The prophylactic effects of latamoxef against the postoperative infections to open heart surgery. Studies on the penetration of latamoxef into the pericardial fluid and the auricle of heart

Latamoxef (LMOX, Siomarin) at a dose of 2 g was intravenously administered to each of 23 patients undergoing the open heart surgery and the concentrations in serum, pericardial fluid and auricle of heart were measured. Pharmacokinetic observations are summarized below. The peak serum concentration (t = 0) was 227.3 micrograms/ml and the serum half-life (T1/2 beta) was 1.74 hours. In pericardial fluid, LMOX reached the peak concentration of 28.44 micrograms/ml at 4.9 hours and the half-life was 9.99 hours. In auricle of heart, LMOX reached the peak concentration of 42.78 micrograms/g at 6.9 minutes and the half-life was 1.74 hours. It was shown that LMOX penetrates well into the pericardial fluid and the auricle of heart, and it is considered that their levels exceed the minimal inhibitory concentration against a majority of clinical isolates except Pseudomonas aeruginosa.     

Pharmacokinetics of cefoperazone concentration in human lung tissue

In 11 patients, the concentration of cefoperazone (CPZ) in the lung tissue were studied after a 2 g intravenous bolus injection. Samples of lung tissue and blood were taken during surgery at 15, 30, 60, 120, 180, 240, and 300 minutes after administration of CPZ. All samples were assayed by the paper disc method using Micrococcus luteus ATCC 9341 as the indicator strain. All assay results of lung tissue were corrected for the amount of blood contained in the tissue samples by the hemoglobin content in the homogenate of lung tissue. The CPZ levels in the lung tissue were 116.2 micrograms/g at 15 min., 94.1 micrograms/g at 30 min., 74.6 micrograms/g at 60 min., 67.9 micrograms/g at 120 min., 54.6 micrograms/g at 180 min., 29.2 micrograms/g at 240 min. and 22.7 micrograms/g at 300 min. after administration, respectively. These values were higher than MIC90 values of CPZ for Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae and Enterobacteriaceae. The level of CPZ in the lung tissue was higher than 50% of the level in the serum until 180 minutes after administration of CPZ.     

A study of cefoperazone levels in the cerebrospinal fluid of patients with hydrocephalus

Eleven neurosurgical patients without intracranial infection were given 4 g cefoperazone (CPZ) intravenously for 30 minutes. Ventricular drainage was performed in 10 cases, and 1 case with cisternal drainage. Eight of 11 cases showed moderate to severe ventricular dilatation. Serum and ventricular cerebrospinal fluid (CSF) concentrations of CPZ were measured for 8 hours after injection. Average peak serum concentration of CPZ was 476 micrograms/ml and the half-life was 150 minutes. Patients with obstructive hydrocephalus showed relative good penetration of CPZ in CSF (2.74 approximately 5.29 micrograms/ml). Especially, those who had severe dilatation of ventricles demonstrated sequential increased concentration (5.48 approximately 6.25 micrograms/ml at 8 hours). In poor risk patient and intracerebral hemorrhage with ventricular hemorrhage cases, who had normal range of CSF cell counts and protein, CPZ level was low, less than 2 micrograms/ml. In cases with severe subarachnoid hemorrhage, sufficient concentration (11 micrograms/ml) of CPZ was observed in cisternal CSF. The CPZ concentrations in CSF after 4 g administration did not seem to exceed comparing to 2 g dosing.     

