Pharmacological properties of the drug Sulcef
Pharmacodynamics. The antibacterial component of the sulbactam/cefoperazone combination is cefoperazone, a third-generation cephalosporin antibiotic that acts on sensitive microorganisms in the active reproduction stage by inhibiting the biosynthesis of cell membrane mucopeptide. Sulbactam does not have antibacterial activity only against Neisseriaceae and Acinetobacter . However, biochemical studies on cell-free bacterial systems have revealed that sulbactam has the ability to irreversibly inhibit the most important β-lactamases produced by microorganisms resistant to β-lactam antibiotics. The potential of sulbactam to prevent the destruction of penicillins and cephalosporins by resistant microorganisms was confirmed in studies on whole strains of resistant microorganisms, in which sulbactam demonstrated pronounced synergism with penicillins and cephalosporins. Because sulbactam also binds to certain penicillin-binding proteins, sensitive microorganisms become more susceptible to the action of sulbactam/cefoperazone than to the action of cefoperazone alone. The combination of sulbactam and cefoperazone is active against all microorganisms sensitive to cefoperazone. In addition, when using this combination, a synergistic effect of its components is observed (a decrease in the MIC by approximately 4 times compared to the MIC for each of its components separately) against the following microorganisms: Haemophilus influenzae, Bacteroides spp., Acinetobacter calcoaceticus, Enterobacter aerogens, Escherichia coli , Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus. Sulbactam/cefoperazone in vitro against a wide range of clinically significant microorganisms. Gram-positive microorganisms: Staphylococcus aureus (strains producing or not producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae (mainly Diplococcus pneumoniae), Streptococcus pyogenes (β-hemolytic streptococcus group A); Streptococcus agalactiae (group B β-hemolytic streptococcus) , most other β-hemolytic streptococcal species; many strains of Streptococcus faecalis (enterococci). Gram-negative microorganisms: Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii (mainly Proteus morganii), Providencia rettgeri (mainly Proteus rettgeri), Providencia spp., Serratia spp. ( including S. marcescens), Salmonella spp. and Shigella spp., Pseudomonas aeruginosa and some species of Pseudomonas, Acinetobacter calcoaceticus, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica. Anaerobic microorganisms:
- gram-negative bacilli (including Bacteroides fragilis, Bacteroides species and Fusobacterium spp.) ;
- gram-positive and gram-negative cocci (including Peptococcus spp., Peptostreptococcus spp. and Veillonella spp.);
- Ram-positive bacilli (including Clostridium spp., Eubacterium spp. and Lactobacillus spp.).
Pharmacokinetics. Approximately 84% of sulbactam and 25% of the drug administered are excreted through the kidneys. Most of cefoperazone is excreted in bile. After administration of sulbactam/cefoperazone, the average half-life of sulbactam is 1 hour, and that of cefoperazone is 1.7 hours. Plasma concentrations are proportional to the administered dose. These data correspond to the pharmacokinetic parameters of the components when used separately. The average values of the maximum concentrations of sulbactam and cefoperazone after administration of 2 g sulbactam/cefoperazone (1 g sulbactam, 1 g cefoperazone) intravenously over 5 minutes were 130.2 and 236.8 μg/ml, respectively. This indicates a larger volume of distribution of sulbactam (Vα=18.0–27.6 L) compared to the distribution of cefoperazone (Vα=10.2–11.3 L). Both sulbactam and cefoperazone are intensively distributed in tissues and body fluids, including bile, gallbladder, skin, appendix, fallopian tubes, ovaries, uterus, etc. There is no evidence of any pharmacokinetic interaction between sulbactam and cefoperazone when used simultaneously in combination There are no sulbactam/cefoperazone. After repeated administration, no significant changes were detected in the pharmacokinetics of the components of sulbactam/cefoperazone and any accumulation when used every 8–12 hours. Cefoperazone is largely excreted in the bile. The half-life of cefoperazone from serum is increased, and the rate of urinary excretion is usually increased in patients with liver disease and/or biliary tract obstruction. Even in cases of severe liver dysfunction, the amount of the drug in the bile reaches a therapeutic concentration, while the half-life of the drug from the blood plasma increases only 2-4 times. The average half-life of cefoperazone is 1.6-2.4 hours, it increases to 4.3-11 hours with biliary obstruction. In premature babies it is 6.9 hours, in children aged 2 months–11 years - 2.2 hours. The average half-life of sulbactam is 0.91-1.42 hours.
