Cefoxitin (CFX) was evaluated for its safety and efficacy in children. Fifteen patients were treated with 73-125mg/kg per day of CFX by intravenous administrations. The diagnosis of the patients were acute pharyngitis (4), pneumonia (2), pertussis and pneumonia (1), urinary tract infection (3); and the remaining 5 patients were esteemed to have nonbacterial infections. All the 10 patients of bacterial infections were cured after the CFX therapy. The pathogens recovered were Streptococcus pyogenes(1),Streptococcus pneumoniae(3),Haemophilus influenzae(2), Escherichia coli(2), enteropathogenic Escherichia coli(1), and Klebsiella pneumoniae(1). All the strains isolated were susceptibleto CFX, but the 2 isolates of Haemophilus influenzae had relatively high MIC values (12.5mcg/ml). Diarrhea (3cases) and transient neutropenia (1 case) were found to be associated with the CFX therapy. However, nosevere adverse reactions were encountered. Half-life of the serum level was short (24.1minutes) and excretion into the urine was rapid. CSF concentration obtained 30 minutes after an intravenous injection of 50mg/kg of CFX in 1 case with inflamed meninges was considerably high (8.3mcg/ml). CFX appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections.

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Following are the results obtained from studies made with cefoxitin in the field of pediatrics:
(1) The peak serum level observed upon completion of the one hour drip infusion in a dose of20-25 mg/kg of cefoxitin varied from 66.4 to 93.0 mcg/ml. This fell to a remarkably low level after 2 hours. The serum half-life varied from 18.84 to 27.86 minutes.
(2) The cumulative quantity of cefoxitin excreted in the active form in the urine by the end of 6 hours after completion of the drip infusion was 92.9-93.8%.
(3) All of the 42 patients with acute pediatric infection such as various kinds of acute upper or lower respiratory tract infection, urinary tract infection were treated with either cefoxitin by a single shot (23 patients), or by drip infusion (19 patients). The dosage employed was approximately 50-100 mg/kg/day divided into two to three treatments. There was no major difference in the clinical efficacy between administering two times or three times, the efficacy rates being 96% and 89% respectively. The overall efficacy rate was 93%.
(4) In either case of intravenous injections by either a single shot or drip infusion, excellent clinical responses were obtained in most patients. These people had a variety of infections, which were considered to be caused by various kinds of Gram-positive cocci, E. coli (including ABPC resistance), P. mirabilis,Kl. oxytoca and Haemophilus.
(5) Out of the 42 patients who received cefoxitin in a daily dose of 50-100 mg/kg divided intotwo or three times either by a single shot or drip infusion, no hepatic or renal function abnormality was observed except for 2 cases of temporary eosinophilia.
(6) On the basis of these results, cefoxitin was found to be a highly useful antibiotic in the treatment of acute pediatric infection caused by microorganisms which are sensitive to cefoxitin.

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Laboratory and clinical studies were performed on a newly introduced antibiotic of the cephamycin series, cefoxitin (CFX), and the results obtained were as follows:
1. Employing clinical isolates, MICs were determined and comparisons made with those of cephalosporins. The MICs of CFX against S. aureus and S. pyogenes slightly inferior to those of the cephalosporins, while the MICs of CFX against Gram-negative bacilli such as E. coli, Proteus sp. and Klebsiellasp. were considerably superior to those of CER and CET, and slightly superior to those of CEZ.
2. The peak serum concentrations were 34.7mcg/ml and 67.6 mcg/ml at 30 minutes after an in travenous injection in doses of 12.5mg/kg and 25mg/kg, respectively. The peak serum concentration was 40.8mcg/ml at the end of 60 minutes intravenous drip infusion when it was given in a dose of 25mg/kg. In these cases, the serum half life were 25.8-51.2 minutes, and their urinary recovery were 67-90%.
3. Clinically, CFX was given to the 29 children with a total of 31 of varying bacterial infections: 6 cases of urinary tract infection (U. T. I.), 19 of respiratory tract infection (R. T. I.), 2 of staphylococcal scalded skin syndrome (S. S. S. S.), 2 of purulent lymphadenitis and 2 cases of soft tissue dermatorogical infections. Overall efficacy rate was 83.9% (26 cases). No significant adverse reaction was noted except for 1 case of rash. Abnormal laboratory findings observed were elevation of GOT and GPT in 1 patient, and of GPT in 1 patient.

