Cefosulfine

Cefosulbin is a complex antibacterial drug with a large range of therapeutic activity.

Indications Cefosulfamine

It is used for therapy in the case of infections triggered by the action of bacteria that are sensitive to the medication:

• lesions in the respiratory tract (lower and upper part);
• infection of the urethra (lower and upper areas);
• cholecystitis with peritonitis, and in addition cholangitis and other infections affecting the peritoneum;
• meningitis or septicemia;
• lesions of the subcutaneous layer and epidermis;
• infection of the joints with bones;
• inflammations affecting the organs in the pelvic area, as well as endometritis and gonorrhea with other genital infections.

Release form

The release of the medication is realized in the form of a combined lyophilisate for the manufacture of injection fluid in portions of 1 g (0.5 g of cefoperazone and 0.5 g of sulbactam) or 2 g (1 g of cefoperazone and 1 g of sulbactam) inside the 1st bottle.

Pharmacodynamics

The drug contains components of cefoperazone (cephalosporin of the 3rd generation), as well as sulbactam (a substance that irreversibly slows down the activity of most of the major β-lactamases produced by microbes resistant to penicillin).

The antibacterial element of drugs is cefoperazone, which affects sensitive microbes at the stage of their active reproduction - inhibiting the biopsynthesis of mucopeptide in the region of the walls of bacterial cells.

Sulbactam has no real antibacterial effect, excluding the effect on acinetobacters and Neisseriaceae. But biochemical tests involving cell-free microbial systems determined the ability of sulbactam to irreversibly inhibit the activity of the most important β-lactamases produced by penicillin-resistant bacteria. The potential of the substance to prevent the destruction of cephalosporins with penicillins under the influence of resistant bacteria was confirmed by tests on strains of resistant microbes, within which sulbactam showed significant synergism with cephalosporins, as well as penicillins. Due to the fact that sulbactam is also synthesized with individual proteins that bind penicillin, bacteria that have a sensitivity are even more strongly affected by cefoperazone and sulbactam (compared to the effect of cefoperazone only).

The combination of sulbactam with cefoperazone actively affects all bacteria that are susceptible to cefoperazone. Along with this, the use of this combination is observed synergistic effect of its elements with respect to the following microbes: Bacteroides, E. Coli, bacillus influenzae, Acinetobacter calcoaceticus, Klebsiella pneumonia, and in addition, Enterobacter cloacal, Enterobacter aerogenes, tsitrobakter Freund, Morgan bacteria Proteus mirabilis and Citrobacter diversus

In vitro cefoperazone with sulbactam exhibits activity against a relatively large range of clinically important bacteria.

Gram-positive bacteria: Staphylococcus aureus (strains that produce or do not produce penicillinase), epidermal staphylococci, pneumococci (mainly Diplococcus pneumoniae), pyogenic streptococci (β-hemolytic form of Streptococcus from subtype A). In addition, the list of streptococcus agalactia (β-hemolytic form of streptococcus from subtype B), most of the other types of streptococci are β-hemolytic type, and most strains of fecal streptococcus (enterococci).

Gram-negative microbes: Klebsiella, E. Coli, citrobacter, common proteus, enterobacteria and influenza bacilli. In addition, Proteba Mirabilis, Providences, Morgan's bacteria (mainly Morgan's protea), Rettger's Providence (often Rettger's Protea), Salmonella along with serrations (among them Marrazenese serration), and Shigella are on the list. Also included are pseudomonas of the pseudomonas and certain types of pseudomonads, meningococci, Yersinia enterocolitis, gonococci, and Acinetobacter calcoaceticus with pertussis.

Anaerobes: Gram-negative nature of the microorganisms (here included Bacteroides fragilis Bacteroides and other types, as well as fuzobakterii), and together with this and gram -positive cocci (here includes peptostreptokokki with peptokokki and veylonelly) and gram-positive bacilli character (here included Clostridium, eubacteria and lactobacilli).

The drug has the following effective dosage spectra (IPC, µg / ml size for cefoperazone): the presence of sensitivity is below 16, intermediate values are within 17-36, resistant -> 64.

Pharmacokinetics

Approximately 84% of sulbactam, as well as 25% of cefoperazone, is excreted by the kidneys. The main part of cefoperazone is excreted in the bile. After using the drug, the average half-life of sulbactam is 60 minutes, and that of cefoperazone is approximately 1.7 hours. Plasma drug indicators are proportional to the size of the portion used. This pharmacokinetic information is registered with the separate use of components.

