Ceftriaxone + water for injection
Pharmacodynamics Ceftriaxone is a third-generation cephalosporin antibiotic for parenteral use, has a bactericidal effect, inhibits cell membrane synthesis, and in vitro inhibits 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). Effective against the following microorganisms
Gram-positive
Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus viridans, Streptococcus pyogenes.
Note: Staphylococcus spp., resistant to methicillin, is also resistant to ceftriaxone. Most strains of enterococci (eg Streptococcus faecalis) are also resistant to ceftriaxone
Gram-negative
Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp. (some strains are resistant), Eschenchia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella 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 Salmonella typhi), Serratia spp. (including Serratia marcescens), Shigella spp., Vibrio spp. (including Vibrio cholerae), Yersinia spp. (including Yersinia enterocolitica)
Note: many strains of the listed microorganisms that multiply steadily in the presence of other antibiotics, for example, penicillins, first-generation cephalosporins and aminoglycosides, are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone both in vitro and in animal experiments. According to clinical data, ceftriaxone has good efficacy in primary and secondary syphilis.
Anaerobic pathogens
Bacteroides spp. (including some strains of Bacteroides fragilis), Clostridium spp. (including Clostridium difficile), Fusobacterium spp. (except Fusobacterium mostiferum. Fusobacterium varium), Peptococcus spp., Peptostreptococcus spp.
Note: Some strains of many Bacteroides spp. (eg, Bacteroides fragilis) that produce beta-lactamase are resistant to ceftriaxone. To determine the sensitivity of microorganisms, it is necessary to use disks containing ceftriaxone, since it has been shown that in vitro certain strains of pathogens can be resistant to classical cephalosporins.
Pharmacokinetics
When administered parenterally, ceftriaxone penetrates well into body tissues and fluids.
Bioavailability - 100%, time to reach maximum concentration in blood serum (Tcmax) after IM administration is 2-3 hours, after IV administration - at the end of the infusion.
The maximum concentration (Cmax) after intramuscular administration in doses of 0.5 and 1 g is 38 and 76 mcg/ml, respectively. Cmax at IV doses of 0.5, 1 and 2 g – 82, 151, 257 mcg/ml, respectively.
Penetrates well into the cerebrospinal fluid during inflammation of the meninges. Communication with plasma proteins – 83-96%. Volume of distribution – 0.12-0.14 l/kg (5.78-13.5 l), in children – 0.3 l/kg, plasma clearance – 0.58-1.45 l/h, renal clearance – 0.32-0.73 l/h.
The half-life (T½) after intramuscular administration is 5.8-8.7 hours, after intravenous administration at a dose of 50-75 mg/kg in children with meningitis - 4.3-4.6 hours, in patients undergoing on hemodialysis (CC 0-5 ml/min-14.7 hours, CC 5-15 ml/min-15.7 hours), 16-30 ml/min-11.4 hours, CC 31-60 ml/min-12.4 hours .
It is excreted unchanged - 33-67% by the kidneys, 40-50% - with bile into the intestines, where inactivation occurs. In newborns, about 70% of the drug is excreted through the kidneys. Hemodialysis is ineffective.
Penetration into the cerebrospinal fluid: in newborns and children with inflammation of the meninges, ceftriaxone penetrates into the cerebrospinal fluid, while in the case of bacterial meningitis, an average of 17% of the drug concentration in the blood serum diffuses into the cerebrospinal fluid, which is approximately 4 times more than in aseptic meningitis 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 patients with meningitis, 2-25 hours after administration of ceftriaxone at a dose of 50 mg/kg body weight, the concentration of ceftriaxone many times exceeded the minimum inhibitory dose that is necessary to suppress the pathogens that most often cause meningitis
Ceftriaxone
Hypersensitivity reactions
As with other β-lactam antibiotics, severe hypersensitivity reactions, some fatal, have been reported. If a severe hypersensitivity reaction develops, therapy with Ceftriaxone should be immediately discontinued and appropriate emergency treatment measures taken. Before starting therapy with Ceftriaxone, it is necessary to determine whether the patient has had hypersensitivity reactions to ceftriaxone, cephalosporins or severe hypersensitivity reactions to other β-lactam antibiotics (penicillins, monobactams and carbapenems).
Caution should be exercised when using ceftriaxone in patients with a history of mild hypersensitivity reactions to other β-lactam antibiotics (penicillins, monobactams and carbapenems).
Sodium content
1 g of Ceftriaxone contains 3.6 mmol of sodium. This should be taken into account in patients on a sodium controlled diet.
Hemolytic anemia
As with the use of other cephalosporins, autoimmune hemolytic anemia may develop during treatment with Ceftriaxone. Cases of severe hemolytic anemia have been reported in adults and children, including deaths.