Clinical studies with cefoperazone in the biliary disease

The concentration of cefoperazone (CPZ) in serum and bile was estimated after intravenous drip infusion of 1 g of the drug in 11 patients, who have performed cholecystectomy, choledocholithotomy and T-tube drainage for gallstone diseases. Administration of cefazolin (CEZ) 1 g was compared by the cross over method. After 1 g intravenous drip infusion of CPZ, the mean serum concentration was 88.3 +/- 24 micrograms/ml at 1 hour, 52 +/- 11.7 micrograms/ml at 2 hours and 36.5 +/- 10 micrograms/ml at 4 hours. The maintenance period of serum concentration was inclined to be longer in CPZ than in CEZ. After 1 g intravenous drip infusion of CPZ, the mean bile concentration reached to 810 +/- 459 micrograms/ml in 2 hours and it was maintained as high as 562 +/- 319 micrograms/ml even after 4 hours. On the other hand, after 1 g intravenous drip infusion of CEZ, the mean bile concentration was only 28.7 +/- 26 micrograms/ml in 1 hour and was low level in the progress. As compared with the highest concentration of CPZ and CEZ in same patient, the mean bile concentration of CPZ (942 +/- 525 micrograms/ml) was about 30 times higher than that of CEZ (28.6 +/- 26.3 micrograms/ml). There was no difference in the group of Gram-positive cocci between minimum inhibitory concentration (MIC) of CPZ and that of CEZ. While MIC of CEZ in the group of Gram-negative bacilli was from 0.78 to over 400 micrograms/ml, MIC of CPZ in that group was from 0.10 to 50 micrograms/ml. The value in CPZ was lower than that in CEZ at all strains. No side effects was seen in all patients.     

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.     

Transfer of injected sulbactam/cefoperazone into burn blister fluid

Transfer of sulbactam/cefoperazone (SBT/CPZ) into the burn blister fluid was studied in 10 burn patients after one shot intravenous injection of 50 mg/kg SBT/CPZ (CPZ 25 mg/kg, SBT 25 mg/kg). CPZ and SBT concentrations in serum and burn blister fluid were determined using bioassay and high performance liquid chromatography (HPLC). The concentration of CPZ in serum reached 109.5 +/- 9.2 micrograms/ml (mean +/- S.E.) at 0.25 hour after injection, and decreased to 6.8 +/- 2.3 micrograms/ml after 8 hours. The concentration of CPZ in burn blister fluid peaked at 4 hours and reached 28.2 +/- 8.0 micrograms/ml. The concentration of SBT in serum reached 75.7 +/- 8.3 micrograms/ml at 0.25 hour after injection, and decreased to 2.3 +/- 0.7 micrograms/ml after 8 hours. The peak concentration of SBT in burn blister fluid was 13.5 +/- 1.8 micrograms/ml at 3 hours. The data obtained were analysed pharmacokinetically. Cmax of CPZ and SBT levels in burn blister fluid were calculated to be 30.4 micrograms/ml and 13.6 micrograms/ml, respectively. The AUC0-8 hrs. (area under the burn blister fluid concentration of drug-time curve between 0 and 8 hours after injection), absorption rate constant (ka) and therapeutic AUC (AUC where drug concentrations were above minimum effective concentration) of CPZ were calculated to be 194.0 micrograms.hr/ml, 1.52 hr-1 and 97.1 micrograms.hr/ml (0.3-11.1 hours), respectively. The AUC0-8 hrs. and ka of SBT were also calculated as 68.3 micrograms.hr/ml and 0.62 hr-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of aztreonam transfer into the fetus and amniotic fluid in early pregnancy

The materno-fetal transfer of aztreonam by a single intravenous dose of 1 g was examined in 7 volunteer women undergoing induced abortion in early pregnancy and the following results were obtained. After administration of the drug, maternal blood levels at 15, 30, 60 and 120 minutes were 77.24 +/- 6.09 micrograms/ml (Mean +/- S.E.), 37.84 +/- 5.85 micrograms/ml, 25.62 +/- 3.15 micrograms/ml and 18.10 +/- 2.22 micrograms/ml, respectively. Amniotic fluid level of the drug was low in 3 cases, of which amniotic fluid levels were determined; 0.74 microgram/ml after 229 minutes, 0.83 microgram/ml after 280 minutes and 0.74 microgram/ml after 328 minutes. Fetal tissue concentration of the drug was below our detection limit at 120 minutes. Tissue levels of villus and decidua in 6 cases were also too low to be detectable between 89 and 328 minutes after injection.     