The average level of Сmax of sulbactam, as well as of cefoperazone, with the use of 2000 mg of drugs (1000 mg of both components) intravenously, equals 130.2 and 236.8 µg / ml respectively for 5 minutes. From this we can conclude that sulbactam has a more extensive distribution volume (Vα is within 18.0-27.6 l) in comparison with similar values of cefoperazone (Vα is approximately 10.2-11.3 l). Both elements of Cefosulbina undergo intensive distribution within liquids with tissues, including the gallbladder with bile, the appendix, the uterus with the ovaries and fallopian tubes, the epidermis, and so on.

In children, the half-life of sulbactam is equal within 0.91-1.42 hours, and that of cefoperazone is within 1.44-1.88 hours. Information regarding the pharmacokinetic interaction of cefoperazone with sulbactam in the case of their combined use is not registered.

With repeated use, no noticeable changes in the pharmacokinetic parameters of the elements of drugs, as well as any accumulation of them when used at 8-12 hour intervals, were found.

A substantial part of cefoperazone is excreted in the bile. The half-life of a substance inside the blood plasma and the degree of excretion in the urine often increases in people with obstruction of the grave and liver diseases. Even with severe forms of liver disorders, the level of drug inside the bile reaches a drug concentration, despite the fact that the half-life of drugs from the blood plasma increases only twice / fourfold.

Dosing and administration

The drug can be administered in / m or in / in the way.

For adults per day on average requires the introduction of 2-4 g of drugs (with 12-hour intervals). If infections have severe severity, the daily portion can be increased to 8 g with a proportion of active elements 1k1 (the level of cefoperazone is 4 g). People who use both components of a drug in the 1k1 proportion may need to have a separate supplemental use of cefoperazone. At the same time, it should be administered in equal dosages with 12-hour intervals. It is recommended to use no more than 4 g of sulbactam per day.

Use in patients with disorders in the work of the kidneys.

The dosage regimen in the case of treatment of people with a significant weakening of the renal activity (the level of QC below 30 ml / minute) must be adjusted to compensate for the reduced clearance of sulbactam.

Persons with CK in the range of 15-30 ml / minute require a maximum portion of sulbactam (1000 mg), which is administered at 12-hour intervals (no more than 2000 mg of sulbactam can be used per day).

For people with a QA level below 15 ml / minute, sulbactam is prescribed in a maximum portion of 0.5 g, administered at 12-hour intervals (a maximum of 1000 mg of substance is used per day).

With the development of severe forms of the disease, there may be a need for additional use of cefoperazone.

The pharmacokinetics of sulbactam is noticeably disturbed during hemodialysis sessions. The plasma half-life of cefoperazone from hemodialysis is slightly reduced. Therefore, when performing dialysis, the dosage regimen needs to be adjusted.

Comprehensive treatment.

Due to the fact that cefosulbine has a wide range of antibacterial activity, many infections can be cured by monotherapy. But sometimes the medicine is allowed to combine with other antibiotics. When drugs are combined with aminoglycosides, renal and hepatic activity is monitored throughout the entire treatment cycle.

Use in People with Hepatic Disorders.

Changing the dosage may be necessary in obstructive obstructive nature in severe form, and also in severe hepatic pathologies or if a disorder of renal activity is noted in the background of this disease.

In people with liver problems and concomitant disorders of the kidney activity, the plasma values of cefoperazone should be monitored and portions adjusted accordingly, if necessary. In the absence of careful observation of the plasma level of the drug, the portion of cefoperazone should be a maximum of 2000 mg per day.

Use in children.

Children need to enter 40-80 mg / kg per day. The drug is applied at 6-12 hour intervals in evenly divided portions.

In severe stages of the disease, it is allowed to increase the portion to 160 mg / kg per day with the proportions of the active components 1k1. The dosage should be applied, divided into 2-4 uniform portions.

For infants up to 7 days of age, the drug is used at 12-hour intervals. During the day, a maximum of 80 mg / kg of substance can be administered.

Intravenous method of administration.

When infusing through a dropper, the lyophilisate from the vials is diluted in the required amount of a 5% glucose solution, 0.9% NaCl solution, or sterile injectable water. Next, using a similar solvent, the substance is diluted to 20 ml, and then injected through an IV for 15-60 minutes.

Diagram of the selection of the dosing regime:

• the total dose of the drug is 1 g (dosage of 2 active elements is 500 + 500 mg) - the volume of solvent used is 3.4 ml, and the maximum permissible final concentration is 125 + 125 mg / ml;
• The total dosage of the drug is 2 g (2 active ingredients 1000 + 1000 mg) - the volume of the solvent used is 6.7 ml, and the maximum concentration level is 125 + 125 mg / ml.

The drug can be combined with injectable water, 5% glucose liquid in a 0.225% NaCl solution, as well as a 5% glucose solution in an isotonic NaCl liquid (drug concentrations range from 10-125 mg / ml drug) .

