Laboratory and clinical studies on cefuroxime (author's transl)]

The authors have carried out the laboratory and clinical studies of cefuroxime (CXM). The results were as follows: The sensitivity was measured by plate dilution method on 26 strains of S. aureus, 22 strains of E. coli and 24 strains of K. pneumoniae isolated from patients. The distribution of sensitivity of S. aureus was 0.78 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 1.56 approximately 50 micrograms/ml and the peak was 6.25 micrograms/ml. The growth of 79.2% K. pneumoniae was inhibited in concentration of less than 3.13 micrograms/ml. CXM was given intravenously for 30 minutes at a single dose of 20 mg/kg to 3 children. The serum mean levels of CXM were 99.0 +/- 10.6 micrograms/ml at 30 minutes, 18.0 +/- 10.7 micrograms/ml at 1 hour, 7.0 +/- 2.0, 2.2 +/- 0.6, 0.79 +/- 0.2 microgram/ml at 2, 4 and 6 hours after drip infusion for 30 minutes, respectively. Mean half life was 48 minutes. The mean urinary recovery rate was 96.2% up to 8 hours after administration. CXM was effective in 9 of 10 cases of bacterial infections. No side effect was observed except for 1 case with elevation of serum transaminase.     

Laboratory and clinical studies of cefoperazone in pediatric field (author's transl)

The authors have carried out the laboratory and clinical studies of cefoperazone (CPZ). The results were as follows: The sensitivity was estimated by plate dilution method on 26 strains of S. aureus, E. coli and K. pneumoniae, 25 strains of P. aeruginosa, 14 strains of Salmonella sp. and 9 strains of GM resistant P. aeruginosa isolated from patients. The distribution of sensitivity of S. aureus was 1.56 approximately 25 mcg/ml and the peak of distribution was 3.13 mcg/ml. The growth of 96.2% of E. coli was inhibited at concentration of less than 12.5 mcg/ml. The growth of 50.0% of K. pneumoniae was inhibited at concentration of less than 6.25 mcg/ml. The peak of distribution of P. aeruginosa was 12.5 approximately 25 mcg/ml (GM sensitive) and 12.5 mcg/ml (GM resistant). CPZ was given by drip infusion for 30 minutes at a single dose of 25 mg/kg to 2 children, and by drip infusion for 60 minutes at a single dose of 46.9 mg/kg to a child. The serum mean level of CPZ was 127.5 +/- 8.5 mcg/ml at 30 minutes, 30.5 +/- 7.5 mcg/ml at 1 hour, 23.5 +/- 3.5 mcg/ml at 2 hours, 10.5 +/- 1.5 mcg/ml at 4 hours and 6.8 +/- 2.4 mcg/ml at 6 hours after administration at a single dose of 25 mg/kg, respectively. The serum level was 102.0 mcg/ml at 1 hour, 32 mcg/ml at 2 hours, 14.5 mcg/ml at 5 hours and 12.5 mcg/ml at 7 hours after administration at a single dose of 46.9 mg/kg. Half-life time was 92 minutes. The mean urinary excretion rate was 32.0 +/- 7.3% in the drip infusion for 30 minutes up to 8 hours after administration. CPZ was effective in 6 of 8 cases with pediatric bacterial infections. No side effects were observed except for 1 case with elevation of GOT.     

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 BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field