Clinical studies of cefoperazone in neurosurgery

A multicenter trial consisting of 164 institutions through out Japan, has been conducted to study the transfer of cefoperazone (CPZ) into the cerebrospinal fluid (CSF), and the clinical effectiveness of CPZ as a therapeutic or prophylactic agent in neurosurgery. The levels of CPZ in serum and CSF were determined in 96 patients. After initial dose of 2 g CPZ (intravenous drip infusion for 30 minutes), the serum level of CPZ after 1 hour was 124.5 +/- 6.6 micrograms/ml (Mean +/- S.E.), and even after 6 hours, it maintained as high as 47.8 +/- 16.6 micrograms/ml. The peak CPZ levels in CSF in patients with normal or minimal impairment in blood-CSF-barrier (BCB) (group I) and in those of localized impairment in BCB (group II) were 1.0 +/- 0.5 micrograms/ml at 2 hours and 3.0 +/- 1.8 micrograms/ml at 3 hours, respectively. The highest CSF level was seen in patients with meningitis (group III) and showed 5.0 +/- 2.4 micrograms/ml at 6 hours. After multiple dose of 2 g CPZ (intravenous drip infusion for 30 minutes), the serum kinetics of CPZ were not significantly different from those obtained after initial dose. However, the CPZ levels in CSF were higher than those observed after initial dose in all 3 groups and were higher than MIC75 against relevant pathogens for meningitis such as Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. Moreover, in group III peak level of CPZ in CSF exceeded the MIC75 against Pseudomonas aeruginosa which is also frequently isolated from patients with meningitis in neurosurgery. As a therapeutic agent CPZ administered as sole agent was effective in 42 out of 55 cases (76.4%) in meningitis, in 78 out of 116 cases (67.2%) in pneumonia and in 36 out of 47 cases (76.6%) in urinary tract infection (UTI). Its efficacy rate against all infections treated was 72.2% (184/255). Regarding CPZ's prophylactic use, 39 out of 514 cases (7.6%) were judged as having or possibly having infections as follows; meningitis (13/514, 2.5%), pneumonia (15/514, 2.9%), UTI (2/514, 0.4%). In prophylactic use of CPZ, the incidence rates of postoperative meningitis and other central nervous system (CNS) infection following ventricular drainage and supratentorial craniotomy for aneurysm were higher than those observed in other types of operation, 12.0% (3/25) and 6.2% (8/130), respectively. Also, regarding prophylactic use of CPZ, the organisms isolated by culture from 13 cases of postoperative CNS infections included 2 strains of Staphylococcus sp., 1 strain of Serratia sp. and 3 strains of other Gram-negative bacteria (GNB).(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical study of diffusion of cefotiam into myocardial tissue

In 11 patients undergoing open-heart operation, 1 g of cefotiam (CTM) was administered intravenously by bolus technique at the start of operation. Samples of serum were obtained at 30, 60 and 90 minutes following administration. Samples of right atrial appendage tissue and serum were obtained simultaneously at the time of heart cannulation. Antibiotic concentrations of all samples were determined by agar well method using P. mirabilis ATCC21100 as the test organism. The results were as follows: Serum levels of CTM after 30, 60 and 90 minutes were 53.1 +/- 17.6 micrograms/ml (Mean +/- S.D., n = 10), 26.1 +/- 10.4 micrograms/ml (n = 11) and 13.5 +/- 5.5 micrograms/ml (n = 7) respectively. Myocardial tissue levels of CTM after 60 and 90 minutes were 9.4 +/- 4.7 micrograms/g (n = 4) and 4.8 +/- 2.7 micrograms/g (n = 7) respectively. The concentration ratios of the myocardial tissue to serum were 0.36 +/- 0.10 (n = 4) after 60 minutes and 0.35 +/- 0.09 (n = 7) after 90 minutes. CTM can transmigrate from blood to myocardial tissue easily as compared with other cephalosporins. Therefore, CTM, a new broad spectrum cephalosporin, can be considered as one of the highly useful antibiotics for the prevention and treatment of infections following cardiac operation.     