Sulcef®
Cefoperazone and sulbactam are well distributed into various tissues and fluids, including bile, gallbladder, skin, appendix, fallopian tubes, ovaries, uterus, etc.
The maximum concentrations of cefoperazone and sulbactam after intravenous administration of 2 g of the drug over 5 minutes average 130.2 and 236.8 mcg/ml, respectively. The volume of distribution of sulbactam is from 18.0 to 27.6 l, cefoperazone - from 10.2 to 11.3 l. About 84% of a dose of sulbactam and 25% of a dose of cefoperazone are excreted by the kidneys. The remaining part of cefoperazone is excreted mainly by bile.
The half-life of cefoperazone averages about 1.7 hours, sulbactam - 1 hour. The serum concentration of cefoperazone and sulbactam is proportional to the administered dose.
With repeated administration, the pharmacokinetic properties of the drug do not change.
When the drug is administered every 8-12 hours, no accumulation is observed.
Pharmacokinetics in liver dysfunction
:
Cefoperazone is actively excreted in bile. The half-life of cefoperazone is usually prolonged and renal excretion of the drug is increased in patients with liver disease and/or biliary tract obstruction. Even with severe liver dysfunction, a therapeutic concentration of cefoperazone is achieved in the bile, and the half-life increases by 2-4 times.
Pharmacokinetics for renal impairment:
In patients with varying degrees of renal impairment receiving the drug, a high correlation was found between the total clearance of sulbactam from the body and the calculated creatinine clearance. In patients with end-stage renal failure, a significant prolongation of the half-life of sulbactam was detected (on average 6.9-9.7 hours in various studies). Hemodialysis causes significant changes in the half-life, total body clearance, and volume of distribution of sulbactam.
Pharmacokinetics in the elderly:
In elderly people with renal failure and impaired liver function, there is an increase in the half-life, decreased clearance and increased volume of distribution of both sulbactam and cefoperazone.
The pharmacokinetics of sulbactam correlates with the degree of renal dysfunction, and the pharmacokinetics of cefoperazone correlates with the degree of liver dysfunction.
Pharmacokinetics in children:
In children there are no significant differences in the pharmacokinetics of the drug components compared to adults. The average half-life of sulbactam in children is from 0.91 to 1.42 hours, cefoperazone - from 1.44 to 1.88 hours.
Use of the drug Sulcef
IM, IV. IM injection. To prepare solutions for intramuscular administration, it is recommended to use lidocaine solution, but not for initial dilution. The solution is prepared using sterile water for injection and 2% lidocaine solution. IV administration. For intravenous injection, the contents of the Sulcef vial are diluted using any compatible solvent. Sulbactam/cefoperazone is compatible with water for injection, 5% glucose solution, 0.9% sodium chloride solution. Inject over at least 3 minutes. For drip infusion, the contents of each bottle of Sulcef must be dissolved in an appropriate amount of 5% dextrose solution in water, 0.9% sodium chloride solution or sterile water for injection, and then before use diluted to 20 ml with a similar solution, after which is administered dropwise over 15–60 minutes. Ringer's solution lactate is acceptable for diluting Sulcef during intravenous infusion, but not for primary dilution. Adults. The recommended dose for adults is 2–4 g 2 times a day with an interval of 12 hours. For severe infections, the daily dose of Sulcef can be increased to 8 g at a ratio of 1:1. In patients receiving a 1:1 ratio, additional separate administration of cefoperazone may be necessary. The course of treatment is 7 days; for severe infections, the course of treatment can last 14 days. Children. For children, the following dosage regimen for Sulcef is recommended: 40–80 mg/kg/day (20–40 mg/kg/day), administered every 6–12 hours in equal parts. For severe infections, the daily dose can be increased to 160 mg/kg/day at a ratio of 1:1. The dose must be administered, distributing it into 2-4 equal doses. Infants. For children aged 1 week, the drug should be administered every 12 hours. The maximum daily dose for infants should not exceed 80 mg/kg. For elderly patients, the dosage regimen should be selected individually. Renal dysfunction. The dosage regimen when using Sulcef in patients with a significant decrease in renal function (creatinine clearance ≤30 ml/min) is subject to adjustment in order to compensate for the reduced clearance of sulbactam. For patients with a creatinine clearance of 15–30 ml/min, sulbactam is prescribed at a maximum dose of 1 g every 12 hours (maximum daily dose is 2 g), and for patients with a creatinine clearance ≤15 ml/min, sulbactam is prescribed at a maximum dose of 500 mg every 12 hours ( the maximum daily dose is 1 g). For severe infections, additional administration of cefoperazone may be necessary. The pharmacokinetic profile of sulbactam changes with the use of hemodialysis. The half-life of cefoperazone from blood plasma during hemodialysis is slightly reduced. Thus, the dosage regimen when using dialysis must be adjusted. Liver dysfunction. In patients with impaired liver function and concomitant impaired renal function, it is necessary to monitor the concentration of cefoperazone in the blood plasma and, if necessary, appropriate dose adjustment. In cases where it is impossible to regularly monitor the concentration of the drug in the blood plasma, the dose of cefoperazone should not exceed 2 g/day. Dose adjustment may be required in cases of severe obstructive jaundice and severe liver disease or when such pathology is accompanied by impaired renal function.
