Products

Cefoperazone Sodium and Sulbactam Sodium for Injection

Instructions for Cefoperazone Sodium and Sulbactam Sodium for Injection
Please read the instructions carefully and use under the guidance of a physician or pharmacist

[Name of the drug]
Generic name: Cefoperazone Sodium and Sulbactam Sodium for Injection
Product name: Cefoperazone Sodium and Sulbactam Sodium for Injection
Hanyu Pinyin: Zhusheyong Toubaopaitongna Shubatanna  【 Ingredients 】
This product is a compound preparation, the active ingredients are cefoperazone sodium and sulbactam sodium (cefoperazone and sulbactam are 1:1), and no excipients are included.
Cefoperazone sodium
Chemical Name: (6 R R,7 R )-3-[[(1-methyl-1H-tetrazole-5-yl H)sulfur]methyl]-7-[( R ). )-2-(4-ethyl-2,3-dioxo-1-piperazinecarbonylamino)-2-p-hydroxyphenyl-acetylamino]-8-oxo-5-thio-1-azabicyclic [4.2.0]oct-2-en-2-carbamate sodium salt.
Chemical structural formula:
 
Molecular formula:C ₂₅ H ₂₆ N ₉ NaO ₈ S ₂
Molecular weight: 667.65
Sulbactam sodium
Chemical Name: ( S2S,5R R)-3,3-dimethyl-7-oxo-4-thio-za-1-azabicyclic [3.2.0]Sodium heptane-2-carboxylate-4,4-dioxide.
Chemical structural formula:

 
Molecular formula: C ₈ H ₁₀ NNaO ₅ S
Molecular Weight: 255.22
According to the amount indicated on the label, this product contains 32mg of sodium per bottle of 0.5g size, 64mg of sodium per bottle of 1.0g size, 96mg of sodium per bottle of 1.5g size, and 128mg of sodium per bottle of 2.0g size.
[Characteristics]
This product is a white or white-like powder.
[Indications]
Medication alone
Cefoperazone/sulbactam is indicated for the treatment of the following infections caused by sensitive bacteria:
1) Upper and lower respiratory tract infections;
2) Upper and lower urinary tract infections;
3) peritonitis, cholecystitis, cholangitis and other intra-abdominal infections;
4) sepsis;
5) meningitis;
6) skin and soft tissue infections;
7) Bone and joint infections;
8) Pelvic inflammatory disease, endometritis, gonorrhea, and other genital tract infections.
Combination medication
Because of its broad-spectrum antibacterial activity, cefoperazone/sulbactam can treat most infections on its own, but cefoperazone/sulbactam is sometimes used in combination with other antibiotics. When this product is combined with aminoglycoside antibiotics (participate in the aminoglycoside antibiotic part of [drug interaction] compatibility contraindication), the patient's renal function should be monitored during treatment (participate in the medication part of patients with renal dysfunction in [Dosage]).
[Specifications]
1.5g(C ₂₅ H ₂₇ N ₉ O ₈ S ₂ 0.75g 与 C ₈ H ₁₁ NO ₅ S 0.75g)
[Usage and dosage]
Adult medication
The recommended daily dose of cefoperazone/sulbactam for adults is as follows:

The above doses are administered in equal doses every 12 hours. The daily dose of cefoperazone/sulbactam can be increased to 8g (1:1 cefoperazone/sulbactam, i.e., 4g cefoperazone) when treating severe or refractory infections. When the condition requires,
Patients receiving 1:1 cefoperazone/sulbactam may be additionally increased in cefoperazone separately at equal doses administered every 12 hours. The maximum recommended daily dose of sulbactam is 4g.
Medication for patients with hepatic dysfunction : See [Precautions].
Medication for patients with renal dysfunction
Patients with significantly reduced renal function (creatinine clearance <30 ml/min) with decreased clearance of sulbactam should adjust the regimen of cefoperazone/sulbactam. The maximum daily dose of sulbactam for patients with creatinine clearance of 15~30ml/min is 2g in equal doses every 12 hours. The maximum daily dose of sulbactam in patients with creatinine clearance < 15 ml/min is 1 g in equal doses every 12 hours. In case of severe infection, the dose of cefoperazone can be increased separately if necessary.
