Clinical usefulness of cefixime (CFIX), a new oral cephalosporin antibiotic, in pediatric field was investigated. The results obtained were summarized as follows.
1. The clinical efficacy of CFIX was investigated in a total of 138 children including 49 with upper respiratory tract infections (RTI), 22 with acute bronchitis, 18 with pneumonia, 19 with scarlet fever and 21 with urinary tract infections (UTI).
2. Clinical effectiveness was excellent in 58, good in 60, fair in 14 and poor in 3, with an overall efficacy rate of 87.4%. The efficacy rate classified according to types of infection were
85.7% in upper RTI, 89.5% in acute bronchitis, 94.4% in pneumonia, 78.9% in scarlet fever, and 90.5% in UTI.
3. Out of the suspected causative organisms, 43 strains of a total of 50 strains isolated were eradicated. The bacteriological eradication rate was 86.0%.(Haemophilus influenzae 100%, Haemophilus parainfluenzae 100%, Streptococcus pyogenes 88.5%, Escherichia coli 85.7%).
4. One hundred forty four children were analyzed for side effect. Side effects were observed in 2 children (1.4%) with diarrhea in 1 and anorexia in another. Abnormal laboratory test results were recorded in 4 children (3.3%).
The above results suggest that CFIX is a very useful new oral cephalosporin for the treatment of bacterial infections in children.

View full abstract

Cefixime (CFIX, Cefspan®) a, new oral cephem, was used in the treatment of urinary tract infections, and was evaluated for its therapeutic effectiveness and safety at the Department of Urology, Osaka Rosai Hospital. In a total 129 cases, to which daily doses of 200 mg of CFIX were divided into 2 doses and administered clinical efficacies in 35 cases of women with acute uncomplicated cystitis treated for 3.9 days in average and 79 cases with complicated urinary tract infections (UTIs) treated for 5.9 days in average were assessed, according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI (3rd ed.) recommended by the Japan UTI Committee with our own minimum modifications. Mid term urine and catheterized urine were examined as urine samples for bacteriological evaluation.
Clinical efficacies in 35 cases with acute uncomplicated cystitis were excellent in 24 (69%) and moderate in 11 (31%), with an overall clinical efficacy rate of 100%.
Clinical efficacies in 79 patients with complicated UTIs were excellent in 24 (30%), moderate in 26 (33%) and poor in 29 (37%), with an overall clinical efficacy rate of 63%.
All of the 35 bacterial strains isolated from urine samples of uncomplicated UTIs patients were totally eradicated by the CFIX treatment, while 85 strains (79%) were eradicated among 107 strains isolated from urine samples of complicated UTIs patients.
Subjective adverse reactions were observed in 4 cases (3.1%) out of a total of 128 patients, as general malaise in 1 and lower abdominal symptoms in 3 were recorded. All of them disappeared after the termination of CFIX administration. In conclusion, CFIX is considered as a clinically useful oral antibiotic in the treatment of UTI.

View full abstract

The efficacy and the safety of a combination regimen using cefbuperazone (CBPZ) and amikacin (AMK) were evaluated in severe infections in patients with hematological diseases.
Twenty two patients were subjected to this combination therapy; among these, 18 patients were evaluable for the effectiveness. They included 9 cases of leukemia, 5 cases of malignant lymphoma, 2 cases of aplastic anemia, and 2 cases of angio-immunoblastic lymphadenopathy with dysproteinemia.
Excellent responses were obtained in 5 patients and good responses in 5 patients, with a total effectiveness of 55.6%. Efficacy rates for individual types of infections were; 2/2 in sepsis, 614, or 42.9% in suspected sepsis, 1/1 in urinary tract infection, and and 1/1 in upper respiratory infection.
The combination treatment was also effective in 4 of 6 cases in which neutrophil counts were less than 500/mm³ prior to therapy.
Side effects were observed in only one patient. Mild proteinurea occured in a 80-year-old male in 6 days after the regimen was started, but was not serious.
These results indicate that a combination of CBPZ and AMK is safe and effective for the treatment of infections even in patients with compromised immunodefenses.

