Eleven infants ranging 2 days to 3 months of age were studied for clinical evaluation.Ten of them were diagnosed as sepsis or suspected to be septic.Another one contracted umbilical infectio.In 7 of 10 cases, causative bacteria were detected by blood culture, that is S.epidermidis in 3 cases, E.cloacae in 2 cases, K. pneumoniae in 1 case and A.calcoaceticus in another.
Those infants were treated by parenteral LMOX.Dosage was 30 to 75 mg/kg per day.Clinical results were excellent in 6 cases (3 cases of S.epidermidis, 2 of E.cloacae and 1 of K.pneumoniae) and good in another case (A.calcoaceticus).The other 3 infants clinically diagnosed as sepsis but not proven by blood culture were also treated successfully. The result of the umbilical infection in 1 case was good.
Another group of 5 infants ranging 4 to 22 days of age were also treated by LMOX bacause of suspected bacterial infections. With these infants pharmacokinetic study was done. Peak serum levels after 1 hour drip infusion of 20 mg/kg ranged from 43 to 53μg/ml.Average of half-lives was 2.7 hours.Estimation of distribution volume resulted in 350 to 523ml/kg body weight.

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1. Fundamental and clinical studies in infants including neonates on latamoxef (LMOX) were carried out, and following results were obtained.
2. In fundamental studies, half-lives of LMOX were 5.79, 4.38 hours, at dose 10 mg/kg by intravenous injection and intravenous drip infusion in neonates, respectively.And urinary excretions were 6.8, 15.6% for 6 hours, respectively.In 28-50 day-old neonates, half-lives were 2.26-4.3 hours at dose 20mg/kg, and urinary excretions were renged from 14.3 to 37.0%.
3. Clinical results were following.In 8 cases of bronchopneumonia and 2 cases of pertussis, the clinical efficacy rate was 100% at daily dose 38-100 mg/kg twice or third a day by intravenous injection or intravenous drip infusion for 6-9 days duration.
4. All causative organisms (K. pneumoniae 1, S.aureus 1) were eliminated after LMOX 43 or 38 mg/kg/day dose administration.
5. Side effect and laboratory abnormal value were not noticed in all cases. We finally have a conclusion that LMOX should be administered 40-70 mg/kg/day, and given twice or third a day by intravenous injection or intravenous drip infusion.

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Latamoxef (LMOX) was used in the treatment and prophylaxis of infections in neonates and immature infants. The following results were obtained.
1. Mean serum concentrations (bioassay) 30 minutes after a single intravenous injection of about 20 mg/kg of LMOX were 49.9mcg/ml in neonates and 47.3 mcg/ml in immature infants aged 0-3 days, 54.1 mcg/ml in neonates and 60.6mcg/ml in immature infants aged 4-7 days, 48.9mcg/ml in neonates and 46.7 mcg/ml in immature infants aged 8-28 days and 62.1mcg/ml in immature infants aged over 29 days.Six-hour values were 24.1mcg/ml, 22.5mcg/ml, 15.9mcg/ml, 27.2mcg/ml, 12.9mcg/ml, 19.1mcg/ml and 12.8mcg/ml, respectively.
2. Mean serum concentration half-lives were 6.70 hours in neonates and 8.16 hours in immature infants aged 0-3 days, 3.68 hours in neonates and 5.83 hours in immature infants aged 4-7 days, 3.06 hours in neonates and 4.47 hours in immature infants aged 8-28 days and 2.59 hours in immature infants aged over 29 days.
3. Adequate clinical efficacy can be expected by the intravenous injection of LMOX in doses of 20mg/kg 1-2 times daily, in neonates and immature infants aged 0-3 days, 20mg/kg 2-3 times daily, in neonates and immature infants aged 4-7 days and 20mg/kg 3 times daily, in neonates and immature infants aged 8-28 days.
4. The clinical efficacy of LMOX was good in 5 cases of sepsis (including suspected cases), 5 cases of urinary tract infection, 2 cases of respitary tract infection and 6 cases of intrauterine infection (including suspected cases).Only a case of respiratory tract infections due to P.aeruginosa was thought to be ineffective.
5. Bleeding tendency was noted in 3 cases, which results from secondary vitamin K deficiency should be checked carefully during the administration of LMOX.

