Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders]

The combination therapy of sulbactam/cefoperazone (SBT/CPZ) and piperacillin (PIPC) was evaluated in 49 patients with severe infections associated with hematological disorders. Clinical responses in 43 evaluable patients out of the 49 patients were excellent in 12, good in 18, thus, overall efficacy rate was 69.8% (excellent plus good). Efficacy rates of this combination therapy were 60% (3/5) for sepsis, 75% (21/28) for suspected sepsis, and 50% (4/8) for pneumonia. The efficacy rate was 71.4% (10/14) in patients with neutrophil counts less than 200/microliters; this combination therapy was highly effective even in the neutropenic patients. Transient increases in hepatic function test values were observed in 2 patients, but no other side effects were observed during the combination therapy. From these observations it appears that the combination therapy of SBT/CPZ and PIPC is a very useful empiric therapy for severe infections associated with hematological diseases.     

Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders

The effectiveness of sulbactam/cefoperazone (SBT/CPZ) on severe infections associated with hematological diseases was evaluated in a nation-wide multicenter clinical study. SBT/CPZ (4-6 g/day), a 1:1 combination of SBT and CPZ, was given intravenously to 437 patients with hematological disorders. The underlying diseases included acute nonlymphocytic leukemia, acute lymphocytic leukemia, malignant lymphoma, multiple myeloma, myelodysplastic syndrome and others. Thus, 94.3% of the patients had hematological malignancies. The complicating infections included sepsis in 41 cases; sepsis suspected in 205; pneumonia in 47; urinary tract infection in 15; fever of unknown origin in 59; and others in 70. Clinical efficacies of SBT/CPZ were as follows; markedly effective, 83 cases; effective, 170; fairly effective, 59; and ineffective, 110. The efficacy rate (markedly effective plus effective) was 60.0% as a whole. The efficacy rate of SBT/CPZ in sepsis and suspected cases, which accounted for 56.3% of the infections, was 59%. Mild side effects such as skin rash were observed in 15 patients (3.1%). As for abnormal laboratory test results, transient increases in GOT, GPT, A1-P, LDH, etc. were observed in 42 patients (8.6%). Therefore, SBT/CPZ is considered to be a useful drug in empiric therapy for severe infections associated with hematological diseases.     

An evaluation of combination antibiotic therapy in infections with hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders

A clinical study was undertaken to determine the effects of combination antibiotic therapy in 104 patients with infections associated with hematological disorders. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) plus an aminoglycoside as an empiric therapy for fever. The overall efficacy rate of the therapy was 63.5%. Efficacy rates were 61.2% and 71.9% when initial neutrophil counts were less than 500/mm3 and over 500/mm3, respectively. No significant difference was found between the cases in which initially used antibiotics were continued (efficacy rate 62.5%) and those in which antibiotics were switched during the course of therapy (65.6%). Antibiotic therapy with SBT/CPZ plus an aminoglycoside provides adequate antibiotic coverage against infections associated with hematological disorders. This combination was highly effective even in the neutropenic periods of febrile patients.     

Clinical experience with chemotherapy using sulbactam/cefoperazone for severe infections accompanying malignant hematological disorders

Clinical and bacteriological efficacies of sulbactam/cefoperazone (SBT/CPZ) were studied in 44 patients with serious infections associated with hematological malignancy. 1. SBT/CPZ was clinically effective in 33 cases (76.7%). Excellent effects were obtained in 23 cases, good effects in 10 cases and fairly good effects in 7 cases. Clinical effectiveness of SBT/CPZ was not dependent on neutrophil number in peripheral blood. 2. Bacteriologically SBT/CPZ was effective against all of the isolated organisms from 21 cases. 3. Adverse reactions were not significant except one case with eruption, 2 cases with abnormalities in hepatic function tests and 3 cases with abnormalities in renal function tests.     

