Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field

Pharmacokinetic and clinical studies of sulbactam/ampicillin (SBT/ABPC) were conducted and the obtained results are summarized as follows. For pharmacokinetic investigation, SBT/ABPC at 30 or 60 mg/kg was administered by intravenous drip infusion over 30 minutes. The maximum blood concentration was reached just after the completion of the drip infusion in both groups. The mean peak serum concentrations of SBT and ABPC were 22.4 +/- 0.8 micrograms/ml and 32.8 +/- 1.0 micrograms/ml, respectively, in the 30 mg/kg group, and they were 54.2 micrograms/ml and 93.8 micrograms/ml, respectively, in the 60 mg/kg group. The concentrations were dose-related. The mean half-lives of SBT and ABPC following 30 mg/kg SBT/ABPC administration were 0.91 +/- 0.04 hour and 0.90 +/- 0.05 hour, respectively, and those following 60 mg/kg SBT/ABPC were 1.08 hours and 0.84 hour, respectively. The highest urinary concentration occurred 0-2 hours after the 30 minutes drip infusion. Mean urinary excretion rate of SBT and ABPC over 6 hours were 71.4 +/- 2.5% and 54.6 +/- 3.3%, respectively, in the 30 mg/kg group, and they were 80.0% and 63.7%, respectively, in the 60 mg/kg group. In the clinical investigation conducted with a total of 24 patients (15 with respiratory tract infections, 3 with urinary tract infections, 2 with lymphadenitis, and others), SBT/ABPC was found to be excellent in 14 cases, good in 9, fair in 1. The efficacy rate was, therefore, 95.8%. In the bacteriological evaluation, 9 out of 11 clinically isolated strains were eradicated, 1 unchanged and 1 unknown. The elimination rate was 90.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, a slight elevation of GOT was observed.     

Pharmacokinetic, bacteriological and clinical studies on sulbactam/ampicillin in pediatric field

Clinical trials were carried out on the use of sulbactam/ampicillin (SBT/ABPC) (combination rate of 1:2) in pediatric infections. Results were as follows: 1. The mean half-lives of SBT and ABPC in the serum following intravenous injection of SBT/ABPC were about 1.05 and 0.90 hours, respectively. 2. The mean urinary excretions of SBT and ABPC in 6 hours after intravenous injection of SBT/ABPC were 71.2% and 62.2%, respectively. 3. SBT/ABPC was administered to 23 pediatric patients with various infections: 17 patients with pneumonia, 3 with tonsillitis, 2 with urinary tract infection and 1 with cervical lymphadenitis. The overall efficacy rate was 95.7%. In particular, 2 urinary tract infections caused by highly beta-lactamase producing Escherichia coli were improved by the treatment with SBT/ABPC. 4. No adverse reactions were observed except 2 cases of mild diarrhea. Abnormal laboratory test values included thrombocytosis in 4 and slight elevation of GOT and GPT in 1, but they were transient.     

Laboratory and clinical studies of sulbactam/cefoperazone in the pediatric field

The authors have carried out the laboratory and clinical studies of sulbactam/cefoperazone (SBT/CPZ) and obtained the following results. The antibacterial activities of SBT/CPZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, P. aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to SBT/CPZ ranged from 0.39 to 6.25 micrograms/ml, and the peak of distribution was 1.56 micrograms/ml. The peak of susceptibility distribution of K. pneumoniae was 0.20 microgram/ml, and the distribution of E. coli and E. aerogenes ranged from 0.10 to 12.5 micrograms/ml and that of S. marcescens, from 0.2 to 25 micrograms/ml. The growth of 80.8% of P. aeruginosa was inhibited at the concentration of 12.5 micrograms/ml. The distribution of E. cloacae ranged from 0.1 to 50 micrograms/ml. For pharmacokinetic study, SBT/CPZ was given in a single dose of 20 mg/kg by drip infusion for 1 hour in 2 children and 40 mg/kg by drip infusion for 1 hour in 1 children. With drip infusion of SBT/CPZ, the peak serum level were 17.8/43.9 micrograms/ml, 21.8/75.5 micrograms/ml on completion of the infusion, respectively. SBT/CPZ was effective in 14 cases out of 16 cases with clinical effect. No side effect was observed except for eosinophilia in 1 case.     

