shock, which requires immediate therapy – first intravenous adrenaline is given and then glucocorticoids.

Sometimes an ultrasound examination of the gallbladder shows a shadow indicating sedimentation. This symptom disappears after termination or temporary cessation of ceftriaxone therapy. Even in the presence of pain syndrome such cases do not require surgical intervention, conservative treatment is sufficient.

In vitro studies have shown that, like other cephalosporin antibiotics, ceftriaxone is able to displace bilirubin bound to serum albumin. Therefore, in newborns with hyperbilirubinemia and especially in premature infants the use of ceftriaxone requires even greater caution. Since the drug penetrates into breast milk, you should not continue breastfeeding during treatment with ceftriaxone.

In long-term use, periodic monitoring of blood counts is necessary. Ceftriaxone is used only under hospital conditions.

Contraindications

Hypersensitivity to cephalosporins and penicillins. First trimester of pregnancy.

Side effects

Systemic side effects:

gastrointestinal tract (about 2% of patients): diarrhea, nausea, vomiting, stomatitis and glossitis.

Changes in blood pattern (about 2% of patients) in the form of eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia.

Skin reactions (about 1% of patients) in the form of exanthema, allergic dermatitis, urticaria, edema, erythema multiforme.

Other rare side effects: headaches, dizziness, increased liver enzyme activity, gallbladder congestion, oliguria, increased serum creatinine, genital mycosis, chills, anaphylaxis or anaphylactic reactions. Pseudomembranous enterocolitis and clotting disorders are exceptionally rare.

Local side effects:

Phlebitis has been noted in some cases after intravenous administration.

This phenomenon can be prevented by slow (within 2-4 minutes) administration of the drug. The side effects described usually disappear after discontinuation of therapy.

Overdose

Excessively high plasma concentrations of ceftriaxone cannot be reduced by hemodialysis or peritoneal dialysis.

Symptomatic measures are recommended to treat cases of overdose.