MICs and MBCs of cefotaxime, desacetylcefotaxime and ceftriaxone against four principal bacteria causing meningitis

The MICs and MBCs of cefotaxime (CTX), desacetylcefotaxime (Des-CTX) and ceftriaxone (CTRX) were determined in relation to 4 of the principal bacterial species which cause meningitis, i.e., S. pneumoniae, S. agalactiae, H. influenzae and E. coli. These tests were performed using final inocula of 10(8) cells/ml and 10(6) cells/ml. Comparison was made with the MIC and MBC values of benzylpenicillin (PCG) and ampicillin (ABPC). 1. Against 25 strains of S. pneumoniae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.024 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml, respectively; and PCG, less than 0.012 micrograms/ml at both size. Similarly, the MBC 90 values were: CTX, 0.01 and 0.05 micrograms/ml; Des-CTX, 0.78 and 0.39 micrograms/ml; CTRX, 0.20 and 0.10 micrograms/ml; and PCG, 0.024 and 0.012 micrograms/ml, respectively. It is thus apparent that PCG showed the lowest values for both the MIC and MBC, followed by CTX, CTRX and then Des-CTX. Against 25 strains of S. agalactiae, the MIC 90 values with inocula of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and PCG, 0.39 and 0.20 micrograms/ml, respectively. Similarly, the MBC 90 values of Des-CTX were 0.78 and 0.39 micrograms/ml, while the other 3 antibiotics showed the same values with both the 10(8) and 10(6) cells/ml inocula: 0.10 micrograms/ml for CTX, 0.20 micrograms/ml for CTRX and 0.39 micrograms/ml for PCG. Accordingly, CTX showed the lowest values, followed by CTRX and then PCG being about the same as Des-CTX. Against 25 strains of H. influenzae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.10 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.39 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and ABPC, 50 and 6.25 micrograms/ml, respectively. Similarly, the MBC 90 values were: CTX, 0.20 and 0.10 micrograms/ml; Des-CTX, 1.56 and 1.56 micrograms/ml; CTRX, 0.39 and 0.20 micrograms/ml; and ABPC, greater than 100 and 50 micrograms/ml, respectively. Accordingly, in terms of the MIC 90, CTX and CTRX showed the same values, but in terms of the MBC 90 CTX was superior. (ABSTRACT TRUNCATED AT 400 WORDS)     

Studies on the transfer of cefotaxime into bone marrow blood

Cefotaxime (CTX) was administered in a dose of 2 g to 20 adult patients prior to orthopaedic surgery. Samples of the bone marrow blood and the forearm venous blood were collected at 30, 60, 90 and 120 minutes after the CTX administration, and the concentration of the drug in each sample was determined. The results are described below. The mean concentration of CTX transferred into the bone marrow blood was 59.7, 28.9, 14.7 and 7.2 micrograms/ml at 30, 60, 90 and 120 minutes after the CTX administration, respectively. The mean concentration of CTX in the venous blood was 84.0, 39.1, 19.0 and 13.8 micrograms/ml at 30, 60, 90 and 120 minutes after the CTX administration, respectively. The mean ratio of the CTX concentration in the bone marrow blood to that in the venous blood was 73.9%, 71.0%, 75.1% and 51.6% at 30, 60, 90, 120 minutes after the CTX administration. From the above results, CTX is considered to be a useful antibiotic if it is administered prior to orthopaedic surgery to prevent infections.     

Concentration of imipenem/cilastatin sodium in bone marrow blood following intravenous drip infusion