Bacteriological, pharmacokinetic and clinical studies of sulbactam/ampicillin in the pediatric field

The usefulness of sulbactam/ampicillin (SBT/ABPC) in the treatment of pediatric infections was evaluated. 1. Twenty pediatric patients with infection were treated with SBT/ABPC and an intravenous dosage of 27.8-47.4 mg/kg, 3 to 4 times a day. Clinical efficacies in 18 patients excluding 2 patients of Mycoplasma pneumonia (9 cases of pneumonia, 6 urinary tract infection, 1 tonsillitis, 1 maxillary sinusitis and 1 osteomyelitis) were judged to be excellent in 13 patients and good in 5. There was no case of failure. 2. Bacteriological efficacies against 16 strains (1 Staphylococcus aureus, 3 Enterococcus faecalis, 4 Haemophilus influenzae, 2 Haemophilus parainfluenzae, 5 Escherichia coli and 1 Serratia sp.) isolated from 13 of the 18 patients were rated as "eradicated" for 13 strains, "decreased" for 1 and "unchanged" for 2 with an eradication rate of 81.3%. Of 13 strains eradicated, 3 were those with high beta-lactamase productivity. 3. Rash as a side effect developed in 1 patient and eosinophilia and elevated GOT and GPT were observed in 7 patients but none of them were serious. 4. Blood levels of the drug following an intravenous dose of 30 mg/kg were determined in 2 pediatric patients. Blood levels of SBT and ABPC at 30 minutes after intravenous administration were 19.0 and 29.2 micrograms/ml in one patient and 21.0 and 31.6 micrograms/ml in another, respectively, and those at 4 hours were 0.48 and 0.62 microgram/ml in one patient and 0.59 and 0.89 microgram/ml in another, respectively. The half-lives of SBT were 0.67 and 0.70 hour and those of ABPC were 0.64 and 0.69 hour in the 2 patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic, bacteriological and clinical studies of sulbactam/ampicillin in pediatric patients

Plasma and urine concentrations of sulbactam (SBT) and ampicillin (ABPC) were determined following bolus administration of injectable SBT/ABPC combined in a fixed ratio of 1:2 to 6 pediatric patients, 3 at a dose of 30 mg/kg and the other 3 at 60 mg/kg. Clinical and bacteriological efficacies of SBT/ABPC were evaluated in a total of 65 patients composed of 45 cases with pneumonia, 3 cases each with bronchitis, urinary tract infections, staphylococcal scalded skin syndrome, purulent lymphadenitis, 2 cases each with tonsillitis, pleuropneumonia, phlegmon and 1 case each with pyothorax, submaxillitis. The dosage used was 101.2 mg/kg daily given in 3 or 4 divided doses (t.i.d. in 24 patients and q.i.d. in 41 patients) by bolus intravenous injection for 7 days on an average. Side effects and effects on clinical laboratory parameters were monitored in the 65 patients. The results of these evaluations are summarized as follows. 1. Mean serum concentrations of SBT and ABPC in 3 children each given an intravenous bolus injection of 30 mg/kg and other 3 each given 60 mg/kg reached peak levels at 5 minutes after administration with values of 49.8 and 90.3 micrograms/ml, respectively, for SBT and 99.8 and 189.7 micrograms/ml, respectively, for ABPC. The latter values were about twice as high as SBT, and both were dose-related. Mean half-lives were 0.889 hour for SBT and 0.857 hour for ABPC in the 30 mg/kg group and 0.882 hour for SBT and 0.834 hour of ABPC in the 60 mg/kg group, showing similarities between the 2 dosage groups as well as between SBT and ABPC. 2. Mean urine concentrations in the 2 groups mentioned above were the highest for both SBT and ABPC during the first 2 hours after administration, with values of 1,677 micrograms/ml for SBT and 2,730 micrograms/ml for ABPC in the 30 mg/kg group and 2,693 micrograms/ml and 3,623 micrograms/ml, respectively, in the 60 mg/kg group. Mean recovery rates in urine in the first 6 hours were 72.4% for SBT and 56.8% for ABPC in the low dosage group and 72.7% and 52.0%, respectively, in the high dosage group. In the 2 groups, the amounts of ABPC recovered were less than those of SBT. 3. Clinical efficacies of SBT/ABPC in 65 patients with various bacterial infections were excellent or good in 62 (95.4%) patients. 4. The bacteriological efficacy was evaluable with 10 patients. The pathogenic bacteria were eradicated in 9 patients and the efficacy rate was 90%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Basic and clinical studies of sulbactam/cefoperazone in pediatric field