If anemia develops in a patient being treated with ceftriaxone, the diagnosis of cephalosporin-associated anemia cannot be excluded and treatment must be discontinued until the cause is determined.
Diarrhea caused by Clostridium difficile
As with the use of most other antibacterial drugs, cases of diarrhea caused by Clostridium difficile (C. difficile )
, varying in severity: from mild diarrhea to fatal colitis.
Treatment with antibacterial drugs suppresses the normal microflora of the colon and provokes the growth of C. difficile.
In turn,
C. difficile
produces toxins A and B, which are factors in the pathogenesis of diarrhea caused by
C. difficile
.
strains of C. difficile
are infectious agents with a high risk of morbidity and mortality due to possible resistance to antimicrobial therapy, and treatment may require colectomy.
C. difficile
diarrhea in all patients with diarrhea after antibiotic therapy.
A thorough history taking is necessary, because There have been cases of diarrhea caused by C. difficile
occurring more than 2 months after antibiotic therapy.
C. difficile
diarrhea is suspected or confirmed
-C. difficile
may need to be discontinued .
In accordance with clinical indications, appropriate treatment should be prescribed with the administration of fluids and electrolytes, proteins, antibiotic therapy for C. difficile, and
surgical treatment. Do not use medications that inhibit intestinal motility.
Superinfections
As with treatment with other antibacterial drugs, superinfections may develop.
Changes in prothrombin time
Rare cases of changes in prothrombin time have been described in patients receiving Ceftriaxone. Patients with vitamin K deficiency (impaired synthesis, malnutrition) may require monitoring of prothrombin time during therapy and administration of vitamin K (10 mg/week) if the prothrombin time increases before or during therapy.
Formation of precipitates of ceftriaxone calcium salt
Cases of fatal reactions resulting from the deposition of ceftriaxone-calcium precipitates in the lungs and kidneys of newborns have been described. Theoretically, there is a possibility of interaction of ceftriaxone with calcium-containing solutions for intravenous administration in other age groups of patients, therefore ceftriaxone should not be mixed with calcium-containing solutions (including for parenteral nutrition), and also administered simultaneously, including through separate access for infusions at different areas. Theoretically, based on the calculation of the 5 half-lives of ceftriaxone, the interval between the administration of ceftriaxone and calcium-containing solutions should be at least 48 hours. There are no data on the possible interaction of ceftriaxone with calcium-containing drugs for oral administration, as well as ceftriaxone for intramuscular administration with calcium-containing drugs (intravenously or orally).
After using ceftriaxone, usually in doses exceeding the standard recommended (1 g per day or more), ultrasound examination of the gallbladder revealed precipitates of the calcium salt of ceftriaxone, the formation of which is most likely in pediatric patients. Precipitates rarely cause any symptoms and disappear after completion or cessation of therapy with Ceftriaxone. If these phenomena are accompanied by clinical symptoms, conservative non-surgical treatment is recommended, and the decision to discontinue the drug is left to the discretion of the attending physician and should be based on an individual assessment of benefit and risk.
Although there is evidence of the formation of intravascular precipitates only in neonates when using ceftriaxone and calcium-containing infusion solutions or any other calcium-containing drugs, Ceftriaxone should not be mixed or prescribed to children and adult patients simultaneously with calcium-containing infusion solutions, even using different venous approaches (see sections “Contraindications”, “Interaction with other drugs”).
Pancreatitis
In patients receiving Ceftriaxone, rare cases of pancreatitis, which may have developed due to bile duct obstruction, have been described. Most of these patients already had risk factors for biliary congestion, such as previous therapy, severe illness, and total parenteral nutrition. At the same time, it is impossible to exclude the triggering role in the development of pancreatitis of precipitates formed under the influence of the drug Ceftriaxone in the biliary tract.
Use in children
The safety and effectiveness of Ceftriaxone in neonates, infants, and young children have been determined at the dosages described in the Dosage and Administration section. Studies have shown that, like other cephalosporins, ceftriaxone can displace bilirubin from binding to serum albumin. Ceftriaxone should not be used in newborns, especially premature infants, who are at risk of developing bilirubin encephalopathy (see section “Contraindications”).
Long-term treatment
With long-term treatment, it is necessary to regularly monitor the peripheral blood picture, indicators of the functional state of the liver and kidneys.
Blood test monitoring
During long-term treatment, a complete blood count should be performed regularly.
Serological studies
When treated with ceftriaxone, false-positive results of the Coombs test, galactosemia test, and determination of glucose in urine may be observed (it is recommended to determine glucosuria only by the enzyme method).