BACTAZONE POWDER 1.5G
Instructions
Trade name of the drug: Baktazone
Active ingredients: Comb.drug (cefoperazone, sulbactam)
Pharmacotherapeutic group: Antibiotics (cephalosporin group), Antibiotics (cephalosporin group).
Release form:
1.5 g in bottles; 1 or 10 bottles in a pack.
Dosage form: Powder for solution for injection (0.5 g + 1.0 g) (bottles)
Composition: 1 bottle contains cefoperazone sodium salt, in terms of cefoperazone - 1.0 g, and sulbactam sodium salt, in terms of sulbactam - 0.5 g.
Pharmacological properties:
The antibacterial component of Baktazone is cefoperazone, a third generation cephalosporin that acts bactericidal by inhibiting the synthesis of the bacterial wall. Sulbactam has no real antibacterial activity other than against Neisseriaceae and Acinetobacter, but it is an inhibitor of beta-lactamases, enzymes that are produced by microorganisms that are resistant to beta-lactam antibiotics. Sulbactam prevents the destruction of penicillins and cephalosporins by resistant microorganisms and demonstrates pronounced synergy with penicillins and cephalosporins. Because sulbactam also binds to certain penicillin-binding proteins, sensitive microorganisms become more susceptible to the action of sulbactam/cefoperazone than to the action of cefoperazone alone. The combination of sulbactam and cefoperazone is active against the following microorganisms: Haemophilus influenzae, Bacteroides species, Acinetabacter calcoaceticus, Enterobacter aerogens, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus. Sulbactam/cefoperazone exhibits in vitro activity against a wide range of clinically significant microorganisms. Gram-positive microorganisms: Staphylococcus aureus (including penicillinase-producing and non-penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae (mainly Diplococcus pneumoniae), Streptococcus pyogenes (group A beta-hemolytic streptococcus), Streptococcus agalactiae (group B beta-hemolytic streptococcus), most other species of beta-hemolytic streptococci, many species of Streptococcus faecalis. Gram-negative microorganisms: Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii (important Proteus morganii), Providencia rettgeri (important Proteus rettgeri), Providencia spp., Serratia spp. (including S. marcescens ), Salmonella and Shigella species, Pseudomonas aeruginosa, some Pseudomonas species, Acinetobacter calcoaceticus, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica. Anaerobic microorganisms: gram-negative bacilli (including Bacteroides fragilis, other Bacteroides spp. and Fusobacterium spp.); gram-positive and gram-negative cocci (including Peptococcus, Peptostreptococcus and Veillonella species); gram-positive bacilli (including Clostridium, Eubacterium and Lactobacillus species).