Clinical study of cefmenoxime in thoracic surgery. Transfer of cefmenoxime to lung tissue and pleural fluid and prophylaxis of postoperative infections

Twenty-six patients who underwent pulmonary resection for the lung disease were administered 1 g of cefmenoxime (CMX) by intravenous drip infusion just before the operation. The CMX levels in the serum, lung tissue and pleural fluid were measured using the agar-well technique. The effect of the drug on the prophylaxis of postoperative infections was investigated. The obtained results are summarized as follows; 1. The peak concentration of CMX in the serum was 58.23 micrograms/ml 1 hour after starting the drip infusion of 1 g of CMX. The serum half-life of CMX (beta-phase) was 2.15 hours. 2. The ratio of the CMX concentration in lung tissue to the peak serum level was 14.9% 202 minutes after starting the drip infusion. In the pulmonary lesion, the ratio was 9.72% at the 201 minutes. In the bronchiole, the ratio was 20.7% 191 minutes after starting the drip infusion. 3. The concentration of CMX in the pleural fluid was 2.53 micrograms/ml 12 hours after starting the drip infusion. 4. CMX is useful as a prophylaxis of postoperative infections after thoracotomy, because no postoperative infectious complications were observed.     

Study of imipenem/cilastatin sodium in the perinatal period

The placental passage and therapeutic efficacy of imipenem/cilastatin sodium (IPM/CS) were studied in the perinatal period. The results obtained are summarized as follows: 1. The mean biological half-life of IPM in maternal serum was 30 minutes. 2. The umbilical cord serum concentration of IPM was about 70% of that in maternal serum after 30 minutes. 3. A significant level of IPM was found in the amniotic fluid. The amniotic fluid concentration of IPM was over 1 micrograms/ml at 45 minutes after administration and equal to that in maternal serum at about 90 minutes. 4. In 4 patients, the time course of placental transfer of IPM was investigated. The level of IPM in amniotic fluid was higher than that in maternal serum at 90 minutes after administration and gradually increased afterward. 5. The level of IPM was 3.96 micrograms/g in the fetal membranes at 17 minutes after administration. 6. In the treatment of 12 patients with perinatal infections, the preparation showed excellent efficacies in 3 patients and good efficacies in 7 patients. 7. An adverse effect (vomiting) was observed in only one patient. In conclusion, this drug showed satisfactory placental transfer as well as sufficient safety and excellent efficacy in the treatment of perinatal infections.     

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 study on transfer into lung tissue and postoperative prophylactic effect of new cephamycin antibiotics, particularly cefotetan and cefbuperazone

The following findings were obtained in our clinical study on the transfer of cefotetan (CTT) and cefbuperazone (CBPZ), new antibiotics of cephamycin series, into the lung tissue and on their postoperative prophylactic effect. 1. The mean serum concentration 30 minutes after the start of an intravenous drip infusion of 1 g of CTT over a period of 30 minutes was 99.4 micrograms/ml, and it decreased gradually thereafter with the half-life of 2.45 hours. After an intravenous drip infusion of 1 g of CTT over a period of 1 hour, the mean peak concentration of 104.1 micrograms/ml appeared 1 hour after the start of the infusion, and mean concentrations at 2, 4 and 6 hours after the infusion were 63.4, 34.3 and 27.0 micrograms/ml, respectively, with the half-life of 2.35 hours during phase beta. 2. Following 30 minutes of an intravenous drip infusion of CTT, the tissue CTT level in normal lung tissues was Tmax 1.82 hours and Cmax 19.8 micrograms/g. After 1 hour of an intravenous drip infusion the mean concentration in the tissues was at the peak of 39.7 micrograms/g in 2 hours after the start of an administration, while mean levels at 3, 4 and 6 hours after an administration were 32.2, 22.2 and 8.76 micrograms/g, respectively, with Tmax of 1.82 hours and Cmax of 30.5 micrograms/g. 3. Following an intravenous drip infusion of 1 g of CBPZ over a period of 1 hour, the mean serum drug concentration 1 hour after the start of infusion was at its peak, 83.3 micrograms/ml, while mean values at 2, 4 and 6 hours after the start of an administration were, respectively, 40.4, 19.8 and 9.62 micrograms/ml, with the beta-phase half-life of 2.03 hours. 4. By 1 hour after the start of intravenous drip infusion of CBPZ, the mean tissue level in normal lung tissues was at the peak of 31.6 micrograms/g, while mean levels at 3, 4 and 8 hours after an administration were 16.2, 11.0 and 4.56 micrograms/g, respectively, with Tmax of 1.67 hours and Cmax of 21.9 micrograms/g. 5. Infused CBPZ was transferred into bronchiole tissues. Drug concentrations in these tissues at 3 and 5 hours after the start of the infusion were 7.87 and 4.85 micrograms/g, respectively, with their ratios to the peak serum level were 9.4 and 5.8%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on aztreonam in the perinatal period in obstetrics and gynecology