A solution of 0.5 g of imipenem (MK-0787) and 0.5 g of cilastatin sodium (MK-0791) in 100 ml of saline was administered to adult patients before the surgery by intravenous drip infusion during 30 minutes. Fifty samples of bone marrow blood were obtained from 26 clinical cases. After centrifugation, the supernatant was mixed with the same amount of a solution of stabilizer then stored at -80 degrees C. The peripheral blood was obtained at the same time as bone marrow blood was sampled and serum was served as control. The concentration of MK-0787 in bone marrow blood at 35 minutes after the start of the infusion was 50 micrograms/ml in 1 case, and decreased to 3.8 micrograms/ml at 260 minutes. The half-life was 1.62 hours. When the concentration of MK-0787 in bone marrow blood was compared to that in serum, the former was higher than the latter in 26 of the 50 samples (52%). In remained 24 samples, the concentration of MK-0787 in bone marrow blood showed to be lower than that in serum (48% of 50 samples). The half-life of MK-0791 in bone marrow blood was 1.10 hours and the level of the drug in bone marrow blood was similarly higher than that in serum in 18 of 40 samples (45%). In other 22 samples, the concentration of MK-0791 in bone marrow blood was lower than that in serum (55%). It was also found that the concentration of MK-0787 in bone marrow blood decreases with time along a similar curve of decrease observed in serum. This agent appears useful for the treatment of bone and joint infections and also for prophylaxis for major surgeries of skeletal tissues.     

Penetration of cefotaxime into human bone marrow blood

Concentrations of cefotaxime (CTX) in bone marrow blood and venous blood were examined with the passage of time in 21 cases which received operations of bone and joint. Concentrations of CTX in bone marrow blood at 30 minutes of a single intravenous administration 2 g each of CTX were found to be 85.2 +/- 24.5 micrograms/ml. Concentration ratio of CTX in bone marrow blood to that in venous blood was reached the peak at 120 minutes after administration. Concentrations of CTX observed were higher than the MIC of CTX against major pathogens responsible for the postoperative infections in orthopaedic field. The CTX, therefore, is expected to have an effective antibiotic in prophylaxis.     

OGP_(10～14)及其衍生物改善化疗后小鼠造血功能的研究

目的观察人工合成的成骨生长肽羧基端片段(OGP(10～14))及其衍生物G38I、G38K对环磷酰胺化疗后骨髓抑制小鼠外周血象和骨髓造血功能的影响。方法 40只BALB/C小鼠随机分为5组,均给予环磷酰胺(CTX)腹腔注射诱导骨髓抑制。分别给予OGP(10～14)、G38I、G38K或粒细胞集落刺激因子(G-CSF)治疗,未给予治疗的CTX组为阴性对照。实验中多次采集小鼠外周血测定外周血象并于注射CTX后第7天处死。观察骨髓有核细胞数的变化。结果 CTX组小鼠注射CTX后外周血白细胞和血小板下降,出现骨髓造血抑制。注射CTX前OGP(10～14)及其衍生物对小鼠外周血象无明显影响。注射CTX后OGP(10～14)组和G38I组外周血白细胞较CTX组显著升高,疗效与G-CSF接近,G38I组和G38K组血小板升高。OGP(10～14)及其衍生物G38I、G38K和G-CSF处理使小鼠骨髓有核细胞数增多,OGP(10～14)和G38I疗效更优于G38K。结论 OGP(10～14)及其衍生物G38I、G38K促进骨髓抑制小鼠外周血白细胞和血小板升高,刺激骨髓造血干细胞活性,加速骨髓造血功能的恢复。     

Concentrations of cefpiramide in bone and joint tissues

A single intravenous dose of 2 g of cefpiramide (CPM) was administered prophylactically to 11 patients at 30, 60, 120, or 180 minutes before hip surgery. Peak concentrations in different tissues of CPM were observed in 30 minutes after intravenous injection. Mean concentrations of CPM were 246.0 micrograms/ml in peripheral blood, 298.5 micrograms/ml in bone marrow blood and 77.5 micrograms/g in cancellous bone at 30 minutes after administration. Half-lives of CPM were 152 minutes in peripheral blood and 105 minutes in bone marrow blood. The concentrations of CPM observed in the above study were higher and its retention longer than expected values.     