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Basic and clinical studies of latamoxef (LMOX) were carried out in neonates.In basic study, these neonates consisted of 16 mature babies and 12 premature babies.
LMOX was administered at dose of 10 and 20mg/kg, either as a single intravenous injection or as a 60 minutes intravenous drip infusion.Both the mature babies and the premature babies were divided into 3 subgroups as a function of the number of days after birth (0-3, 4-7 and 8-25 days).
A clinical study of LMOX was performed in 12 neonates aged between 0-35 days, consisting 6 males and 6 females.(Purulent meningitis 4 cases, septicemia 1 case, bronchopneumonia 5 cases, pertussis pneumonia 1 case, urinary tract infection 1 case),
1. Serum concentration and urinary excretion
(1) 10mg/kg, one shot intravenous injection
In the 3 subgroups of neonates the peak serum concentrations of LMOX were found to range from 14.6 to 28.9μg/ml.Although there was no significant difference, the half-life of the drug became shorter as the age of the neonates increased, these values were 4.46, 3.85 and 3.30 hours, respectively.
(2) 10mg/kg, 60 minutes intravenous drip infusion
As above, the peak LMOX serum concentrations were found to range from 23.7 to 38.9μg/ml, the half-lives of the 3 subgroups were 4.83, 2.48 and 3.01 hours, respectively.And urinary excretions were ranged from 46.0 to 56.5% for 6 hours.
(3) 20mg/kg, one shot intravenous injection
The peak serum concentrations were found to range from 31.0-82.5μg/ml, and it was found out 3.29-15.9g/ml at 8 hours after the injection.There was a tendency for the half-life to be shorter in more mature μ subjects in 3 subgroups.
(4) 20mg/kg, 60 minutes intravenous drip infusion
In the 3 subgroups, the peak concentration was the level existing at the end of the intravenous drip infusion, and that showed a range of 41.8-58.6μg/ml.Half-lives were found out the significant difference to their age, these showed 4.08, 2.31 and 2.52 hours.
2. Cerebrospinal fluid concentrations of LMOX
Cerebrospinal fluid concentrations of LMOX were studied in 2 cases at the dose about 50mg/kg.
In 1 case, that's meningitis estimated E.coil organism, the cerebrospinal fluid concentrations of LMOX were found to range from 29.0 to 49.9μg/ml in that acute state.
In another case from N.meningitidis, that values were found to range 12.1 to 21.3μg/ml.These cerebrospiral levels were superior value at it's penetration ratio.
3. Clinical studies
The 12 cases who were clinically treated with LMOX were intravenously administered a daily dose of 40-300mg/kg, given in 2-6 divided doses.(Purulent meningitis 4 cases, septicemia 1 case, bronchopneumonia 5cases, pertussis pneumonia 1 case, urinary tract infection 1 case).The overall efficacy rate in these 12 cases was 91.7%.The causative organism had been identified in 9 of these patients (E.coli in 3 cases, K.pneumoniae in 2 cases, S.pneumoniae in 2 cases, N.meningitidis, group B Streptococcus, in 1 case, respectively).All those organism disappeared from the culture of specimens after the therapy.The bacteriological efficacy rate was 100%.
4. Conclusion
When LMOX was administered at 20mg/kg, almost all serum concentration maintained 10μg/ml forup to 6-8 hours after the administration, at 10mg/kg it maintained 6μg/ml to 6 hours, and in viewof the half-lives' values and the bacterial activity of LMOX, it can be concluded that, in the infections of moderate state, it should be appropriate to administer this drug in a dose of 20mg/kg, given 3 times a day.Moreover, it may possible to give 2 times to neonates who are 3 days old or less.
In the such serious infections as meningitis and septicemia, the causative organism should be established. Based on those findings, we can be confident of obtaining good results if LMOX is administered intravenously in a dose of 50mg/kg, 4 times a day.