Pharmacokinetics:
Approximately 84% of the dose of sulbactam and 25% of the dose of cefoperazone received with the administration of the drug Baktazon is excreted by the kidneys. Most of the dose of cefoperazone is excreted in the bile. After administration of sulbactam/cefoperazone, the average half-life of sulbactam is 1 hour, and that of cefoperazone is 1.7 hours. Plasma concentrations are proportional to the administered dose. The average maximum concentrations of sulbactam and cefoperazone after administration of 1.5 g of sulbactam/cefoperazone intravenously over 5 minutes were 130.2 and 236.8 mcg/ml, respectively. This indicates a larger volume of distribution of sulbactam (Vα = 18.0-27.6 L) compared to the distribution of cefoperazone (Vα = 10.2-11.3 L). Both sulbactam and cefoperazone are subject to intensive distribution in tissues and body fluids, including bile, gallbladder, skin, appendix, fallopian tubes, ovaries, uterus and others. In children, the average half-life of sulbactam ranges from 0.91 to 1.42 hours, and cefoperazone ranges from 1.44 to 1.88 hours. There are no data regarding any pharmacokinetic interaction between sulbactam and cefoperazone when used together in the form of a complex drug. After repeated administration, no significant changes were detected in the pharmacokinetics of the components of sulbactam/cefoperazone and any accumulation when used every 8-12 hours.
Indications for use:
As monotherapy for the treatment of infections caused by sensitive microorganisms: • respiratory tract infections (upper and lower); • intra-abdominal infections (peritonitis, cholecystitis, cholangitis, etc.); • urinary tract infections (upper and lower); • septicemia; • meningitis; • skin and soft tissue infections; • infections of bones and joints; • pelvic inflammatory diseases, endometritis; • gonorrhea and other genital infections. For certain indications, Baktazone can be used as part of combination therapy together with other antibiotics.
Mode of application:
Bactazone is intended for intravenous and intramuscular administration. Before starting therapy, it is necessary to exclude the presence of hypersensitivity in the patient by performing a skin test. Use in adults. The recommended daily dose of Baktazone is 2-4 g. The drug should be administered every 12 hours in an evenly distributed dose. For severe or refractory infections, the daily dose of Baktazone can be increased to 8 g. In patients receiving Bactazone, it may be necessary to additionally prescribe cefoperazone (should be administered every 12 hours in an evenly distributed dose). The maximum daily dose of sulbactam is 4 g. Use for liver dysfunction. Dose adjustment may be necessary in cases of severe obstructive jaundice and severe liver disease, or when both are accompanied by impaired renal function. In patients with impaired liver function and concomitant impaired renal function, monitoring of cefoperazone plasma concentrations and, if necessary, appropriate dose adjustment is necessary. In the absence of careful monitoring of drug concentrations in plasma, the dose of cefoperazone should not exceed 2 g per day. Use for renal dysfunction. When using Baktazon in patients with creatinine clearance less than 30 ml/min, a dose adjustment of the drug is necessary to compensate for the reduced clearance of sulbactam. With a creatinine clearance of 15-30 ml/min, the maximum single dose of sulbactam is 1 g every 12 hours; with creatinine clearance less than 15 ml/min – 500 mg every 12 hours. Therefore, in case of severe infections, it may be necessary to additionally prescribe cefoperazone drugs. When using dialysis, adjustment of the dosage regimen of the drug Baktazon is necessary (see Peculiarities of application). Use in children. The recommended daily dose of Baktazone is 40-80 mg/kg body weight. The drug should be administered every 6-12 hours in evenly distributed doses. For severe or refractory infections, the daily dose of Bactazone can be increased to 160 mg/kg and divided into 2-4 equal doses. For infants 1 week of life, the drug should be administered every 12 hours. The maximum daily dose for infants should not exceed 80 mg/kg. Intravenous use. For drip infusion, the contents of 1 bottle (1.5 g) should be dissolved in 6.7 ml of a 5% glucose solution in water, 0.9% sodium chloride solution or sterile water for injection, and then diluted to 20 ml with the same solvent before use. . The drug is administered by infusion over 15-60 minutes. Bactazone is compatible with water for injection, 5% glucose solution in 0.225% sodium chloride solution, 5% glucose solution in 0.9% sodium chloride solution in concentrations from 10 mg/ml cefoperazone and 10 mg/ml sulbactam to 250 mg/ml cefoperazone and 250 mg/ml sulbactam. Lactated Ringer's solution is suitable for dilution for intravenous infusion, but not for initial dilution. For intravenous injection, the contents of the vial should be dissolved as described above and administered over at least 3 minutes. Intramuscular use. Lidocaine solution is suitable for dilution for intramuscular use, but not for initial dissolution.
