Ceftriaxone

Ceftriaxone is a 3rd generation cephalosporin antibiotic. It has bactericidal properties that develop when the binding of bacterial cell membranes is slowed down.

The drug acetylates wall-bound transpeptidases, thereby destroying the cross-linking of peptide glycans, which helps strengthen the strength of cell walls. The drug demonstrates a wide range of antimicrobial activity, which includes a variety of anaerobes with aerobes, as well as gram-positive and -negative bacteria.

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Indications Ceftriaxone

It is used for the following disorders:

• respiratory tract infections (for example, the development of pneumonia );
• lesions of ENT organs;
• diseases associated with the urethra, kidneys and genitals (including gonorrhea );
• meningitis;
• infection of the subcutaneous layer and epidermis;
• disorders in the area of the peritoneal organs (for example, peritonitis);
• infections in people with reduced immunity;
• lesions of the gallbladder;
• infections affecting bones and joints;
• wound lesions;
• sepsis (general infection);
• disseminated tick-borne borreliosis (early or late stages of the pathology).

In addition, it is prescribed to prevent the occurrence of infections after operations in the area of the biliary tract, urinary tract, digestive or gynecological organs (exclusively in case of possible or diagnosed contamination).

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Release form

The therapeutic substance is released in the form of an injection lyophilisate – 500 or 1000 mg.

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Pharmacodynamics

Ceftriaxone has activity against the following microbes:

• methicillin-sensitive Staphylococcus aureus, Streptococcus agalactiae (subcategory B and β-hemolytic), Streptococcus pyogenes (β-hemolytic, as well as subgroup A), and β-hemolytic streptococci not belonging to subcategories A or B;
• pneumococcus, viridans streptococcus, coagulase-resistant staphylococci, Alcaligenes faecalis, alkagen-like microorganisms, Acinetobacter anitratus with Borrelia burgdorferi, as well as Acinetobacter lwoffi, Enterobacter cloacae and Aeromonas hydrophila;
• Escherichia coli, Citrobacter freundii, Enterobacter, with Haemophilus influenzae, Alcaligenes odorans, Ducrey's bacillus and Capnocytophaga spp., and in addition Citrobacter diversus, Klebsiella oxytoca, Moraxella with Moraxella catarrhalis and Enterobacter aerogenes;
• Haemophilus parainfluenzae, Klebsiella pneumoniae, Pasteurella multocida, Meningococcus with Neisseria gonorrhoeae, Hafnia alvei, Morgan's bacillus with Proteus mirabilis and Proteus vulgaris, and Moraxella osloensis with Proteus penneri;
• plesiomonas shigelloides, salmonella, serratia with serratia marcescens, providencia with pseudomonas, fluorescent pseudomonas, providencia roettgerii, shigella with bacteroides and Salmonella typhi;
• Plaut's bacillus, fusobacteria, peptostreptococci, yersinia with yersinia enterocolitica, vibrios, clostridia (excluding clostridium difficile) and Gaffkia anaerobica.

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Pharmacokinetics

The pharmacokinetic characteristics of ceftriaxone are not linear. The main properties associated with the general drug parameters (protein-synthesized and free ceftriaxone), except for the half-life term, are determined by the dosage size. [ 27 ]

• Absorption

Intraplasmic Cmax values after administration of 1000 mg of the drug are equal to 81 mg/l and are observed after 2-3 hours from the moment of administration. With 1-fold intravenous infusions of 1 and 2 g of the drug, after half an hour, the values of 168.1±28.2 and 256.9±16.8 mg/l are observed, respectively.

The intraplasmic AUC level is the same in the case of intravenous and intramuscular injections. Thus, the bioavailability of the drug when administered intramuscularly is 100%.

• Distribution processes

The distribution volume of the medicine is 7-12 liters. After use, the medicine enters the tissue fluid at high speed, in which the bactericidal indicators for sensitive microbes are preserved for the next 24 hours.

When a medicinal dose of 1000-2000 mg is administered, the component passes well into various fluids along with tissues. Over a period of over 24 hours, the drug level is much higher than the minimum inhibitory values for most infectious agents in over 60 fluids with tissues (including the biliary tract, middle ear, bones, heart with nasal mucosa, liver, pleural fluid, lungs, prostate secretions and synovium with cerebrospinal fluid).

Ceftriaxone undergoes reverse synthesis with albumin (it should be noted that the synthesis rate decreases with increasing concentration - for example, it decreases from 95% in the case of a plasma level of less than 0.1 g / l to 85% in the case of a mark of 0.3 g / l). Low albumin values in the tissue fluid lead to the fact that the part of free ceftriaxone inside it has a higher value than the intraplasmic concentrations.

The drug has the ability to pass through the membranes of the brain affected by inflammation in a child (also in a newborn baby). The Cmax values in the cerebrospinal fluid are observed after 4 hours after the injection and on average equal 18 mg / l with portions of 0.05-0.1 g / kg.

The drug crosses the placenta and is excreted in low concentrations in breast milk (3-4% of the mother's plasma levels after 4-6 hours).

• Exchange processes

The drug does not participate in general metabolism – ceftriaxone is transformed into inactive metabolites under the influence of intestinal microflora.

• Excretion

The values of systemic clearance of drugs are within 10-22 ml per minute. The level of intrarenal clearance is 5-12 ml per minute.

50-60% is excreted unchanged through the kidneys, and another 40-50% (also unchanged) is excreted in the bile. The half-life is approximately 8 hours.

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Dosing and administration

The medication should be administered intravenously or intramuscularly. Before starting the treatment course, the possibility of an allergic reaction should be excluded by performing an epidermal test.

For adolescents over 12 years of age or with a weight of >50 kg and adults, use 1000-2000 mg once a day (24-hour intervals). In case of weak effect of the drug or severe infection, it is allowed to increase the daily dose to 4000 mg.