View full abstract

Usefulness of ceftazidime (CAZ) was studied in 56 cases of intractable respiratory tract infections. CAZ was administered at a daily dose of 2-4g in 2 divided doses by intravenous drip infusion for 3-15 days.
1. Analysis was carried out in 38 cases and the following result was obtained. Efficacy rate was: 68% (17/25) in pneumonia, 60% (3/5) in chronic bronchitis and 67% (4/6) in secondary infections in chronic respiratory disease cases, and the overall efficacy rate was 63.2% (24/38).
2. In bacteriological study, 68.2% (15/22) of eradication rate was obtained. Against Staphylococcus aureus, eradication was obtained in all strains (4 strains). Against Pseudomonas aeruginosa, eradication occurred in 4 strains out of 10, and decrease in number in 2 strains.
3. As for adverse effects, mild hepatic disorder was observed in 2 cases (3.6%) out of 56.
4. From the above result, CAZ is considered to be very useful when used as monotherapy for aged patients and in the treatment of severe and intractable infections accompanied by underlying diseases.

View full abstract

Imipenem/cilastatin sodium (IPM/CS) was administrated to patients with severe infections complicated by hematological disorders and solid tumors to assess its efficacy and safety. Primary diseases in this series of 76 cases included 37 cases of hematological disorders (acute leukemia in 25 cases, malignant lymphoma in 7 cases, aplastic anemia in 3 cases and 2 other diseases) and 38 cases of solid tumors (lung cancer in 7 cases, gastric cancer in 11 cases, esophageal cancer in 6 cases, pancreatic cancer in 3 cases, bile ductcancer in 4 cases, hepatocellular cancer in 3 cases, and 4 other diseases).
Following results were obtained.
1. Types of infection in hematological diseases were sepsis in 5 cases, suspected sepsis in 24 cases, pneumonia in 5 cases and 3 others. The efficacy rates were 100% in sepsis, 62.5% in suspected sepsis, 80% in pneumonia and 73% in all cases.
2. Types of infection in solid tumors were sepsis in 2 cases, suspected sepsis in 13 cases, pneumonia in 10 cases, cholecystitis in 2 cases, cholangitis in 5 cases, liver abscess in 2 cases, and 4 others. The efficacy rates were 50% in sepsis, 69.2% in suspected sepsis, 80% in pneumonia, and 71.1% in all cases.
3. IPM/CS was administrated in single use in 66 cases and in combination with other antibiotics in 9 cases. The efficacy rate in the single use was 72.7% and that in the combination use was 66.7%.
4. The efficacy rate in 35 cases of first use was 71.4% and that in 40 cases of second use was 72.5%.
5. The relationship between neutrophil cell count and the efficacy was studied in hematological disorders. The efficacy rate of 8 cases in which neutrophil cell count was 100/mm³ or less was significantly lower than that of 29 cases in which neutrophil cell count was more than 100/mm³.
6. Side effects observed during the treatment were skin rash in 1 case, nausea and vomiting in 1 case, diarrhea in 1 case and chest pain in 1 case. They disappeared after discontinuation. Mild abnormality of the liver function test was observed in 5 cases.
These results indicate that IPM/CS has a high therapeutic efficacy for severe infections in compromised hosts.

View full abstract

Twenty-three newborn and young infants, including 13 low-birth-weight infants, were treated with cefmenoxime (CMX) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 to 102 days, and their weights ranged from 0.83 to 4.19kg. Doses given were 18-42mg/kg every 6 to 12 hours for 2 to 16 days.
Among 12 infants with bacterial meningitis and sepsis, the results were excellent in 2, good in 7 and fair in 3 patients. The drug was well tolerated and no adverse effects were observed in the 23 patients.
Pharmacokinetic studies of CMX were done in 5 infants whose mean body weight was 3.03 kg (range 2.4 to 4.2kg). Serum concentrations at 15 minutes after 10mg/kg intravenous bolus injections were 35.6 and 55.7μg/ml in two 12-and 18-day-old patients. In 3 patients with ages of 7, 7 and 24 days, serum concentrations were 54.6, 102 and 100μg/ml, respectively, at 15 minutes after 20mg/kg doses. Elimination half-lives of the drug were 1.3 to 1.5 (mean 1.4) hours in these patients. Excretion rates into urine in the first 8 hours were 30.3, 74.2, 77.6 and 85.6% in four patients given 10 or 20mg/kg doses.
The cerebrospinal fluid level at 3 hours after the dose was 0.4μg/ml on 15th day of treatment in 1 patient with bacterial meningitis given 20mg/kg every 6 hours. Cerebrospinal fluid levels at 1, 2 and 0.58 hours after dose were 0.6, 0.54 and 2.48μg/ml on 2nd, 5th and 8th day of treatment, respectively, in another patient with aseptic meningitis given 42mg/kg every 8 hours.

