Cefazoxime sodium for injection, developed by Wuhan Pusheng Pharmaceutical Co., Ltd. and Chengdu Xinjie High-tech Development Co., Ltd., belongs to the fourth class of new compounds, approved by the State Food and Drug Administration (drug clinical research approval number: 2003L02046), and is under the responsibility of the National Drug Clinical Research Base of the First Affiliated Hospital of Chongqing Medical University. Taking the First Affiliated Hospital of Chongqing Medical University, the Second Affiliated Hospital of Chongqing Medical University and xinqiao hospital of the Third Military Medical University as the participating units, according to the requirements of new drug evaluation, 80 pairs of randomized double-blind controlled studies were conducted on respiratory tract infections and urinary tract infections to evaluate the effectiveness and safety of this product in treating bacterial infections. The study was designed as a multicenter randomized double-blind controlled trial.
Drugs and Administration Methods Test drugs: ceftizoxime sodium for injection, each bottle 1.0g, provided by Wuhan Pusheng Pharmaceutical Factory, batch number: 03080 1. Reference drug: Cefazoxime sodium for injection (Yibaoshiling), each bottle contains 1.0g, which is repackaged by Southwest Pharmaceutical Co., Ltd., batch number: 2003090 1. The administration method is: 2.0g each time, twice a day, intravenous drip, and the course of treatment is 7~ 14 days. Selection criteria: 18~70 years old inpatients or outpatients. The skin test of ceftizoxime sodium was negative before medication. ⑶ Patients who are clinically diagnosed as bacterial infection and need intravenous administration for at least 3 days. Through bacteriological examination, more than 80% of the subjects need positive bacterial culture, and a few subjects with negative bacterial culture must have clinical symptoms and signs of bacterial infection and corresponding laboratory test results. Subjects did not receive other antibiotics within 72 hours before the trial, or received the drug alone after receiving other antibiotics and being positive for bacteriology. Subjects need to sign an informed consent form. (7) Diagnostic criteria of diseases: refer to the 10th edition of Practical Internal Medicine (edited by Chen Haozhu, Editorial Committee of Practical Internal Medicine of Shanghai Medical University, published by People's Health Publishing House).
Exclusion criteria: those with allergic history to penicillin or cephalosporin, or those with high sensitive constitution, or those with positive skin test of ceftizoxime sodium in this experiment. Severe heart and liver (heart function is divided into four grades, belonging to grade 3~4, TBIL or ALT >；; ; Normal value 1.5 times), renal insufficiency (Cr >；; 133μmol/L) or patients with hematopoietic dysfunction, bleeding tendency and hemorrhagic diseases; Patients with mental illness, nervous system diseases and advanced tumors; Children, pregnant women or lactating women; (5) Non-bacterial infected persons with poor compliance or dying and unable to complete the course of treatment; Participated in this trial or participated in other drug trials within three months before being selected; Patients with urinary tuberculosis or tumor, patients with active pulmonary tuberculosis, or patients complicated with lung cancer, empyema, collagen diseases affecting the lungs, cystic fibrosis, etc. , thus affecting the research results; Immunodeficiency; ⑽ Infected persons caused by bacteria resistant to ceftizoxime sodium; Drug addicts; ⑿ Patients who need systemic combined application of other antibacterial drugs.
Rejection criteria: those who do not meet the test plan are found during the test; Add or switch to other antibiotics during the trial; The drug has not been used for 72 hours or the treatment is interrupted for some reason, and the curative effect cannot be evaluated; Those who stop taking drugs due to serious adverse reactions are not included in the efficacy analysis, but should be included in the statistics of adverse reactions; 5] lost visit; (6) The situation that the researcher thinks it is necessary to withdraw from the experiment.
Exit criteria: (1) poor compliance, unable to complete the test according to the test plan; Serious adverse reactions or obvious abnormal detection values, it is not appropriate to continue to use drugs; ⑶ The patient's condition has not improved after taking the medicine for 72 hours, or the patient's condition is aggravated, or the patient or his family members request to stop taking the medicine.
Diseases and strains are respiratory and urinary tract infections, mainly moderate and severe acute bacterial infections, and pathogenic bacteria sensitive to experimental drugs and control drugs are selected. During the clinical observation trial, the changes of symptoms and signs of patients were observed in detail every day, and recorded accurately according to the requirements of the observation table. Adverse reactions were recorded.
Laboratory and auxiliary examination of blood routine, urine routine, liver and kidney function, electrocardiogram in 24 hours before medication and 65438 0 days after drug withdrawal. Women of childbearing age need to do urine pregnancy test before joining the group. Chest X-ray examination: urinary system infection does not need this examination; Do it once before taking medicine for lower respiratory tract infection. If there is anything abnormal before taking the medicine, do it again after stopping taking the medicine. Bacterial culture: the positive rate of pathogenic bacteria should reach above 80% before medication and the first day after drug withdrawal. Contingency reserve.
Drug sensitivity test of paper: After the pathogenic bacteria were separated, the research institute conducted bacterial sensitivity tests on ceftizoxime sodium, cefotaxime/clavulanic acid, ceftriaxone, azithromycin, levofloxacin and amikacin paper.