In hemodialysis patients, the pharmacokinetic properties of sulbactam are significantly altered. The serum half-life of cefoperazone is slightly shortened in hemodialysis patients. Therefore, it should be given after the end of hemodialysis.
Intravenous administration
1) When using intermittent intravenous infusion, each bottle of cefoperazone/sulbactam should be dissolved with an appropriate amount of 5% glucose solution or 0.9% injection with sodium chloride solution or sterile water for injection (refer to [Dosage] for the dissolution part of this product), and then diluted to 20ml with the same solution mentioned above, and the intravenous infusion time should be at least 15~60 minutes.
Although Sodium Lactate Ringer Injection can be used as a solvent for cefoperazone/sulbactam IV injection, it cannot be used in the initial dissolution process of this product (see [Drug Interactions] Compatibility Contraindications Sodium Ringer Lactate Injection and [Dosage] Use  用/ Operation Instructions ). Sodium lactate Ringer injection part).
2) When using intravenous bolus, each bottle of cefoperazone/sulbactam should be dissolved in the above way, and the intravenous bolus time should be at least more than 3 minutes.
Intramuscular injection
Although 2% lidocaine hydrochloride injection can be used as a solvent for cefoperazone/sulbactam intramuscular injection, it cannot be used in the initial dissolution process of this product (see [Drug Interactions] Compatibility Contraindications for Lidocaine and [Dosage] Instructions for Use /  Operation of Lidocaine).
Instructions for use / operation
1) Dissolution of this product
This product can be dissolved per 1.0g of cefoperazone/sulbactam according to the table below.

Cefoperazone/sulbactam can be combined with water for injection, 5% glucose injection, normal saline, 5% glucose and 0.225% sodium chloride injection within the concentration range of 10~250mg/ml and 5~125mg/ml for cefoperazone and sulbactam, respectively
5% glucose and 0.9% sodium chloride injection are compatible.
2) Sodium lactate Ringer injection
Cefoperazone/sulbactam should be dissolved with sterile water for injection (see [Drug Interactions] Compatibility Contraindications Sodium Lactate Ringer Injection). A two-step dilution method was used: first dissolved in sterile water for injection (as shown in the table above), then diluted with sodium Ringer Lactate Injection to a solution of 5mg/ml of sulbactam (diluted with 2ml of primary solution to 50ml of Sodium Lactate Ringer Injection or 4ml of initial solution diluted to 100ml Sodium Lactate Ringer Injection).
3) Lidocaine
Cefoperazone/sulbactam should be dissolved in sterile water for injection (see [Drug Interactions] Compatibility Contraindications to Lidocaine). A two-step dilution method should be used: first dissolved in sterile water for injection (as shown in the table above), and then diluted with 2% lidocaine solution to achieve concentrations of 125mg/ml and 125mg/ml of cefoperazone and sulbactam in about 0.5% lidocaine hydrochloride solution, respectively.
[Adverse reaction]
Adverse reactions and laboratory abnormalities were observed in 1023 (7.99%) of a total of 12,808 patients (at the time of completion of review) after the development study and approval of the study. The main adverse reaction was diarrhea
(0.75%), rash (0.45%), fever (0.21%), etc. The main laboratory abnormalities were elevated ALT (3.41%), elevated AST (3.18%), and elevated ALP (1.05%).
Clinically significant adverse effects (incidence unknown due to spontaneously reported causes.) ）
1) Shock, anaphylactic shock / anaphylaxis (dyspnea, etc .):
In the event of shock, anaphylactic shock/anaphylaxis, etc., the patient should be closely monitored. If any abnormal results are observed, the administration should be discontinued immediately and appropriate treatment measures should be taken.
2 ) Acute renal failure:
Because severe kidney impairment such as acute kidney failure can occur, regular laboratory tests are necessary. If any abnormal results are observed, appropriate therapeutic measures should be taken, such as interrupting dosing.
3 ) Pseudomembranous colitis:
Severe colitis such as pseudomembranous colitis with bloody stools may occur. When abdominal pain or frequent diarrhea occurs, appropriate treatment measures should be taken, such as interrupting the administration.