The authors have carried out laboratory and clinical studies on the BRL 25000 granule (containing 2 parts amoxicillin and 1 part clavulanic acid). The antibacterial activity of BRL 25000 against 29 clinically isolated strains of S. aureus, 30 E. coli and 30 K. pneumoniae were measured by the agar dilution method using an inoculum size of 10(6) cells/ml. beta-Lactamase production was detected by the Nitrocefin method. The MICs of BRL 25000 against S. aureus ranged from 0.2 approximately 12.5 micrograms/ml, with the majority of strains being inhibited by 1.56 micrograms/ml or less. Seven beta-lactamase producing strains of S. aureus were all inhibited by less than 12.5 micrograms/ml. The range against E. coli was 1.56 approximately 100 micrograms/ml, with the majority inhibited by 6.25 micrograms/ml or less. Fifteen beta-lactamase producing strains of E. coli were inhibited by 6.25 approximately 100 micrograms/ml and the majority by 25 micrograms/ml or less. All strains of K. pneumoniae were beta-lactamase producers and the MIC distribution against K. pneumoniae was 1.56 approximately 50 micrograms/ml, with a majority inhibited by 3.13 micrograms/ml or less, 96% of strains, were inhibited by less than 6.25 micrograms/ml. Against K. pneumoniae, BRL 25000 showed a 8 to 16-fold superiority when compared with AMPC. In a pharmacokinetic study, BRL 25000 granules were orally administered to children in the fasting state at single doses of 7.5 mg/kg and 20 mg/kg. The peak serum levels of AMPC were 6.13 and 6.94 micrograms/ml approximately 1 hour after administration and decreased with half-lives of 1.08 and 0.97 hours, respectively. The corresponding serum levels of CVA were 1.16 and 1.90 micrograms/ml at 1 hour after administration, with half-lives of 0.99 and 0.87 hour, respectively. In clinical studies, the BRL 25000 granule was effective in 39 cases of bacterial infection out of a total of 41 treated. Side effects were limited to 2 cases of diarrhea and minor changes in laboratory findings were elevation of serum GOT (1 case), elevation of serum GPT (1 case), and eosinophilia (2 cases).     

Laboratory and clinical studies of imipenem/cilastatin sodium in the pediatric field

Laboratory and clinical studies on imipenem/cilastatin sodium were carried out and the obtained results were summarized below. The antibacterial activity of imipenem against clinical isolates of S. aureus, E. coli, K. pneumoniae, Salmonella sp., S. marcescens and P. aeruginosa was measured by the plate dilution method with an inoculum size of 10(6) cells/ml. The growth of S. aureus was inhibited at an imipenem concentration of 0.025 microgram/ml or lower. The susceptibility distribution of E. coli to imipenem ranged from 0.1 to 1.56 micrograms/ml, and the peak of the distribution was at 0.1 microgram/ml. The peak of the susceptibility distribution of K. pneumoniae was 0.2 microgram/ml, and those of S. marcescens and Salmonella ranged from 0.2 to 1.56 micrograms/ml and from 0.1 to 0.39 microgram/ml, respectively. The growth of P. aeruginosa was inhibited at a concentration of imipenem at 6.25 micrograms/ml. For a pharmacokinetic study, imipenem/cilastatin sodium was given to 1 patient in a single dose of 10 mg/kg or 20 mg/kg by drip infusion over 1 hour. With drip infusion of imipenem/cilastatin sodium, the peak plasma levels obtained with the two doses (10 and 20 mg/kg) were 20.6/26.4 micrograms/ml and 19.4/36.5 micrograms/ml, respectively on completion of the infusion. Clinical responses to imipenem/cilastatin sodium were excellent in 6 patients and fairly good in 1 patient, and the clinical effectiveness ratio was 85.7%. No side effect was observed except for elevations of GOT and GPT in 1 patient.     

Laboratory and clinical studies of T-1982 (cefbuperazone in pediatric field

The authors have carried out the laboratory and clinical studies of T-1982 (cefbuperazone). The results were as follows: The sensitivity was estimated by the plate dilution method on 28 strains of S. aureus 26 strains of E. coli, 27 strains of K. pneumoniae, 25 strains of S. marcescens and 14 strains of Proteus sp. isolated from patients. The distribution of susceptibility of S. aureus was 1.25-25 micrograms/ml and the peak of distribution was 12.5 micrograms/ml. The strains of 84.6% of E. coli were inhibited at concentration of less than 0.39 micrograms/ml. The strains of 77.8% of K. pneumoniae were inhibited at concentration of less than 0.2 microgram/ml. The strains of 96% of S. marcescens was inhibited at concentration of less than 3.13 micrograms/ml. The distribution of susceptibility of Proteus sp. was 0.39-25 micrograms/ml. T-1982 was given to intravenous administration for 5 minutes and drip infusion for 30 minutes a single dose of 20 mg/kg of T-1982 to 2 and 2 children respectively. After intravenous administration of T-1982, the mean serum level was peak 88.4 +/- 8.7 micrograms/ml at 15 minutes, 52.5 +/- 2.7 micrograms/ml at 1 hour, 4.6 +/- 0.15 micrograms/ml at 6 hours respectively. Half-life was 89 minutes. And after drip infusion of T-1982, the mean serum level was 75.5 +/- 3.5 micrograms/ml at 30 minutes and 3.1 +/- 0.6 micrograms/ml at 6.5 hours respectively. Half-life was 82 minutes. The mean urinary excretion rate was 94.7%, 57.4 +/- 11.0% up to 6 hours after intravenous administration and drip infusion respectively. T-1982 was effective in 13 cases out of 13 cases with bacterial infections. No side effects were observed except for 1 case with elevation of serum GOT, 1 case with elevation of serum GPT and 2 cases with eosinophilia.     

