Postoperative changes in acute phase reactants (APR) upon administration of latamoxef (LMOX) were studied in 43 patients who underwent laparotomy (total hysterectomy, cesarean section or resection of ovarian tumor). The results obtained are summarized as follows.
1. Postoperative changes in APR, i. e., amount of granulocyte-elastase, arantitrypsin (α₁-AT), α₁-acid glycoprotein, haptoglobin and CRP, in the maternal blood were determined. These 5 markers increased and tended to decrease at 7 days and 14 days after surgery, respectively, in the total hysterectomy group. The vital defense response to surgical invasion and the reaction occurring during the process of recovery show that changes in level of granulocyte-elastase, α₁-AT and CRP immediately reflect the resulting inflammatory reaction. The changes in elastase and α₁-AT levels upon cesarean section showed a similar tendency, but levels of these markers were high as a whole during pregnancy and postpartum.
2. There were no postoperative complications or subjective or objective side effects of the LMOX treatment in any of the studied patients, suggesting that LMOX is useful for the prevention of postoperative infection.

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The distribution of T-3262 (tosufloxacin tosilate) in salivary glands of rats was investigated with frozen-microautoradiography.
One and 4 hours after oral administration of ¹⁴C-T-3262 at 100mg/kg to rats submandibular glands, parotid glands and sublingual glands were removed, and a microautoradiogram of each was made.
In the submandibular gland and the parotid gland ¹⁴C-T-3262 was distributed at high levels throughout the glands taken at 1 and 4 hours after administration, but lower levels than the other glands were found in the sublingual gland at 1 hour.
The results of this study suggested that T-3262 penetrates effectively into the saliva, because ¹⁴C-T-3262 is distributed well into glandular acinus, striated duct and excretory duct.
The microautoradiography was a useful and reliable method for investigating the distribution of antimicrobial agents in salivary glands.

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T-3262 (tosufloxacin tosilate), a new oral pyridone carboxylic acid agent, was investigated for its biliary excretion and clinical efficacy and safety to evaluate its usefulness in the treatment of cholecystitis.
T-3262 was administered to a total of 4 helthy volunteers for 2 days at a dose of 150mg every 8 hours, and A-, B-or C-bile were collected using the MELTZER-LYON method at 10-11 hours after the final administration. Bile concentrations of T-3262 in 3 cases were 0.33-2.05 μg/ml (A-bile), 6.13-9.50μg/ml (B-bile) and 1.11-2.70μg/ml (C-bile). Thus, T-3262 levels in B-bile were 15-34 times higher than serum levels (0.28-0.41μg/ml). Only a trace of serum concentration of T-3262 was detected in another case with the concentration in B-bile was 0.132 μg/ml.
A total of 10 patients with cholecystitis were treated with T-3262 at a dose level of 150mg per dose 3 times daily for 1 to 20 days. The clinical efficacy was excellent in 1 case, good in 5 cases and fair in 2 cases and unevaluable in 2 cases, thus the clinical efficacy rate was 75%.
Bacteriologically, Klebsiella pneumoniae, Enterococcus faecalis and Haemophilus parahaemolyticus were isolated from biles of 3 patients before treatment. Upon the treatment, E. faecalis was eradicated and K. pneumoniae was unchanged. The fate of H. parahaemolyticus was not known because of examination was not done after treatment.
Side effects were observed in 2 cases with diarrhea in 1 case and epigastric pain in another case. But those symptoms disappeared after cessation of administration of T-3262. Abnormal laboratory test values were not observed.

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The distribution of cefuzonam (CZON) was studied in 20 adults undergoing open heart surgery. In groups I (n=11) and II (n=9), CZON (2g) was intravenously infused at the time of induction of anesthesia; and in group II an additional 2g was administered at the time of commencement of extracorporeal circulation (ECC).
Just prior to and following the ECC, samples of blood and right auricle were taken for examination. CZON concentrations in serum and myocardium were measured using the thinlayer cup method with Esherichia coli NIHJ as the test organism.
CZON concentrations in myocardium prior to ECC were 48.9μg/g and 39.0μg/g for groups I and II, respectively. The ratios of intramyocardial to serum CZON concentration were 0.40 and 0.45 for groups I and II, respectively, revealing no significant difference between the 2 groups. Following ECC, intramyocardial CZON concentrations were 20.8μg/g for group I and 33.2μg/g for group II; while the ratios were 0.43 and 0.59 for groups I and II, respectively. Again, there were no significant differences.
From the above findings it may be concluded that:
1. There was good distribution of CZON in myocardium, with a concentration well above MIC₈₀.
2. Therapeutic concentrations of CZON were maintained in myocardium for 6 hours, suggesting that initial infusion of 2g CZON is sufficient for prophylaxis in routine open heart surgery.

