Zeftera

Zeftera is a systemic drug with antimicrobial properties.

Indications Zeftera

It is indicated in the following cases: elimination of complicated skin infections (including diabetic foot syndrome (infected), against which osteomyelitis is not observed), which were provoked by gram-positive or gram-negative microbes.

Release form

It is produced in the form of a lyophilisate of infusion solutions. The volume of one glass bottle with the medicine is 20 ml. One package may contain 1 or 10 such bottles.

Pharmacodynamics

Medocaril ceftobiprole is a water-soluble prodrug that has bactericidal activity against a large number of gram-positive microbes, including methicillin-resistant staphylococci, penicillin-resistant pneumococci, and ampicillin-sensitive enterococci faecal. In addition, it has activity against many gram-negative microorganisms, including strains of enterobacteria and pseudomonas aeruginosa.

The active ingredient is tightly synthesized with many important gram-negative and gram-positive microbes, as well as PBP. Ceftobiprole is synthesized with PBP2a by staphylococci (among them methicillin-resistant Staphylococcus aureus), which is why it is active against methicillin-resistant Staphylococci.

There is evidence that ceftobiprole has activity against many isolates of the microbes listed below, both in hospital infections and in vitro.

Aerobic bacteria (gram-positive): Enterococcus faecalis (only isolates susceptible/resistant to vancomycin), Staphylococcus aureus (only isolates resistant/sensitive to methicillin), Staphylococcus epidermidis, Streptococcus agalactiae, and Streptococcus pyogenes. Also coagulase-negative staphylococci (isolates that are resistant/sensitive to methicillin; among these are Staphylococcus hemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, and Staphylococcus lugdunensis), pneumococci (isolates that are resistant/moderately resistant/sensitive to penicillin), and viridans streptococci.

Aerobic microorganisms (gram-negative): Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa. In addition, bacteria of the genus Citrobacter (including Citrobacter freundii and Citrobacter koseri), as well as Enterobacter aerogenes, Klebsiella oxytoca, Moraxella catarrhalis and Morgana bacteria. Along with these, microbes of the genus Neisseria, Providencia and Serratia marcescens.

Pharmacokinetics

Pharmacokinetic parameters in adults after administration of a single 1-hour infusion (500 mg) or multiple doses (the same 500 mg) administered by 2-hour infusions every 8 hours are similar in both cases. On average, they are: plasma values - 34.2 mcg/ml (single) and 33.0 mcg/ml (multiple); AUC - 116 mcg.h/ml and 102 mcg.h/ml; half-life - 2.85 hours and 3.3 hours; clearance rate - 4.46 and 4.98 l/hour.

The AUC and peak concentration of ceftobiprole increase in accordance with the increase in dosage (range 125 mg/1 g). The drug reaches a steady state already on the first day of the course. In patients with healthy renal function, administration of the drug every 8 or 12 hours does not cause accumulation of the active component in the body.

Synthesis with plasma protein is 16%, and the degree of this indicator is independent of the concentration level of the substance. The steady-state distribution volume is 18 liters and is approximately equal to the volume of human extracellular fluid.

Biotransformation from ceftobiprole medocaril to the active element ceftobiprole occurs rapidly, after which it is catalyzed by plasma esterases. The prodrug levels are very low, it is detected in urine and plasma only during infusion. The active component is poorly metabolized, turning into a non-cyclic decay product that is microbiologically inactive. Its level is very low - approximately 4% of the ceftobiprole concentration.

Ceftobiprole is excreted mainly unchanged via the kidneys, and the half-life of the drug is approximately 3 hours. The main mechanism of elimination is glomerular filtration, and a small portion of the dose undergoes tubular reabsorption.

Preclinical testing of probenecid has shown that it does not affect the pharmacokinetic properties of ceftobiprole, suggesting that the latter lacks active tubular secretion. Following a single administration of the drug, approximately 89% of the substance is observed in the urine as ceftobiprole in its active form (83%), as well as as an open-ring degradation product (approximately 5%) and the element ceftobiprole medocaril (less than 1%).