Laboratory and clinical studies on ceftizoxime (author's transl)

The authors have carried out the laboratory and clinical studies of ceftizoxime (CZX), and obtained the following results. 1. The antibacterial activities of CZX were measured by plate dilution method against clinical isolates of S. aureus, E. coli, K. pneumoniae and P. aeruginosa. CZX inhibited the growth of S. aureus at concentrations less than 12.5 micrograms/ml, and the peak of sensitivity distribution was obtained at 3.13 micrograms/ml with an inoculum size of 10(6) cells/ml. And the peak sensitivity distribution of E. coli and K. pneumoniae were obtained at less than 0.1 microgram/ml and that of P. aeruginosa was obtained at 6.25 micrograms/ml. 2. Phagocytosis was determined by Quie's method. Phagocytosis of E. coli and K. pneumoniae by human polymorphonuclear neutrophil was more enhanced in the presence of 1 MIC and 1/2 MIC of CZX than of CEZ at 4 and 6 hours after incubation. 3. As for pharmacokinetic study, CZX was given by intravenous injection and drip infusion for 1 hour at a single dose of 10 mg/kg and 30 mg/kg. After intravenous injection of 10 mg/kg and 30 mg/kg of CZX, the mean peak serum levels were 19.1 +/- 3.4 micrograms/ml and 69.1 micrograms/ml at 30 minutes, and half-life times were 1.20 hours and 1.35 hours, respectively. After 1 hour drip infusion of 10 mg/kg and 30 mg/kg of CZX, the mean peak serum levels were 28.8 +/- 3.6 micrograms/ml and 60.9 +/- 5.9 micrograms/ml at the end of infusion, and half-life times were 1.40 hours and 1.77 hours, respectively. The mean urinary excretion rates were between 75.3% and 101% up to 6 hours after intravenous injection and drip infusion. 4. CZX was given to 4 cases with tonsillitis, 3 with pneumonia, 1 with enteritis, 4 with U.T.I., totaling 21 cases. A daily dose of CZX between 350 mg and 2,000 mg was given for 3 to 5 days. Clinical results obtained were good in all cases. No side effects and abnormal laboratory findings were observed.     

Laboratory and clinical studies on cefamandole in pediatric field (author's transl)

Laboratory and clinical studies were performed on a new semisynthetic cephalosporin, cefamandole (CMD), and following results were obtained. (1) Serum concentrations and urinary recovery rates of CMD were determined after an intravenous administration of CMD 30 mg/kg in 13 children with normal renal function. In 5 of 13 children, mean serum levels after a one shot intravenous injection were 112.5 micrograms/ml at 15 minutes, 52.2 micrograms/ml at 30 minutes, 23.3 micrograms/ml at 1 hour, 4.9 micrograms/ml at 2 hours and trace at 4 hours. In other 5 children, mean serum levels after drip infusion for 1 hour were 78 micrograms/ml at 30 minutes, 59 micrograms/ml at 1 hour, 9.8 micrograms/ml at 2 hours and trace at 4 hours, after the onset of drip infusion. In the remaining 3 children who received CMD by drip infusion for 2 hours, mean serum levels were 24.3 micrograms/ml at 30 minutes, 35.3 micrograms/ml at 1 hour, 30.2 micrograms/ml at 2 hours, 5.3 micrograms/ml at 3 hours and 1.5 micrograms/ml at 4 hours after the onset of drip infusion. Urinary recovery rates in 5 children were 154.7%, 98.3%, 93.2%, 111.8% and 66.9%, respectively, during 8 hours. (2) CMD was administered to 40 patients with various infections (acute U.T.I. 8, acute angina lacunaris; 2, acute bronchitis; 5, cervical purulent lymphadenitis; 2, post-measles bronchopneumonia; 3, acute bronchopneumonia; 18, pyothorax; 2, S.S.S. syndrome; 1) by one-shot intravenous injection at a dose of 40-120 mg/kg per day. The clinical efficacy rate was 92.5% and bacteriological efficacy rate was 79.2%. (3) As the side effect of CMD, eosinophilia was observed in 1 case, rash and elevation of GOT and GPT in 1 case, and proteinuria in 1 case.     