Pharmacokinetic and clinical studies on aztreonam (AZT) in the perinatal period in obstetrics and gynecology were performed with the following results. 1. Concentrations of AZT in maternal serum, umbilical cord serum, amniotic fluid and neonatal serum were determined after 1 hour intravenous drip infusion of 1 g. The maternal serum concentration was 32.2 micrograms/ml at 26 minutes after administration, gradually decreasing thereafter to 13.2 micrograms/ml at 2 hours 33 minutes, 4.9 micrograms/ml at 3 hours 21 minutes and 2.9 micrograms/ml at 5 hours 3 minutes. Umbilical cord serum concentration was 17.0 micrograms/ml at 36 minutes after drip infusion and still remained at 4.0-16.1 micrograms/ml at 5 hours after administration. Amniotic fluid concentration was 9.9 micrograms/ml at 3 hours 21 minutes after drip infusion and showed 3.3 micrograms/ml at 16 hours 26 minutes after administration. Most of the maximum serum concentrations of newborns between 3 to 24 hours after delivery were not detectable, with only one case with 2.2 micrograms/ml at 9 hours after delivery. 2. AZT 1 or 2 g x 2/day was given by intravenous drip infusion to 12 cases of perinatal infections in obstetrics and gynecology for 5 to 8 days. Clinical efficacies were evaluated as excellent in 8 cases, effective in 2 and not effective in 2 with 83.3% efficacy rate. With respect to side effects, minor degree of urticaria was observed in 1 case. Another case showed a transient elevations of GOT, GPT and Al-P in laboratory tests.     

The diffusion of cefazedone into heart muscle, prostatic and skin tissue and into bile

The diffusion of cefazedone into human heart muscle, prostatic and skin tissue as well as bile fluid was investigated. 40 to 80 min after a single injection of 100 mg/kg (n = 14) the concentration in the heart muscle was between 10.8 and 85.5 micrograms/g. The respective serum levels were between 117 and 168.1 micrograms/ml. The single i.v. injection of 2 g cefazedone resulted within 30 min in a mean concentration of 34.63 +/- 9.75 micrograms/g in the prostatic tissue and in serum levels of 139.07 +/- 39.68 micrograms/ml (n = 14). In 5 patients additional values were estimated after 60 min. At this time the antibiotic concentrations were 24.92 +/- 1.31 micrograms/g in the tissue, with simultaneous serum levels of 87.25 +/- 20.86 micrograms/ml. 1 h after a 500 mg i.v. dose, concentrations in bile taken from T-tube were between 71.4 and 210 micrograms/ml. After 2 h there was a mean level of 83.2 micrograms/ml which was significantly above the serum concentrations at the same time (1 h = 35.25 +/- 7.17; and 2 h = 20.5 micrograms/ml). The bile concentration of 2 patients taken 5 h after cefazedone injection was 4.95 and 11.6 micrograms/ml. The cefazedone concentrations in the skin were estimated mainly in biopsies from granulating leg ulcer tissues. The mean concentrations in 4 cases were 120 +/- 28.7 micrograms/g 3 h after i.v. injection of 2 g cefazedone. The simultaneous serum levels were between 14.85 and 68.2 micrograms/ml, in one patient with extreme venous stasis the tissue concentration was only 8.1 micrograms/g. Cefazedone should be regarded as an antibiotic with excellent penetration into tissues.     