We conducted several studies using a combination of sulbactam (SBT) and cefoperazone (CPZ) in a ratio of 1:1 with the following results. Serum and cerebrospinal fluid (CSF) concentrations of the drugs were determined in 2 rabbits with meningitis caused by S. aureus. Following intravenous injection, serum concentrations of CPZ were higher than those of SBT in both rabbits whereas CSF concentrations were much higher with sulbactam than with CPZ indicating good penetrability of SBT into CSF. The serum concentration of SBT at 1/2, 1, 2 and 4 hours after an intravenous administration of 9.8 mg/kg of the combination to a child were 3.5, 1.4, 0.3 and 0.1 microgram/ml and those of CPZ 19.0, 13.0, 6.7 and 2.9 micrograms/ml, respectively. The half-lives were 0.705 hours for SBT and 1.31 hours for CPZ. An intravenous dose of this combination (19.6 mg/kg) was given 3 times a day to 13-year-old girl with decreased neutrophil chemotaxis due to periblepharal abscess caused by S. aureus. The therapeutic effect was excellent. Though very slight transient eosinophilia was noted, no adverse reaction was found. The susceptibility of the isolated organism to this drug was not determined, but it was found to be resistant to the CTX using the disc method.     

Experimental and clinical studies of sulbactam/cefoperazone in pediatric field

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

Clinical experience with sulbactam/ampicillin in the pediatric field

Sulbactam/ampicillin (SBT/ABPC) was given intravenously to 20 children with the following acute bacterial infections; 14 cases of pneumonia, 2 cases of purulent cervical lymphadenitis and 1 case each of bronchitis, pyothorax, cellulitis, and purulent meningitis. Good clinical responses were obtained in 18 out of 20 patients, and bacteriologically, all of the 14 isolated strains were eradicated. No side effect was observed except 2 cases of eosinophilia, and 1 case each of loose stool and elevated thrombocyte. From the above clinical results, it is apparent that SBT/ABPC is a useful antibiotic for the treatment of pediatric patients with various kinds of bacterial infections.     

Clinical study on sulbactam/ampicillin in the pediatric field

A combination drug of sulbactam/ampicillin (SBT/ABPC) was intravenously administrated to 18 patients with ages 3 months to 10 years 10 months with various acute infections including 14 cases of pneumonia, 1 case each of tonsillitis, subacute bacterial endocarditis, empyema and suspected sepsis. Clinical responses were excellent in 14 cases and good in 4 cases. Bacteriological responses of 8 isolated strains were: 7 strains were eradicated and 1 strain was decreased. No side effect was observed in any case. Eosinophilia was observed in 2 cases, thrombocytosis in 2 cases, elevation of GOT in 1 case and elevations of GOT and GPT in 1 case. From the above results, it seemed that SBT/ABPC was a useful drug for the treatment of bacterial infections in the pediatric field.     