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The antimicrobial activity of cefoxitin against clinical isolated organisms was measured: Cefoxitin was more active than cefazolin and cephalothin against Escherichia coli.
The serum concentrations of cefoxitin following intravenous injection of 25mg/kg were 267.7, 38.8, 8.3μg/ml at 5, 30,120 minutes after injection, respectively. Cefoxitin was excreted 90.5% in urinewithin 6 hours after injection.
Cefoxitin was administered clinically to 22 pediatric patients with various infections (urinary tract infection 9, respiratory tract infection 10, S.S.S.S. 1, Salmonella enteritis 1, and cervical lymphadenitis 1) at the dose of 45-98mg/kg/day for 4-10 days, and the following satisfactory results were obtained; excellent in 16, good in 5, and poor in 1. The rate of satisfactory clinical response was 95.5%.
Slight elevation of transaminase and Al-P were observed in 4 patients, but no other serious side effects were observed.

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Studies on antimicrobial activity, absorption and excretion and clinical use of cefoxitin in pediatric field were performed.
1. MIC of cefoxitin was compared with that of cefazolin and/or ampicillin for clinical isolates of Staphylococcus aureus (36 strains), Escherichia coli (35 strains), Klebsiella pneumoniae (34 strains) and Haemophilus influenzae (80 strains). MIC of cefoxitin against S. aureus was approximately 1-2 tubes higher than that of cefazolin. Many strains of E. coli and K. pneumoniae that showed high MIC to cefazolin were sensitive to cefoxitin. It is presumed that the results are due to the strong resistance of cefoxitin to β-lactamase degradation. MIC of cefoxitin against H. influenzae was approximately 1-2 tubes lower than that of cefazolin, but approximately 4 tubes higher than that of ampicillin.
2. Serum level and urinary recovery rate of cefoxitin after one shot i.v. injection of 25 mg/kg were examined. The serum mean levels were 33.8 μg/ml at 1/2 hour, 7.0 μg/ml at 1 hour and 2.9 μg/ ml at 2 hours after the injection, respectively, and the drug was not detected in serum at 4 and 6 hours after the injection. The mean half-life of serum level was 27.1 minutes. The mean urinary recovery rate within 6 hours after injection was 96.0% and most of the drug were excreted into urine within 2 hours after the injection.
3. In order to evaluate clinical response, bacteriological response and side effects, cefoxitin was applied to 19 cases, i.e., 12 cases of either acute lobar pneumonia or acute bronchopneumonia, 2 cases of acute pyelitis, 1 case each of acute bronchitis, acute purulent tonsillitis, acute purulent arthritis, acute orbital phlegmone and acute buccal abscess. As for clinical response, the overall efficacy rate (the percentage of cases showed excellent and good efficacy) was 88.9%. As for bacteriological response, among the 13 strains which were determined or supposed to be causative organisms, i.e., 6 strains ofStreptococcus pneumoniae, 2 strains of H. influenzae and 1 strain each of Streptococcus pyogenes, α-Streptococcus, Enterococcus, E. coli and Neisseria sp., all strains were disappeared except for Enterococcus which was reduced by the treatment with cefoxitin. No side effect was observed in any case. Abnormalities of laboratory findings were observed in 3 cases, i.e., 1 case each of reduction of RBC and Hb, elevation of GOT and GPT and elevation of GPT, but all of them returned to normal following completion of the dosage term.