4 ) Interstitial pneumonia, PIE syndrome:
Interstitial pneumonia with fever, cough, dyspnea, abnormal x-rays or eosinophils, and pulmonary infiltrates with eosinophilic syndrome may occur. If such symptoms are observed, the drug should be stopped immediately and appropriate treatment should be taken, such as adrenocorticosteroids.
5 ) Mucosa-skin-ocular -皮肤- syndrome ( Stevens Johnson syndrome) and toxic epidermal necrolysis (Lyell's   syndrome):
Mucosa-skin-eye syndrome (Stevens Johnson syndrome) and toxic epidermal necrolysis may occur
(Lyell syndrome). If such symptoms are observed, the administration should be interrupted immediately and appropriate treatment measures should be taken.
6 ) Blood dyshydration:
Severe blood dyshydra such as hemolytic anemia, pancytopenia, granulocytopenia (including agranulocytosis), thrombocytopenia, etc. may occur, and it is necessary to take measures such as careful observation through regular laboratory tests. If any abnormal results are observed, appropriate treatment should be taken, such as interrupting dosing.
7 ) Fulminant hepatitis:
Because fulminant hepatitis can occur, it is necessary to take measures such as careful observation through regular laboratory tests. If any abnormal results are observed, appropriate therapeutic measures should be taken, such as interrupting dosing.
Adverse events are typically collected from reports during clinical trials and after the product is launched. Many events can be caused by factors other than medication, such as latent disease. Since it is not possible to determine a specific causal relationship in most cases (and even many adverse events are not adverse drug reactions), we report all adverse events collected here, even when it is not possible to determine whether it is caused by cefoperazone/sulbactam.
Cefoperazone/sulbactam is generally well tolerated, with most adverse effects being mild or moderate and tolerable without affecting continued treatment. The following adverse effects have been observed from clinical trials (comparative and non-comparative studies) and post-marketing experience.
All adverse reactions in the package inserts are listed according to the MedDRA system classification and are ranked by clinical importance.
Adverse reaction table

Systematic organization classification	Very common ≥ 1/10	Common ≥ 1/100 to<1/10	Rare ≥1/1000 to<1/100	The frequency is unknown (None according to available data Legal estimate).
blood and lymphatic system The system is abnormal	Neutropenia† leukocytes Reduce † and direct Combs test positive Sexual reaction †, hemoglobin drops † Decreased hematocrit † platelets Reduce †	Coagulation disorders*, eosinophilia There are many †	Platelets	Vitamin K deficiency (low Prothrombinemia*, bleeding tendency, etc.), anemia
Abnormal immune system				anaphylactic shock*§, allergic Reaction*§, anaphylaxis§ (including shock*), hypersensitivity should *§
Neurological abnormalities			Headache	Convulsions
Vascular abnormalities				Bleeding*§, vasculitis*, hypoheemia Press*
Gastrointestinal abnormalities		diarrhea, nausea, Vomiting	Loose manure	Pseudomembranous enteritis*, stomatitis, candidiasis
Abnormalities in the liver and bile ducts	Alanine aminotransferase is elevated† aspartate aminotransferase is elevated† and blood alkaline phosphatase is elevated, †	Bilirubin is elevated †		Jaundice*
Skin and subcutaneous groups Weaving is abnormal			Itching, hives Measles, pesticides Rash	Toxic epidermal necrolysis , Stevens-Johnson syndrome*§, exfoliative dermatitis*§, maculopapular rash*, erythema
kidneys and urinary system The system is abnormal				Hematuria*
General abnormalities and administration sites			Veins at the injection site inflammation, injection site	B vitamin deficiency (glossitis, anorexia, god
			pain, fever, Chills	Menstritis, etc.).

*Post-marketing adverse reactions.
† all available laboratory values, including those with abnormal baseline, are included in the calculation of the frequency of abnormal laboratory adverse reactions. This conservative approach is used because the raw data do not distinguish between patients with baseline abnormalities with significant laboratory changes in treatment and patients with baseline abnormalities without significant laboratory changes. For leukocytes, neutrophils, platelets, hemoglobin, and hematocrit, studies only reported abnormalities and did not distinguish between elevated or decreased values.
§ There are reports of fatal incidents.
[Contraindication]
It is contraindicated in those who are known to be allergic to penicillins, sulbactam, cefoperazone and other cephalosporin antibiotics or have a history of shock to the ingredients of this product.