Fundamental and clinical studies of sulbactam/cefoperazone in the pediatric field

To 6 cases of children in 2 groups of 3 each, newly developed sulbactam/cefoperazone (SBT/CPZ) was given at 20 and 40 mg/kg by intravenous bolus injection, respectively, and the serum and urinary concentrations and recoveries of SBT and CPZ were determined. To 1 case of purulent meningitis, this drug was given at 40 mg/kg by intravenous bolus injection, and the cerebrospinal fluid and serum concentrations of SBT and CPZ were determined. Susceptibility tests to SBT/CPZ and CPZ of total 289 strains were conducted; Gram-positive cocci tested consisted of 26 S. aureus strains, 20 S. pyogenes strains and 21 S. pneumoniae strains, and Gram-negative bacilli consisted of 24 H. influenzae strains, 22 E. coli strains, 26 K. pneumoniae strains, 24 E. cloacae strains, 21 E. aerogenes strains, 19 Citrobacter sp. strains, 20 S. marcescens strains, 23 P. mirabilis strains, 23 indole-positive Proteus sp. strains and 20 P. aeruginosa strains. SBT/CPZ was given to total 43 cases at a mean daily dosage of 80.4 mg/kg, in 3 or 4 divided doses (6 cases in 3 and 37 cases in 4), 1 case receiving the drug by drip infusion over 30 minutes (in 3 divided doses) and all the other 42 cases by intravenous bolus injection, for 7 days on an average. They consisted of 2 cases of tonsillitis, 1 case of otitis media, 1 case of otitis media associated with mastoiditis, 30 cases of pneumonia, 1 case of suspected septicemia, 1 case of purulent meningitis, 5 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of submaxillaritis. And the clinical and bacteriological effects were evaluated. Also, side reactions and laboratory examinations for abnormal values due to administration of this drug were made on 47 cases including 4 drop-outs. The following results were obtained: After administration of this drug to 2 groups of 3 children each at 20 and 40 mg/kg by intravenous bolus injection, mean serum concentrations of both SBT and CPZ reached the peaks in 5 minutes; SBT levels were 60.9 and 124.7 micrograms/ml for the 2 groups and CPZ levels were 105.0 and 214.1 micrograms/ml, respectively. In either group, CPZ levels were 1.7 times as high as SBT levels, and there was observed a dose-response in both. In the 20 mg/kg group, mean half-lives of SBT and CPZ were 0.96 and 1.24 hours, respectively, and in the 40 mg/kg group, they were 1.01 and 1.32 hours, CPZ values tending to be longer.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on sulbactam/ampicillin in children

Laboratory and clinical studies of sulbactam/ampicillin (SBT/ABPC) in children have been carried out, and the following results were obtained. 1. Antibacterial effect MICs of SBT/ABPC were only one-tube less than or similar to those of ABPC against susceptible organisms. Against ABPC-resistant organisms at the inoculum size of 10(8) cells/ml however, SBT/ABPC was superior to ABPC when evaluated in terms of their MIC values. When MICs of SBT/ABPC were compared to those of ABPC against organisms with high beta-lactamase producing activities, it was found that many of ABPC-resistant organisms were much susceptible to SBT/ABPC. 2. Absorption and urinary excretion In 2 cases to which 50 mg/kg and 20 mg/kg SBT/ABPC were respectively given over 30 minutes by drip infusion, peak serum levels were obtained at the end of the drip infusion with peak levels of SBT of 45.5 micrograms/ml, 12.5 micrograms/ml, respectively and those of ABPC of 83.0 micrograms/ml, 22.9 micrograms/ml, respectively. The half-lives of SBT and ABPC were 0.94 hour and 0.98 hour, respectively. The mean urinary excretion rates in the first 6 hours after the end of administration were 84.4% for SBT and 63.1% for ABPC. 3. Clinical results Clinical efficacies were evaluated in 24 cases including 9 cases of pneumonia, 2 cases of upper respiratory infection, 7 cases of urinary tract infection and 1 case each of bronchopneumonia, pyothorax, tonsillitis, streptococcal infection, ++ phlegmon and staphylococcal scalded skin syndrome. Clinical efficacies were excellent or good in 19 cases with an overall efficacy rate of 86.4%. Adverse effect was found in 1 case with nausea and vomiting, and abnormal laboratory test values observed were 2 cases each of eosinophilia, slight elevation of GOT and GPT and elevation of LDH, but they were not serious.     