Clinical experience on sulbactam/cefoperazone in the pediatric field

Approximately 20 mg/kg/day of sulbactam/cefoperazone (SBT/CPZ) was given by one shot intravenous injection to 16 pediatric inpatients with respiratory tract infections (13 cases), urinary tract infection (1 case), skin infection (1 case) or gastrointestinal tract infection (1 case). An excellent efficacy in 6 cases and a good efficacy in 10 cases were observed. Causative organisms were not identified in the respiratory tract infections, even though the efficacy was excellent or good. Side effects were not noticed in particular and SBT/CPZ was judged as safe enough agent. Concentrations of SBT/CPZ in the spinal fluid were determined in 3 patients. Their low concentrations suggested the poor transfer into the spinal fluid. Finally, SBT/CPZ is a very useful agent since it is effective also against resistant organisms which produce penicillinase-type beta-lactamases.     

Fundamental and clinical studies of sulbactam/cefoperazone in obstetrics and gynecology

The study was done to evaluate the usefulness of sulbactam/cefoperazone (SBT/CPZ) injection for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made and the following results were obtained. In the clinical studies, SBT/CPZ was given to 19 cases with female genital organ infections. As for the clinical effects, responses were excellent in 4 cases, good in 15 cases among 19 cases in total. The efficacy rate was 100%. The efficacy rate on disease was 100% in all cases (9 cases of puerperal uterine infection, 1 case of endometritis, 1 case of pyometra, 5 cases of adnexitis, 2 cases of pelveoperitonitis and 1 case of abscess of vulva). As for causative bacteria, the efficacy rate was 100% for all infections due to single or mixed infection, due to aerobic Gram-negative, -positive or anaerobic bacteria. Side effect was observed in 1 case with diarrhea. SBT/CPZ showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infection in the field of obstetrics and gynecology, and it has been concluded that SBT/CPZ will be a useful addition to the antibiotics for the therapy of these infections.     

Clinical evaluation of sulbactam/cefoperazone for infections in the field of obstetrics and gynecology

A daily dose of 2 or 4 grams of sulbactam/cefoperazone (SBT/CPZ) by drip infusion was given to 12 patients with gyneco-obstetrical infections and the results were following: The clinical effect was judged excellent in 2 cases, good in 9 cases and poor in 1 case, and the effective rate was 91.7%. Except for Streptococcus faecalis, the bacteriological effect was sufficient. A good effect was also seen in Pseudomonas cepacia resistant organism to other cephem antibiotics. Diarrhea was observed in 1 patient, and increases of GOT and GPT, possibly attributable to concomitantly used anticancer agent, were detected in another patient. In conclusion, SBT/CPZ with a 91.7% of efficacy rate, was useful in infections caused by beta-lactamase producing organisms and, thus, a useful agent for gyneco-obstetrical infections.     

Fundamental and clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology

Fundamental and clinical studies on sulbactam/cefoperazone (SBT/CPZ), a combination drug of sulbactam and cefoperazone, were carried out in the field of obstetrics and gynecology. The following results were obtained: Transfer into female genital organ tissues Following 1 hour intravenous drip infusion of SBT/CPZ, favourable transfers of both of SBT and CPZ to female genital organ tissues and pelvic dead space exudate were observed. Clinical evaluation A total of 12 cases comprising 6 with intrauterine infection, 1 with pyometra, 1 with abscess of portio vaginalis, 2 with parametritis, 1 with pelvioperitonitis and 1 with purulent lymphocyst was treated with SBT/CPZ. Clinical efficacy was excellent in 6 cases, good in 5 cases and poor in 1 case, with overall efficacy rate of 92%. The bacteriological efficacy was judged as eradicated in 3, and as decreased in 2 out of 5 evaluable cases. In all of the 5 cases, isolated organisms were beta-lactamase producing organisms. No notable side effects or abnormal laboratory findings were observed except 1 case with elevations of GOT and GPT.     