Patients with a history of hypersensitivity to the ingredients of this product or cephalosporin drugs are generally prohibited from using cefoperazone sodium for injection sulbactam sodium, and if it is really necessary to use cefoperazone sodium for injection sulbactam sodium, it should be administered with caution.
[Precautions]
Warning: Severe bleeding, including fatality, associated with cefoperazone sodium for injection sulbactam has been reported. Bleeding, thrombocytopenia, and signs of coagulation disorders should be monitored. If there is unexplained persistent bleeding, the drug should be discontinued immediately.
A small number of patients develop vitamin K deficiency leading to coagulation disorders after treatment with this product, and the mechanism is likely related to the inhibition of the gut flora that synthesizes the vitamin, including malnutrition, malabsorption (eg, patients with pulmonary cystic fibrosis), patients with alcohol poisoning, and long-term intravenous infusion of highly nutritious preparations. Hypothrombinemia (with or without bleeding) is reported. Vitamin K deficiency causes bleeding tendencies. Prothrombin time should be monitored in these patients and in patients treated with anticoagulants, and vitamin K should be supplemented if needed.
Independent risk factors for bleeding may include an injury or condition that increases the risk of clinically significant bleeding, such as a recent cerebral infarction (ischemic or hemorrhagic); Active peptic ulcer with recent bleeding; Patients with impaired spontaneous or acquired hemostatic balance; Liver disease with coagulation disorders and clinically relevant bleeding risk; Systemic concomitant use of medications known to affect hemostasis.
1. Hypersensitivity
βSevere, occasionally fatal hypersensitivity (anaphylactic) reactions, including cefoperazone/sulbactam, have been reported in patients treated with β-lactam or cephalosporin antibiotics. These reactions are more likely to occur in patients with a history of hypersensitivity to multiple allergens. In the event of an allergic reaction, the drug should be stopped immediately and appropriate treatment should be given.
For patients with a tendency to cause allergic reactions such as bronchial asthma, rash, hives, etc. or the patient's parents
Parents, brothers, or sisters, should use cefoperazone sodium for injection with caution.
Patients with severe allergic reactions should be given emergency treatment with epinephrine immediately, and if necessary, oxygen, intravenous kinesis, and unobstructed airway including endotracheal intubation should be used.
Serious epidemical, lethal cutaneous adverse reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and exfoliative dermatitis, have been reported in patients treated with cefoperazone/sulbactam. In the event of a severe skin reaction, the drug should be discontinued immediately and appropriate treatment should be given.
Because there is no definitive way to predict the occurrence of shock or anaphylactoid shock associated with this type of drug, the following measures must be taken:
1) Before treatment, the patient's relevant situation should be understood in detail, so as to find out the patient's drug allergy history. In particular, it is necessary to confirm whether the patient has a history of antibiotic allergy.
2) Prior preparation for shock first aid should be carried out before treatment.
3) Patients should be kept quiet and closely monitored during the administration of this drug. In particular, patients should be closely monitored for a period of time after administration of this drug.
2. Medication for patients with liver dysfunction
Cefoperazone is mainly excreted through bile. When patients have liver disease and/or biliary obstruction, the serum half-life of cefoperazone is usually prolonged and the amount of drug excreted in the urine increases. Even if the patient has severe liver dysfunction, cefoperazone can still reach therapeutic concentrations in bile and its half-life is only 2~4 times longer.
If you encounter severe biliary obstruction, severe liver disease, or renal dysfunction, you may need to adjust the dosage.
Patients with hepatic dysfunction and renal impairment should monitor the serum concentration of cefoperazone and adjust the dose as needed. The daily dose of cefoperazone should not be exceeded in these patients if serum concentrations of this product are not closely monitored
2g。
3. General Notes
Severe bleeding cases have been reported with cefoperazone/sulbactam, including fatal. As with other antibiotics, a small number of patients develop vitamin K deficiency leading to coagulation disorders after treatment with cefoperazone/sulbactam, and the mechanism is likely related to the inhibition of the gut microbiota that synthesizes the vitamin, including malnutrition, malabsorption (eg, in patients with pulmonary cystic fibrosis), and long-term intravenous infusion of highly nutritious preparations. Vitamin K deficiency causes bleeding tendencies.