Pharmacokinetic and clinical studies of cefpirome in pediatric field]

We conducted a study on the pharmacokinetics and clinical application of cefpirome (CPR) in children. 1. A single intravenous injection of 20 mg/kg of CPR was given to a two-month-old boy, and the concentration of the drug in the blood was measured. Fifteen minutes after administration, the concentration was 53.3 micrograms/ml, and it gradually decreased thereafter, reaching a level of 5.18 micrograms/ml after 8 hours with a half-life in the plasma of 2.36 hours. 2. A single intravenous injection of 700 mg (50 mg/kg) of CPR and that of cefotaxime (CTX) were given to a girl with suppurative meningitis (3 years old, 14 kg, causative bacteria, Haemophilus influenzae), and concentrations of the drugs in plasma and cerebrospinal fluid after 1 hour were measured. On the second day of illness, the concentration of CTX in the plasma was 39.4 micrograms/ml and the concentration of desacetyl-CTX (D-CTX) was 25.2 micrograms/ml, while concentrations in the cerebrospinal fluid were 6.22 micrograms/ml (15.8%) for CTX and 3.94 micrograms/ml (15.6%) for D-CTX. On the third day of illness, concentration of CPR in the plasma was 59.3 micrograms/ml, while its concentration in the cerebrospinal fluid was 7.44 micrograms/ml (12.5%). 3. CPR was intravenously administered in daily dosages of 37.7-75.0 mg/kg in 2-3 portions for periods of 4-15 days to 2 patients with septicemia (causative bacteria, Klebsiella pneumoniae in 1 case and Escherichia coli in the other), 1 patient with bronchitis (K. pneumoniae), 9 patients with pneumonia (1 case of Staphylococcus aureus, 3 cases of H. influenzae, 2 cases of Haemophilus parainfluenzae, 1 case of K. pneumoniae + Pseudomonas cepacia, 2 cases of H. influenzae + Branhamella catarrhalis), 2 patients with cellulitis (1 case of S. aureus, 1 case, causative agent unknown), 1 patient with suppurative lymphadenitis (causative agent, unknown), 1 patient with staphylococcal scalded skin syndrome, 1 patient with renal abscess (causative agent, unknown), and 1 patient with a urinary tract infection (E. coli), for a total of 18 patients, with excellent results in 9 cases and good results in 9 cases, hence an efficacy rate of 100% was obtained. 4. As an accompanying side-effect, eruption was observed in 1 of the 18 patients, but when administration was discontinued, the symptom gradually receded, and it disappeared by the 4th day.(ABSTRACT TRUNCATED AT 400 WORDS)     

Concentrations of cefmenoxime and cefotiam in the human bone marrow blood (author's transl)

In order to examine the venous blood and bone marrow blood concentrations of cefmenoxime (CMX) and cefotiam (CTM) in man, 1 g of CMX or CTM was administered by one shot intravenous injection prior to surgery of the hip joint. At 30, 60, 120 and 180 minutes after the administration, venous blood and bone marrow blood were collected from each of 3 patients and the concentration assayed by the agar well method. Both CMX and CTM showed excellent distribution to bone marrow blood with peak levels of 50.1 micrograms/ml and 50.9 micrograms/ml on the average 30 minutes after administration. The levels of CMX in bone marrow blood exceeded those in the venous blood at 60 minutes and thereafter and CTM at 30 minutes of administration and thereafter. It is therefore considered that both CMX and CTM appear to be useful drugs for the prophylaxis and treatment of bone marrow infection, e.g. osteomyelitis.     

Pharmacokinetic Study of Cefotaxime (CTX) in Dogs

Cefotaxime (CTX) was injected either intravenously or intramuscularly in dogs, and its pharmacokinetics in plasma and urine were determined with the use of HPLC assay. Cephalothin (CET) was administered in a similar manner as a reference agent. While both CTX and CET rapidly disappeared from plasma after intravenous injection, the half-life of CET was approximately 2.5 times shorter than that of CTX. Both drugs were deacetylated, and desacetyl-CTX and desacetyl-CET appeared in plasma. Both drugs were rapidly excreted into urine either in unchanged or deacetylated form, the sum of which accounted for 77 % and 63 % of the CTX and CET dose, respectively. The ratio of the amount of unchanged drug over that of deacetylated drug in the urine was 1:1 for CTX and 1:2 for CET. When CTX and CET were intramuscularly injected, the plasma levels of CTX and CET reached a maximum 30 min and 15 min after injection, respectively, followed by a rapid decline. The pattern of urinary CTX excretion was similar after i.m. and i.v. injections. In contrast, the amount of desacetyl-CET in the urine was larger after i.m. than i.v. injections. CTX metabolites other than desacetyl-CTX (M₂ and M₃) that were also assayed by HPLC accounted for only 2–4 % of the dose of CTX in the urine, but were below detectable levels in this plasma.     