Experimental and clinical studies of sulbactam/cefoperazone in pediatric field

Clinical trials were carried out with sulbactam/cefoperazone (SBT/CPZ) (combination ratio of 1:1) in pediatric infections. Results were as follows. The mean half-lives of SBT and CPZ in the serum following intravenous injection of SBT/CPZ were about 0.7 and 1.2 hours, respectively. Urinary excretions of SBT and CPZ within 6 hours after intravenous injection of SBT/CPZ were 81.9% and 28.1%, respectively. SBT/CPZ was administered to 33 pediatric patients with various infection; 18 respiratory tract infections, 12 urinary tract infections and 3 Salmonella enterocolitis. The overall efficacy rate was 87.9%. In particular, 7 of 8 urinary tract infections caused by beta-lactamase producing organisms were improved after administration of SBT/CPZ. Diarrhea in 8 and soft stool in 3 of 33 patients occurred, and slight elevation of GOT/GPT was observed in 2 patients.     

Clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology

Efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) was studied on gynecological infections. The results obtained are as follows: In the treatment of 31 cases of gynecological infections, the clinical efficacy of SBT/CPZ was assessed as excellent in 9 cases and effective in 22 cases. As for the bacteriological effects of SBT/CPZ, clinically isolated organisms were completely (100%) eradicated. In comparison with MICs of CPZ, SBT/CPZ was found to show a combined effect on Gram-negative and Gram-positive organisms in the order mentioned, but this effect was not observed against anaerobes. The combined effect of SBT/CPZ on beta-lactamase producing bacteria was also investigated in the same manner. As a result, SBT/CPZ was found to exert a combined effect on beta-lactamase strains of S. aureus, S. epidermidis, E. coli, B. catarrhalis and B. fragilis. The laboratory tests performed before and after administration of SBT/CPZ revealed rise in GOT and GPT values in 1 case, GPT values in 2 cases and eosinophil in 1 case. However, these rises were all mild and required no particular measures.     

Clinical trial of sulbactam/cefoperazone in the field of obstetrics and gynecology

Sulbactam/cefoperazone (SBT/CPZ) was administered to 19 patients with various infections in the field of obstetrics and gynecology. The clinical efficacy was judged as excellent in 1 case and as good in 16 cases; hence, the efficacy rate was 89.5%. SBT/CPZ was not effective in a patient with end-stage carcinomatous peritonitis and nor in a patient with pyosalpinx caused by E. coli and Peptococcus magnus. Except a case by E. coli, SBT/CPZ was highly effective for pyosalpinx and pelvic peritonitis where E. coli or K. pneumoniae was the causative organism. No side effects were observed.     

Clinical assessment of sulbactam/cefoperazone in comparison with ceftizoxime in patients with postoperative infections by well controlled method

The clinical effectiveness in postoperative infections of sulbactam/cefoperazone (SBT/CPZ, (SBT 0.5 g+ CPZ 0.5 g) X 2/day) was compared to that of ceftizoxime (CZX, 1.0 g X 2/day) by a well controlled comparative study, to have the following results. The overall effectiveness rate of SBT/CPZ and CZX as judged by Judgement Committee was 84.0% (63/75) and 80.6% (50/62), respectively, and the effectiveness of SBT/CPZ and CZX as assessed by the attending surgeons was 84.0% (63/75) and 71.0% (44/62), respectively. No significant difference was noted in both assessments. In a total of 36 SBT/CPZ-treated patients with intraabdominal infections, the clinical efficacy was judged by attending surgeons to be excellent in 13 patients (36.1%), and to be excellent or good in 31 (86.1%). In the 30 CZX treated patients, it was judged to be excellent in 6 patients (20.0%), and to be excellent or good in 19 (63.3%). These results presented a significant difference (P less than 0.05, U-test) between the 2 drug groups. The final global improvement ratio judged by attending surgeons was 85.3% (64/75) for SBT/CPZ, and 79.0% (49/62) for CZX with no significant difference. In assessment of time-course improvement, the improvement ratio of SBT/CPZ on day 4 was significantly better than that of CZX (P less than 0.05, U-test). The usefulness rate of SBT/CPZ and CZX was 84.0% (63/75) and 73.0% (46/63), respectively. There was no significant difference between the 2 drug groups. To assess the bacteriological efficacy, the eradication rate of SBT/CPZ was compared to that of CZX. There was no significant difference between 85.7% (36/42) for SBT/CPZ and 73.5% (25/34) for CZX. After SBT/CPZ administration, 2 patients (2.5%) complained of side effects. In the clinical laboratory tests, abnormality related to SBT/CPZ medication was observed in 6 patients (7.5%), and that related to CZX, in 5 patients (6.4%). As to the types of side effects and frequency, no significant difference was observed between SBT/CPZ and CZX. It is concluded from the above assessments that SBT/CPZ is a useful drug in the treatment of post-operative infections.     