View full abstract

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and premature infants were conducted. The results are summarized as follows.
1. Intravenous administration of CMX at 20mg/kg, via bolus injection or 1-hour drip infusion, produced at sufficiently high blood concentration. As it is the case with other cephem antibiotics, the half-life varied with age and tended to become shorter with aging.
2. There were intergroup differences in urinary recovery of the drug, but urinary concentrations were generally high.
3. In the clinical evaluation, 12 out of 15 cases which were evaluable for efficacy were rated “excellent” or “good”.
4. Side effects were evaluated in 27 cases. A bleeding tendency was found in 1 case, eosinophilia in 1 case, elevated GOT in 1 case, and positive PIVKA II in 4 cases.
It is, therefore, concluded that CMX is a highly useful drug for the treatment of bacterial infections in neonates and premature infants.

View full abstract

Serum concentrations and urinary recovery rates of cefmenoxime (CMX) were determined in 41 mature and premature infants (with ages 0-24 days) after one shot intravenous injection of 10, 20 (1-hour intravenous drip infusion was also carried out) or 30mg/kg for treatment and prophylaxis of various infections. Because the number of cases included was small, a comparison study was conducted by classifying them into 3 groups; 3 days or younger, 4 to 7 days, and 8 days or older, rather than dividing them into groups of mature and premature infants. Clinical evaluation was conducted in 7 male and 1 female cases 1 to 29 days old, whose diseases comprised 1 case each with septicemia, purulent otitis media and phlegmonous cellulitis, 3 with pneumonia and 2 with urinary tract infection.
1. Changes in serum concentrations and urinary recovery rates
(1) Intravenous bolus injection of 10mg/kg:
Serum concentrations of the drug in the 3 age groups peaked at 28.9, 29.5 and 29.1μg/ml, respectively, all at 30 minutes after the drug administration, and thereafter gradually declined. The mean level in the 3rd group was the lowest at 1.9μg/ml at 6 hours. Average serum halflives of CMX were shorter in older subjects, 3.0, 1.9 and 1.4 hours, respectively in the 3 groups. Urinary recovery rates were relatively high, 68.9 to 84.9% in the 3 cases examined during the first 6 hours, and 15.4 to 66.2% during the first 2 hours.
(2) Intravenous bolus injection of 20mg/kg:
Serum concentrations of the drug in the 3 groups peaked at 65.2, 60.5 and 65.8μg/ml, respectively, all at 30 minutes after the drug administration, with no significant differences noted among the groups. The levels gradually declined thereafter in all groups, but remained rather high at 20.1, 6.5 and 9.5μg/ml, respectively, at 6 hours. Average serum half-lives of CMX were 3.5, 1.7 and 1.9 hours, respectively. The inversion of values obtained between the 2nd and 3rd groups appears to be attributable to that all of the 3rd group were premature infants, and the body weight of 2 cases of them were less than 2, 000 g each. Urinary recovery rates ranged widely from 37.0 to 89.4% in the 4 cases examined during the first 6 hours.
(3) One-hour intravenous drip infusion of 20mg/kg:
Serum concentrations of the drug in the 3 groups peaked at 57.7, 60.2 and 72.4μg/ml, respectively, all at the termination of the drug infusion. The levels remained rather high at 19.1, 7.4 and 8.8μg/ml, respectively, at 6 hours. Average serum half-lives of CMX were 1.7 hour in the subjects with ages of 4 days or older and 3.2 hours in the subjects with ages of 3 days or younger. Urinary recovery rates were 33.3 and 60.9% in 2 cases.
(4) Intravenous bolus injection of 30mg/kg:
Serum concentrations of the drug in 3 cases 2 to 6 days old peaked at 98.7 to 108.0μg/ml at 30 minutes to 1 hour. Serum half-lives of CMX were 1.5 to 4.7 hours. Urinary recovery rates were 19.3 and 22.0% during the first 3 to 4 hours.
2. Clinical results
CMX at 50 to 160mg/kg/day was given in 3 to 4 divided doses to 8 patients. In all cases, including 3 cases with pneumonia, 2 with urinary tract infection and 1 each with purulent otitis media and phlegmonous cellulitis and septicemia, the efficacy was good or excellent. Pathogens were detected in all cases, including 2 strains of Staphylococcus aureus, 3 of Streptococcus pneumoniae, 2 of Escherichia coli and 1 of Klebsiella pneumoniae. All of these bacteria were eradicated during the therapy.
3. Dose and frequency of administration
Serum concentrations of the drug, although they fluctuated to some extent, remained at least 3μg/ml at 6 hours after administration of 20mg/kg. Serum half-lives of CMX, although they were a little different among different ages, were 1.7 to 3.5 hours.