Clinical laboratory approach in estimating the effective dosage of cefamandole

Reliability of the cefamandole (CMD) disc susceptibility test in estimating approximate values of MICs was studied using various clinical isolates totaling 246 strains with Showa discs (8 mm diameter containing 30 micrograms of CMD). Clinical significance of a 4 category system for the interpretation of the CMD disc tests, which is normally used in Japan, was also evaluated to determine whether this system would be suitable or not for the evaluation of a proper dose of administration. The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The results of the CMD disc susceptibility test were well correlated with MICs, showing the reliability of the disc method to estimate approximate values of MICs. Break points in MIC values proposed for the classification of bacteria into 4 categories of susceptibility are () MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. Only 4 (1.6%) out the 246 strains tested showed false positive results and 11 (4.5%) showed false negative results, showing the excellent reliability of this test. In this study, approximately 90% of strains of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolated from clinical materials randomly were inhibited by CMD at concentrations less than 3.13 micrograms/ml. Proteus vulgaris and Enterobacter aerogenes were sensitive to CMD at 67 and 69% of strains, respectively, at concentrations below 6.25 micrograms/ml. CMD was not active against Pseudomonas aeruginosa, Serratia marcescens and Enterococcus faecalis. About 90% of Staphylococcus aureus were inhibited at dose levels smaller than 6.25 micrograms/ml and 70% of the strains at levels less than 3.13 micrograms/ml. Susceptibilities to 15 micrograms/ml CMD of highly methicillin-resistant strains (MIC greater than 30 micrograms/ml) of S. aureus were examined. Ten of 12 strains examined were found susceptible to CMD, but only 6 of the 12 to cefmetazole. Imipenem/cilastatin was effective to 5 of the 12 strains at levels lower than 3 micrograms/ml and to one at a level less than 15 micrograms/ml. Minocycline was effective against 11 strains at concentrations below 2 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Laboratory and clinical studies of ceftazidime in the pediatric field

The authors have carried out the laboratory and clinical studies of ceftazidime ( CAZ ) and obtained the following results. The antibacterial activities of CAZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, C. freundii and P. aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to CAZ ranged from 3.13 to 100 micrograms/ml, and the peak of distribution was 12.5 micrograms/ml. The peak of susceptibility distribution of E. coli, K. pneumoniae and E. cloacae was 0.2 micrograms/ml, and the distribution of E. aerogenes ranged from 0.1 to 100 micrograms/ml and that of S. marcescens, from 0.05 to 3.13 micrograms /ml. The growth of 92% of P. aeruginosa was inhibited at the concentration of 3.13 micrograms/ml or lower. For pharmacokinetic study, CAZ was given in a single dose of 10 mg/kg by intravenous administration for 5 minutes in 1 child and by drip infusion for 30 minutes in 2 children. After intravenous administration of CAZ , the serum level got to the peak of 41.0 micrograms/ml at 15 minutes, and was 1.0 micrograms /ml at 6 hours. Half-life time was 1.30 hours. With drip infusion of CAZ , the mean peak serum level was 52.45 +/- 2.05 micrograms/ml on completion of the infusion, and 1.05 +/- 0.05 micrograms/ml at 6 hours. Half-life time was 1.30 hours. CAZ was effective in 9 cases out of 11 cases with bacterial infection. No side effect was observed except for elevation of serum GOT and GPT in 1 case and eosinophilia in 1 case.     