Clinical studies on sulbactam/ampicillin in the field of pediatrics

During 8 months from October 1986 to May 1987, the clinical efficacy of sulbactam/ampicillin (SBT/ABPC) was evaluated in 63 pediatric inpatients with various infections. Clinical efficacies were evaluable in 58 patients among them (consisting of 2 patients with sepsis, 3 with tonsillitis, 12 with bronchitis, 6 with bronchopneumonia, 24 with pneumonia, 1 with phlegmon, 2 with lymphadenitis, 1 with impetigo and 7 with urinary tract infection) and were excellent in 40 patients and good in 17 with an overall efficacy rate of 98.3%. Bacteriological efficacies were assessed in 25 patients and 27 strains of organisms (consisting of 3 strains of Staphylococcus aureus, 2 Streptococcus pneumoniae, 1 Streptococcus pyogenes, 2 beta-Streptococcus, 1 Gram-positive cocci, 5 Escherichia coli, 1 Enterobacter aerogenes, 7 Haemophilus influenzae, 2 Haemophilus parainfluenzae, 1 Branhamella catarrhalis, 1 Proteus mirabilis and 1 Salmonella subgenus I). Bacteriological eradication rates were 88.9% for Gram-positive organisms, 66.7% for Gram-negative organisms and 74.1% overall. No superinfection was observed in any of patients treated. Side effects and clinical laboratory parameter abnormalities observed consisted of diarrhea in 7 (11.1%) of the 63 patients, eosinophilia in 2 (3.3%) of 61 tested, thrombocytosis in 3 (5.5%) of 55, elevation of direct bilirubin in 1 (3.3%) of 30, elevation of total bilirubin in 1 (3.1%) of 32, elevation of GOT in 4 (6.8%) of 59 and elevation of GPT in 1 (1.7%) of 59 patients tested. As an effect on the hemostatic mechanism of this drug, PIVKA II was detected in 1 patient (4.2%) of 24 tested, but findings of other coagulation tests were normal and none of patients showed bleeding tendency or inhibition of platelet aggregation. From the above results, it appears that SBT/ABPC is an efficacious and safe drug in the treatment of bacterial infections of pediatric patients.     

Bacteriological, pharmacokinetic and clinical studies on sulbactam/cefoperazone in the pediatric field

Bacteriological and clinical effect of a newly developed SBT/CPZ in the treatment for pediatric patients was assessed by a study group consisting of 15 institutions. The results were as follows. Antibacterial effect Susceptibility studies were performed with 93 clinical isolates. The MIC of SBT/CPZ was one-tube inferior or almost similar to that of CPZ in susceptible organisms. In CPZ-resistant organisms at the inoculum of 10(8) cells/ml, however, SBT/CPZ was much superior to CPZ on the basis of the MIC. When the MIC of SBT/CPZ was compared to that of CPZ in 27 strains which have high beta-lactamase-producing activity, it was found that many of CPZ-resistant organisms were susceptible to SBT/CPZ. Serum concentration and urinary excretion The serum concentrations of SBT and CPZ were 33.2 micrograms/ml, respectively at 15 minutes after 20 mg/kg SBT/CPZ was administered by intravenous bolus injection, and those of SBT and CPZ, 51.0 micrograms/ml and 108.3 micrograms/ml, respectively following 40 mg/kg SBT/CPZ therapy. The serum concentrations of CPZ were 2.1-2.4 times as high as those of SBT. The concentrations were dose-related. The half-lives of SBT and CPZ following 20 mg/kg SBT/CPZ administration were 0.94 hour and 1.50 hours, respectively, and those following 40 mg/kg SBT/CPZ were 0.95 hour and 1.53 hours, respectively. There was no significant difference between 20 mg/kg and 40 mg/kg administrations. When compared between SBT and CPZ, CPZ had slightly longer half-lives. At the termination of 1 hour drip infusion of 20 mg/kg SBT/CPZ, the serum concentrations of SBT and CPZ were 16.7 micrograms/ml and 40.1 micrograms/ml, respectively. In the case of 40 mg/kg, the levels of SBT and CPZ were 38.6 micrograms/ml and 94.9 micrograms/ml, respectively. The concentrations were found to be dose-related as were following intravenous bolus injections. The SBT half-lives obtained after 20 mg/kg and 40 mg/kg SBT/CPZ administrations were 1.39 hours and 0.89 hour, respectively; those of CPZ, 2.00 hours and 1.44 hours, respectively. The highest urinary concentration occurred 0-2 hours after intravenous bolus injections of 20 mg/kg or 40 mg/kg SBT/CPZ. Urinary excretion of SBT over 6 hours was 60.0% and 67.7%, and that of CPZ, 21.2% and 25.0%, indicating higher urinary excretion for SBT. When 20 mg/kg SBT/CPZ or 40 mg/kg was administered over 1 hour by drip infusion, urinary excretion became the highest at 1-3 hours after administration. Urinary excretion of SBT over 7 hours following 20 mg/kg and 40 mg/kg SBT/CPZ was 68.8% and 80.3%, respectively, and that of CPZ, 24.4% and 27.3%. The results were similar to those observed following intravenous bolus injections.     

