[Effect of midecamycin acetate on intestinal bacterial flora of children, and results of clinical study on midecamycin acetate in the treatment of mycoplasma pneumonia].
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Biomedical subjects
Publications and source records attributed to K Ishimoto.
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Cefmetazole (CMZ) is an antibiotic agent belonging to the cephamycin group, which is resistant to beta-lactamase and has a broad antibacterial spectrum covering from Gram-negative to -positive organisms. Although this agent has been proved to have an antibacterial activity against Staphylococcus spp., it has not been used for treatment of the infections caused by the organism. Thus, 62 strains of S. aureus isolated clinically were compared for their sensitivity to CMZ, cefoxitin (CFX), cefuroxime (CXM), cefazolin (CEZ), and ampicillin (ABPC). In addition, 5 children suffering from septicemia due to S. aureus were treated with CMZ 158 mg/kg at a mean daily dose for a mean period of 14 days. The dose was used after dividing into 3 and 4 equal parts in 1 and 4 children, respectively. One old patient with septicemia was given 2,000 mg of CMZ twice daily for 4 days and once daily for subsequent 3 days. Another child with bacterial meningitis was treated with 50 mg/kg of CMZ 4 times daily for 63 days. The drug was given intravenous injection by one-shot or drip infusion in all cases under observation of clinical effects, bacteriological effects and side effects. The MIC of CMZ against S. aureus at inoculum sizes of 10(6) and 10(8) cells/ml was 1.56 mcg/ml in 72.6 and 56.5% of the strains, respectively. When 5 drugs were compared on the basis of the MIC to which the largest number of strains were sensitive, CEZ was most active, and CMZ was ranked in the next place and similar to CXM in activity. However, when the whole range of the MIC was considered, CMZ was more excellent than CXM, its MIC was lower than those of CEZ, CFX and ABPC in a greater number of strains. It was considered from the results that the serum level of CMZ was effective against 100 and 93.5% of strains at an inoculum size of 10(6) cells/ml and against 100 and 83.9% of strains at an inoculum size of 10(8) cells/ml until 4 and 6 hours after a one-shot intravenous injection of 50 mg/kg of Moni-trol I standard, respectively in the children. Thus, CMZ is expected to manifest a sufficient effect on septicemia caused by S. aureus in children who receive a one-shot intravenous injection of 50 mg/kg of it 4 times daily. Treatment with CMZ was clinically evaluated to be excellent in 3, good in 3 and poor in none of 6 patients with septicemia due to S. aureus, and fair in the 1 with Staphylococcal meningitis. The bacteriological result was excellent, since the causal organisms were eradicated in all cases. With regard to side effects, abnormal eosinophilia was found in 2 cases, but it was no ascribable to this drug in 1 of them. GOT showed an abnormal rise in 1 case and both GOT and GPT in 1, although they were considered not to be related to this drug in either case. It is considered from these results that CMZ is a valuable drug in treatment of septicemia due to S. aureus.