View full abstract

1. Cefmenoxime (CMX) was administered with a dosage regimen of 20-25mg/kg, 2-3 times daily (40-45mg/kg/day) by intravenous drip over 30 minutes to 9 neonates with bacterial infections including purulent meningitis and septicemia. Clinical responses to the treatment were excellent in 7 and poor in 2. Bacteriological responses were “eradication of pathogens” from 8 of them except another patient with an infection due to Staphylococcus aureus.
2. Adverse reactions to CMX were observed in 6 of 18 neonates treated with the drug: diarrhea, oral thrush, and the elevation of S-GOT, S-GPT, LDH and alkaline phosphatase. None of the reactions, however, necessitated the discontinuation of the treatment.
3. Changes in blood concentrations of CMX in neonates with ages between 0 and 30 days were followed. These subjects included 16 mature neonates and 10 neonates with low birth weights. Intravenous drip infusion of 20mg/kg of CMX over 30 minutes was immediately followed by peak blood CMX concentrations of 34.6-72.7mcg/ml (mean±S. D.: 50.4±11.3mcg/ml) in the mature neonates, and 22.3-78.2mcg/ml (55.5±16.5mcg/ml) in the neonates with low birth weight. Blood half-lives of the drug in the mature neonates were in the range from 1.7 to 20.7 hours (5.9±6.6 hours) in subjects with ages of 0-3 days, and 1.1-3.5 hours (2.0± 0.8 hours) in subjects of 4-5 days. In neonates with low birth weight, they were 3.4-10.2 hours (7.2±2.7 hours) in subjects of 0-2 days, and 1.4-5.5 hours (3.0±1.5 hours) in subjects of 4-30 days. In other words, the blood half-lives of the drug tended to be longer in younger subjects.
4. Concentration of CMX in cerebrospinal fluid (CSF) were determined in a patient in acute stage with purulent meningitis caused by Mycoplasma hominis. Intravenous drip infusion of 80mg/kg of CMX over 30 minutes was followed by CSF concentrations of 7.7-15.5mcg/ml.
5. MICs of CMX for clinical isolates were determined. The drug was proved to have excellent antibacterial activities against Escherichia coli (3 strains) and group B hemolytic streptococci (2 strains) and these MICs were comparable to those of cefotaxime. The MIC of CMX for S. aureus (1 strain) was high at 25mcg/ml with an inoculum size of 10⁸CFU/ml. This MIC value of CMX was higher than that of cefmetazole.

View full abstract

The antimicrobial activity of cefmenoxime (CMX) against B group Streptococcus was investigated. The clinical efficacy of CMX was determined in neonates and premature infants. The results are summarized below.
1. MIC's of CMX against 39 strains of B group Streptococcus obtained from the pregnant vagina were below 0.05μg/ml.
2. CMX was given in a dose of 20mg/kg by intravenous bolus injection to 3 neonates with birth weight over 2,500 grams. Peak serum concentrations ranged from 54.0 to 199μg/ml and the mean half-life was 1.8 hours.
3. Efficacies of CMX were good to excellent in 5 cases administered for treatment and in 4 cases for prophylaxis. As abnormal laboratory parameteres, elevation of GOT and eosinophilia were obserbed in each 2 cases.
4. Examinations on intestinal bacteria in 2 cases revealed that CMX gave as much influences to the flora as other third-generation cephems.
5. The vitamin K defficiency were observed in 2 out of 6 cases examined.

View full abstract

Pharmacokinetic and clinical studies on cefmenoxime (CMX) were performed in infants given by the drug intravenous drip infusion or one shot intravenous injection. The results obtained are summarized as follows.
1. Serum concentrations of CMX in infants given CMX at 10mg/kg by intravenous drip infusion peaked at 12.0 to 26.5μg/ml at the termination of the administration, and the levels were 8.62 to 26.3μg/ml in 1 hour after dosing. Half-lives were 2.9 to 3.8 hours.
2. Serum concentrations of CMX in infants given the drug at 20mg/kg by the same manner for 30 minutes to 1 hour peaked at 40.8 to 74.3μg/ml at the termination of the administration, and drug levels decreased to 17.6 to 45.4μg/ml in 1 hour after dosing. Half-lives were 0.8 to 2.7 hours. Those of CMX in infants given the same dose by one shot intravenous injection peaked at 61.7 to 90.6μg/mi immediately after dosing, and decreased to 22.3 to 48.2 g/ml at 1 hour. Half-lives were 1.2 to 2.7 hours.
3. As described above, dose-response was observed between the doses of 10mg/kg and 20mg/kg.
4. Urinary recovery rates were 2.6 to 47.7% during the first 6-8 hours in most of 1 to 2 day-old infants, and 17.6 to 72.4% in most of 5 day-old or older ones.
5. Twelve infants with various bacterial infections were given CMX by intravenous injection or drip infusion. Clinical efficacies of CMX were excellent or good in all the 9 infants with pneumonia, septicemia, amniotic fluid-aspiration syndrome or intra-placental infection etc., while 3 cases were excluded: 1 each with congenital syphilis (0 day old), acute bronchitis (56 days old) and whooping cough (54 days old).
6. Dosages of CMX used in the present study were 33 to 79mg/kg/day, and durations of treatment ranged from 4 to 13 days. No abnormal laboratory test values were observed. Moreover, neither systemic nor local adverse effects attributable to CMX were encountered in any of the infants.