Side effects:
From the digestive system: diarrhea, nausea, vomiting, pseudomembranous colitis. From the central nervous system and peripheral nervous system: headache, muscle twitching. Allergic reactions: maculopapular rash, urticaria, itching, fever, Stevens-Johnson syndrome, anaphylactic shock. From the hematopoietic system: reversible neutropenia, leukopenia, decreased hemoglobin and hematocrit levels, cases of eosinophilia, thrombocytopenia and hypoprothrombinemia. From the cardiovascular system: hypotension, vasculitis. From the urinary system: hematuria. Laboratory indicators: increased liver function tests AST, ALT, alkaline phosphatase and bilirubin levels. Local reactions: pain at the injection site, phlebitis at the infusion site (when administered through an intravenous catheter).
Contraindications:
Hypersensitivity to any component of the drug and/or penicillins, cephalosporins.
Drug interactions: The simultaneous use of Baktazone and alcohol-containing drugs or the simultaneous use of alcohol during or for 5 days after the end of treatment can lead to effects similar to those of disulfiram (teturam): abdominal cramps, nausea, vomiting, headache, palpitations, shortness of breath, facial redness. These effects are observed within 15-30 minutes after drinking alcohol and disappear on their own after a few hours. This is due to the presence of an N-methylthiotetrazole side chain in the structure of the cefoperazone molecule, which inhibits the activity of the enzyme acetaldehyde dehydrogenase, which leads to the accumulation of acetaldehyde in the blood,
Side effects of the drug Sulcef
Sulcef is usually well tolerated. Most side effects are mild or moderate and do not require discontinuation of the drug. From the side of the central nervous system: headache. Cefoperazone may displace bilirubin from binding to plasma albumin, which increases the risk of developing bilirubin encephalopathy in newborns with jaundice. From the gastrointestinal tract: diarrhea, nausea and vomiting. From the blood system: there may be a slight decrease in the number of neurotrophils, the development of reversible neutropenia, a decrease in hemoglobin or hematocrit, eosinophilia, thrombocytopenia and hypoprothrombinemia, leukopenia, bleeding, vitamin K deficiency. From the cardiovascular system: arterial hypotension, vasculitis. Changes in laboratory parameters: there was a temporary increase in liver function tests - the activity of AST, ALT, alkaline phosphatase and bilirubin levels. Allergic reactions: anaphylactic reactions, Stevens-Johnson syndrome, urticaria. From the urinary system: hematuria. Other manifestations: Rarely, pain and irritation may occur at the injection site.
Special instructions for the use of the drug Sulcef
Increased sensitivity. During treatment with the drug, the development of severe allergic (anaphylactic) reactions in patients has been reported. Such reactions are more likely to develop in individuals with a history of hypersensitivity to many allergens. There have been cases of severe reactions in patients with a history of allergic reactions to penicillins. If allergic reactions develop, it is necessary to immediately discontinue the drug and prescribe appropriate treatment. Severe anaphylactic reactions require immediate emergency treatment, in particular the administration of adrenaline. According to indications, it is recommended to use oxygen therapy, intravenous administration of corticosteroids, ensuring airway patency, including tracheal intubation. General precautions. As with the use of other antibiotics, treatment with cefoperazone in some patients can lead to the development of vitamin K deficiency. The mechanism of this phenomenon is probably associated with inhibition of the intestinal microflora, which normally synthesizes this vitamin. Thus, the risk group includes patients with limited nutrition, malabsorption (for example, with fibrosis of the gallbladder) and people who have been on parenteral nutrition for a long time. In such patients, prothrombin time should be monitored. Similar monitoring should be carried out in patients receiving anticoagulant therapy. In these cases, it is necessary to additionally prescribe vitamin K. As with the use of other antibiotics, prolonged treatment with Sulperazone can lead to increased growth of resistant microflora. During treatment, patients must be under medical supervision. If superinfection develops, the drug must be discontinued and/or appropriate therapy prescribed. During long-term treatment with the drug, it is recommended to periodically monitor the functions of internal organs, including the kidneys, liver and hematopoietic system. Liver dysfunction. In case of biliary obstruction, severe liver disease, or in the presence of concomitant renal impairment, dose adjustment of the drug may be necessary. When drinking alcohol during the course of treatment and within 72 hours after stopping treatment with cefoperazone, reactions such as facial flushing, increased sweating, headache, and tachycardia were observed. Therefore, during the use of the drug and in the next 3 days after its discontinuation, it is necessary to refrain from drinking alcoholic beverages. Children. Before starting treatment in premature infants or newborns, the balance between the potential benefits and possible risks of therapy must be carefully assessed. During pregnancy and breastfeeding. Sulbactam and cefoperazone penetrate the placental barrier. Do not use the drug during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus. Sulbactam and cefoperazone are excreted into breast milk in small quantities. The drug is prescribed with caution during lactation. The effect on reaction speed when driving vehicles and operating other mechanisms is unknown.