Prothrombin time should be monitored in these patients and in patients treated with anticoagulants, and vitamin K should be supplemented if needed. If there is unexplained persistent bleeding, the drug should be discontinued immediately.
As with other antibiotics, long-term use of cefoperazone/sulbactam can cause an overgrowth of insensitive bacteria. Therefore, in
During treatment, the patient's condition changes should be carefully observed. As with other systemic antibiotics, it is recommended that the patient be regularly examined for dysfunction of various systems and organs, including the kidneys, liver, and blood system, during a longer course of treatment. This is especially important for newborns, especially premature babies and other babies.
4. Clostridium difficile associated diarrhea C (DAD) has been reported in almost all antimicrobial applications, including cefoperazone sodium/sulbactam sodium, which can manifest in severity from mild diarrhea to fatal enteritis. Antimicrobial therapy can cause changes in the normal flora of the colon, leading to the overgrowth of Clostridium difficile.
Toxin A and toxin B produced by Clostridium difficile are associated with the pathogenesis of CDAD. The highly toxin-producing Clostridium difficile leads to increased morbidity and mortality, and these infections may not be refractory to antimicrobial therapy and may require colon resection. The possibility of CDAD must be considered in all patients with diarrhea after antibiotic use. Because CDAD has been reported more than 2 months after antimicrobial therapy, a careful history should be asked.
5. Impact on the ability to drive and operate the machine
Experience with cefoperadone/sulbactam clinical use shows that it does not reduce the patient's ability to drive and operate the machine.
[Medication for pregnant and lactating women]
Medication during pregnancy
Reproductive studies have been conducted in rats, using doses up to 10 times the human dose, and no fertility has been found to be impaired, nor has any teratogenic effect of the drug been found. Both sulbactam and cefoperazone can cross the placental barrier, but adequate and well-controlled trials have not been conducted in pregnant women. Since the results of animal reproduction studies do not always predict the human condition, pregnant women should only use this product if the doctor deems it necessary.
Lactation medication
Only small amounts of sulbactam and cefoperazone are secreted into the body's breast milk. Although only small amounts of sulbactam and cefoperazone can enter breast milk, breastfeeding women should use this product with caution.
[Children's medication]
The recommended daily dose of cefoperazone/sulbactam for children is as follows:

The above doses are divided into equal doses and injected every 6 to 12 hours.
The above dose can be increased to 160mg/kg per day in a 1:1 ratio when treating severe infections or refractory infections
Administer in equal doses 2~4 times a day (see [Children's Medication] Infant Medication and [Pharmacology and Toxicology] Toxicology Studies).
Neonatal medication
Newborns in the first week of life should be given every 12 hours. The maximum daily dose of sulbactam in children should not exceed 80 mg/kg per day (see Pediatric Medications for Infants and Pharmacology and Toxicology). Toxicological research
Infant medication
Cefoperazone/sulbactam has been used effectively in the treatment of infections in infants. Extensive research has not been done in preterm infants and neonates, so physicians should weigh the pros and cons before using cefoperadone/sulbactam in preterm and neonatal infants.
Cefoperazone does not replace bilirubin from plasma protein binding sites.
[Medication for the elderly]
See [Clinical Pharmacology] Pharmacokinetics for Elderly Patients.
[Drug Interactions]
Interaction with alcohol
Alcohol consumption during cefoperazone and within 5 days of discontinuation has been reported to cause characteristic reactions such as flushing, sweating, headache, and tachycardia, and similar reactions have been reported with some other cephalosporins. Therefore, patients should be careful when using cefoperazone/sulbactam when drinking alcoholic beverages at the same time. When patients require enteral or parenteral nutrition, they should avoid giving liquids containing alcohol.
Drug interactions in laboratory tests
False positives can occur when urine glucose is checked with Bennedict solution or Fehling reagent.
Compatibility taboos
1) Aminoglycoside antibiotics
Since there are physical compatibility contraindications between cefoperazone/sulbactam and aminoglycoside antibiotics, the two solutions cannot be mixed directly. If cefoperazone/sulbactam is required in combination with aminoglycoside antibiotics (see [Indications] Combination Administration), sequential intermittent intravenous infusion may be used, but a different IV line must be used, or the previously used IV line must be fully flushed with an appropriate dilution during the interfusion period. In addition, it is recommended that the interval between cefoperazone/sulbactam and aminoglycoside antibiotics be as long as possible during the whole day.