View full abstract

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and infants were conducted.
1. CMX 20mg/kg was administered by intravenous bolus injection to 6 neonates (with ages 2 to 20 days) and 5 infants (with ages 36 to 107 days) and its serum concentration and urinary excretion rates were determined.
In the neonates, serum concentrations of CMX after intravenous administration reached peak levels of 48.2 to 90.7μg/ml (mean 70.4±14.3μg/ml) in 1/4 hour, then declined with halflives of 1.27 to 5.19 hours (mean 2.28±1.56 hours), and were 3.6 to 16.9μg/ml (mean 8.3±6.0μg/ml) at 6 hours. In the infants, serum concentrations at 1/4 hour were 67.5 to 111.0μg/ml (mean 95.5±18.0μg/ml) ; half-lives were 0.64 to 0.94 hour (mean 0.81±0.13 hour) ; and the serum concentrations at 6 hours were 0.2 to 1.1μg/ml (mean 0.7±0.4μg/ml). Mean peak serum concentrations in the neonates tended to be lower than those in the infants, but higher than those in children. Regarding the age differences of serum concentrations due to age in the neonates, their peak levels tended to be lower in younger ones. Half-lives were shorter in older subjects and, in early infancy, approached values observed in children.
Urinary recovery rates in the first 6 hours after intravenous administration ranged from 43.6 to 87.5% (mean 61.6±14.6%) in the neonates and from 52.1 to 90.8% (mean 78.0±15.1%) in the infants. Thus, recovery rates were high even in younger subjects and tended to be higher in older subjects.
2. CMX was administered to 27 neonates and 4 infants to investigate its clinical effect, bacteriological effect and side effects.
Clinical efficacy ratings of the drug in 19 neonate cases that could be evaluated (1 with purulent meningitis, 2 with suspected septicemia, 1 with acute bronchitis, 12 with acute pneumonia, 1 with impetigo, 1 with periumbilical abscess and 1 with acute pyelonephritis) were “excellent” in 14 cases, “good” in 4, and “poor” in 1. The efficacy rate covering “excellent” and “good” was 94.7%. In 4 infants (2 with acute pneumonia, 1 with periumbilical abscess and 1 with acute pyelonephritis), “excellent” was obtained in 2 cases and “good” in 2 cases. Thus, all the cases showed “good” or higher ratings.
Bacteriologically, 1 strain of Staphylococcus aureus and 3 strains of Escherichia coli in neonates were eradicated while, in infants, 1 strain of S. aureus persisted but 1 of E. coli was eradicated.
Clinically, no side effect was found at all.
The abnormal laboratory test values included, in neonates, elevations of GOT and GPT in 2 cases and elevation of GOT alone in 4 cases and, in infants, elevation of GOT alone in 2 cases and eosinophilia in 1 case. However, these abnormalities were invariably mild and normalization was obtained in all the 5 cases for which subsequent observations were made.