Lactate form of Ringer's solution can be used for the manufacture of infusion, but is prohibited for primary dissolution. For the injection portion, the lyophilisate is dissolved according to the above scheme, and then injected for at least 3 minutes. With direct injections, the maximum allowable adult single dose is 2000 mg, and children - 50 mg / kg.

Intramuscular method of administration.

Lidocaine hydrochloride can be used to dissolve during use, but not during initial dissolution.

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Use Cefosulfamine during pregnancy

The drug passes through the placenta. Prescribing it to pregnant women is allowed only in situations where the likely benefit to the woman is more expected than the risk of complications in the fetus.

Contraindications

A contraindication is the use of allergy to penicillins, sulbactam or cephalosporins in people with a history of allergies.

Side effects Cefosulfamine

Often, Cefosulbin is tolerated without complications. Most of the negative symptoms have mild or moderate severity, so there is no need to cancel the use of drugs. Among the side effects are:

Disorders of the digestive activity: vomiting, superinfection or hyperesthesia of the oral mucosa, and in addition the pseudomembranous form of colitis, diarrhea and nausea;

Lesions of the subcutaneous layer and epidermis: erythema, maculopapular rash, TEN, urticaria, and besides this exfoliative form of dermatitis, Stevens-Johnson syndrome and itching. The described manifestations most often occur in people with a history of allergies (often in relation to penicillins);

Dysfunction of the lymph and blood system: there is information about a small decrease in the level of neutrophils. Curable neutropenia may also develop. Individual patients may experience a positive response from a direct Coombs test. In addition, a decrease in hematocrit or hemoglobin or the occurrence of leuko- and thrombocytopenia, as well as anemia and hypoprothrombinemia can be expected;

Problems associated with the work of the central nervous system: cefoperazone can significantly reduce the reserves of albumin, and during the treatment of newborns with jaundice, increases the likelihood of bilirubin-type encephalopathy;

Disorders in the work of the cardiovascular system: vasculitis, a decrease in the level of blood pressure, tachycardia or bradycardia, and in addition cardiac arrest and cardiogenic shock;

Immune lesions: signs of intolerance and anaphylactoid symptoms (among them shock);

Other manifestations: drug fever, chills, headaches, anxiety, changes and pain in the injection area, as well as muscle twitching;

Disorders of the urinary system and kidneys: hematuria;

Digestive problems: jaundice;

Signs of the respiratory system: sometimes bronchial spasms appear in people with asthma in history and obstruction of the respiratory ducts in the chronic stage, and besides that there is laryngospasm. Occasionally marked dyspnea and runny nose allergic nature;

Changes in laboratory test data: a transient increase in liver function values (ALT or AST), bilirubin or alkaline phosphatase parameters, increased PTV levels and a false positive response during the determination of indicators of sugar inside urine (using non-enzymatic methods);

Local signs: with injections, the drug is usually tolerated without complications; only occasionally there is pain in the injection area. As with the use of other penicillins with cephalosporins, after the use of drugs through a catheter for intravenous injection, individual patients may appear phlebitis in the area of infusion.

Overdose

In case of overdose with medication, potentiation of negative symptoms may occur. It is necessary to take into account that large portions of β-lactam antibiotics inside the cerebrospinal fluid can lead to the appearance of neurological signs (for example, seizures).

Due to the fact that sulbactam with cefoperazone is excreted from the body through hemodialysis, this procedure can increase the elimination of drugs in case of poisoning in people with kidney disorders.

Interactions with other drugs

The use of drugs inside one syringe together with aminoglycosides causes their mutual inactivation. If there is a need for the simultaneous use of these categories of antibacterial agents, it is required to enter them in different areas with a 1-hour interval. Cefosulbin increases the likelihood of neurotic toxicity of furosemide and aminoglycosides.

Bacteriostatic substances (among them sulfanidamide and chloramphenicol with tetracyclines and erythromycin) weaken the therapeutic properties of the drug.

Probenecid weakens the secretion of sulbactam through the tubules. The result is an increase in plasma values and half-life of drugs, which increases the likelihood of poisoning.

When used together with NSAIDs, the risk of bleeding increases.

In the case of drinking alcohol during the treatment cycle, as well as for 5 days after the end of the use of cefoperazone, the following symptoms were recorded: hyperhidrosis, facial hyperemia, tachycardia and headaches. Similar manifestations were observed when using other cephalosporins. Patients should be extremely careful to combine alcohol and drug administration.

If the patient is on an artificial diet (parenteral or oral method), do not use ethanol-containing solutions.

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Storage conditions

Cefosulbin must be kept in a place that is closed to small children. Temperature indicators - a maximum of 25 ° C.

Shelf life

Cefosulbin can be used within 24 months of the manufacture of the therapeutic agent.

Analogs

Analogues of the medication are drugs Gepatsef Kombi, Tsebaneks with Cefopektam, as well as Sultsef and Cefoperazone + Sulbactam.