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A study was made with the newly developed cefroxadine (CXD) dry syrup by measuring the serum level, urine excretion and recovery rate in 10 children who were orally administered 5, 10 and 20 mg/kg at 1 hour after meals and the following results were gained. Also, its clinical efficacies and side effects were investigated in the following cases who were treated with a mean dose of 33 mg/day divided into 3 to 4 portions for a period of 9 days on the average; viz. a total of 151 cases consisting of 9 cases of pharyngitis, 39 of tonsillitis, 11 of streptococcal infection, i.e. scarlet fever, 7 of bronchitis, 6 of pneumonia, 1 of otitis media, 6 of purulent lymphadenitis, 1 of purulent parotitis, 1 of subcutaneous abscess and 3 of impetigo. 1. The serum level tends to reach its maximum level within 1 hour after administration. The mean concentrations of 5, 10 and 20 mg/kg dose in the foregoing time were 6.35, 9.12 and 21.62 mcg/ml respectively and dose response was observed. CXD showed higher concentration than CEX, CED and CFT. The mean half-life periods of the 3 dose were 72, 84 and 66 minutes respectively and variations were observed, but the drugs maintains a satisfactory serum level. 2. The time which showed highest urine excretion was mainly in the 0 to 2 hours bracket and the average concentrations of 5 , 10 and 20 mg/kg dose in the foregoing time were 381.2, 771.7 and 1,577.7 mcg/ml respectively. The dose response was more evident than in the serum concentrations. The average recovery rates within 6 hours were 93.6, 88.3 and 94.3% respectively and they were similar to those of CEX, CED and CFT. 3. The clinical effects were evaluated were in 148 cases out of the total of 151 and 136 cases, or 91.9% showed good or excellent efficacy response. 4. The daily dose groups of less than 30 mg/kg and 31 to 40 mg/kg formed the majority and there was no difference in the comparison of the clinical effectiveness in these 2 groups. Administration of a daily dose of 20 to 40 mg/kg is sufficient for the treatment of the aforementioned mild diseases except for pneumonia. 5. The clinical effects were compared between the 3 and 4 times a day treatment groups, but there was no difference between these two groups with regard to the foregoing daily dose. The 3 times a day treatment is acceptable, but the 4 times a day treatment is preferable when pharmacokinetics if taken into account. 6. The bacteriological effects in 41 cases, or 97.6% out of the 42 cases were above the efficacy base line and a high efficacy rate was achieved. 7. With regard to side effects, diarrhea developed in 4 cases and eosinophilia in 6 cases, abnormal simultaneous increases in GOT and GPT in 1 case and 1 case each for abnormal values in LDH and BUN were seen in the clinical test values. The foregoing results show that CXD has high efficacy and safety and it can be said that it is a drug required in the pediatric field.
CXD was administered orally at an average dose of 28.6 mg/kg (18.3 approximately 42.3 mg/kg) for an average 6 days (3 approximately 12 days) to a total of 99 pediatric cases with skin and soft tissue infections (impetigo 89, abscess 7 and furuncle 3) ranging from 3 months to 9 years old. The drug was given twice to 4 times per day after meals. The clinical and bacteriological effects and adverse reactions of CXD as well as the susceptibility of the causative organisms against CXD and CEX were studied, and the results obtained are as described below: 1. According to judgement of the attending doctors, CXD had a high global efficacy rate of 90.9%. 2. Analysis of the attending physicians' evaluations of the clinical effects on impetigo revealed that a dose of CXD 20.5 approximately 30.4 mg/kg t.i.d. can produce satisfactory responses. 3. According to the assessments by Evaluation Committee, the global clinical effects after 3, 5 and 7 days were 81.4, 91.2 and 94.6%, respectively. This indicates that clinical responses increased with prolongation of the treatment period, viz. better responses obtained after 5 and 7 days. This suggests that a minimum of 5 days administration is required for treating these infections. 4. As for impetigo having the largest number of patients in this study, a dose of CXD 20.5 approximately 30.4 mg/kg per day seemed to produce satisfactory clinical effects. 5. As for dose per day, the t.i.d. regimen of CXD 20.5 approximately 30.4 mg/kg seemed to exhibit satisfactory clinical responses, as already mentioned. Because of quite a small number of patients on the q.i.d. regimen of higher doses, however, the question of whether the t.i.d. treatment with 20.5 approximately 30.4 mg is adequate or not should be determined by a comparative study between the q.i.d. and t.i.d. treatments. 6. As for bacteriological responses, a high global effect of 87.1% was obtained with CXD against S. aureus and S. pyogenes isolated from 74 and 1 cases, respectively. 7. As for impetigo with predominant number of cases, CXD was highly effective bacteriologically at a daily dose of 20.5 approximately 30.4 mg/kg t.i.d. As an appropriate comparative evidence with the q.i.d. treatment was lacking, however, therapeutic validity of the t.i.d. treatment could not be determined definitely. 8. Utility was evaluated by the attending physicians on the total 99 cases, and CXD showed as high as 88.9%. 9. There were neither non-compliances nor adverse reactions to this treatment. 10. CXD showed a distribution of antimicrobial activity similar to that of CEX, against 74 isolates of S. aureus with the MICs of CXD ranging from 1.56 to 25 mcg/ml and those of CEX ranging from 0.78 to 25 mcg/ml, with peak MIC being 3.13 mcg/ml for both drugs. As for S. pyogenes, only one isolate from the same species, CXD was antimicrobial activity at 0.2 mcg/ml and CEX was antimicrobial at 0.39 mcg/ml. The above findings suggest that CXD is highly effective against acute skin and soft tissue infections in pediatrics.