2) Sodium lactate Ringer injection
Since this product has compatibility contraindications after mixing with Sodium Lactate Ringer Injection, the use of this solution should be avoided when it is initially dissolved. In the two-step dilution method, the initial dissolution is carried out with water for injection, and then further diluted with sodium Ringer lactate injection to obtain a mixture that can be compatible with each other (see [Dosage] Instructions for Use / Operation 说明 Sodium Ringer Injection section).
3) Lidocaine
Since this product has compatibility contraindications when mixed with 2% lidocaine hydrochloride injection, the use of this solution should be avoided when it is initially dissolved. In the two-step dilution method, the initial dissolution is carried out with water for injection, and then further diluted with 2% lidocaine hydrochloride injection to obtain a mixture that can be compatible with each other (see the Lidocaine section of the [Dosage] Use / Operation Instructions ).
4) When this product is used at the same time as drugs that can produce hypothrombinemia, thrombocytopenia or gastrointestinal bleeding, the effect of these drugs on coagulation function and increased risk of bleeding should be considered.
[Drug overdose]
There is little information on acute human poisoning of cefoperazone sodium and sulbactam sodium. The expected clinical manifestations of overdose of this product are mainly those that have been reported to be magnified. High concentrations of ββ-lactam antibiotics in cerebrospinal fluid can cause adverse reactions of the central nervous system, such as convulsions. Since both cefoperazone and sulbactam are removed from the blood circulation by hemodialysis, hemodialysis treatment can increase the excretion of this product from the body in the event of an overdose in patients with renal impairment.
[Clinical Pharmacology]
Pharmacokinetics
After cefoperazone/sulbactam injection, about 84% of sulbactam and 25% of cefoperazone are excreted by the kidneys, and most of the remaining cefoperazone is excreted through bile. After cefoperazone/sulbactam injection, the average half-life is about 1 hour for sulbactam and 1.7 hours for cefoperazone. Blood concentration is proportional to the dose administered. The values are consistent with the published values used separately for the two.
After 5 minutes of intravenous administration of 2g cefoperazone/sulbactam (1g cefoperazone and 1g sulbactam), the mean peak blood concentrations of cefoperazone and sulbactam were 236.8μg/ml and 130.2μg/ml, respectively, suggesting that the distribution volume of sulbactam (Vd =18.0~
27.6L) was greater than the volume of distribution of cefoperazone (Vd =10.2~11.3L).
After intramuscular administration of 1.5g of cefoperadone/sulbactam (1g cefoperazone, 0.5g sulbactam), serum concentrations of sulbactam and cefoperazone peaked at 15 minutes to 2 hours, and the mean serum peak concentrations of cefoperazone and sulbactam were respectively
64.2μg/ml 和 19.0μg/ml。
Both cefoperazone and sulbactam are well distributed to various tissues and body fluids, including bile, gallbladder, skin, appendix, fallopian tubes, ovaries, uterus, and other tissues and body fluids.
There is no evidence of pharmacokinetic interactions between the two components after injection of the cefoperazone/sulbactam combination formulation.
It has been reported that there is no significant change in the pharmacokinetic parameters of the two components after multiple doses of cefoperadone/sulbactam, and no drug accumulation is observed when injected every 8~12 hours.
Medication for patients with liver dysfunction
See the [Notes] section.
Medication for patients with renal dysfunction
After cefoperazone/sulbactam injection in patients with varying degrees of renal dysfunction, the total drug clearance of sulbactam was closely related to the estimated creatinine clearance. In patients with renal failure, the half-life of sulbactam was significantly extended (on average 6.9 hours and 9.7 hours in both studies). In hemodialysis patients, the half-life, total drug clearance and apparent volume of distribution of sulbactam were significantly altered. No significant differences in the pharmacokinetic parameters of cefoperazone were observed in patients with renal failure.