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Basic and clinical studies were carried out on latamoxef (LMOX) in relation to the use of this antibiotic in the treatment of infections in newborn infants.The results were as follows.
1. The MICs of LMOX were determined for various clinical isolates of Gram-negative bacteria: 22 strains of E.coil, 18 strains of K.pneumoniae, 4 strains of K.oxytoca, 19 strains of P.mirabilis, 4 strains of P. vulgaris, 5 strains of P.morganii and 3 strains of C.freundii and 60 strains of H.influenzae.The MIC distributions against all of these strains for each species were 0.1, 0.2, 0.1, 0.2, 0.1, 0.1, 6.25 and 0.78μg/ml or less, respectively. The antibacterial activity of LMOX against all of these Gram-negative isolates was thus found to be excellent. For 38 strains of P.aeruginosa, the MIC distribution was from 6.25 to 200μg/ml;accordingly, although this antibiotic does show antibacterial activity against this microbe, it is not very potent. As Gram-positive bacteria, 28 clinical isolates of S.pyogenes and 34 strains of S.aureus were tested;their respective MIC distributions were 0.39-1.56μg/ml and 3.13-25μg/ml.Therefore, it is clear that the antibacterial activity of LMOX against these Gram-positive bacteria is not as good as against the above-mentioned Gramnegative species.
2. LMOX was injected intravenously as a one-shot dose of 20μg/kg to 5 newborn infants (ranging in age from 0 to 13 days) and to 2 suckling infants (49 and 60 days of age), and then the concentration of the drug in the serum was monitored with time.The mean serum concentrations in the newborn group at various times were as follows: 38.5μg/ml at 0.5 hour, 31.6μg/ml at 1 hour, 26.9μg/ml at 2 hours, 17.8μg/ml at 4 hours and 15.5μg/ml at 6 hours. For the 2 suckling infants, the mean values at those same time points were 30.5, 23.9, 16.3, 7.4 and 4.0μg/ml.In addition the value for the mean serum half-life was 4.46 hours in the newborn infant group and 1.96 hours in the suckling infant group.The urinary recovery rate was 32.3% in the newborn infant group and 49.7% in the suckling infant group during 6 hours or 8 hours.
Considering the extent of differences between the individuals, it can be said that there was very little variation in the peak serum concentrations (the value at 30 minutes after the dosing) recorded in the newborn infant group since their values were almost the same regardless of age. Similarly, there was no big difference seen between the 2 suckling infahts. However, the half-life of the drug in the serum decreased as the age of the subject increased, and it was surmised that the value at around 1 month of age was close to that for schoolchildren.
In addition, as a separate experiment, approximately 20mg/kg and 10mg/kg of LMOX were administered to 2 newborn infants (15 and 26 days of age) by means of intravenous drip infusion over a period of 1 hour;the absorption and excretion of the drug were then investigated. It was found that the serum concentration of LMOX showed a clear dose response.
3. LMOX was administered to 3 patients with acute bronchopneumonia (1 patient was excluded from the subsequent clinical efficacy evaluation), 2 cases of acute pyelonephritis and 1 case of purulent meningitis. The clinical efficacy of the treatment was analyzed. For all 5 of the patients, the clinical efficacy was evaluated as good or excellent.With regard to the bacteriological efficacy, the 2 strains of E. coil that had initially been isolated as the causative bacterium could no longer be detected after the LMOX therapy.No clinical side effects to the drug treatment were seen. In 1 of the patients, the laboratory tests revealed a slight elevation in the values for GOT and GPT, but these returned to normal thereafter.
It was concluded that the above clinical results are indicative of the usefulness and safety of LMOX in the treatment of infections in newborn infants.