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Clinical trials of cefoxitin, a new cephamycin antibiotic were carried out on 17 infantile patients with infections (respiratory tract infection 15, meningitis 1 and sepsis 1). Two patients of the above patients were excluded from the clinical evaluation except side effects because diseases were out of the object of this study. Cefoxitin was given at a dose of 50-104 mg/kg/day q.i.d. except 1 patient (b.i.d.) by a single intravenous injection for 2-27 days.
The clinical efficacy obtained was good in 11 patients, fair in 2 patients and poor in 2 patients.The efficacy rate was 73.3%. Side effects were observed in 4 patients (eosinophilia 1, skin rash 2 and transient elevation of GOT, GPT and LDH 1).

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The authors have carried out the laboratory and clinical studies of cefoxitin. The results were as follows:
The sensitivity was estimated by plate dilution method on 26 strains of S. aureus, 25 strains of E.coli, 24 strains of K. pneumoniae, 27 strains of Serratia and 17 strains of Salmonella isolated from patients.
The distribution of sensitivity of S. aureus was 1.56-3.13 μg/ml and the peak of distribution was 3.13 μg/ml. The strains of 76.0% of E. coli was inhibited at concentration of less than 3.13 μg/ml. The strains of 91.7% of K. pneumoniae was inhibited at concentration of less than 3.13 μg/ml. The distribution of sensitivity of Serratia was 6.25-more than 100 μg/ml and the peak of distribution was 100 μg/ ml. The all strains of Salmonella were inhibited at concentraion of less than 3.13 μg/ml.
Cefoxitin was given by intravenous administration for 5 minutes at a single dose of 25 mg/kg of cefoxitin to 2 children, and by drip infusion for 60 minutes at a single dose of 25 mg/kg of cefoxitin to 4 children.
After intravenous administration of cefoxitin, the mean peak of serum level was 67.3±6.3 μg/ml at 15 minutes, and at 4 and 6 hours after administration was not detected. Half-life time was 22 minutes. And after drip infusion of cefoxitin for 60 minutes, the mean peak of serum level was 35.7±5.3 μg/ ml at 1 hour, and at 4 and 6 hours after administration was not detected. Half-life time was 20 minutes.
The mean urinary recovery rate was 82.4±3.0% and 90.2±6.8% up to 6 hours after intravenous administration and drip infusion respectively.
Cefoxitin was effective in all of 15 cases with bacterial infections. No side effect was observed.

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Fundamental and clinical evaluations were made on cefoxitin, a new cephamycin antibiotic, and the following results were obtained.
1) MIC of the drug to clinical isolates was determined and was higher than that of cefazolin to Gram-positive bacilli. Among Gram-negative rods, the drug howed a sufficient antibacterial activity even to cefazolin-resistant strains. However, the MIC of cefoxitin to cefazolin-sensitive strains tended to be higher than that of cefazolin.
2) As to the passage of cefoxitin in experimental staphylococcal meningitis in rabbits, a percentage of CSF/serum ratio of AUC was 10.7% up to 3hours and CSF/serum ratio of T1/2 was 1.78, of which value was an intermediate between those of ampicillin and cefazolin. There were, however, larger individual differences.
3) Blood concentrations and urinary recovery rates were determined in 2 children. In 1 patient, in whom the drug was given intravenously at a dose of 25mg/kg, a blood concentration after 30 minutes was 50μg/ml, T1/2 was 57.2 minutes. This patient, however, showed a slight renal dysfunction. In another patient, who received an intravenous injection of 12.5mg/kg, a 30minutes blood concentration was 14.6μg/ml and T1/2 was 31.8minutes. Urinary recovery rates up to 6hours were 85.8% and 73.5%, respectively.
4) Thirty patients with the following bacterial infections were treated with cefoxitin, i.e., urinary tract infection (24 cases), respiratory tract infection (4 cases), each one case of peritonitis and suspected sepsis. An overall efficacy rate was 93.3%, i.e., excellent in 13 cases, good in 15, and failure in 2. Disappearance rate of the causative organism of the 23 clinical isolates was 87.0%, i.e., that the causative organism disappeared in 20 strains, reduced in 1 and persisted in 2.
5) Based on the above results, it was concluded that cefoxitin is a potent new antibiotic in bacterial infections in children, particularly respiratory and urinary tract infections. The optimal recommended dose will be about 25mg/kg which should be given 3-4times daily intravenously or by drip infusion.