View full abstract

Cefmenoxime (CMX) was evaluated for its absorption and excretion as well as for therapeutic effectiveness in neonates and premature infants, The following results were obtained.
1. Serum concentrations of the drug were examined in 3 premature infants 1 to 11 days old upon intravenous administration of about 10mg/kg body weight (1st group), in 2 premature infants 18 and 32 days old and 1 neonate 17 days old upon intravenous administration of about 20mg/kg (2nd group), and in 1 neonate 15 days old with meningitis upon intravenous administration of 45.2mg/kg. Concentrations of CMX at 30 minutes after administration were 43, 29 and 27μg/ml, respectively, in the 1st group, 46, 37 and 44μg/ml, respectively, in the 2nd group and 208μg/ml in the other neonate, and appeared to be dose-dependent. Concentrations of CMX at 6 hours after administration were 18.2, 6.6 and 8.1μg/ml, respectively, in the 1st group, 9.6, 11 and 1.35μg/ml, respectively, in the 2nd group and 5.2μg/ml in the other subject. Serum half-lives were, respectively, 4.59, 2.85 and 3.48 hours in the 1st group, 2.52, 2.73 and 1.14 hours in the 2nd group and 1.0 hour in the other subject.
Urinary recovery rates during the first 6 hours after administration were 45.8, 87.0, 50.2 and more than 100% in 4 cases examined. Two of these cases, in which recovery rates were 45.8 and 50.2%, were premature infants of low birth weight.
Spinal fluid concentrations of the drug at 80 to 90 minutes after dosing to 1 neonate with purulent meningitis (causative organism presumed: Escherichia coli) given 48.3mg/kg tended to decline gradually with the recovery of the disease, 3.8, 1.72 and 1.32μg/ml on the 2nd, 6th and 8th day, respectively.
2. The drug was given to 9 neonates 0 to 24 days old. The therapeutic effectiveness on bacterial infections was evaluated in 7 cases (10 diseases) including 1 disease of purulent meningitis presumably caused by E. coli, 4 of septicemia caused by E. coil, Staphylococcus aureus and Streptococcus agalactiae (1, 2 and 1, respectively), 3 of urinary tract infection caused by E. coil, Serratia and Enterococcus faecalis (1 each), 1 of purulent parotitis caused by S. aureus and 1 of pneumonia (causative organism was unknown). Therapeutic efficacies were assessed as “Excellent” in all of meningitis, septicemia and urinary tract infection cases, and “Good” in 1 each of purulent parotitis and pneumonia cases.
For prophylactic use, the drug was given to 2 newborn infants in intravenous doses of 18.9 to 28.8mg/kg b. i. d. or t. i. d., and no infection occurred in any cases.
3. No adverse reactions were obtained in any of the 9 cases described above. Slight and transient increase in GPT was observed in 1 case.
4. These results suggested that CMX would be useful for the treatment of neonatal bacterial infections.

View full abstract

Cefmenoxime (CMX) was administered by intravenous bolus injection to a total of 23neonates and premature babies with ages of 1 to 26 days at a dose of 10 or 20mg/kg and their plasma and urine concentrations and urinary recovery rates were determined up to 6 hours after administration. In addition, for the treatment of bacterial infections, diagnosed or suspected, or for the prophylaxis of bacterial infections, the drug was administered to a total of 27 neonates, premature babies and infants, with ages of 0 day to 3 months. It was possible to evaluate therapeutic efficacy and prophylactic efficacy in 15 cases and 7 cases, respectively. In these cases, side effects and bacteriological effects and, in some of them, changes in laboratory test values were also investigated. The obtained results are summarized below.
1. At a dosage level of 10mg/kg (n=7), peak plasma concentrations at 5 minutes after administration, were 42.6μg/ml in neonates with ages of 15 to 21 days and 45.9μg/ml in those with ages of 22 to 28 days in a group of <2,500g b. w.(birth weight), and 36.9μg/ml in neonates with ages of 4-7 days and 38.9μg/ml in those of 8-14 days in the other group of≥2,500g b. w., indicating no large differences among the 4 subgroups (each of the above concentration values is either the value for an individual when only one neonates was involved or a mean value when 2 or more neonates were involved. The same applies her inafter.). Though 1 exceptional case showed a biphasic change, its cause is unknown. Half-lives in the above-mentioned 4 subgroups were 1.5, 1.6, 2.4 and 1.9 hours, respectively. The half-life of 2.4 hours in 1 patient with an age of 5 days of the ≥2,500g b. w. group was longer than in any of the other 3 subgroups.
2. At 20mg/kg (n=16) dosage level, mean peak plasma concentrations were 63.8μg/mlin the infants of 0-3 days, 68.1 μg/ml in those of 8-14 days and 59.4μg/ml in those of 15-21 days in the group of<2,500g b. w., and 109.9μg/ml in the neonates aged 8-14 daysand 79.7μg/ml in those of 15-21 days in the group ≥2,500g b.w. The mean concentration in the 0-3 days old subgroup of the<2,500g b. w. group was the highest at 15 minutes after administration, partly because the peak concentration in one 3-day-old neonate in this group occurred at 15 minutes after administration rather than 5 minutes after administration though thecause of this delay is unknown. Some variations such as the above were observed in individual values or in mean values. Three cases showed biphasic changes due to unknown caused. The mean half-life was longest at 4.0 hours in the 0-3 days old subgroup (<2,500g b. w.) because, in this subgroup, one neonate with age of 1 day showed a remarkably prolonged half-life of 6.0 hours. The mean half-lives in the other 4 subgroups were 1.9, 1.4, 1.5 and 1.9 hours, respectively.
3. In 7 cases given CMX at 10mg/kg, it was possible to determine urine concentrations of the drug in all or some of the periods during 0-2, 2-4 and 4-6 hours after administration and the values were in a range of 9.86 to 1,245.0μg/ml. The 0-6 hour urinary recovery rates were 56.7% in the neonates of ages ranging 15-21 days and 64.6% in those of ages ranging 22-28 days in the group of <2,500g b. w., and 36.7% in the neonates of 4-7 days and 73.5% in those of 8-14 days in the group of≥2,500g b. w. The rate in the 4-7 day subgroup (≥2,500g b. w.), though the subgroup consisted of 1 case only, was lower than in any of the other 3 subgroups.
4. In 16 cases given the drug at 20mg/kg, it was possible to determine urine concentrations in all or some of the periods during 0-2, 2-4 and 4-6 hours after administration and the values were in a range of 70.1 to 3,330.0μg/ml.