Concentrations of cefotaxime in serum and myocardial tissue

Serum and myocardial concentrations of cefotaxime (CTX) were measured in 20 adult patients undergoing cardiac surgery. To all of these patients 1.0 g of CTX was given intravenously (in the range of 13.7--29.0 mg/kg) at the beginning of operation. The serum concentrations of CTX were determined at 5, 10, 30, 60 minutes and 120 minutes after administration. Myocardial concentrations of CTX were also determined at about 30 minutes (group I), 60 minutes (group II) and 120 minutes (group III). The following results were obtained. Average serum CTX concentrations were 132.8 +/- 34.1 micrograms/ml at 5 minutes, 92.0 +/- 23.1 micrograms/ml at 10 minutes, 44.6 +/- 12.3 micrograms/ml at 30 minutes, 24.5 +/- 7.7 micrograms/ml at 60 minutes and 12.3 +/- 4.9 micrograms/ml at 120 minutes after administration. Average myocardial CTX concentrations were 10.0 +/- 3.7 micrograms/g in group I, 3.6 +/- 2.1 micrograms/g in group II and 2.3 +/- 1.8 micrograms/g in group III. The myocardial/serum concentration ratio was 0.22 +/- 0.14 in group I, 0.15 +/- 0.08 in group II and 0.18 +/- 0.12 in group III, respectively. These results suggested that the serum and myocardial concentrations of CTX were high enough to be prophylactic and therapeutic against not only aerobic but also anaerobic and opportunistic infections during and after cardiac surgery.     

Pharmacokinetics and clinical studies on ceftriaxone in the field of obstetrics and gynecology

Ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of CTRX into intrapelvic genital organs were good. The peak serum level in the uterine artery after a single intravenous injection and that after an intravenous drip infusion for 30 approximately 60 minutes, both with 1 g, were 162.5 micrograms/ml and 84.4-93.8 micrograms/ml, respectively. High concentrations were obtained also in genital organ tissues; the maximum concentration was 93.8 micrograms/g by intravenous injection and 56.3-59.4 micrograms/g by intravenous drip infusion. Changes in the tissue concentration were similar to those in the serum, the level over MIC80 against main pathogenic organisms being maintained for a long time. The penetration of CTRX into intrapelvic dead space exudate was good. The level reached a peak of 18.8 micrograms/ml 2 hours after an intravenous injection with 1 g and 13.3 micrograms/ml after 12 hours, while the level over MIC80 against main pathogenic organisms was maintained for a long time. CTRX was effective in 15 out of 16 cases (93.8%) with gyneco-obstetric infections such as intrauterine, intrapelvic, adnexal infections, and postoperative would infections, administered with 1 g twice a day. No side effects were observed.     

The penetration of cefoperazone into the cerebrospinal fluid in patients on acute or chronic stage

Cefoperazone (CPZ) was administered to 10 patients with cerebrovascular disturbances at acute and chronic phases to investigate its passage into the cerebrospinal fluid. The antibiotic was administered at dosages of 1 g and 2 g to patients in the acute phase to examine the dose-dependency. The results obtained are summarized as follows: 1. Serum concentrations Peak values of CPZ were 46.9 +/- 4.42 microgram/ml in acute phase patients in 1 g dosage group (acute group 1), 253.1 +/- 63.2 micrograms/ml in acute phase patients in 2 g dosage group (acute group 2), and 197.9 +/- 15.7 micrograms/ml in chronic phase patients in 2 g dosage group (chronic group 2) at 1 hour after CPZ administration. Concentrations of CPZ varied about 5-fold between the 1 g dosage group and the 2 g dosage groups. The acute group 2 showed generally higher values of CPZ concentrations than the chronic group 2. 2. Cerebrospinal fluid concentrations. Peak values were 0.96 +/- 0.30 microgram/ml (at 3 hours) in acute group 1, 4.55 +/- 3.41 micrograms/ml (at 1 hour, except 1 case) in acute group 2, and 1.29 +/- 1.28 micrograms/ml (at 1 hour) in chronic group 2. Acute group 2 showed generally higher values than chronic group 2. 3. CPZ was considered useful for the prevention of postoperative infections in the field of brain surgery.     