Study of concentrations of clindamycin phosphate in bone marrow blood and tissue

Clindamycin phosphate (CLDM) was administered to 33 surgical cases in orthopedics to treat or prevent infection (600 mg in 15 cases and 1,200 mg in 18 cases by intravenous drip infusion over 60 minutes) and the concentrations of CLDM in the bone marrow blood and tissue of the operative field as well as in venous blood were determined with the cup plate method of bioassay by collecting specimens immediately after completion of infusion or 30 or 60 minutes later. The concentration of CLDM in bone marrow blood averaged 104.3 approximately 105.5% of the corresponding concentration in venous blood in the cases receiving 600 mg and 101.3% in those receiving 1,200 mg. The concentration of CLDM in bone marrow tissue averaged 154.0 approximately 163.7% of the corresponding concentration in venous blood in the group receiving 600 mg but 78.8 approximately 86.2% in the group receiving 1,200 mg. This difference between the 2 groups was considered to reflect largely the difference in specimens collected. Thus, the concentration of CLDM in bone marrow tissue was interpreted as the amount of drug penetrating and remaining in bone marrow tissue and its adjacent area. The MIC75 of CLDM for clinical isolates were 0.20 micrograms/ml for S. aureus, 0.78 micrograms/ml for B. fragilis and 0.20 micrograms/ml for Peptostreptococcus spp. The concentrations of CLDM attained in bone marrow blood and tissue and its adjacent area after administration of 600 mg or 1,200 mg were thus sufficient to eliminate these organisms. The above results indicate that CLDM is a useful antibiotic for treatment and prevention of infection in orthopedics.     

Fundamental and clinical evaluation of ceftriaxone in the field of pediatrics

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed in the field of pediatrics and the following results were obtained. The antibacterial activity of CTRX was determined against clinically isolated strains at our department. CTRX was definitely superior to CEZ and CMZ and almost equal or slightly superior to CTX in activity against Gram-negative bacteria, while the MIC of CTRX against Gram-positive bacteria was higher than that of CEZ and CMZ and about equal to that of CTX. The blood concentration of CTRX after one shot intravenous injection with 10 mg/kg was 67.98 micrograms/ml at 15 minutes, 51.96 micrograms/ml at 30 minutes, 37.51 micrograms/ml at 1 hour, 28.91 micrograms/ml at 2 hours, 20.71 micrograms/ml at 4 hours, 13.97 micrograms/ml at 6 hours and 6.45 micrograms/ml at 12 hours, while the half-life time was 3.74 hours. The blood concentration of CTRX after one shot intravenous injection with 20 mg/kg was 179.55 micrograms/ml at 15 minutes, 120.01 micrograms/ml at 30 minutes, 100.01 micrograms/ml at 1 hour, 53.75 micrograms/ml at 2 hours, 33.13 micrograms/ml at 4 hours, 26.41 micrograms/ml at 6 hours and 21.49 micrograms/ml at 12 hours, while the half-life time was 4.15 hours. The blood concentration of CTRX after intravenous drip infusion for 1 hour with 10 mg/kg was 19.54 micrograms/ml at 15 minutes, 27.19 micrograms/ml at 30 minutes, 36.57 micrograms/ml at 1 hour, 23.83 micrograms/ml at 2 hours, 19.69 micrograms/ml at 3 hours, 14.46 micrograms/ml at 5 hours, 11.02 micrograms/ml at 7 hours and 7.27 micrograms/ml at 13 hours, while the half-life time was 6.59 hours. The blood concentration of CTRX after intravenous drip infusion for 1 hour with 20 mg/kg was 61.72 micrograms/ml at 30 minutes, 108.1 micrograms/ml at 1 hour, 54.95 micrograms/ml at 2 hours, 35.68 micrograms/ml at 3 hours, 28.13 micrograms/ml at 5 hours, 20.51 micrograms/ml at 7 hours and 11.43 micrograms/ml at 13 hours, while the half-life time was 4.23 hours. There was noticed a tendency of the blood level being elevated by consecutive administration. The urinary recovery rate of CTRX ranged from 36.5 to 71.6%. The excretion rate of CTRX into the cerebrospinal fluid ranged from 5.2 to 11.6%. The excretion rate of CTRX into the pleural fluid was 31.0%. The clinical efficacy rate was 87.5% (excellent or good) in 8 children with infections treated with CTRX. The eradication of bacteria was observed in all of 5 cases bacteriologically evaluation.(ABSTRACT TRUNCATED AT 400 WORDS)     