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The reliability of the tobramycin (TOB) disc susceptibility test in estimating approximate values of MICs was studied using various clinical isolates totaling 261 strains and using Showa discs (8mm diameter containing 30μg of TOB) and Difco discs (6mm diameter containing 10μg of TOB). Clinical significance of a 4 category system for the interpretation of the disc tests, which is widely used in Japan, and that of a 3 category system used in USA and Europe, were also evaluated to determine which system would be more suitable for the evaluation of proper dose levels of administration. Furthermore, the evaluation was made using these discs with respect to the in vitro MIC break points for therapeutic use of antibiotics proposed by the British Society for Antimicrobial Chemotherapy (J. Antimicr. Chemoth. 21: 701-710, 1988).
The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 10⁶ CFU/ml. The results of the TOB disc susceptibility test either with Showa or Difco discs 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 the 4 categories of susceptibility are (+++) MIC≤2μg/ml,(++) MIC>2-10μg/ml,(+) MIC>10-50μg/ml,(-) MIC>50μg/ml. Those proposed in the 3 categories of susceptibility are Sensitive (S) MIC≤4μg/ml, Intermediate (I)MIC>4-8μg/ml, Resistance (R) MIC>8μg/ml.
In the 4 category classification system of the Showa disc susceptibility test, 16 out of 261 strains (6.1%) tested showed false positive results and 7 (2.7%) did false negative results. If the classification was modified as follows: (+++) MIC≤3μg/ml,(++) MIC>3-15μg/ml,(+) MIC>15-60μg/ml,(-) MIC>60μg/ml, false positive results were markedly reduced. Only 6 out of 261 strains (2.3%) showed false positive results, and 7 (2.7%) did false negative results. With Difco disc, in the 4 category interpretation system, 8 out of 261 strains (3.1%) tested showed false positive and 35 (13.4%) did false negative results. No inhibitory zones were observed against a majority of strains with MIC>25μg/ml, thus unable to assess (+) susceptibility.
The British Society for Antimicrobial Chemotherapy has, recently, proposed in vitro MIC break points for TOB in therapeutic use, recommending MICs 1 and 4μg/ml. Therefore, an evaluation was made using Showa and Difco discs, to see whether it was possible or not to make break points on inhibitory zone diameter equivalent to MICs 1 and 4μg/ml. In this preliminary study, the tentative interpretive break points for inhibitory zone diameters were made at 21mm (Showa) and 17 mm (Difco) for MIC 1μg/ml, and 20mm (Showa) and 15mm (Difco) for MIC 4μg/ml. False positive results for strains with MICs≤1 and 4μg/ml, were observed in (11.42%) and 7 (2.7%) out of 261 strains with Showa discs and 6 (2.3%) and 5 (1.9%) with Difco discs, respectively.
In this study, MIC₇₀ of TOB against Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis were 25, 100, and>100μg/ml, respectively. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris were 0.78, 0.78, 1.56, and 6.25μg/ml, respectively. MIC₇₀ against Pseudomonas aeruginosa, Serratia marcenscens, and Enterobacter aerogenes were 0.78, 25, and 0.78μg/ml, respectively.
Antimicrobial activities of antibiotic agents have been reported to be reduced by serum protein binding. Antibiotics with stronger protein binding have lower ratios of free drugs available to penetrate into tissues than antibiotics with weaker protein bindings.