Basic and clinical evaluation of sulbactam/cefoperazone in the field of pediatrics

Sulbactam (SBT) in a novel beta-lactamase inhibitor from Pfizer and combined with cefoperazone (CPZ) ina 1:1 ratio (SBT/CPZ). Fundamental and clinical studies on SBT/CPZ were executed. The antibacterial activity of SBT/CPZ was compared with those of SBT, CPZ and CEZ against clinical isolates of S. aureus and E. coli which were not susceptible to CEZ. SBT alone did not show any activity against S. aureus, MICs against all strains were over than 100 micrograms/ml on the inoculations of undiluted and 100-fold diluted specimen. CPZ showed MICs over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, and on the 100-fold diluted inoculation, the MIC50 and MIC70 were 12.5 micrograms/ml and 100 micrograms/ml, respectively. SBT/CPZ showed better activity than CPZ by 2-8 folds against the strains highly resistant to CPZ; the MIC50 on the undiluted inoculation was 50 micrograms/ml. Against E. coli, the characteristic of SBT/CPZ was shown more clearly. The MICs of CPZ were over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, but SBT/CPZ showed MIC50 at 25 micrograms/ml. On the 100-fold diluted inoculation, SBT/CPZ was 4 approximately 8-fold superior than CPZ against strains on which MICs of CPZ were over than 12.5 micrograms/ml. Serum levels were determined by a bolus intravenous injection and by intravenous drip infusion of 10, 20, 40 mg/kg of SBT/CPZ. When administered by a bolus injection, the peak level was seen at 30 minutes in most patients: 8.7, 14.7 or 27.0 micrograms/ml of SBT and 30.1, 42.5 or 76.4 micrograms/ml of CPZ were detected with the 3 different doses. These levels were dose-dependent, and decreased slowly to 0.3, 0.3 or 0.3 micrograms/ml of SBT and 2.9, 2.8 or 3.3 micrograms/ml of CPZ at 6 hours after administration. Half-lives were 1.39, 1.20 or 0.98 hour for SBT and 1.77, 1.59 or 1.42 hours for CPZ. The same 3 doses were given by intravenous drip infusion. The peak levels obtained at the end of infusion (1 hour after initiation of infusion) were 15.3, 14.4 or 43.2 micrograms/ml for SBT and 33.4, 38.2 or 104.2 micrograms/ml for CPZ, respectively. The levels were somewhat low in 20 mg/kg group. After the end of infusion, these levels decreased fairly rapidly, and after 6 hours almost the same levels of 0.4, 0.5 or 0.3 micrograms/ml for SBT and 1.4, 3.9 or 3.3 micrograms/ml for CPZ were detected.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on aztreonam in the perinatal period

Pharmacokinetic and clinical studies of aztreonam (AZT) in perinatal infections in the field of obstetrics and gynecology were performed with the following results. 1. At one shot intravenous injection, 1 g AZT showed rapid distribution to the umbilical-cord serum with concentrations higher than 15 micrograms/ml in 1 hour 36 minutes after injection and higher 10 micrograms/ml even in 4 hours 30 minutes after injection. Significant difference in concentrations was not observed between arterial serum sample and venous serum sample of the umbilical-cord in a single subject. The concentration in the amniotic fluid reached a level higher 10 micrograms/ml in 3 hours 37 minutes after injection. 2. Distribution into milk reached a concentration between less than 0.4 micrograms/ml to 1.0 micrograms/ml by 6 hours after administration. 3. AZT 1 g x 2/day was given by intravenous drip infusion to 4 cases of perinatal infection in obstetrics and gynecology for 5 to 9 days. Clinically, AZT was effective for all the cases. Neither side effect nor abnormal laboratory value was observed. Consequently, AZT was considered to be highly effective and safe for its clinical use in the parturition and the puerperium.