Sulcef powder for solution for injection 1 g/1 g in a bottle
Hypersensitivity. Severe and sometimes fatal hypersensitivity reactions (anaphylactic reactions) have been reported in patients treated with beta-lactam or cephalosporin antibiotics, including sulbactam/cefoperazone. The development of such reactions is more likely to occur in individuals with a history of hypersensitivity reactions to many allergens.
Before starting therapy with sulbactam/cefoperazone, the patient's history should be carefully examined for hypersensitivity reactions to cephalosporins, penicillins or other drugs (see Section "Contraindications"). Antibiotics should be prescribed with caution to patients who exhibit some form of allergy, especially to drugs.
If allergic reactions develop, use of the drug should be discontinued and appropriate treatment prescribed. Severe anaphylactic reactions require immediate use of epinephrine. If necessary, oxygen therapy should be administered, intravenous steroid drugs should be used, and airway patency should be ensured, including intubation (see section “Adverse Reactions”).
Severe, sometimes fatal skin reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome and exfoliative dermatitis, have been reported in patients receiving sulbactam/cefoperazone. If a severe skin reaction occurs, sulbactam/cefoperazone therapy should be discontinued and appropriate treatment should be initiated (see section "Adverse Reactions").
Use for liver dysfunction. Cefoperazone is largely excreted in the bile. In patients with liver disease and/or biliary obstruction, the serum half-life of cefoperazone is generally prolonged and urinary excretion is increased. Even with severe liver dysfunction, therapeutic concentrations of cefoperazone are observed in the bile, and the half-life increases by 2-4 times.
Dose adjustment may be required in case of severe biliary obstruction, severe liver disease or in case of renal dysfunction associated with any of these conditions.
In patients with impaired liver function and concomitant impaired renal function, the concentration of cefoperazone in the blood serum should be monitored and the dose adjusted if necessary. Unless serum concentrations are closely monitored, the dose of cefoperazone should not exceed 2 g/day.
General precautions. Cases of serious hemorrhage, sometimes fatal, have been reported with the use of sulbactam/cefoperazone. As with other antibiotics, vitamin K deficiency has been observed in patients receiving sulbactam/cefoperazone, causing coagulopathy. The mechanism of this phenomenon is probably associated with the inhibition of the intestinal bacterial flora, which normally synthesizes vitamin K. The risk group includes patients with limited nutrition, patients with malabsorption and patients on long-term parenteral () nutrition. In such patients and patients taking oral anticoagulants, it is necessary to monitor the prothrombin time (or international normalized ratio) to detect possible bleeding, thrombocytopenia, and, if indicated, prescribe vitamin K. In the event of prolonged bleeding, if there are no other causes for this phenomenon, Sulbactam/cefoperazone should be discontinued.
As with the use of other antibiotics, long-term use of the drug Sulcef can lead to increased growth of insensitive microflora. During treatment, patients should be carefully monitored. As with the use of other potent systemic drugs, with long-term use of the drug Sulcef it is recommended to periodically monitor the patient's condition regarding manifestations of dysfunction of organ systems, including dysfunction of the kidneys, liver and hematopoietic system, especially in premature newborns and infants in general.
Diarrhea associated with Clostridium difficile has been reported with almost all antibacterial agents, including sulbactam sodium/cefoperazone sodium. The severity of manifestations can range from mild diarrhea to fatal colitis. The use of antibacterial drugs alters the normal intestinal flora and leads to increased growth of C. difficile.
C. difficile produces toxins A and B, which in turn contribute to the development of C. difficile-associated diarrhea. Hypertoxin-producing C. difficile strains increase morbidity and mortality because such infections may be resistant to antibiotic therapy and require colectomy. This diagnosis should be considered in all patients with diarrhea that occurs during antibiotic therapy. A careful history review is warranted as C. difficile-associated diarrhea has been reported 2 months after completion of antibiotic therapy.