Pharmacokinetic and bacteriological studies on sulbactam/ampicillin in the field of pediatrics

Pharmacokinetic and bacteriological studies were carried out on sulbactam/ampicillin (SBT/ABPC) in the field of pediatrics. The results obtained are summarized as follows: 1. A total of 248 clinical isolates were employed to determine minimum inhibitory concentrations (MIC) of SBT/ABPC against various bacterial species. SBT/ABPC showed stronger antibacterial activity against Gram-positive organisms than against Gram-negative rods. 2. The peak serum level of ABPC was about twice as high as that of SBT, and serum levels of ABPC and SBT declined with time. Both drugs showed almost the same trend of changes in concentrations. The half-lives of both drugs were about 1 hour. 3. The urinary recovery rates over 6 hours after administration were 52-80% for ABPC and 70-73% for SBT. 4. The effect of SBT/ABPC on coagulation system was examined. No case showed changes in PT, APTT, TT and HPT before and after administration of SBT/ABPC. Platelet aggregation during administration of SBT/ABPC was slightly faster than that before administration, suggesting that SBT/ABPC had no effect on platelet aggregation. Generally speaking, it seemed that SBT/ABPC was a safe antibiotic for bleeding. 5. The effect of SBT/ABPC on the intestinal bacterial flora in experimental animals was examined. Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve were reduced after administration of SBT/ABPC, suggesting that the intestinal bacterial flora was affected by the administration of SBT/ABPC more greatly than by the administration of ABPC alone. In a similar investigation being made with clinical cases, both aerobes and anaerobes showed great changes. Concentrations of the drugs in feces increased with increasing dosage, resulting in greater changes of the intestinal bacterial flora. Thus, the total number of aerobes and anaerobes was reduced. No diarrhea was observed in any subjects examined. From the above results, it appeared that SBT/ABPC was a safe and useful antibiotic for various bacterial infections in the field of pediatrics.     

Laboratory and clinical studies of cefodizime in pediatric field

Clinical trials of cefodizime (CDZM, THR-221) were carried out in pediatric infection. Results are summarized as follows. 1. The mean half-life of CDZM in the serum following intravenous injection of CDZM (20 mg/kg) was about 2.06 hours. 2. The mean urinary excretion rate of CDZM within 8 hours after intravenous injection of CDZM was 60.1%. 3. CDZM was administrated to 19 pediatric patients with various infections; 9 cases of pneumonia, 3 bronchitis, 1 cervical lymphadenitis, 2 tonsillitis and 4 urinary tract infections. The overall efficacy rate was 94.7%. 4. No adverse reactions were observed. Abnormal laboratory test values found were thrombocytosis in 2, slight elevation of GOT and GPT in 1 and eosinophilia in 1 patient.     