The penetration of cefotaxime into the cerebrospinal fluid. Comparison between acute and chronic stages in intracranial diseases

Two grams of cefotaxime (CTX) were administrated by drip infusion to 10 patients (11 material) with acute or chronic stage of intracranial diseases. Concentrations of CTX in the serum and the cerebrospinal fluid (CSF) were determined at 15, 30, 60, 120, 240 and 300 minutes after injection. The results obtained were summarized as follows: Serum levels: Peak levels of CTX in sera were 66.2 +/- 10.23 (S.E.) micrograms/ml in the acute stage group (ASG), and 75.7 +/- 31.39 (S.E.) micrograms/ml at 15 minutes after injection in the chronic stage group (CSG). There were no significant difference between the 2 groups. CSF levels: Peak levels of the drug in CSF were 1.35-4.32 micrograms/ml in ASG and 0.18-0.7 microgram/ml in CSG. Average concentration at 60 minutes after injection was 1.11 +/- 0.09 (S.E.) micrograms/ml in ASG and 0.30 +/- 0.08 (S.E.) micrograms/ml in CSG. The value in ASG was significantly higher than the value in CSG by t-test. The ratio between CSF and serum levels: The levels increased as time passed in both groups and the values in ASG were higher than those in CSG at all time points. Average ratios at 60 minutes after injection were 3.85 +/- 0.29 (S.E.)% in ASG and 1.12 +/- 0.50 (S.E.)% in CSG. The value in ASG was significantly higher than that in CSG by t-test. From the above results, it is considered that CTX is useful for the prophylaxis of postoperative infections in intracranial diseases.     

Concentrations of cefpiramide in the human bone marrow blood and bone tissues

Cefpiramide (CPM) 2 g was preoperatively administered to 29 patients by intravenous drip infusion for 20 minutes. Concentrations of CPM in bone marrow blood, peripheral blood, and bone tissue were determined at 30, 60, 120, 180, 240 and 360 minutes after CPM administration. Mean concentrations of CPM in peripheral blood, bone marrow blood were peaked at 60 minutes after injection, those in bone tissues (cortex, cancellous bone) peaked at 30 minutes after injection. The mean ratio of the CPM concentration in bone marrow blood to peripheral blood was 105.5%, that in cortex (/g) to peripheral blood (/ml) was 17.7%, and that in cancellous bone (/g) to peripheral blood was 18.2%. These concentrations were maintained above MIC80 for 6 hours. From the above results, CPM appears useful for the prevention of infection in orthopaedic operation (skeletal surgery).     

Basic and clinical studies on cefotaxime

The most frequently encountered infectious disease in the field of internal medicine is respiratory tract infections. One of the most important requirements for an antibiotic in the treatment of infections is that it must be efficiently transferred to the infected site to attain a high concentration there. In the case of respiratory tract infections, it is desirable for the drug concentration in the sputum to be higher than the MIC for the causative bacterium. Cefotaxime (CTX) expresses potent antibacterial activity against Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pneumoniae, which are the major causative bacteria of respiratory tract infections. CTX also exerts antibacterial effects against a wide range of other bacteria. We administered CTX to patients with respiratory tract infections, then measured and compared the drug concentrations in the serum and sputum. The results are described below. When 2 g of CTX was drip-infused, the drug concentration in the serum was 113.0 micrograms/ml at 5 minutes after the completion of infusion, 64.9 micrograms/ml at 30 minutes, 38.7 micrograms/ml at 1 hour, 19.0 micrograms/ml at 2 hours, 8.9 micrograms/ml at 4 hours and 3.8 micrograms/ml at 6 hours. The drug concentration in the sputum was 1.29 micrograms/ml at 5 minutes after completion of infusion, 1.54 micrograms/ml at 5 to 30 minutes, 1.36 micrograms/ml at 30 minutes to 1 hour, 1.47 micrograms/ml at 1 to 2 hours, 1.12 micrograms/ml at 2 to 4 hours and 1.35 micrograms/ml at 4 to 6 hours. The drug concentration in the serum was the highest at 5 minutes after completion of the drip-infusion, and then it gradually decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on the transplacental passage of cefotaxime in late pregnancy