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Laboratory and clinical studies of CFX were conducted on 30 pediatric inpatients at the Department of Pediatrics of Mie University. The results of the sensitivity evaluation conducted on 37 clinical isolates consisting of 16 species were in accordance with the findings reported hitherto in the literature, i. e., CFX was superior to CEZ and CET in terms of the growth inhibitory effect against Gram-negative rods.
The serum peak level was obtained 5 minutes after an intravenous injection of 25 mg/kg, and 15 minutes after a drip infusion of 30 minutes using the same dose. The average terminal half life was 13 minutes 15 seconds for the former and 20 minutes for the latter.
Clinical evaluation was made on a total of 22 eligible patients. The results were classified as follows: Excellent in 4 cases, good in 12, fair in 4 and poor in 2. The effective rate of CFX was 72.7%. Side effects observed were vascular pain, rash and vomiting, all of which were mild in nature and disappeared immediately after discontinuation of, or change in the route of drug administration.

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A total of 19 pediatric patients received cefoxitin for the treatment of various infections by intravenous injections of a daily dose ranging from 68 to 125 mg/kg body weight dividing the dose into 3 to 4 times per day.
The therapeutic efficacy was excellent in 14 cases, good in 4 and fair in 1, the efficacy rate being 95%.
As for side effects, 1 case each of rash, diarrhea and eosinophilia were observed, but none of them were serious.

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Cefoxitin was given intravenously to 20 children with the following acute bacterial infections: 10 cases of bronchopneumonia, 6 cases of urinary tract infection, 2 cases of cervical purulent lymphadenitis, 1 case of streptococcicosis and 1 case of omphalitis.
Clinical effectiveness was obtained in 16 cases out of 20 cases and bacteriological effectiveness in 11 strains out of 15 strains.
No side effect was observed except for 1 case with eruption and 1 case with slight elevation of GOT.
From the above clinical results, it is apparent that cefoxitin is a useful antibiotic for treating pediatric patients with various kinds of bacterial infections.

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Using a new cephamycin antibiotic, cefoxitin, clinical studies were carried out, and the following results were obtained:
(1) Cefoxitin was administered to 52 children with 38 respiratory tract infections, 2 urinary tract infections, 1 acute otitis media and others, who ranged in age from 2 months to 11 years old.
(2) Cefoxitin was given intravenously at a daily dose of 27.3mg/kg to 110.5 mg/kg.
(3) The overall efficacy rate was 80% in 46 cases, i. e., excellent in 10, good in 27, fair in 7 and poor in 2.
(4) Clinical side effects were not seen except exanthema in 1 patient. Elevation of GOT and GPT was seen in 2 patients, elevation of Al-P in 1 and eosinophilia in 2 by laboratory tests. However, these findings were alleviated rapidly following the cessation of therapy.

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1. The in vitro antibacterial activity of cefoxitin was nearly equal to that of CEZ and CET against the 6 species of clinically isolated strains. Cefoxitin, furthermore, had an antibacterial activity against the strains of P. morganii resistant to CEZ and CET.
2. Cefoxitin was applied to a total of 17 patients including 6 cases of bronchitis, 5 of pneumonia, 2 of enteritis, and 1 each of pharyngitis, laryngitis, sinusitis and lymphadenitis. The results showed an efficacy rate of 88%. In the 6 patients from whom the isolation of pathogenic organisms was possible, the bacteriological response to cefoxitin was appreciable the efficacy rate being 83%. Thus, it is considered that cefoxitin also has a significant antibacterial activity in vivo.
3. As to the side effects following the administration of cefoxitin, urticaria-like eruption was observed in 1 case, and an elevation of transaminase in another. These findings, however, became normal soon after discontinuation of cefoxitin treatment.