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The reliability of the cephalothin (CET) disc susceptibility test in estimating approximate values of MICs was studied using various clinical isolates totaling 248 strains and using Showa discs (8mm diameter containing 30μg of CET) and Difco discs (6mm diameter containing 30μg of CET). Clinical significance of a 4 category system for the interpretation of the CET disc tests, which is widely used in Japan, was reevaluated to determine whether this system would be suitable or not for the evaluation of proper dose levels of administration.
The results obtained with the disc methods were compared with MICs determined using the agar dilution method at an inoculum level of 10⁶ CFU/ml. The results of the CET 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≤3μg/ml,(++) MIC>3-15μg/ml,(+) MIC>15-60μg/ml,(-) MIC>60μg/ml. With the Showa disc suscep tibility test, 15 out of the 248 strains (6.0%) tested showed false positive results and 6 strains (2.4%) showed false negative results. With the Difco disc test, 18 out of the 248 strains (7.3%) tested showed false positiveresults and 6 (2.4%) showed false negative results. Excluding Enterococcus faecalis from the test, results because better in the quantitative estimation of MICs, resulting false positive rates of 3.2% (Showa), and 4.4% (Difco).
A 3 category system of the interpretation of disc test is generally used in the USA and Europe. MIC break points proposed for the classification of the CET test are sensitive, MIC≤8μg/ml, and resistance, MIC≥32μg/ml. With the Showa disc susceptibility test, 14 out of the 248 strains (5.6%) tested showed false positive results and 6 strains (2.4%) showed false negative results. With the Difco disc test 7 out of the 248 strains (2.8%) showed false positive results and 21 strains (8.5%) showed false negative results.
In this study, MIC₇₀s of CET against Staphylococcus aureus and Staphylococcus epidermidis were 1.56 and 0.78μg/ml, respectively. CET was not so effective against Gram-negative rods except Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli. MIC₇₀s against K. pneumoniae, P. mirabilis, and E. coli were 6.25, 3.13, and 3.13μg/ml, respectively.
Antimicrobial acitvities of antibiotic agents have been reported to be reduced by serum protein binding. Furthermore, antibiotics with stronger protein bindings have lower ratios of free drugs available to penetrate into tissues than antibiotics with weaker protein bindings. Therefore, to evaluate antimicrobial activities in blood and the distribution of antibiotics in the body, blood levels of free and bound forms must be considered. In blood, 70% of CET is in the protein bound form and 30% in the unbound free form.
Based on the antimicrobial activity of CET, the pharmacokinetic data and the recommended dose schedule of CET (4-8g a day), MIC break points of 3μg/ml and 15μg/ml in a 4 category system appear to be more useful than those of 8μg/ml and 32μg/ml utilized in a 3 category system for evaluation of a proper administrative dose. However, from the present study it seems to be more meaningful to make the in vitro MIC break points of 1.5, 3.0 and 15μg/ml in a 4 category system instead of break points 3.0, 15, 60μg/ml presently used. It would be possible to make MIC break point at 1.5μg/ml judging from the present results using Showa and Difco discs.

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A case of infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) was successfully treated with a combination therapy with cefmetazole (CMZ) and fosfomycin (FOM). A 55 year old man was admitted to the Keio Hospital because of fever of unknown origin. Physical examination revealed blood pressure of 132/62 mmHg, heart rate of 118/min and body temperature of 39.8°. Diastolic regurgitant murmur (Levine II/VI) was heard at the left sternal border on the third intercostal space. Chest X-ray showed mild cardiomegaly. Two dimensional echocardiography and color flow mapping demonstrated mildly dilated and hyperkinetic left ventricle, redundant aortic valve, giant vegetation from the aortic valve and severe aortic regurgitation. MRSA was isolated from the blood of this patient. Bacteriostatic synergism between CMZ and FOM against S. aureus isolated from the blood of this patient was detected both by the KIRBY-BAUER method and by the checker-board method. The combination therapy with CMZ and FOM cleared the clinical symptoms and normalized the inflammatory reactions. No relapse was observed for at least 10 months. We concluded that the combination therapy with CMZ and FOM was invaluable for the treatment of infections endocarditis by MRSA.

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Ceftazidime (CAZ) was studied on its penetration into uterine tissues and its prophylactic effect on postoperative infections in patients who underwent vaginal hysterectomy. The results obtained are summarized below.
1. Following 2 CAZ drip infusion (over 30 minutes), the maximum drug concentration in each uterine part was: 99.7μg/g in portio vaginalis, 83.4μg/g in cervix uteri, 73.9μg/g in myometrium and 70.1μg/g in endometrium. In ovary it was 116μg/g and in oviduct it was 98.6μg/g.
2. When compared a group administered with CAZ (total dose of 7g in 3 day administration) and a group with other antibiotics (total dose of 10-20g in 5 days) results in terms of total fever index were 1.8±3.1 degree hours with the former group and 1.8±2.8 with the latter, thus there was no difference between the 2 groups.
3. The good penetration of CAZ into uterine tissues, as shown above, suggests that CAZ has high clinical usefulness in prophylaxis of postoperative infections.