Dosing and administration

The sublimated injection powder is dissolved in 10 ml of water, and then in a 5% glucose solution. After diluting the powder, shake the bottle. Wait about 10 minutes for complete dissolution. Before starting dilution in the infusion solution, wait until the foam formed in the container settles.

To eliminate infectious processes caused by gram-positive microbes, it is necessary to administer 500 mg of the drug every 12 hours (in the form of infusions lasting 1 hour). In people with diabetic foot syndrome (infected type), the regimen of administration every 12 hours has not been studied.

As a rule, the treatment course lasts approximately 1-2 weeks, depending on the location of the infectious process, the course of the pathology and the clinical response of the patient.

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Use Zeftera during pregnancy

Preclinical testing has shown that ceftobiprole has no teratogenic activity and does not affect fetal weight, ossification, or intrauterine development. However, no testing has been performed on the use of the drug by pregnant women.

The results of tests that tested the drug's effect on the reproductive system of animals cannot be extrapolated to the human system. Therefore, Zeftera is only allowed to be prescribed to pregnant women in situations where the potential benefit to the mother's health outweighs the risk of adverse effects to the fetus.

Contraindications

Among the contraindications of the drug:

• intolerance to the active substance or any of the auxiliary elements included in the drug, as well as other cephalosporins;
• the patient has a history of allergy to β-lactams;
• children under 18 years of age.

Use with caution in cases of:

• renal failure (creatinine clearance rate below 50 ml/min);
• epileptic seizures;
• seizures (history);
• pseudomembranous form of colitis (present in the anamnesis).

Side effects Zeftera

Clinical trials have shown that the most common side effects associated with the use of the drug are:

The sublimated injection powder is dissolved in 10 ml of water, and then in a 5% glucose solution. After diluting the powder, shake the bottle. Wait about 10 minutes for complete dissolution. Before starting dilution in the infusion solution, wait until the foam formed in the container settles.

To eliminate infectious processes caused by gram-positive microbes, it is necessary to administer 500 mg of the drug every 12 hours (in the form of infusions lasting 1 hour). In people with diabetic foot syndrome (infected type), the regimen of administration every 12 hours has not been studied.

As a rule, the treatment course lasts approximately 1-2 weeks, depending on the location of the infectious process, the course of the pathology and the clinical response of the patient.

Common reactions include nausea (approximately 12%), manifestations at the injection site (8%), and also vomiting, headaches, and diarrhea (approximately 7%), as well as dysgeusia (approximately 6%). Nausea is usually quite mild and quickly disappears without the need to discontinue the drug. This side effect was observed less frequently in people who received 2-hour infusions (approximately 10%). In people who received 1-hour procedures, this figure was higher – 14%. Other adverse reactions:

• nervous system organs: dizziness often develops;
• subcutaneous tissue and skin: mainly rashes (papular, macular, as well as maculopapular and generalized forms) occur, and in addition, itching;
• Gastrointestinal tract: dyspeptic symptoms often occur, colitis caused by Clostridium difficile occurs occasionally;
• metabolic phenomena: hyponatremia often occurs;
• invasions and infectious processes: fungi usually develop (in the vaginal and vulvar area, as well as on the skin and in the mouth);
• immune system: usually hypersensitivity reactions (including urticaria and drug intolerance); rarely, anaphylaxis may develop;
• hepatobiliary system: increased liver enzyme levels (including increased AST and ALT levels).

Storage conditions

The medicine must be stored at a temperature of 2-8°C, in a place protected from sunlight. The packaging must be original. The storage place must also be inaccessible to small children.

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Shelf life

Zeftera is suitable for use for 2 years from the date of manufacture of the medicinal product. The prepared solution can be stored for 1 hour at a temperature of 25°C, and for 24 hours at a temperature of 2-8°C.