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)     

Laboratory and clinical studies on 6059-S in children (author's transl)

Laboratory and clinical studies were performed on 6059-S in the field of pediatrics, a new semi-synthetic 1-oxacephem antibiotic, and results were as follows. 1. MICs of 6059-S were compared with those of cefazolin (CEZ) and cefmetazole (CMZ) on 31 strains of S. aureus, 29 strains of E. coli, 30 strains of K. pneumoniae and 16 strains of P. aeruginosa. With the inoculum size of 10(8) cells/ml an 10(6) cells/ml, the peak of distribution of MICs were S. aureus 6.25, 3.13 micrograms/ml, E. coli 0.2, 0.1 micrograms/ml, K. pneumoniae 0.2, 0.05 micrograms/ml and P. aeruginosa 12.5, 6.25 micrograms/ml, respectively. MICs 6059-S against S. aureus was more less 2 to 3 tubes than CEZ and CMZ, but against E. coli and K. pneunoniae were more higher than 3 to 4 tubes than CEZ and CMZ. 2. The serum concentrations and urinary recovery rate of 6059-S were measured in 5 pediatric patients. 6059-S was given 20 mg/kg by an intravenous injection to 2 cases or a 30 minutes intravenous drip infusion to 3 cases. The mean concentration of the former were 64.3, 44.3, 26.8, 11.7 and 5.0 micrograms/ml at 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.51 hours. The urinary recovery rates was 75.0% within 6 hours after the injections. The mean concentration of the latter were 65.3, 86.3, 63.0, 40.3, 17.8 and 8.9 micrograms/ml at 0.25, 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.63 hours. The urinary recovery rates was 52.1% within 6 hours after the injection. 3. Eleven cases with acute pneumonia, 1 case with acute bronchitis, 3 cases with acute purulent tonsillitis, 1 case with acute purulent parotitis and 1 case subcutaneous abscess were treated with 6059-S by intravenous injection. All cases were above effective clinically. Five strains of H. influenzae, 3 strains of S. pneumoniae, 2 strains of S. pyogenes and 1 strain of S. aureus were eradicated in all strains. No clinical adverse reaction and abnormal laboratory findings were noted.     

Evaluation of in vitro antibacterial potencies of oral antibiotics against sputum isolates

Susceptibility of 162 sputum isolates to oral antibiotics was measured by an agar dilution method. The sputum isolates included S. pneumoniae 25 strains, S. aureus 30 strains, H. influenzae 37 strains, K. pneumoniae 51 strains and E. coli 19 strains. Minimal inhibitory concentration (MIC) values of cefaclor (CCL), cephalexin (CEX), ampicillin (ABPC) and minocycline (MINO) were measured for each strains. Eighty percent of S. pneumoniae strains were inhibited at 0.024 to 0.05 micrograms/ml of ABPC, 0.39 to 0.78 micrograms/ml of CCL, and 1.56 to 3.13 micrograms/ml of CEX and MINO. ABPC, CCL and CEX were considered to be effective clinically when they were used with the usual dosage. However, about 30% of strains were resistant to the usual dosage of orally administrated MINO. Eighty percent of S. aureus strains were inhibited at 0.20 to 0.39 microgram/ml of MINO and 3.13 to 6.25 micrograms/ml of the other 3 drugs. MINO is the most effective with the usual dosage. Twenty to 40% of strains showed resistance to CCL, CEX and ABPC. Eighty percent of H. influenzae strains were inhibited at 0.39 micrograms/ml of ABPC, 0.78 to 1.56 micrograms/ml of MINO, 3.13 micrograms/ml of CCL and 12.5 to 25 micrograms/ml of CEX. ABPC should be selected as the first choice antibiotic. However, there were 2 ABPC-resistant strains that were highly susceptible to CCL. Eighty percent of K. pneumoniae strains were inhibited at 0.39 to 0.78 micrograms/ml of CCL, 3.13 to 6.25 micrograms/ml of MINO and CEX, and 12.5 to 25 micrograms/ml of ABPC. CCL seemed to be only effective oral antibiotic for K. pneumoniae infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fundamental and clinical studies on cefuzoname in the pediatric field