Pharmacokinetics of cefoxitin, a new injectable semisynthetic-cephamycin, was studied in 12 healthy children and also was studied cerebrospinal fluid levels in 1 patient with bacterial meningitis received 44.5 mg/kg of cefoxitin and thoracic fluid levels in 2 patients were measured. Cefoxitin was administered intravenously to 50 patients with various types of infections an average dose of 130 mg/kg/day for an average of 9 days. The results were as follows: 1. Favorable plasma levels were obtained comparing with those off conventional injectable cephalosporins after 15 mg/kg and 25 mg/kg of cefoxitin for one shot intravenous injection. The half lives of cefoxitin in the plasma were about 15.9 minutes up to 1 hour and 25.5 minutes up to 2 hours after an intravenous administration of cefoxitin at a dose of 15 mg/kg, and while, those were 15.9 minutes and 27.5 minutes after an intravenous administration of cefoxitin at a dose of 25 mg/kg, respectively. 2. Cefoxitin was excreted with high concentration up to 2 hours after the administration and thereafter, urinary concentration of cefoxitin declined rapidly with the lapse of time. The time course urinary concentration reflected those of plasma levels. Approximately 94.7% and 90.6% of dosed cefoxitin were recovered in the urine for 6 hours after the administration at the dose of 15 mg/kg and 25 mg/kg, respectively. 3. The cerebrospinal fluid levels of cefoxitin were only determined in a patient of bacterial meningitis. Therefore, further study should be performed. 4. The thoracic fluid levels with 2 patients were higher than cerebrospinal fluid levels. 5. Among the 50 patients with various infections, cefoxitin was clinically effective in 84% and bacterial response in 87%. 6. As adverse reactions, in total 79 patients included exclusive 29 patients, diarrhea occurred in 1 patient, sweating and cough in 1 patient, rash with fever in 4 patients, vascular pain in 2 patients, and leukopenia was observed in 1 patient, eosinophilia in 1 patient, and increase of GOT and LDH were observed in each 2 patients. The other adverse reactions were not experienced.
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Clinical trial of cefoperazone (CPZ) for the treatment of whooping cough and whooping cough syndrome was performed and the following results were obtained. 1) In 18 cases suffering from whooping cough, CPZ was given 47 approximately 106 mg/kg/day (average 72 mg/kg/day) by intravenous route. The clinical efficacy rates judged by doctors in charge were 44% on the 3 rd day, 75% on the 7 th day, 86% on the period day. And in these cases, the clinical efficacy rates judged by committee members were 56%, 83% and 86%. 2) In 6 cases diagnosed as whooping cough syndrome, CPZ was given 49 approximately 96 mg/kg/day (average 59 mg/kg/day) by the same route. The clinical efficacy rates judged by doctors in charge were 67% on the 3 rd day, 80% on the 7 th day and 75% on the period day. And in these cases, those judged by committee members were 83%, 80% and 100%. 3) In 1 case, Bordetella pertussis was searched and showed 0.012 mcg/ml of MIC. It was eliminated on the 1 st day after administration. 4) Doctors in charge judged the utility of CPZ for whooping cough. Twelve cases were useful and 6 cases were slightly useful. 5) No side effects were observed except for elevation of GOT and LDH. These results suggest that CPZ might be useful drug against whooping cough.