Medication for elderly patients
Pharmacokinetic parameters of cefoperazone/sulbactam were studied in older adults with renal dysfunction and impaired hepatic function, and both sulbactam and cefoperazone showed prolonged half-lives, decreased drug clearance, and increased apparent volume of distribution compared to normal healthy subjects. The pharmacokinetic parameters of sulbactam are highly correlated with the degree of impairment of renal function, while the pharmacokinetic parameters of cefoperadone are closely related to the degree of impairment of liver function.
Medication for children
Studies in pediatric patients showed no significant change in the pharmacokinetic parameters of the cefoperazone/sulbactam components compared to adult data. The half-life of sulbactam in children ranges from 0.91 to 1.42 hours and for cefoperazone from 1.44 to 1.88 hours.
[Pharmacology and Toxicology]
Pharmacological effects
The antibacterial component of cefoperazone/sulbactam is cefoperazone, which is a third-generation cephalosporin that achieves bactericidal effect by inhibiting the biosynthesis of cell wall mucopeptides of sensitive bacteria during the bacterial reproduction period. Sulbactam does not have any effective antibacterial activity against other bacteria except Neisseriaceae and Acinetobacter. However, biochemical studies with bacteria have shown that sulbactam has irreversible inhibitory effects on most important β-lactamases produced by antibiotic-resistant strains of β-lactam classes.
The study of drug-resistant bacteria in whole cells confirmed that sulbactam can prevent the destruction of penicillin and cephalosporin antibiotics by drug-resistant bacteria, and that sulbactam has obvious synergistic effect with penicillin and cephalosporin antibiotics. Because sulbactam can bind to certain penicillin-binding proteins, sensitive strains are generally more sensitive to cefoperazone/sulbactam than to cefoperazone alone.
The cefoperazone/sulbactam combination has antimicrobial activity against all cefoperazone-sensitive bacteria. In addition, it showed synergistic antibacterial effects on a variety of bacteria, especially the following bacteria (the minimum inhibitory concentration (MIC) value of the cefoperazone/sulbactam combination was reduced by up to 4 times compared with the single component).
Haemophilus influenzae
Bacteroidetes
Staphylococcus spp
Acinetobacter calcium acetate Enterobacteriaceae aerogeniensis
E. coli
Proteus miraculous
Pneumoniae Klein
Morganella Morse
Citrate bacteria fraudi Enterobacteriaceae claude
Heteromorphic citric acid bacillus
In vitro tests, cefoperadone/sulbactam has antimicrobial activity against many clinically important pathogens:
Gram-positive bacteria:
Staphylococcus aureus, a strain that produces and does not produce penicillinase Staphylococcus epidermidis
Streptococcus pneumoniae (formerly known as pneumococcus).
Streptococcus pyogenes (group A) - Streptococcus hemolyticus).
Streptococcus agalactiac (group B 阝) Most strains of Streptococcus agaemolyticus
Many strains of Enterococcus faecalis gram-negative bacteria:
E. coli
Craig albaifungus
Enterobacteriaceae
Citrate acid bacteria
Haemophilus influenzae Proteus mirabacter common Proteus commonis
Morganella moseii (formerly known as Proteus mogi
Providence reiferi (formerly known as Proteus reiferi).
Providence fungi
Serratia spp. (including Serratia marcescens) Salmonella and Shigella spp
Pseudomonas aeruginosa and certain other pseudomonas belong to Acinetobacter acetate
Gonococcus
Meningococcus pertussis bacillus
enterocolitis Yersinia anaerobic bacteria:
Gram-negative bacilli (including Bacteroidetes fragilis, other Bacteroidetes, and Fusobacterium).
Gram-positive and gram-negative cocci (including Pyrococcus, Pyrococcus, and Veronella spp.) Gram-positive bacilli (including Clostridium, Eobacterium, and Lactobacillus spp
The established sensitivity ranges for cefoperazone/sulbactam are shown below:
Minimum inhibitory concentration ( MIC ), ( μg/ml , in terms of cefoperazone concentration).

Diameter of the sensitive paper inhibition zone , ( mm  , Kirby-Bauer method).