Cefuzoname (CZON) one of the aminothiazolyloxyiminoacetamido cephalosporins, was studied for its antibacterial activity, absorption and excretion, concentration in the cerebrospinal fluid (CSF) and the penetration, and clinical efficacy. The following are a summary of the results: 1. Antibacterial activity; The antibacterial activity of CZON was studied on clinically isolated Staphylococcus aureus (cefazolin (CEZ)-susceptible and CEZ-tolerant strains), Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis. Compared with CZON were cefmenoxime (CMX), latamoxef (LMOX), cefoperazone, cefmetazol (CMZ), cefotiam and CEZ, but for S. aureus cefamandole (CMD) was replaced for CPZ. Activities of CZON against S. aureus, both CEZ-susceptible and CEZ-tolerant strains, were superior to those of 6 control drugs. The distribution of MICs for the CEZ-susceptible strains was 0.10-12.5 micrograms/ml, and for the CEZ-tolerant strains 0.20-greater than 100 micrograms/ml. MIC peaks were 0.39 micrograms/ml and 0.78-1.56 micrograms/ml for CEZ-susceptible and CEZ-tolerant strains, respectively. Against both susceptible and tolerant strains, CZON showed superiority to CMZ and CMD, which are used prevalently and used for Methicillin-resistant S. aureus also. Distributions of MICs of CZON (and the peak of MICs) on E. coli, K. pneumoniae, and P. mirabilis were less than or equal to 0.025-1.56 (less than or equal to 0.025), less than or equal to 0.025-25 (less than or equal to 0.025-0.05), less than or equal to 0.025-25 (less than or equal to 0.025) micrograms/ml, respectively, showing CZON's similar antibacterial activity to those of cephalosporins, CMX and LMOX, which are 5th group. 2. Absorption and excretion: Eight patients, aged 10 months to 15 years, were administered with CZON 20 mg/kg, one shot intravenously. Serum concentrations somewhat varied from patient to patient, but the mean value was 48.7 micrograms/ml after 30 minutes of administration which decreased rapidly to 13.3 micrograms/ml after 1 hour, to 3.4 micrograms/ml after 2 hours, to 1.14 micrograms/ml after 4 hours, and to 0.15 microgram/ml after 6 hours. Half-lives were 0.67-1.47 hours, with the mean of 0.87 hour. Urinary recovery rates were 24.7-55.9%, with the mean of 45.1%, in 6 hours after administration. 3. CSF concentration and penetration rate: To 4 pediatric patients with purulent meningitis, CZON 25 mg/kg or 50 mg/kg was administered and the concentration in CSF was measured.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Evaluation of cefpiramide, a new cephem parenteral preparation developed in Japan, in pediatrics

Fundamental and clinical studies of cefpiramide (CPM), a newly developed cephem antibiotic with a broad spectrum, were performed and the following results were obtained. The serum levels of CPM after the intravenous injection or the drip infusion of CPM at dose of 10.0 approximately 46.7 mg/kg reached the peak of 75.8 approximately 274.0 micrograms/ml at 30 approximately 60 minutes after infusion and were 3.9 approximately 55.1 micrograms/ml at 8 hours after the infusion. Half-life of CPM in the blood was between 2.4 and 7.0 hours. The excretion rates of CPM into urine up to 24 hours after the infusion were 5.7 approximately 20.4%. Twenty-five patients with acute respiratory tract infection (RTI, 15 cases), urinary tract infection (UTI, 8 cases), cellulitis (1 case) and salmonellosis (1 case) were treated with CPM. The treatment by intravenous injection or drip infusion of 22 approximately 55 mg/kg/day (40 approximately 50 mg/kg/day) for mean 6 days resulted in 100% of good response in 15 cases of RTI and in 88% of good response in 8 cases of UTI. S. aureus, H. influenzae, E. coli, Proteus, Klebsiella and Salmonella group B were isolated from the culture of sputum or urine in the patients, and they were all eradicated by the treatment with CPM. No side effects were observed except eosinophilia in 1 case and the elevation of GOT and GPT in 1 case.     