Experience with sulbactam/cefoperazone in the field of obstetrics and gynecology

Sulbactam/cefoperazone (SBT/CPZ) was studied for clinical efficacy in the field of obstetrics and gynecology, and following results were obtained: In the treatment of 6 cases of gynecological infection, the clinical efficacy of SBT/CPZ was assessed as excellent in 1 case and effective in 5 cases. Neither adverse effects nor abnormalities in laboratory findings due to SBT/CPZ were observed. Based on these results, SBT/CPZ is considered to be a highly effective antibiotic with clinical efficacy in obstetric and gynecological infections in the daily dosage of 2 g given in two divided doses.     

Studies on sulbactam/cefoperazone in the field of pediatrics

Microbiological, pharmacokinetic and clinical studies on sulbactam/cefoperazone (SBT/CPZ) were carried out in the field of pediatrics. Antimicrobial activity The MIC80 of SBT/CPZ was 6.25 micrograms/ml for clinically isolated 24 strains of S. aureus (24 beta-lactamase producing strains), 0.39 micrograms/ml for 17 strains of S. pyogenes, 3.13 micrograms/ml for 24 strains of E. coli (22 beta-lactamase producing strains), 3.13 micrograms/ml for 22 strains of K. pneumoniae (22 beta-lactamase producing strains), 1.56 micrograms/ml for 22 strains of P. mirabilis and 0.20 microgram/ml for 15 strains of H. influenzae (13 beta-lactamase producing strains). In comparison with CPZ in respect to the MIC, SBT/CPZ exhibited synergistic effect on 31 strains out of 81 beta-lactamase producing strains (included 6 strains of S. aureus, 9 of E. coli, 5 of K. pneumoniae and 11 of H. influenzae) which was scarcely observed against 43 non-beta-lactamase producing strains. Absorption and excretion Serum levels and urinary excretion of SBT/CPZ were studied in 7 children aged 5 to 12 years. The mean serum concentration of SBT at 15 minutes following a single intravenous injection of 10 mg/kg of SBT/CPZ was 14.2 micrograms/ml and that of CPZ was 30.4 micrograms/ml. The mean urinary recovery rates at 6 hours following the intravenous injection were 57.8% and 18.3%, respectively. The mean serum concentrations of SBT and CPZ after 1-hour infusion of 10 mg/kg of SBT/CPZ were 10.9 micrograms/ml and 17.6 micrograms/ml, respectively. The urinary recovery rates of SBT and CPZ at 7 hours after the infusion were 100.0% and 27.7% on average, respectively. The mean serum levels of SBT and CPZ at 15 minutes after a single intravenous injection of 20 mg/kg of SBT/CPZ were 25.6 micrograms/ml and 66.0 micrograms/ml, respectively and urinary elimination until up to 6 hours were 72.5% on average for SBT and 21.1% for CPZ. Clinical study SBT/CPZ was used for the treatment of a total of 20 pediatric patients aged 1 month to 14 years to evaluate its clinical effectiveness, bacteriological efficacy and adverse effects. The clinical efficacy in 6 patients with acute pneumonia, 3 with staphylococcal scalded skin syndrome, 2 each with acute purulent tonsillitis and acute pyelonephritis, 1 each with acute purulent lymphadenitis, acute sinusitis, acute bronchitis, peritonitis and acute enteritis was judged to be excellent in 15 cases and good in 3 cases with an efficacy ratio of 100%. The clinical efficacy in 6 patients whose infections were caused by beta-lactamase producing strains was judged to be excellent in all the cases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of sulbactam/cefoperazone in lower respiratory tract infections