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In order to ascertain the therapeutic effects of cefoxitin (CFX), a new semisynthetic cephamycin antibiotic, it was administered to pediatric patients with several infections. There were 8 patients with acute respiratory disease (ARD), 3 with urinary tract infection (UTI), 2 with appendicitis complicated with peritonitis, 2 with scarlet fever, one each of left coxitis, infected medial cervical cyst, febrile illness after a V-P shunt operation, purulent parotitis and intractable diarrhea with fever, namely, a total of 20 patients aged from one month to 11 years 6 months.
A CFX vial which contained 1 g of CFX was used in two ways, i. e., one shot intravenos injection and drip infusion. The dosage of the drug varied from 57 to 121 mg/kg/day and the administration was continued from 2 to 20 days. Clinical effects were evaluated as follows: when cardinal symptoms disapperared within 3 days it was considered to be ‘excellent’ ; within 5 days ‘good’ and no change of clinical symptoms within 5 days ‘poor’. The bacteriologicalcal effect was expressed as ‘eliminated’, ‘unchanged’ and ‘undetermined’.
Clinical efficacy evaluated as ‘excellent’ occured in 11 cases, ‘good’ in 8 cases and ‘poor’ in 1 case, the efficacy rate being 95.0% When classified by the disease, the efficacy rate was as follows: ‘good’ to ‘excellent’ in 7 out of the 8 cases of ARD, ‘excellent’ in all of the 3 cases of UTI, ‘good’ and ‘excellent’ in the 2 cases of scarlet fever and in the 2 cases of peritonitis, ‘excellent’ ineachcase of left coxitis, purulent parotitis and intractable diarrhea with fever, ‘good’ in each case of infected medial cervical cyst and febrile illness after a V-P shunt operation.
From the bacteriological point of view, ‘eliminated’ occured in 5 cases, ‘reduced’ in 1 case and ‘undetermined’ in the 2 cases of ARD, ‘eliminated’ in all of the 3 cases of UTI, ‘eliminated’ in 1 case and ‘undetermined’ in the 1 case of peritonitis, ‘undetermined’ in the 2 cases of scarlet fever, ‘eliminated’ in each case of infected medial cervical cyst and purulent parotitis and ‘undetermined’ in the other cases.
Antimicrobial efficacy measured by MIC was compared with CEZ and CET, and the results were as follows: CFX was inferior to the two cephalosporins for S. aureus, it was between CEZ and CET for H. influenzae and H. parainfluenzae, and CFX was superior to CEZ and CET for E. coli All of the 3 antibiotics had poor antimicrobial efficacy for P. aeruginosa and S. faecalis.
There were neither clinical side effects nor abnormal laboratory findings which were obviously attributable to CFX during and after administration of the drug.

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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 44.5mg/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 130mg/kg/day for an average duration of 9 days.
The results were as follows:
1. Favorable plasma levels were obtained comparing with those of conventional injectable cephalosporins after 15mg/kg and 25mg/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 15mg/kg, and while, those were 15.9 minutes and 27.5 minutes after an intravenous administration of cefoxitin at a dose of 25mg/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 15mg/kg and 25mg/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 occured 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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tezole, an antibiotic of cephalosporin C derivative was applied to treatment in 39 patients withodontogenic inflammation or postoperative infections.
The drug was administered intravenously (1-5g/day) for the period of 5-10 days. Twenty of them were administered jointly with γ-globulin (Gamma-Venin®). Therefore, we compared clinically between the group of ceftezole with Gamma-Venin® and the other group without it. But no difference was noticed statistically between these groups.
No side effect was observed with throughout all the cases.