Basic and clinical studies on T-1982 (cefbuperazone) in the field of pediatrics

T-1982 (cefbuperazone), a new cephamycin antibiotic, was basically and clinically studied in the field of pediatrics, and the following results were obtained. 1. The antibacterial activity of T-1982 was compared with that of CEZ, CMZ and ABPC. T-1982 was more active than the other drugs against Gram-negative bacteria, the sensitivity of E. coli (22 strains), K. pneumoniae (18 strains), P. mirabilis (19 strains), P. vulgaris (4 strains), P. morganii (5 strains) and K. oxytoca (4 strains) distributing less than 0.39, 0.1, 1.56, 0.39, 6.25 and 0.2 microgram/ml, respectively. Two of 3 strains of C. freundii were inhibited by 12.5 micrograms/ml. Against Gram-positive bacteria, the activity of T-1982 was inferior to that of the other drugs. S. pyogenes (28 strains) were inhibited by 0.78 microgram/ml or less, but the sensitivity of S. aureus (34 strains distributed 12.5-100 micrograms/ml). 2. T-1982 was administered to each 3 children at a dose of 20 mg/kg by one shot intravenous injection or 1 hour drip infusion, or at dose of 40 mg/kg by 1 hour drip infusion. The mean serum levels at 0.25, 0.5, 1, 2, 4 and 6 hours after one shot intravenous injection of 20 mg/kg were respectively 74.3, 56.3, 42.3, 17.6, 5.7 and 1.2 micrograms/ml with the mean half-life of 1.01 hours. The values were 32.9, 50.0, 73.7, 27.5, 12.4 and 4.5 micrograms/ml and 1.31 hours by intravenous drip infusion of 20 mg/kg and 50.4, 104.7, 136.3, 62.3, 18.6 and 6.9 micrograms/ml and 1.16 hours by intravenous drip infusion of 40 mg/kg. The mean urinary recovery rates within 6 hours were 47.7, 67.6 and 60.9%, respectively. 3. Treatment with T-1982 was made in 28 cases of pediatric infections; 1 case of acute bronchitis, 19 cases of acute bronchopneumonia or lobar pneumonia, 2 cases of acute purulent cervical lymphadenitis, 4 cases of acute pyelonephritis and each 1 case of subcutaneous abscess and suspected bacterial endocarditis. The clinical responses assessed in 27 cases were excellent in 21 cases, good in 5 cases and poor in 1 case, the efficacy rate being 96.3%. Bacteriologically, 2 strains of S. aureus, 3 strains of S. pneumoniae, 4 strains of H. influenzae, 2 strains of E. coli and 1 strain of P. mirabilis were eradicated. One strain of S. faecalis was reduced. No side effects were observed in any cases. Slight elevation of GOT and GPT and that of GOT were noted in each 1 case.     

Fundamental and clinical studies on imipenem/cilastatin sodium in the pediatric field

Fundamental and clinical studies were performed on a newly developed carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), and results were summarized as follows. The antibacterial activity of MK-0787 at an inoculum of 10(6) cells/ml against strains of S. aureus which were sensitive or resistant to cefazolin (CEZ), E. coli, P. mirabilis, K. pneumoniae, S. marcescens and P. aeruginosa were determined and compared with activities of ceftazidime (CAZ), CEZ, cefmetazole (CMZ), ceftizoxime (CZX), latamoxef (LMOX), cefamandole (CMD), cefoperazone (CPZ), cefsulodin (CFS) and piperacillin (PIPC). The peak MIC of MK-0787 was less than or equal to 0.024 micrograms/ml against S. aureus, which were sensitive or resistant to CEZ, 0.10 micrograms/ml against E. coli, P. mirabilis, or K. pneumoniae, 0.39 micrograms/ml against S. marcescens and 1.56 micrograms/ml against P. aeruginosa. The antibacterial activity of MK-0787 against these bacteria was, on the whole, superior to that of CAZ, CEZ, CMZ, CZX, LMOX, CMD, CPZ, CFS or PIPC. The pharmacokinetics of MK-0787/MK-0791 was studied in 10 children at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg by a 30-minute intravenous drip infusion. Maximum serum levels of MK-0787, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg were 41.6 micrograms/ml and 72.9 micrograms/ml, respectively, at the end of infusion and 0.1 micrograms/ml at 6 hours, respectively, after drip infusion. The half-life of both dose levels was 0.9 hour. Mean peak serum levels of MK-0791, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 49.7 micrograms/ml and 87.0 micrograms/ml, respectively, with half-life of 1.1 and 0.6 hour, respectively. Urinary recovery rates of MK-0787 for 6 hours at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 47.8-82.7% and 25.5-78.0%, respectively, and of MK-0791 for 6 hours were 51.7-93.4% and 40.3-94.4%, respectively. Twenty-four patients, including 1 with purulent meningitis, 1 with septicemia, 1 with pyothorax, 10 with bronchopneumonia, 7 with pyelonephritis and 4 with infections of cutaneous soft tissue were treated with MK-0787/MK-0791 at dose levels of over 100 mg/100 mg/kg/day with purulent meningitis and septicemia and 28.8 mg/28.8 mg-72.8 mg/72.8 mg/kg/day with other infections. The clinical response in all patients was excellent or good.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of ceftriaxone in the pediatric field