Laboratory and clinical studies of sultamicillin in pediatric field

We have carried out laboratory and clinical studies on sultamicillin (SBTPC). The results are summarized as follows. SBTPC was given by oral administration to 2 children in a single dose at 5 mg/kg and to 3 children in a single dose at 10 mg/kg. After the oral administration, mean peak serum levels of ampicillin (ABPC) and sulbactam (SBT) obtained for the 2 dose levels were 1.91 +/- 1.34 and 2.06 +/- 1.06 micrograms/ml and 2.43 +/- 0.68 and 2.96 +/- 0.77 micrograms/ml at 1 hour, respectively, and mean half-lives were 0.80 +/- 0.10 and 0.98 +/- 0.46 hour and 1.57 +/- 0.57 and 2.01 +/- 0.70 hours, respectively. SBTPC was given to 2 children in a single dose at 15 mg/kg. After oral administration, the mean serum levels of ABPC and SBT at 30 minutes were 6.55 +/- 1.63 and 6.00 +/- 1.00 micrograms/ml, and the mean half-lives were 0.90 +/- 0.13 and 0.82 +/- 0.16 hour. SBTPC was given to 1 child at a single dose of 20 mg/kg. The peak serum levels of ABPC and SBT were 11.3 and 8.64 micrograms/ml, and the half-lives were 0.87 and 0.92 hour. Mean urinary excretion rates of ABPC and SBT were 38.4 +/- 2.7 and 34.6 +/- 4.7%, 43.0 +/- 3.6 and 41.6 +/- 5.8%, 47.7 +/- 5.2 and 51.6 +/- 3.5% in 6 hours and 66.1 and 59.2% in 8 hours after oral administration of 5 mg/kg, 10 mg/kg, 15 mg/kg and 20 mg/kg, respectively. Treatment with SBTPC was made in 34 cases of pediatric bacterial infections; 2 cases of pharyngitis, 19 cases of tonsillitis, 2 cases of bronchitis, 3 cases of impetigo, 2 cases of staphylococcal skalded skin syndrome, 4 cases of urinary tract infection and 1 case each of pneumonia and scarlet fever. Results obtained were excellent in 20 cases, good in 13 cases and poor in 1 case. No significant side effect due to the drug was observed in any cases.     

Laboratory and clinical studies of cefodizime in pediatric field

We have carried our laboratory and clinical studies on cefodizime (CDZM, THR-221). The results were summarized as follows. CDZM was given by 30-minute drip infusion to 2 children at a single dose of 10 mg/kg and to 2 children at a single dose of 20 mg/kg and to 3 children at a single dose of 40 mg/kg. After the 30-minute drip infusion, mean serum levels of CDZM obtained for the 3 dose levels were 76.16 +/- 5.52 micrograms/ml, 170.49 +/- 16.70 micrograms/ml, 270.01 +/- 50.44 micrograms/ml at the end of injection, respectively, and serum half-lives were 2.03 +/- 0.78 hours, 2.03 +/- 0.38 hours, 2.28 +/- 0.30 hours, respectively. The mean urinary excretion rate of CDZM were 83.3 +/- 22.3%, 73.1 +/- 13.9%, 51.1 +/- 8.5% in the first 8 hours after the 30-minute drip infusion of 10 mg/kg, 20 mg/kg, 40 mg/kg, 40 mg/kg, respectively. Treatment with CDZM was made in 28 cases of pediatric bacterial infections; 5 cases of tonsillitis, 2 cases of bronchitis, 10 cases of pneumonia, 6 cases of enteritis, 3 cases of urinary tract infection and 1 case each of maxillary sinusitis and laryngitis. Results obtained were excellent in 13 cases, good in 7 cases, fair in 2 cases, poor in 6 cases. No significant side effect due to the drug was observed except one case of thrombocytosis and 2 cases each of elevated GOT and elevated GOT and GPT.     

Laboratory and clinical studies of cefpirome in pediatric field

We have carried out laboratory and clinical studies on cefpirome (CPR, HR 810). The results are summarized as follows. CPR was given by 30-minute drip infusion to 3 children at a single dose of 20 mg/kg. After the 30-minute drip infusion, the mean peak serum level of CPR was 65.7 +/- 2.2 micrograms/ml at the end of infusion, and the mean half-life was 1.49 +/- 0.046 hours. The mean urinary excretion rate of CPR was 57.0 +/- 25.8% in the first 8 hours after the 30-minute drip infusion of 20 mg/kg. Treatment with CPR was made in 9 cases of pediatric bacterial infections; 1 case each of tonsillitis, pharyngitis, and bronchopneumonia, 4 cases of pneumonia, 2 cases of urinary tract infection. Results obtained were excellent in 6 cases, good in 3 cases. No significant side effects due to the drug were observed except one case of elevated GOT and GPT, and 3 cases of eosinophilia.     