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A combination of aztreonam (AZT) and clindamycin (CLDM) was evaluated for severe infections associated with leukemia and related disorders. AZT is a monobactam antibiotic which has strong bactericidal effect against Gram-negative bacteria including Pseudomonas aeruginosa. CLDM which has strong antibacterial spectrum against Gram-positive and anaerobic bacteria, was chosen as a partner of AZT in order to complement the weak points of AZT.
Fifty six patients were treated with the combination therapy. Among them, 51 patients were evaluable for the effectiveness. Five patients were excluded from the evaluation because 3 patients were subjected to additional therapy with other agents such as amikacin, miconazole and pulse therapy of a large dose of methylprednisolone, one had a fever episode apparently due to primary disease, and the remaining one was discontinued of the combination therapy of administration due to mild nausea after 3 days.
Excellent responses were obtained in 17 (33.3%) patients and good responses in 20 (39.2%) patients, with a total rate of effectiveness of 72.5%.
One patient with whom the combination therapy was stopped due to nausea, was included in the final evaluation of side effects. Side effects were observed in 2 patients of 50 and 40 years of ages (2/52, 3.8%), both of whom suffered with nausea. In the 50 years patient of acute myeloblastic leukemia, nausea occurred in a slight degree in 3 hours after the combined regimen was started. But, it disappeared during the continuation of the combination therapy. In the 40 years patient of acute myelomonocytic leukemia, mild nausea occurred after 3 day administration of the combined regimen. It disappeared soon after the cessation of the treatment.
These results indicated that a combination of AZT and CLDM was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

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Cefteram pivoxil (CFTM-PI, T-2588), a new oral cephem antibiotic of ester type, was evaluated for its safety, efficacy and pharmacokinetics.
1. One child, 4 years of age (18kg body weight), was administered orally 3mg/kg after meal. The peak serum level of CFTM was 0.78μg/ml after 2 hours, and cumulative urinary excretion rate during the first 6 hours was 15.0%.
2. Clinical studies on CFTM-PI were carried out in 17 pediatric patients; 1 with acute pharyngitis, 2 with acute tonsillitis, 1 each with pertussis, acute bronchitis, 2 with bronchopneumonia, 4 with scarlatina, 3 with acute otitis media, and 1 each with lymphadenitis, acrobystitis and urinary tract infection. Clinical responses were excellent in 9, good in 6, fair in 1, poor in 1, and the overall clinical efficacy rate was 88.2%.
3. Bacteriological efficacy was investigated with 10 strains of 5 species (Streptococcus pyogenes 4, Streptococcus pneumoniae 2, Haemophilus influenzae 2, Enterococcus and Bacteroides 1) isolated from 9 patients. All strains were eradicated.
4. As to adverse reactions, mild diarrhea was observed in 1 patient. But therapy had to be continued without procedure and the diarrhea disappeared after 6 days. No adverse hematological, renal or hepatic effects were noted.