Ceftriaxone (Ro 13-9904, CTRX), developed by F. Hoffmann-La Roche Ltd. in Switzerland, was used for the pediatric infections and the following results were obtained. The mean blood level of CTRX in 2 children after a 60-minute intravenous drip infusion with 20 mg/kg was 58.6 micrograms/ml at 30 minutes, 75.0 micrograms/ml at 1 hour, 39.85 micrograms/ml at 2 hours, 27.74 micrograms/ml at 4 hours, 20.71 micrograms/ml at 6 hours, 11.72 micrograms/ml at 12 hours and 3.91 micrograms/ml at 24 hours while the half-life time was 5.9 hours in one child and 7.6 hours in the other. CTRX was used in 22 children with acute infections consisting of 3 with acute pharyngeal tonsillitis, 4 with acute bronchitis, 8 with bronchopneumonia, 6 with infections of skin soft tissue and 1 with salmonellosis. The results were excellent in 5 cases and good in 17, indicating an efficacy rate of 100%. Out of 10 cases where the causative strains were detected, 4 cases were followed about the activities of the respective bacteria, i.e., H. influenzae, Streptococcus group A, S. aureus and Salmonella group B, all of which were eradicated after the end of administration. The daily dose of CTRX ranged from 30 to 50 mg/kg and generally a larger dose was used for serious infections. CTRX was administered twice daily in 20 out of 22 cases, by an intravenous injection in 4 and an intravenous drip infusion in 18, for 2 to 4 days in 16 and 5 to 8 1/2 days in 6. No clinical adverse reactions were observed while the laboratory test found a slight elevation of GOT in one and that of GOT and GPT in another. From the above results, CTRX was judged to be a highly useful drug for treatment of pediatric infections.     

Clinical laboratory approach for estimating effective administrative dose of cefuzonam. Evaluation of disc susceptibility test and its interpretation system

In vitro activities of cefuzonam (CZON) against 273 clinical isolates were studied through the evaluation of MIC's and the results of disc susceptibility test. The MIC's were determined using the agar dilution method at an inoculum level of 10(6)CFU/ml. The MIC80's of CZON against Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae and Citrobacter spp. were less than 0.20 microgram/ml. The MIC80's against Serratia marcescens and Enterobacter aerogenes were both 6.25 micrograms/ml, and that against Pseudomonas aeruginosa was 100 micrograms/ml. The MIC80's against Staphy-lococcus epidermidis were 25 and 6.25 micrograms/ml, respectively. Approximately 70% of strains of S. aureus were inhibited at concentrations less than 1.56 microgram/ml. For the interpretation of the CZON Showa 30 micrograms disc susceptibility test a 4 category system was used. In the 4 category system for Showa disc containing CZON, the following classification inhibitory zone diameters has been proposed: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC less than 60 micrograms/ml. Reliability of the CZON disc tests in estimating approximate MIC values was studied using Showa 30 micrograms discs and discs prepared in this laboratory containing 1-10 micrograms CZON. A good negative correlation was observed between inhibitory zone diameters and MIC's, showing the reliability of the disc method. The results of the test using Showa 30 micrograms disc against various clinical isolates were accurately classified into the 4 groups except those against P. aeruginosa. Some strains of P. aeuruginosa showed false positive results, exhibiting relatively larger inhibitory zone diameters compared with MIC's against these organisms. As CZON is not effective against P. aeruginosa a much better overall correlation between MIC's and the disc test would result when P. aeruginosa was excluded. With Showa 30 micrograms discs of various cephalosporins, sub-classification of strains with MIC less than 3 micrograms/ml cannot be achieved. In this study, however, it was demonstrated that differentiation of strains with MIC's less than 0.5-1.56 micrograms/ml was possible when discs containing 1-10 micrograms of CZON were used. According to recent concepts on pharmacokinetics for antibiotics including penetration of drugs into tissues and inflammatory fluids, serum protein binding of drugs appears to be one of the important determinants of drug distribution in the body.(ABSTRACT TRUNCATED AT 400 WORDS)