Children
Sulcef is effective in infants, but comprehensive studies have not been conducted on the use of the drug in premature or full-term newborns. Therefore, before starting treatment in premature or full-term newborns, the potential benefits and risks of using the drug should be carefully assessed.
In newborns with bilirubin encephalopathy, cefoperazone does NOT replace bilirubin at sites of binding to plasma proteins.
This drug contains sodium, so use the drug with caution in patients with impaired renal function or in patients on a sodium-controlled diet.
Drug interactions Sulcef
Aminoglycosides: when used simultaneously with Sulcef, nephrotoxic reactions may develop. The combined use of these drugs should be avoided in patients with kidney disease. If concomitant use is necessary, monitor renal function. If combined treatment with Sulcef and an aminoglycoside is intended, it should be carried out by alternating intravenous infusions. Before administering the second drug, the entire infusion system should be thoroughly rinsed with the appropriate solution. It is necessary that the time interval between the administration of Sulcef and the aminoglycoside is as long as possible. Anticoagulants: simultaneous use with coumarin, indanedione derivatives, heparin, and thrombolytic agents may increase the risk of bleeding. In case of bleeding disorders, combination treatment is prescribed with caution. It is necessary to adjust the dose of anticoagulants during treatment with Sulcef and after its completion to maintain normal levels of blood clotting. Loop diuretics: combined use with Sulcef may cause a nephrotoxic effect. Concomitant use should be avoided in patients with kidney disease. Alcohol: disulfiram-like reactions were observed when drinking alcohol during the course of treatment and for 72 hours after the end of treatment with cefoperazone. It is necessary to avoid drinking alcohol and alcohol-containing drugs during treatment with Sulcef and for 72 hours after its completion. Laboratory tests: a false positive reaction to glucose in urine is possible when determined using Benedict's or Felling's reagents. In some patients, a direct positive Coombs reaction may be detected during treatment. Sulcef is pharmaceutically incompatible with aminoglycosides, amifostine, filgrastim, labetalol, meperidine, nicardipine, ondansetron, perphenazine, promethazine, sargramostine, vinorelbine.
Sulceph
Combined drug. Cefoperazone is a third-generation cephalosporin antibiotic that is bactericidal and has a wide spectrum of action; highly active against aerobic and anaerobic gram-positive and gram-negative microorganisms (including Pseudomonas aeruginosa), resistant to beta-lactamases of gram-positive and gram-negative microorganisms.
Sulbactam is an irreversible inhibitor of beta-lactamases, which are secreted by microorganisms resistant to beta-lactam antibiotics; prevents the destruction of penicillins and cephalosporins under the influence of beta-lactamases of resistant microorganisms; binding to penicillin-binding proteins, it exhibits synergism when used simultaneously with penicillins and cephalosporins.
The combination of sulbactam and cefoperazone is active against all microorganisms sensitive to cefoperazone and acts synergistically (reduces the MIC of the combination by up to 4 times compared to the values for each component separately) against microorganisms: Haemophilus influenzae, Bacteroides spp., Staphylococcus spp., Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.
Active in vitro against a wide range of microorganisms: gram-positive bacteria - Staphylococcus aureus (including strains that form and do not form penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic strain of group A), Streptococcus agalactiae (beta -hemolytic strain of group B), most strains of beta-hemolytic Streptococcus spp., Enterococcus faecalis;
gram-negative bacteria - Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis, Morganella morganii, Providencia rettgeri, Providencia spp., Serratia spp. (including Serratia marcescens), Salmonella spp., Shigella spp., Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Neisseria gonorrhoeae, Neisseria meningitidis; Bordetella pertussis, Yersinia enterocolitica; anaerobic bacteria - Bacteroides fragilis, Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Veillonella spp., Clostridium spp., Eubacterium spp., Lactobacillus spp.
Overdose of the drug Sulcef, symptoms and treatment
May cause increased side effects. It should be taken into account that high concentrations of β-lactam antibiotics in the CSF can cause the development of neurological symptoms, in particular seizures. Possibly impaired renal function and increased prothrombin time. Treatment: symptomatic and supportive therapy (support of vital functions and water-electrolyte balance). It is necessary to monitor prothrombin time and, if necessary, prescribe vitamin K. In case of seizures, sedative therapy. Since cefoperazone and sulbactam are removed from the systemic circulation during hemodialysis, this procedure may increase drug elimination from the body in the event of overdose in patients with impaired renal function.