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[in Japanese]

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Lincomycin-type and macrolide-type antibiotics are known to be drugs that show potent bactericidal activity against Gram-positive cocci, anaerobic bacteria and Mycoplasma. However, during the years from 1973 through 1976, a problem developed in the form of an increase in the number of strains of group A streptococci having resistance to these antibiotics3). In more recent years, on the other hand, it has been reported that there is a trend for the number of these resistant strains to decrease. The microbial strains that are resistant to lincomycin-type and macrolide-type antibiotics can have either constitutive resistance or induced resistance). Constitutively resistant strains are especially likely to be resistant to all of the macrolide-type antibiotics, and they are commonly seen to develop resistance to lincomycin-type antibiotics as well. For this reason, it is thought to be important-from both the clinical and immunological aspects-to know the actual situation with regard to the distribution of drug sensitivities of clinical isolates against which the lincomycin-type and macrolide-type antibiotics are generally thought to be effective.
The author has been carrying out a clinical microbiological investigation of the bacteria found in primary infections and the changes in the species of the bacteria isolated from those infections. However, on this occasion, I would like to report on the results of an investigation into the antibiotic sensitivities of some bacteria which can be problematic in primary infections. The bacteria tested were Gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae), and anaerobic bacteria that are representative clinical isolates (Bacteroides fragilis and Peptostreptococcus). The antibiotic sensitivities of these isolates were determined in relation to lincomycin-type (clindamycin and lincomycin) and macrolide-type (erythromycin, kitasamycin (leucomycin) and josamycin) antibiotics. The method employed was the Japan Society of Chemotherapy's technique for the determination of the MIC of bacteria-antibiotic combinations.

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[in Japanese]

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[in Japanese]

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Recently, cephalosporins have been developed progressively that the clinical experiences in new cephalosporins have been reported one after another; some of them are widely used in daily medicine. The microbiological studies and other metabolic studies; i.e. absorption, distribution, and excretion, have undertaken simultaneously during the clinical trials of new antibiotics. On the other hand, the necessity of the optimum dose regimen for not only antibiotics but also other drugs has been emphasized to achieve the maximum pharmacological effects with minimal dosage or to prevent the side-effects and sequelae. In such cases, the monitoring of the blood level is essential and the drug concentration is necessary to be measured as soon as possible. The chemical assay has an advantage in this point over the bioassay, and has become available for the routine analysis recently. With cephalosporins, the blood and urine levels of cephalothin (CET), cefoxitin (CFX), cephalexin (CEX) 2, 3), cefazolin (CEZ) 4), cefuroxime (CXM) 5), cephaloridine (CER) 6) and cefradine (CED) 7) determined by high-performance liquid chromatography (HPLC) have been reported.
The author describes a new HPLC method using a reversed phase column which found to be applicable to the routine analysis of CED in serum and urine comparing with bioassay.

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A new antibiotic drug of cephalosporin with marked resistance to β-lactamase, cefotaxime (HR 756) for parenteral use in 8 patients with acute or subacute cholecystitis with cholelithiasis. Cefotaxime was administrated by intravenous injection or drip infusion at a daily dose of 1-4 g. Clinical response was excellent in 1 case, good in 7 cases, and fair or poor was none. Cinical adverse effect was not recognized.
Cefotaxime in a dose of 1 g was given intravenously during operation to those same 8 patients. Tissue specimens of different places were taken from removed organs. The materials of A-bile and B-bile were subsequently taken at intervals. Determination of cefotaxime concentration was performed according to the bioassay method with Micrococcus luteus ATCC 9341 strain.
Cefotaxime concentrations in the A-bile increased gradually until 1 hour after the intravenous administration. Cefotaxime was observed in the B-bile through the gallbladder wall after the intravenous injection.

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