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A newly developed cephalosporin, cefteram pivoxil (CFTM-PI, T-2588), was evaluated clinically in 40 patients. A pharmacokinetic study was also performed with 8 patients.
CFTM-PI was administered as granules. One patient was given CFTM-PI at a dose of 1.5mg/kg, each of 3 patients was given the drug at a dose of 3mg/kg and each of 4 patients at a dose of 6mg/kg. In most cases, serum concentrations of CFTM were determined at 2, 3, 4, and 6 hours after dosing. Urinary concentrations of CFTM were measured for urinary samples collected during periods of 0-2, 2-4, 4-6 and 6-8 hours after dosing. CFTM was assayed using the disk or the cup method using Klebsiella pneumoniae ATCC 10031 as the test organism.
The clinical evaluation was conducted in 40 children including 13 patients of acute tonsillitis, 10 of acute lacunar tonsillitis, 10 of scarlet fever, 2 of acute bronchitis, 2 of pneumonia, and 1 each of pneumonia with enteritis, phlegmon and urinary tract infection. The patients were from 4 months to 13 years old. Daily doses were from 8.7 to 12mg/kg.
After CFTM-PI administration in doses 1.5mg/kg, 3mg/kg and 6mg/kg, peak serum concentrations of CFTM were 0.38μg/ml, 0.73-2.25μg/ml and 1.2-2.9μg/ml, respectively, and half-lives were 1.55, 0.95-2.30 and 0.80-2.72 hours, respectively. Urinary excretion rates up to 6 or 8 hours after dosing were 10.8-24.7%.
Clinical efficacies of CFTM-PI in 40 patients were “excellent” in 27 children, “good” in 12 children and “fair” in 1 with an efficacy rate of 97.5%.
Twenty seven strains of causative organisms, including 15 strains of Streptococcus pyogenes, 1 of Escherichia coli, 1 of Salmonella 04, 6 of Haemophilus influenzae, 1 of Haemophilus parainfiuenzae and 3 of Branhamella catarrhalis, were isolated. After treatment all strains except 1 strain of B. catarrhalis (unchanged), Salmonella 04 (unknown) and 1 strain of H. parainfluenzae (unknown) were eradicated.
Side effects observed clinically were only 1 case of diarrhea. Eosinophilia was observed in 1 case.

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The clinical efficacy and the safety of cefteram pivoxil granule (CFTM-PI, T-2588), a newly prepared drug for pediatric use, were performed.
A total of 60 patients with ages between 6 months and 14 years 3 months with pediatric infections were medicated with CFTM-PI at dose levels of 3.2-9.9mg/kg 3 times daily for 3-11 days.
Clinical responses to the drug were excellent in 3 of 3 patients with acute pharyngitis, excellent in 14, good in 5 and poor in 2 of 21 patients with acute purulent tonsillitis, excellent in 1 and good in 2 of 3 patients with acute bronchitis, excellent in 16 and good in 8 of 24 patients with acute pneumonia, excellent in 3 and good in 1 of 4 patients with acute urinary tract infection and excellent in 2 of 2 patients with acute purulent lymphadenitis, hence the overall clinical efficacy rate was 96.5% in a total of 57 patients.
Bacteriological responses to the drug were as follows: Eradicated, 8 strains of Streptococcus pyogenes, 3 strains of Streptococcus pneumoniae, 19 strains of Haemophilus influenzae (β-lactamase positive; 7, β-lactamase negative; 12), 1 strain of Haemophilus parainfluenzae (β-lactamase positive) and 4 strains of Escherichia coli (β-lactamase positive; 1, β-lactamase negative; 3), decreased, 1 strain of S. pyogenes, hence the eradication rate was 97.2%.
No side effects were encountered in any of the patients but for 3 who had diarrhoea and 1 who had loose stool, though these changes were slight. As abnormal laboratory test data, elevation of GOT was noted in 1 case, thrombocytosis and elevation of GPT in another. Also, none of the patients refused or complained of difficulty in intaking of the drug via oral route.
In conclusion, CFTM-PI appeared to be a safe and highly effective antibiotic against pediatric infections.