MIC determination: Each participating research unit should send the isolated strains to the lead unit of clinical trial to determine the MIC values of the above six antibiotics.
Evaluation standard of curative effect Clinical curative effect is evaluated in four grades: cured, markedly effective, effective and ineffective. The sum of recovery and marked effect is effective, and the effective rate is calculated accordingly. Bacteriological efficacy was evaluated according to five levels: clearance, partial clearance, non-clearance, replacement and reinfection.
According to the judgment of the relationship between adverse events and experimental drugs, the records and reports of adverse events are divided into six levels: definitely related, possibly related, possibly related, unlikely related, unable to evaluate and not evaluated. The first three kinds are counted as adverse reactions, and the incidence of adverse reactions is counted.
The clinical trial data were statistically analyzed by SAS6. 12 statistical software. Clinical efficacy evaluation: 80 patients with respiratory and urinary system were treated with Sinopharm Group, 50 cases were cured, 22 cases were markedly effective, and 8 cases were improved, with a cure rate of 62.50% and a total effective rate of 90%; In the imported group, 80 cases were cured, 45 cases were cured, 27 cases were markedly effective and 8 cases were improved. The cure rate is 56.25%, and the total effective rate is 90%. There was no significant difference between the two groups (P & gt0.05).
Bacteriological efficacy analysis: 62 strains of bacteria were isolated from the domestic product group and the imported product group, and the bacterial clearance rates were 87.65438 0% and 90.3% respectively, and the negative conversion rates were 83.9% and 90.3% respectively. The clearance rate of Gram-positive bacteria in domestic product group was 88%, and that in imported product group was 94. 1%. The clearance rate of gram-negative bacteria was 86.5% in domestic group and 88.9% in imported group. There was no significant difference (p > 0.05). 0.05)。
In vitro antibacterial activity test of isolated bacteria * * * 124 strains of bacteria, including 42 strains of gram-positive bacteria and 82 strains of gram-negative bacteria. The drug sensitivity test by disk method showed that the sensitivity to gram-positive bacteria was 865,438 0%, the sensitivity to gram-negative bacteria was 86.6%, and the total sensitivity was 84.7%. The MIC of 1 18 living bacteria was determined. The results showed that ceftizoxime had strong antibacterial activity against Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus (except Enterococcus) in gram-positive bacteria, and had strong antibacterial activity against common bacteria such as Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Proteus mirabilis and Serratia in gram-negative bacteria.
The national product group of drug safety evaluation found 12 adverse events in 7 patients, with an incidence rate of 8.75%; In the imported product group, 6 patients had 9 adverse events (excluding 1 case), and the incidence rate was 7.50%. 1 patient with mild leukopenia in both groups failed to return to normal after follow-up, and the rest were relieved or returned to normal without special treatment. There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). 0.05)。 Cefazoxime sodium is the third generation cephalosporin antibiotic developed by the Central Research Institute of Fujisawa Pharmaceutical Industry Co., Ltd., Japan. It has a broad antibacterial spectrum. In vitro and in vivo experiments show that it has good antibacterial effect on both gram-positive bacteria and gram-negative bacteria, especially on pneumococcus and streptococcus (except enterococcus) in gram-positive bacteria, Escherichia coli, Klebsiella, Proteus mirabilis, Proteus Indole and Haemophilus influenzae in gram-negative bacteria. In addition, citrobacter, Enterobacter, Serratia and anaerobic bacteria, including Bacteroides, which are resistant to various cephalosporins, also have obvious antibacterial activities.
The product is stable to β -lactamase produced by various bacteria, so it has strong antibacterial activity to β -lactamase producing bacteria. The elimination half-life of this product is about 1.4~ 1.8 hours, and it is not metabolized in the body, and about 90% is excreted by the kidney in the prototype. Cefozoxime sodium has good permeability in sputum, pleural effusion, bile, spinal fluid, tonsil, gallbladder, uterus, prostate and other tissue fluids or organs, and can also enter cerebrospinal fluid when there is inflammation. After repeated intravenous injection, this product has no accumulation in the blood, less adverse reactions and good tolerance. The clinical efficacy and safety of domestic ceftizoxime were studied in this clinical trial. The results showed that the cure rates of domestic group and imported group were 62.5%(50/80) and 56.25%(45/80) respectively, and the effective rate was 90% (72/80). The bacterial clearance rates were 87.65438 0% (54/62) and 90.3%(56/62) respectively, and the negative conversion rates were 83.9% and 90.3% respectively. The in vitro antibacterial test showed that it had good antibacterial activity against clinical common gram-positive bacteria and gram-negative bacteria, and the total sensitivity rate to 124 strains of bacteria was 84.7%. The incidence of adverse reactions was 8.75%(7/80) and 7.50%(6/80) respectively. There was no significant difference in the above statistics (P & gt0.05).
To sum up, compared with imported ceftizoxime, domestic ceftizoxime has similar curative effect in the treatment of respiratory and urinary tract infections, less adverse reactions, strong antibacterial activity and high clearance rate of sensitive bacteria, which is similar to the literature reports.