Laboratory and clinical studies of cefoperazone (CPZ), a new semisynthetic cephalosporin, were investigated and following results were obtained. (1) Blood level: CPZ was given intravenous dose of 25 mg/kg and 50 mg/kg to each 3 children. In the former, the blood level of 15 minutes after injection was 194.2 mcg/ml on average and the half life was 106.2 minutes. In the latter, the blood level was 320.0 mcg/ml on average and half life was 102.2 minutes. (2) Urinary concentration: In the cases of the dose of 25 mg/kg, 35.9% of CPZ was recovered on average from the urine within 6 hours after injection, and the urinary concentration reached to 2,148.6 mcg/ml (0 approximately 2 hours). And in the cases of the dose of 50 mcg/kg, the recovery rate in urine was 43.6%, and the urinary concentration was 3,008.3 mcg/ml. (3) Cerebrospinal fluid level: CSF level was determined in a patient with bacterial meningitis by S. pneumoniae. Ninety mg/kg of CPZ were given intravenous injection. After 60 minutes CSF level was 3.35 mcg/ml, and after 80 minutes the blood level was 192.0 mcg/ml. (4) Bacteriological evaluation: Against 164 strains isolated clinical specimens, the bacteriological evaluation on CPZ was performed in comparison with cefotaxime (CTX), cefazolin (CEZ) and piperacillin (PIPC) by inoculum size of 10(8) cells/ml. CPZ showed antibacterial activity against Gram-negative bacteria almost similar to CTX and PIPC. (5) CLINICAL RESULTS: CPZ was given 48.3 approximately 360 mg/kg/day (average 146.1 mg/kg/day) by intravenous route to 46 patients with various infection. The overall efficacy rate was 80.4%. The rate of bacteriological effectiveness was 78.9% in 19 cases. (6) Side effects: As side effects, diarrhea, fever, rash, urticaria, leukopenia, eosinophilia, elevation of GOT, GPT, and LDH were observed, but not seriously.
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UNLABELLED: Cefamandole (sodium salt) was administered to total 32 cases of bacterial infectious diseases of children, and in 3 cases, there were investigated of these absorption and excretion. The results are as follows; 1. Blood levels: Cefamandole was given intravenous dose of 25 mg/kg to 3 children. The blood level of 15 minutes after intravenous injection was 140.4 micrograms/ml in average, and 0.3 micrograms/ml in average at 4 hours after intravenous injection. T 1/2 was 13.9 minutes. 2. Urinary concentration: Within 6 hours after intravenous injection, 51.8% of the drug was recovered in average from the urine and the urinary concentration reached to 3,050 micrograms/ml in average (0 approximately 2 hours), 1,262 micrograms/ml in average (2 approximately 4 hours), 41 micrograms/ml in average (4 approximately 6 hours) after injection. 3. CLINICAL RESULTS: The drug was given 109 mg/kg/day (t.i.d. or q.i.d.) by intravenous route. The duration of administration was 11 days in average. The overall efficacy rate was 97%. In bacteriological results, excellent in 2, failure in 1, out of 3 strains. As side effects vascular pain was observed in 3 cases at the intravenous injection, and eosinophilia in 2 cases.
PC-904 was administered to 24 patients: urinary tract infections (7 cases), bronchitis (2 cases), pneumonia (3 cases), brain abscess (1 case), septicemia and the suspected cases (10 cases), and buttock abscess (1 case). The daily dosage varied from 60 to 223.4 mg/kg and averaged 86.9 mg/kg. The drug was administered three times a day by 1-hour drip infusion, and the duration of the treatment averaged 11 days. Clinical results were obtained as excellent responses in 5 cases, good in 13, poor in 4, and unknown in 2, giving 75% of the clinical effectiveness. Bacteriological responses were excellent in 7, good in 2, poor in 2, and unknown in 13, and the overall effectiveness was evaluated as excellent in 2, good in 17, and unknown in 5. Antibacterial activities against clinically isolated bacteria were examined. MIC values of PC-904 were over 100 mg/ml 1 strain of E. coli and 2 strains of Klebsiella, however excellent sensitivities were observed in 3 strains of Ps. aeruginosa and MIC values varied 1.56 to 3.12 microgram/ml at 10(8) of inoculum size and 0.78 to 1.56 microgram/ml at 10(8). As to side effects, diarrhea was observed in 1 case, rash in 2, lowering ob blood pressure in 2, elevation of GOT in 1, and elevation of LDH in 2. Abnormal elevations of GOT (10 cases), GPT (5 cases), A1-P (1 case), LDH (7 cases), and BUN (1 case) were noticed in other patients, but it was considered to be due to underlying diseases.
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