The transplacental passage of a single intravenous dose of cefotaxime (CTX), 1,000 mg, was examined in 11 pregnant women undergoing delivery at term by cesarean section. The results were as follows. 1. Measurements by HPLC: After a single 1,000 mg intravenous dose, the maternal blood level of CTX took the following course: 40.1 +/- 3.4 mcg/ml (mean +/- S.E.) at 15 minutes, 22.5 +/- 1.9 mcg/ml at 30 minutes, 10.8 +/- 0.9 mcg/ml at 60 minutes and 3.2 +/- 0.4 mcg/ml at 120 minutes. Slightly high maternal blood levels of 0.7 and 1.1 mcg/ml were obtained at child deliveries made at 200 minutes, but only a trace amount was found at a child delivery at 356 minutes. The CTX level in the umbilical cord blood was comparatively high until the measurement at 222 minutes, and then declined. IN the amniotic fluid, peak levels were observed at 222 to 252 minutes, thereafter decreasing slowly. Desacetyl-CTX, a metabolite of CTX, showed maternal blood levels of 5.8 +/- 0.5 mcg/ml at 15 minutes, 6.3 +/- 0.6 mcg/ml at 30 minutes, 6.8 +/- 0.7 mcg/ml at 60 minutes and 4.9 +/- 0.7 mcg/ml at 120 minutes. Thus, the maternal blood level of desacetyl-CTX showed an increasing tendency until 60 minutes after intravenous administration, and decreased rapidly from 120 minutes onwards. No consistent tendency was noted in desacetyl-CTX levels in the umbilical cord blood and the amniotic fluid. 2. Measurements by bioassay: Maternal blood levels of CTX determined by bioassay were 45.2 +/- 3.3 mcg/ml at 15 minutes, 25.8 +/- 2.2 mcg/ml at 30 minutes, 12.4 +/- 1.0 mcg/ml at 50 minutes adn 4.0 +/- 0.5 mcg/ml at 120 minutes. At the time of child delivery, maternal blood levels of CTX were 1.1 and 2.6 mcg/ml at 200 minutes, and then decreased slowly. Trace levels were noted at 336 minutes and CTX was undetectable at 356 minutes. 3. The HPLC study demonstrated that the level of CTx remained comparatively high in the umbilical cord blood and the amniotic fluid even 6 hours after administration (0.3--0.4 mcg/ml and 4.0 mcg/ml, respectively). This result suggests, in consideration of CTX's MIC values for causative organisms, that CTX will produce a sufficient clinical effect in perinatal infections. No side effects were observed in the mothers or their babies.     

A study of clinical application of cefotaxime in the perinatal period

Pharmacokinetic studies of cefotaxime (CTX) were carried out in perinatal mothers and infants. CTX was promptly absorbed after intravenous injection, intravenous drip infusion and intramuscular injection in pregnant women, producing dose-related peak blood levels. Placental passage to the fetus was favorable. After intravenous injection, intravenous drip infusion and intramuscular injection of 500--1,000 mg of CTX, drug concentrations of the cord blood, amniotic fluid and fetal blood exceeded MICs of the main pathogenic organisms. By administration of this dose 1 to 2 times daily it is possible to successfully prevent or treat uterine infections. Passage of CTX into the milk of lactating mothers was minimal, suggesting that only minute quantities can possibly be transferred from the milk to newborn infants. Absorption of CTX in neonatal infants was prompt. The peak blood levels of 47.9 micrograms/ml were attained 15--30 minutes after intravenous injection of 20 mg/kg. The half-life ranged from 2.4--5.56 hours, depending on the number of days postpartus. CTX was effective in the prophylaxis and therapy of perinatal uterine infections.     