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A pharmacokinetic study on cefteram pivoxil (CFTM-PI) granules and tablets for pediatric use was performed, and pharmacokinetic parameters were calculated using the one-compartment open model with a time lag.
1. Twelve school children were administered orally with CFTM-PI granules at a dose level of 3mg/kg either at 30 minutes before meal or 30 minutes after meal on a crossover design, and serum concentrations and urinary excretion rates of CFTM were determined. T_max, C _max, T 1/2 and urinary excretion rate following the administration before meal were 1.3±0.1 hours, 1.35± 0.11 μg/ml, 1.21±0.07 hours and 13.4±1.5%, respectively. T_max, C_max, T1/2 and urinary excretion rate following the administration after meal were 2.9±0.3 hours, 1.08±0.09 μg/ml, 1.72±0.26 hours and 23.3±2.2%, respectively. Earlier T_max, higher C_max and lower urinary excretion rate were observed when the drug was administered before meal than when administered after meal.
2. Six school children were administered orally with CFTM-PI granules at 30 minutes after meal at a dose level of either 3mg/kg or 6mg/kg on a crossover design, and serum concentrations and urinary excretion rates of CFTM were determined. C_max at a dose level of 3mg/kg was 1.50±0.26μg /ml, C_max at a dose level of 6mg/kg was 2.58±0.29μg/ml. There existed dose response.
3. Eighteen school children, 10 younger children and 6 infants were administered orally with CFTM-PI granules at a dose level of 3mg/kg at 30 minutes after meal, and serum concentrations and urinary excretion rates of CFTM were determined. T_max in school children, younger children and infants were 2.8±0.3, 3.4±0.3 and 2.0±0.4 hours, respectively. Slightly earlier T_max's were observed in infants than in other Children. C_max in school Children, younger children and infants were 1.22±0.11, 1.03±0.12 and 0.94±0.15μg/ml, respectively. It seemed slightly high in the crder school children, younger children, infants. Although T 1/2 were nearly the same in all age groups, it seemed somewhat longer in school children than in others. Urinary excretion rates in school dhildren, younger children and infants were 21.5±1.8, 19.3±2.0 and 7.6±0.1%, respectively. Obviously low excretion rates were observed in infants.
4. Six school children were administered orally with CFTM-PI either in granular or tablet form at a dose level of 4.0±0.2mg/kg at 30 minutes before meal on a crossover design, and 3 school children were administered orally with CFTM-PI either in granular or tablet form at a dose level of 5.2±0.4mg/kg at 30 minutes after meal on a crossover design, and serum concentrations and urinary excretion rates of CFTM were determined. T_max following the administration before meal were nearly the same for either ganules or tablets. Slower T_max were observed following the administration after meal when granules were used than when tablets were used. C_max following the administration before meal were 1.30±0.25μg/ml with granules and 1.93±0.21 μg/ml with tablets. C_max following the administration after meal were 1.93±0.27μg/ml with granules and 2.77±0.50μg/ml with tablets. Higher C_max seemed to result with tablets. T1/2 were nearly the same following either before meal or after meal administration and either in the form of granules or tablets. Urinary excretion rates following the administration before meal were 11.4±2.5% with granules and 15.7±2.1 with tablets. Urinary excretion rates following the administration after meal were 20.7±2.9% with granules and 29.7±9.0% with tablets. Better urinary excretion seemed to result with tablets.

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We have carried out laboratory and clinical studies on cefteram pivoxil (CFTM-PI, T-2588).
The results are summarized as follows.
CFTM-PI was given through oral administration to 2 children each at dose levels of 1.5mg/kg, 3mg/kg and 6mg/kg. After administration, mean peak serum levels of CFTM obtained for the 3 dose levels were 0.66±0.01μg/ml, 1.26±1.05μg/ml and 2.28±0.95μg/ml at 2 hours, respectively, and mean half-lives were 1.07±0.52 hours, 1.32±0.76 hours and 2.53±1.70 hours, respectively.
Mean urinary excretion rates of CFTM were 19.0±4.0%, 9.4±1.5% and 19.9±4.0% in the first 8 hours after administration of 1.5mg/kg, 3mg/kg, 6mg/kg, respectively.
Treatment with CFTM-PI was made in 36 cases of pediatric bacterial infections including 20 cases of tonsillitis, 3 cases of bronchitis, 6 cases of scarlet fever, 3 cases of UTI and 1 case each of bronchopneumonia, abscess, staphylococcal scalded skin syndrome and vaginitis.
Results obtained were excellent in 22 cases, good in 14 cases.
No significant side effect due to the drug was observed in any cases.

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The clinical effectiveness of cefteram pivoxil (CFTM-PI) granule, a new oral cephalosporin, was studied in pediatric patients. The results are summarized as follows.
1. CFTM-PI was given orally to 17 children in daily doses of 9.5 to 31.8mg/kg in 3 to 4 divided portions for 2 to 10 days. Clinical evaluations were made on 14 patients.
Clinical effects of CFTM-PI were excellent in 4, good in 5 of 9 patients with tonsillitis or pharyngitis, excellent in all cases of 2 patients with pneumonia, 1 patient with scarlet fever and 1 patient with pyelonephritis, and fair in 1 patient with purulent cervical lymphadenitis. Overall clinical effects were excellent in 8, good in 5, and fair in 1 with an efficacy rate of 92.9%.
2. No side effects were observed in any of the 17 patients. Hematological tests showed a slight elevation of blood platelet counts in 1 patient.
3. The taste and odor of CFTM-PI granule were well accepted by the children.
4. CFTM-PI is a useful oral antibiotic for the treatment of bacterial infections in pediatrics.