View full abstract

Pharmacokinetic studies and clinical evaluations of cefmenoxime (CMX) were carried out in perinatal mothers and infants. The following results obtained are summarized as follows.
1. CMX was promptly absorbed upon intravenous injection in pregnant women, reached dose-related peak serum level shortly after administration. Placental penetration into the fetus occured quickly and at high levels. After intravenous injection of 1g of CMX, drug concentrations in the cord blood and amniotic fluid exceeded MICs of main pathogenic organisms.
The drug transferred into newborn infants were followed by measuring serum level of the newborn. These levels were related to levels of umbilical cord blood and the drug was eliminated gradually from the newborn without accumulation.
According to the above results, it appears possible to successfully prevent or treat perinatal infections, through administration of the dose of 1 g twice daily.
2. Clinically, CMX was effective in the treatment of perinatal infections and prophylaxis of intra-uterine amniotic infections without any severe side effect.
3. Moreover, newborn infants delivered from mothers receiving CMX treatment were without abnormalities in laboratory test results.
4. The penetration of CMX into mother's milk was hardly observed and the transferance from milk to newborn infants appeared to be occur only at very low levels.
The above results have demonstrated that CMX is a clinically useful antibiotic for prophylaxis and treatment of perinatal infections.

View full abstract

Four neonates and young infants were treated with cefsulodin (CFS) at doses ranging from 20-25mg/kg every 6 hours for 6.25 to 17 days, and clinical efficacy and side effects were evaluated. Among the 4 infants with bacterial infections including meningitis, bronchitis and pneumonia, the results were good in 2 patients with meningitis, but unknown in 2 patients because of additional use of gentamicin. One of the 4 patients had eosinophilia.
Minimal inhibitory concentrations of CFS against 4 isolates of Pseudomonas aeruginosa were 1.56 against one and 12.5μg/ml against other 3 strains with an inoculum size of 103 CFU.
Serum concentrations of CFS were measured in one-and four-month-old infants upon 25.3 and 20.9mg/kg bolus intravenous injection of the antibiotic, respectively. The values were 36.4 and 33.4 at 30 minutes, and 5.1 and 3.2μg/ml at 6 hours after injection, respectively. Serum half-lives were 1.89 and 1.69 hours, respectively. Total body clearances and volume distributions were 3.16 and 3.76ml/min/kg, and 519.0 and 551.2ml/kg, respectively.

View full abstract

Pharmacokinetics and clinical studies on cefsulodin (CFS) were conducted in neonates.
1. MIC's of CFS, sulbenicillin and gentamicin (GM) were determined using 7 strains of Pseudomonas aeruginosa clinically isolated from neonates and maintained as stock cultures. CFS was found to be nearly as active as GM.
2. When CFS 20mg/kg was administered to a 12-day-old neonate by intravenous bolus injection, serum concentrations were 8.7μg/ml before administration and 51.7μg/ml at 30 minutes, 44.4μg/ml at 1 hour, 38.6μg/ml at 2 hours and 11.1μg/ml at 6 hours after administration. The half-life was 2.5 hours.
3. CFS was administered alone or combination with other drugs to 3 neonates. The drug was clinically effective in 2 cases and slightly effective in another. Bacteriologically, one case was rated as decreased, another as replaced, and the remaining one as unchanged.
4. Neither side effects nor abnormal laboratory values attributable to CFS were found.