For newborns under 14 days old (born on time or prematurely) use 20-50 mg/kg once a day. For children over 15 days old and up to 12 years old, 20-80 mg/kg once a day is required.

A dose of 50 mg/kg or higher is administered intravenously via infusion (it lasts at least half an hour).

It is necessary to continue antibiotic therapy for another 48-72 hours from the moment the test results and temperature return to normal.

• Application for children

It is prohibited to prescribe to premature infants (age less than 41 weeks taking into account the terms of gestational age, as well as age after birth), as well as in case of hyperbilirubinemia in a newborn (especially premature). This is due to the fact that the drug can displace bilirubin from synthesis with albumin, resulting in bilirubin-induced encephalopathy.

It is not prescribed to newborns under 28 days of age in case of using intravenous fluids containing Ca (including parenteral nutrition), because this may provoke the formation of a sediment of Ca salts of the drug.

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Use Ceftriaxone during pregnancy

Ceftriaxone can cross the placenta, but its safety in pregnancy has not been studied extensively.

The active ingredient of the drug is excreted in small quantities in breast milk, which is why breastfeeding is discontinued during therapy.

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Contraindications

Contraindicated in case of intolerance to cephalosporins (if the patient has an allergy to penicillins, the risk of cross-effect must be taken into account).

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Side effects Ceftriaxone

Main side effects:

• infectious lesions: mycosis affecting the genitals, secondary fungal infections and infections caused by the activity of resistant microbes;
• disorders of lymph and blood function: leukopenia, thrombocytopenia or granulocytopenia, eosinophilia, increased PT values, hemolytic anemia, agranulocytosis, coagulation disorders and increased creatinine levels;
• problems with digestive activity: glossitis, blockage of the bile duct, diarrhea, pancreatitis, stomatitis and nausea. Occasionally, pseudomembranous enterocolitis develops (caused by the activity of Clostridium difficile);
• hepatobiliary dysfunction: cholelithiasis, calcium salt deposits inside the gallbladder and increased blood levels of liver enzymes (ALT, ALP and AST);
• lesions of the subcutaneous layers and epidermis: swelling, erythema multiforme, rash, exanthema, TEN, urticaria, allergic dermatitis and itching;
• problems with urination: hematuria, oliguria, renal failure, glucosuria and the formation of stones inside the kidneys;
• systemic disorders: headache, fever, chills, anaphylactoid or anaphylactic symptoms and dizziness;
• local manifestations: sometimes inflammation of the venous wall occurs. Such a disorder can be avoided by administering the drug intramuscularly, at a low speed (over 2-4 minutes). It should be taken into account that intramuscular administration without the use of lidocaine will be extremely painful;
• Changes in laboratory test data: false-positive Coombs test result. Like other antibiotics, Ceftriaxone can cause a false-positive result in the test for galactosemia and for the detection of sugar in the urine. Because of this, during therapy, glucosuria must be determined using an alternative enzymatic method.

Overdose

In case of intoxication with Ceftriaxone, hemodialysis or peritoneal dialysis does not give results. The drug has no antidote. In case of poisoning, symptomatic treatment measures are performed.

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Interactions with other drugs

Solvents containing Ca (including Hartmann's or Ringer's solutions) cannot be used for the procedure of reconstitution of the drug in vials or subsequent dissolution of the reconstituted liquid for intravenous injections, because a precipitate may form. In addition, precipitates of the Ca salt of ceftriaxone can form during mixing of the substance with liquids containing Ca within one infusion.

Ceftriaxone should not be used in combination with IV fluids containing Ca for continuous infusion (e.g., fluids for parenteral nutrition) through a Y-type system. However, in all patients, except neonates, the drug and Ca-containing fluids can be used sequentially, one after the other (provided that the system is thoroughly flushed with a suitable fluid between procedures).

In vitro testing using adult umbilical cord blood plasma with neonates has shown that neonates have an increased likelihood of forming calcium salt precipitates of the drug.

The administration of the drug together with anticoagulants for oral administration may potentiate the effect against K-vitamin, as well as the likelihood of bleeding. During the period of therapy with the drug and after its completion, it is necessary to regularly monitor the INR indicators and adjust the dose of K-antivitamins accordingly.

There is conflicting information regarding the potential for potentiation of renal toxicity by aminoglycosides when administered with cephalosporins. Careful monitoring of aminoglycoside levels (and renal function) is advised with such combinations.

In vitro drug testing using chloramphenicol resulted in the development of antagonistic effects. The clinical significance of these findings has not been established.

Use in combination with probenecid does not result in decreased excretion of ceftriaxone.

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Storage conditions

Ceftriaxone should be stored in a dry place, out of the reach of small children. Temperature indicators - no more than 25 ° C.

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Shelf life

Ceftriaxone is approved for use for a period of 2 years from the date of release of the therapeutic substance.

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Analogues

The analogs of the drug are Loraxon, Avexon, Diacef, Maxon with Alvobak, Promocef and Alcison with Belcef, and in addition to this Cefotaxime, Spectracef, Cephalexin with Ceftrax and Cefaxone with Cefosin. In addition, the list includes Oframax, Amoxiclav, Cefantral, Blitsef and Noraxone, Ceftazidime with Auroxon, Sorcef and Emsef 1000 with Denicef, as well as Cedoxime, Lendacin, Cefantral and Cedex.

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Reviews

Ceftriaxone is now considered a fairly popular medication. Patients in their reviews mainly note the high-quality effect of the drug, which allows for quick relief of health conditions from the first day of treatment.

Among the disadvantages, most comments mention the very strong pain of the injections performed - both during the procedure itself and for some time after its completion. In the case of intravenous administration, pain is observed along the vein.

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