Laboratory and clinical studies of cefuzonam in pediatric field

We have carried out laboratory and clinical studies of cefuzonam. The results were summarized as follows: The effectiveness of cefuzonam was estimated by a plate dilution method on 26 strains each of S. aureus, E. coli, K. pneumoniae, Salmonella spp. and P. aeruginosa and 27 strains of S. marcescens isolated from patients. The distribution of MIC's of cefuzonam against S. aureus was 0.39 approximately 1.56 micrograms/ml and the peak of the distribution was 0.39 microgram/ml. Strains of 96.2% of E. coli and Salmonella spp. were inhibited at cefuzonam concentrations less than 0.39 microgram/ml. Strains of 92.3% of K. pneumoniae were inhibited at drug concentrations less than 0.20 microgram/ml. The distribution of MIC's of cefuzonam against S. marcescens was less than or equal to 0.025 approximately 12.5 micrograms/ml and the peak of the distribution was 0.2 microgram/ml and 1.56 microgram/ml. MIC's against P. aeruginosa was 12.5 approximately greater than 100 micrograms/ml. Cefuzonam was given by 5-minute intravenous administration to 4 children and 1-hour drip infusion to 1 child at a single dose of 20 mg/kg. After the intravenous administration, mean serum levels of cefuzonam were 30.8 +/- 4.55 microgram/ml at 30 minutes, 13.8 +/- 1.83 micrograms/ml at 1 hour, 0.4 +/- 0.159 microgram/ml at 6 hours. The half-life was 1.12 +/- 0.198 hours. After the drip infusion, the serum levels of the drug were 38.7 micrograms/ml at 1 hour, 5.25 micrograms/ml at 2 hours and 0.087 microgram/ml at 7 hours. The half-life was 0.93 hour. The mean urinary excretion rate was 58.1% and 33.4% up to 6 hours after the intravenous administration and the drip infusion, respectively. Cefuzoname was effective in 4 out of 5 cases with bacterial infections. No side effect due to the drug was observed in any case.     

Laboratory and clinical studies of norfloxacin in pediatric field

We have carried out laboratory and clinical studies on norfloxacin (NFLX, AM-715). The results are summarized as follows. NFLX was given through oral administration to one child each at dose levels of 1.7 mg/kg, 2.4 mg/kg and 3.2 mg/kg. After administration, peak serum levels of NFLX obtained for the 3 dose levels were 0.16 micrograms/ml at 1 hour, 0.69 micrograms/ml at 2 hours, 0.81 micrograms/ml at 1 hour, respectively, and half-lives were 2.5 hours, 1.8 hours and 2.7 hours, respectively. NFLX was given through oral administration to 2 children at a dose level of 4.4 mg/kg and to another child at a dose level of 4.8 mg/kg. After administration, mean peak serum levels of NFLX obtained were 1.17 +/- 0.48 micrograms/ml and half-lives were 3.0 +/- 0.5 hours. Urinary excretion rates of NFLX were 14.5% and 28.4% in the first 8 hours after administration of 1.7 mg/kg and 3.2 mg/kg, respectively, and 29.1% in the first 6 hours after administration of 2.4 mg/kg. Mean urinary excretion rates of NFLX were 38.5 +/- 13.0% in the first 8 hours after administration of 4.4 mg/kg and 4.8 mg/kg. Treatment with NFLX was made in 33 cases of pediatric bacterial infections including 5 cases of tonsillitis, 14 cases of enteritis, 10 cases of UTI and 1 case each of bronchitis, balanoposthitis, impetigo and pustulosis. Results obtained were excellent in 14 cases, good in 15 cases. No significant side effect due to the drug was observed in any cases.