View full abstract

Fourteen neonates and premature infants with ages ranging 1 to 28 days were intravenously given one shot injection of 20mg/kg of cefsulodin (CFS). Plasma and urine levels and recovery rates of CFS were determined in the first 6 hours after administration. For prophylaxis of infection, a daily average dose of 52.8mg/kg of CFS was injected intravenously to 3 neonates with ages ranging 2 to 16 days in 2 to 3 divided doses during an average period of 7 days. Along with observations of prophylactic effects on infection, side effects and abnormalities in laboratory test values were examined. The results obtained are summarized below:
1. Of the 9 patients with birth weight of 2,500g or above, the plasma levels peaked in 6 patients at 5 minutes, in 2 patients at 15 minutes and in the other at 1 hour after administration, with peak levels ranging between 35.8 and 60.6μg/ml. Subsequently, gradual decreases or bimodal tapering changes were noted in the plasma levels. The cause of the delay in the occurrence of maximum peak observed in the 3 patients at 15 minutes or 1 hour after administration and the cause of the appearance of bimodal tapering changes in 3 subjects are not known. A tendency was observed that the younger the age of subject was, the larger the AUC and the longer the half-life became. Half-lives in all 9 neonates were longer than those in average infants who were given intravenous injection at the same dose.
2. Of 5 patients with birth weight of less than 2,500g, the determination of peak plasma levels was not performed in those within 7 days after birth. Plasma levels, however, were observed to reach their peaks in 4 patients at 5 minutes and in another at 15 minutes after administration, the levels ranging between 41.5 and 56.0μg/ml. Subsequently to this, gradual decreases and bimodal tapering changes of plasma levels were noted. The cause of the delay in plasma levels to reach their maximum peaks values in the 1 patient to 15 minutes after administration and the cause of occurrence of bimodal tapering changes in the 2 partients are not known. A tendency was observed that the younger the age of subjects was, the larger the AUC and the longer the half-life became. This tendency was similar to that observed in the group with birth weight of 2,500g or above. Half-lives in all 5 neonates were longer than those in average infants who were given intravenous injection at the same dose.
3. Urine levels of the drug were measurable in 9 patients with birth weight of 2,500g or above in during 0 to 2, 2 to 4, and 4 to 6 hours after administration, and they ranged between 120.0 and 1,890.0μg/ml. In 5 patients with birth weight of less than 2,500g, urinary levels were measurable during the above specified periods of time, and the measured levels ranged between 65.1 and 619.0μg/ml.
4. In the group with birth weight 2,500g or above, the mean or individual urine recovery rates in the first 6 hours after administration in patients with their ages 3 or less, 4 to 7, 8 to 14, 15 to 21, and 22 to 28 days were 29.7, 46.2, 45.6, 49.2, and 55.5%, respectively. There was only one patient in the 3 or less day-age group and the urine recovery rate of this subject was lower than those of the other age groups. In the group with birth weight of less than 2,500g, urine recovery rate of the drug was not determined in any of them in the first 7 day after birth. However, mean or individual urine recovery rates in the first 6 hours after administration in patients with ages 8 to 14, 15 to 21, and 22 to 28 days were 40.7, 48.9 and 29.9%, respectively. Those in the 22 to 28 day-age group exhibited lower urine recovery rates than those of the other 2 age groups, but the cause for the low recovery rates is unknown.

View full abstract

Pharmacokinetic studies on cefsulodin (CFS) were carried out in perinatal mothers and infants. The results obtained are summarized as follows.
1. CFS was promptly absorbed upon intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus occurred quickly and at high levels. Upon intravenous drip infusion of 1-2g of CFS, drug concentration of the cord blood and amniotic fluid exceeded MICs of clinically isolated strains of Pseudomonas aeruginosa. These levels in cord blood ranged 3.3, 16.9μ/ml upon 1g intravenous drip infusion and 0.8-21.6μ/ml upon 2g intravenous drip infusion, and in amniotic fluid they were 1.3-15.6μ/ml upon 1g administration and 5.5-17.9μ/ml upon 2g administration. The drug was transferred into newborn infant through placenta, showing no tendency to accumulate. According to the above results, it appears possible to successfully prevent or treat perinatal infections through administration of the dose of 1-2g twice daily.
2. Moreover, newborn infants delivered from mothers receiving CFS administration showed no laboratory test abnormalities.
3. The penetration of CFS into mother's milk occurred at low levels, and the transference from milk to newborn infants appeared to occur at even low levels. The above results have demonstrated that CFS is a clinically useful antibiotic for prophylaxis and treatment of perinatal Pseudomonas infections.

View full abstract