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Cefteram pivoxil (CFTM-PI), the pivaloyloxymethyl ester of cefteram (CFTM) in which aminothiazol was also introduced into the 7 position of cephem nucleus, is a new oral cephem antibiotic. CFTM-PI was absorbed through the intestines and hydrolyzed to CFTM by esterases in the intestinal wall and existed in the body fluids as CFTM. A tablet form of this drug has been released in Japan and now a granular form for pediatric patients has been developed.
We have determined MICs of 5 drugs (CFTM, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), erythromycin (EM)), against stock strains and MICs of 6 drugs (CFTM, CEX, CCL, ABPC, methicillin, cloxacillin) against fresh strains from patients received to CFTM-PI, with an inoculum size of 10⁶ cfu/ml. A total of 149 strains included Gram-positive cocci i. e. Staphylococcus aureus (11), Streptococcus pyogenes (85), Streptococcus agalactiae (16) and Streptococcus pneumoniae (4), and Gram-negative rods i. e. Haemophilus influenzae (11), Bordetella pertussis (11), Escherichia coli (9), Proteus mirabilis (1) and Morganella morganii (1).
The granular form of CFTM-PI was administered to 9 boys (age: 8 years 3 months-10years 10 months) to determine serum and urinary concentrations of the drug and its urinary recovery rates using bioassay. Doses of 1.5, 3.0 and 6.0mg/kg were given orally 30 minutes after meal to 3 boys, respectively. Urinary concentrations and its urinary recovery rates of T-2525A, a main metabolite of CFTM, were determined using high performance liquid chromatography (HPLC).
To study clinical and bacteriological effects of this drug, a mean daily dose of 3.3mg/kg divided 3-4 times a day (3 times: 133 cases, 4 times: 9 cases) was administered for 8 days on the average to a total of 142 cases with pharyngitis (22), tonsillitis (12), acute bronchitis (3), pneumonia (11), pleurisy (1), scarlet fever (28), acute purulent otitis media (16), impetigo (13), abscess (2), purulent lymphadenitis (1) and urinary tract infection (33).
Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients.
The results obtained are summarized as follows.
1. With regard to Gram-positive cocci, MICs of CFTM against 11 fresh strains of S. aureus ranged from 3.13 to 6.25μg/ml except for 1 strain, thus CFTM was equally effective to CEX, but less active than the other drugs tested. MIC₉₀ of CFTM against 50 stock strains of S. pyogenes was 0.025μg/ml, hence CFTM was less active than ABPC, but more active than the other drugs. MIC₉₀ of CFTM against 35 fresh strains of S. pyogenes was also 0.025μg/ml. MIC₉₀ of CFTM against 16 stock strains of S. agalactiae was 0.05μg/ml, and CFTM was more active than the other drugs. MIC90 of CFTM against 4 fresh strains of S. pneumoniae ranged from <0.025 to 0.05μg/ml, thus CFTM was equal to ABPC, more active than the other drugs.
Regarding Gram-negative rods, MIC₉₀ of CFTM against 11 fresh strains of H. influenzae was <0.025μg/ml, hence CFTM was more active than the other drugs. MIC₉₀ against 11 stock strains of B. pertussis was 0.78μg/ml, thus CFTM was less active than EM, but more active than the other drugs. MICs of CFTM against 9 fresh strains of E. coli ranged from 0.20 to 0.39μg/ml, and CFTM was more active than the other drugs. MICs of CFTM against a fresh strain of P. mirabilis and a fresh strain of M. morganii were 1.56 and 0.39μg/ml, respectively, this indicated that CFTM was more active than the other drugs.
2. Mean serum peak levels of CFTM were observed at 3 hours after administration in the 1.5mg/kg and the 3.0mg/kg groups and at 4 hours after administration in the 6.0mg/kg group with peak values of 0.62, 1.25 and 2.18μg/ml, respectively.

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