Stepwise dilution of cefoperadone/sulbactam at a ratio of 1:1 or 2:1 by broth dilution or agar dilution method to obtain its lowest bacteriostatic concentration (MIC). Susceptibility paper containing 75 μg cefoperazone and 30 μg sulbactam is recommended. If the sensitivity test reports "sensitive", indicating that cefoperazone/sulbactam may be effective in treating infecting pathogens; If "drug resistance" is reported, it indicates that cefoperazone/sulbactam may not be effective in treating the infected pathogen; A report of "moderate sensitivity" indicates that the pathogen may be sensitive to cefoperazone/sulbactam if given at a higher dose or when the infection is confined to tissues or body fluids with high concentrations of this product.
The following recommendations are the quality control criteria for the 75 μg/30 μg cefoperazone/sulbactam susceptibility test:

Toxicology Research
At present, there are no genotoxicity, reproductive toxicity (except for subcutaneous administration, see cefoperazone part) and carcinogenicity research data of this compound preparation, and the toxicological studies of each single drug can refer to the following relevant data.
Cefoperazone
Genotoxicity: In vivo and in vitro genotoxicity studies have not found that this product has mutagenic effects: the results of chromosomal aberration test in human lymphocytes are negative, but when the whole blood cell culture of this product is carried out, chromosomal breaks are found to increase.
Reproductive toxicity: Daily subcutaneous injection of cefoperazone 1000mg/kg (approximately 16 times the average adult dose) can lead to reduced testicular weight, inhibited spermatogenesis, decreased germ cell number, and intracytoplasmic vacuole formation in rats. In the range of 100~1000mg/kg per day, the severity of the damage is related to the dose. Low doses can cause a slight reduction in sperm cells, which is not observed in adult rats. This histological damage is reversible in all dose groups except the highest dose. Nevertheless, these trials did not evaluate later reproductive function in rats. The relationship between the above findings and the human body has not been established.
Subcutaneous injection of cefoperadone/sulbactam in newborn rats, in a ratio of 1:1 (daily dose of 300mg/kg+300mg/kg) after 1 month of medication, can lead to a decrease in testicular weight in rats and the appearance of immature tubules, due to the large individual differences in the maturation of the testes of young rats, and immature testicles were also found in the control group, so it is uncertain whether the above phenomena are related to drugs. The above was not observed when puppies were given more than 10 times the average adult dose of cefoperazone/sulbactam.
Both sulbactam and cefoperazone can cross the placental barrier, but have not been fully and rigorously tested in pregnant women. Since the results of animal reproduction studies do not always predict the human condition, pregnant women should only use this product if the doctor deems it necessary. Lactation medication: Only a small amount of sulbactam and cefoperazone can be secreted into the body's breast milk. Although only a small amount of sulbactam and cefoperazone can enter breast milk, breastfeeding women should still use it with caution.
Carcinogenicity: There are no studies on the potential carcinogenicity of this product for long-term use.
Shubactam
Genotoxicity: No studies have been reported.
Reproductive toxicity: No fertility damage and fetal toxicity were found when administered to mice, rats, and rabbits at doses up to 10 times the human dose. However, there is no sufficient and rigorous data on pregnant women, and the relevance of animal studies to humans is unclear.
Carcinogenicity: not reported in studies.
[Storage]
Keep away from light, airtight, and store no more than 25°C.
[Packaging]
Medium borosilicate glass molded injection bottles, aseptic powders for injection, coated tetrafluoroethylene copolymer film for injection, butyl chloride rubber stoppers and aluminum-plastic combination caps for antibiotic bottles. 1 bottle/box, 10 bottles/box.
[Validity period]
18 months.
[ Implementation standards]
The National Medical Products Administration YBH03762023 standards
[ Approval number ]
1.5g(C ₂₅ H ₂₇ N ₉ O ₈ S ₂ 0.75g 与 C ₈ H ₁₁ NO ₅ S 0.75g):国药准字 H20066402
[ Marketing authorization holder ]
Name: Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd
Registered address: No. 10, Shennong Road, Torch Development Zone, Zhongshan City, Guangdong Province
【Manufacturer】 Company name: Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd
Guangdong Jincheng Jinsu Pharmaceutical Co.,Ltd.
Production address: No. 10 Shennong Road, Torch Development Zone, Zhongshan City, Guangdong Province
Postal code: 528437
Service hotline: 400-9988-970
Telephone number: (0760) 22830525 (switchboard).
Fax number: (0760) 22578279
Website: http://www.gdjcjs.com