Clinical evaluation, safety and kinetics in serum of sulbactam/cefoperazone (SBT/CPZ) in patients with lower respiratory tract infections have been studied in a multicenter trial participated by 28 institutions in Kyushu area during a period of 13 months from March 1987 to March 1988. 1. Mean peak serum levels of SBT and CPZ in 35 patients up to 4 hours after intravenous infusion of 2 g of SBT/CPZ were 38.2 +/- 17.3 micrograms/ml for SBT and 104.3 +/- 31.4 micrograms/ml for CPZ. Serum half-lives of SBT and CPZ were 0.76 hour and 1.53 hours, respectively. These results were in similar ranges to those reported elsewhere for SBT/CPZ. 2. Serum half-lives of SBT and CPZ after intravenous infusion of 2 g of SBT/CPZ were not significantly prolonged in patients with moderate liver or kidney dysfunctions. 3. Clinical efficacy rates of SBT/CPZ in 217 patients were 93.1% (81/87) for pneumonia, 93.3% (14/15) for lung abscess, 78.9% (15/19) for acute exacerbation of chronic bronchitis, 57.1% (4/7) for diffuse panbronchiolitis, 72.4% (21/29), 74.4% (32/43) and 100% (9/9) for infections concurrent to bronchiectasis, chronic respiratory disease and pulmonary emphysema, respectively. Those were 50% (1/2) for bronchitis associated with lung cancer and 66.7% (4/6) for empyema. The overall efficacy rate was 83.4% (181/217). 4. Clinical efficacy rate of SBT/CPZ for pneumonia in patients with underlying diseases such as lung cancer, pulmonary tuberculosis and pneumoconiosis, etc, was 85.3% (29/34) and was not significantly different from the efficacy rate of 98.1% (52/53) in patients without these underlying diseases. 5. Of 30 patients who failed to respond of previous antibiotic treatments, 21 were effectively treated by SBT/CPZ. 6. Bacteriological eradication rates against Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae were 42.9% (9/21), 87.5% (14/16) and 100% (5/5), respectively. The overall eradication rate in all cases including polymicrobial infections was 72.8% (67/92). 7. The high levels of peak serum concentration of CPZ, and the difference between serum levels of SBT and of CPZ seemed to contribute to the high clinical efficacy. 8. Adverse reactions occurred in 2.8% (6/217) of the patients, and consisted primarily of rash and diarrhea. Laboratory abnormalities were observed in 8 patients during the study. These were elevations of S-GOT and S-GPT, and eosinophilia. 9. SBT/CPZ is a very useful drug in the treatment of lower respiratory tract infections as it has become available just in time when increase in resistant organisms to beta-lactams is notable.     

Fundamental and clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology

A combination of sulbactam, a beta-lactamase inhibitor, plus cefoperazone (SBT/CPZ = 1/1) was studied in the field of obstetrics and gynecology, and the results were following: Absorption and transfer into genital organ tissues were good. With the 1g intravenous injection the maximum serum concentrations in the uterine artery were 88.6 micrograms/ml for CPZ and 50.0 micrograms/ml for SBT, and the maximum tissue concentrations were 12.2-17.4 micrograms/g for CPZ and 9.8-21.4 micrograms/g for SBT. When the 2 g was administered, the maximum tissue concentrations were 11.9-26.7 micrograms/g for CPZ and 6.0-8.0 micrograms/g for SBT. These elimination showed the similar trend as their serum levels, and their tissue levels were higher than MIC80 for the main organisms. Their penetration into the intrapelvic dead space exudate was also good and showed that the peak levels were 30.1 micrograms/ml for CPZ and 17.4 micrograms/ml for SBT at 2 hours after the 2 g intravenous injection. The peak levels of 34.4 micrograms/ml for CPZ and 8.8 micrograms/ml for SBT at 6 hours after 2 g intravenous drip infusion were obtained. Their elimination was slow, and the concentration higher than MIC80 for main organisms was maintained for a long period of time. For gyneco-obstetrical infections such as adnexitis, intrauterine, intrapelvic and external genital organ infections, a daily dose of 2-4 g of SBT/CPZ produced a 100% clinical efficacy in 10 patients and a 88.9% bacteriological effect. The eradication ratio was more than 80% against beta-lactamase producing organisms. Side effects were few. The above results indicated that SBT/CPZ was useful in the field of obstetrics and gynecology.     