Fundamental and clinical studies on cefamandole in pediatric treatment (author's transl)]

Cefamandole (sodium salt) was administered to total 32 cases of bacterial infectious diseases of children, and in 3 cases, there were investigated of these absorption and excretion. The results are as follows; 1. Blood levels: Cefamandole was given intravenous dose of 25 mg/kg to 3 children. The blood level of 15 minutes after intravenous injection was 140.4 micrograms/ml in average, and 0.3 micrograms/ml in average at 4 hours after intravenous injection. T 1/2 was 13.9 minutes. 2. Urinary concentration: Within 6 hours after intravenous injection, 51.8% of the drug was recovered in average from the urine and the urinary concentration reached to 3,050 micrograms/ml in average (0 approximately 2 hours), 1,262 micrograms/ml in average (2 approximately 4 hours), 41 micrograms/ml in average (4 approximately 6 hours) after injection. 3. Clinical results: The drug was given 109 mg/kg/day (t.i.d. or q.i.d.) by intravenous route. The duration of administration was 11 days in average. The overall efficacy rate was 97%. In bacteriological results, excellent in 2, failure in 1, out of 3 strains. As side effects vascular pain was observed in 3 cases at the intravenous injection, and eosinophilia in 2 cases.     

Study on cefotaxime in respiratory surgery: transfer to lung tissue and kinetics in serum

Cefotaxime (CTX) was intravenously administered in a dose of 1 g to patients just prior to lung surgery. Lung tissue specimens were collected at 1, 2 and 3 hours after the CTX administration, and the concentration of CTX in each specimen was determined. At the same time, the concentration of CTX in the serum was also measured. The results are summarized below. 1. Determination of the CTX concentration in the lung tissue using bioassay showed values of 3.78 +/- 1.93 micrograms/g at 1 hour after CTX administration, 1.91 +/- 0.92 microgram/g at 2 hours, and 1.19 +/- 1.04 micrograms/g at 3 hours. 2. Determination of the CTX concentration in the serum using bioassay showed values of 36.9 +/- 14.4 micrograms/ml at 30 minutes after CTX administration, 22.5 +/- 10.5 micrograms/ml at 1 hour, 12.8 +/- 6.32 micrograms/ml at 2 hours, 8.52 +/- 5.54 micrograms/ml at 3 hours, and 3.98 +/- 3.19 micrograms/ml at 6 hours. The serum half-life was calculated to be 1.82 hours. 3. The CTX concentration of 3.78 +/- 1.93 micrograms/g in the lung tissue at 1 hour after CTX administration was more than 10 times higher than the MIC80 values for Streptococcus pneumoniae (MIC80 less than or equal to 0.025 microgram/ml) and Klebsiella pneumoniae (0.05 micrograms/ml), 2 of the principal causative organisms of respiratory tract infections. The pattern of change in concentrations of CTX in the serum of these surgical patients was concluded to be similar to the pattern in healthy adult subjects. On the basis of the results summarized above, it appears that CTX is a useful antimicrobial agent for application in the field of respiratory surgery.     

Fundamental and clinical evaluation on ceftriaxone in the pediatric field

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(ABSTRACT TRUNCATED AT 400 WORDS)     

螺旋藻多糖对小鼠和犬造血系统的化学和放射防护作用

目的：研究螺旋藻多糖（PSp)对环磷酰胺和^60Co-γ射线所致小白鼠和犬造血系统抑制的影响。方法：腹腔注射环磷酰胺以及用^60Co-γ射线照射分别诱发小鼠和犬的骨髓损伤。全血细胞计数和骨髓有核细胞计数,用紫外分光光度计检测骨髓DNA的含量。结果：环磷酰胺和^60Co-γ射线分别造成小鼠和犬骨髓造血系统抑制性损伤。PSp 30,60mg/kg能升高小鼠全血白细胞数和骨髓有核细胞数以及DNA含量;PSp 12mg/kg能使犬骨髓有核细胞数,以及外周血红细胞、白细胞及血红蛋白水平得以回升（P＜0．01）,其疗效优于盐酸小壁胺。结论：PSp对造血系统有化学保护和放射保护作用。