Effects of sulbactam/cefoperazone in patients with respiratory infections in aged and/or with underlying respiratory diseases

Sulbactam/cefoperazone (SBT/CPZ), a new antibacterial drug, was administered to 14 cases with respiratory infections for a duration of 5 approximately 13 days at a daily dose of 4 g. Diagnoses of these patients were 7 respiratory tract infections, and 7 bronchopneumonias. The underlying diseases were chronic pulmonary emphysema in 6 cases, bronchial asthma in 2 cases, and one each of bronchiectasis, diffuse panbronchiolitis and lung cancer with bronchoesophageal fistula. All patients had underlying respiratory diseases and/or were more than 70 years old. The rate of clinical efficacy was 78.6%. The incidence of penicillinase production by isolated bacteria was 18.2% and that of cephalosporinase was 63.6%. SBT/CPZ was expected to be more effective than CPZ alone in 3 cases judging from the susceptibility of the bacterial strains concerned, to antibiotics. No side effects were observed. We conclude that SBT/CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases.     

Enhancement of susceptibility of sulbactam/cefoperazone-treated bacteria to phagocytes

Effects of sulbactam/cefoperazone (SBT/CPZ) on the host-parasite relationship were studied using an established mouse macrophage cell line. Since SBT inactivates some types of beta-lactamase strongly, a combination of SBT with CPZ shows marked antibacterial activities against the bacteria producing beta-lactamases. In addition, sub-MIC levels of SBT/CPZ made Escherichia coli more susceptible to bactericidal activity of macrophage. This study provides evidence that SBT/CPZ works in partnership with host defense mechanism against bacterial infections in clinical situations.     

舒巴克坦对头孢哌酮体外抗生素后效应的影响

目的 考察合用β-内酰胺酶抑制剂舒巴克坦（ＳＢＴ）前后头孢哌酮（ＣＰＺ）对４种致病菌抗生素后效应（ＰＡＥ）的变化。方法 采用特异性β-内酰胺酶鉴定试剂Ｎｉｔｒｏｃｅｆｉｎ挑选大肠埃希氏杆菌、金黄色葡萄球菌、变形杆菌和绿脓假单胞菌的产酶菌株，用比浊法测定受试菌株在不同ＣＰＺ浓度时的ＰＡＥ值。结果 合用ＳＢＴ后，ＣＰＺ对产酶菌株的ＰＡＥ均有不同程度的延长，低浓度时（１／２，１倍ＭＩＣ）ＰＡＥ增加更明显（Ｐ＜０．０５）。结论 合并ＣＰＺ和ＳＢＴ的给药方案对治疗产β-内酰胺酶菌株引起的感染有利，尤其在体内药物浓度较低时，合并用药可以更长时间地抑制细菌生长。     

Clinical evaluation of ceftazidime monotherapy for infections complicated with hematological disorders]

Fifty patients with infections associated with hematological disorders were treated with ceftazidime (CAZ). Among them 44 cases were evaluable, including 21 with acute leukemia, 17 with malignant lymphoma, and 6 with other hematological disorders. Excellent responses were observed in 15 patients (34.1%) and good responses in 15 (34.1%), with an overall efficacy rate of 68.2%. The efficacy rate among sepsis and suspected sepsis cases was 67.6%. This treatment was also effective in 7 of 10 cases in which neutrophil counts were less than 500/mm3 through the course of administration. Laboratory abnormalities included mild eosinophilia in 1 case, slight elevation of GOT in 1 case and slight elevation of GPT in 1 case. These results suggest that CAZ is an effective and safe antibiotics for the treatment of infections in patients with hematological disorders.