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The authors have carried out the pharmacokinetic and clinical studies of latamoxef (LMOX) in mature and premature neonates.The results were as follows.
The serum mean peak levels of LMOX after intravenous administration at a single dose of 10 mg/kg (20mg/kg) were 40.7±20.8 (76.6±12.7) μg/ml in 1 to 3 day-old-neonates, 39.3±29.3 (52.5±6.6) μg/ml in 4 to 7 day-old-neonates and 26.0±2.1 (47.4) μg/ml in 8 to 15 day-old neonates at 15 minutes.
The serum mean levels at 6 hours after dosage were 12.5±5.2 (25.6±9.2) μg/ml 10.3±5.3 (11.8±1.6) μg/ml and 4.2±0.9 (7.2) μg/ml, respectively.The mean half-life times were 4.25 (6.0) hours in 1 to 3 day-old-neonates, 3.4 (3.3) hours in 4 to 7 day-old-neonates and 2.2 (2.2) hours in 8 to 15 day-old-neonates.
The serum levels of LMOX after intravenous drip infusion for 30 minutes at a single dose of 10mg/kg were 17.6μg/ml at completion of infusion, 6.9μg/ml at 6.5 hours, and the half-life was 3.8 hours in 2 day-oldmature neonates.
In 3 day-old-premature neonates, the serum levels were 21.1μg/ml at the completion of infusion, 12.7μg/ml at 6.5 hours, and the half-life was 12.2 hours.
After intravenous drip infusion for 30 minutes a single dose of 20 mg/kg of LMOX, the serum mean levels were 58.5±6.4μug/ml at the completion of infusion, 19.3±1.14ug/ml at 6.5 hours, respectively.
The half-life times were 4.0 hours in 2 day-old-neonates and 4.5 hours in 4 day-old-neonates.
The urinary excretion rate of LMOX in 3 day-old-neonate was 31.7% up to 6 hours after intravenous administration at a single dose of 10mg/kg.
LMOX were clinically effective in a case of pneumonia, but not effective in a case of septicemia.
No side effect was observed except for 1 case with elevation of GOT.

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The usefulness of latamoxef (LMOX) in the treatment of newborn infants was investigated.The results that were obtained are summarized below.
1. LMOX was injected intravenously in a dose of about 20mg/kg, and 30 minutes later the concentration of the drug in the serum was determined.In a very low-birth-weight infant, weighing only 978g at the time of birth, the serum concentration on the 3rd day after birth was 94μg/ml, while it was found to be 100μg/ml when the dosing and determination were performed on the 37th day after birth.Another premature infant weighed 1,980g at birth, and on the 8th day of life the serum concentration was 73μg/ml.The half-lives of LMOX in these 3 administrations were 4.74, 3.95 and 3.20 hours, respectively.
2. LMOX was administered by intravenous injection to 4 patients diagnosed as having 6 diseases (2 patients each had both septicemia and a urinary tract infection;1 patient had pneumonia;1 patient had septicemia). Each dose ranged from about 15 to 25mg/kg, and 3 doses were administered daily (in 1 patient, 4 doses were given over a 2-day period).The evaluation of the clinical results for each disease case showed 4 excellent cases and 2 poor cases. The 2 poor cases consisted of 1 case of pneumonia caused by S. aureus, and 1 case of a mixed urinary tract infection caused by E.coil and S.faecaiis.
3. With regard to side effects and the development of abnormal laboratory test values as a result of the LMOX administration, only 1 subject was seen to experience a temporary elevation of both the GOT and GPT values.
4. Based on the above results and the previously reported results concerning the efficacy of LMOX in the treatment of purulent meningitis, it is thought that LMOX is a useful antibiotic for the treatment of newborn infants for infections caused by bacteria that are susceptible to the antibacterial action of this drug.

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Latamoxef (LMOX) was administered as a one-shot intravenous injection of 10mg/kg or 20mg/kg to 28 newborn and immature infants of 1 to 28 days of age.For 6 hours following the administration, the concentrations of the drug in the plasma and in the urine were monitored and the urinary recovery rate was determined.
In addition, 17 patients, consisting of newborns, immature infants and suckling infants, aged 0 days to 2 months and diagnosed as having various bacterial infections, were also treated with LMOX;the mean daily dosage was 103mg/kg, administered in 2 to 6 divided doses as one-shot intravenous injections for an average duration of 11 days.These patients were subjected to the analysis for the clinical efficacy and bacteriological efficacy of the therapy.Furthermore, with the inclusion of 35 drop-out cases, a total of 52 patients was investigated for the occurrence of side effects by the LMOX therapy.The findings of these studies are summarized below.
1. The patients were divided into 5 groups on the basis of age: 3 days old or less, 4-7 days, 8-14 days, 15-21 days and 22-28 days.Only in the 8-14 day-old group administered LMOX at 20mg/kg, the maximum mean plasma concentration of the drug occurred at the time of 15 minutes postadministratin, although some individuals showed peaks at 5 minutes.In all of the other age groups, for both the 10 and 20 mg/kg dosings, the maximum plasma concentration of LMOX occurred 5 minutes postinjection.In each of the age groups, a dose response was seen between the 2 dosage levels.However, a comparison of each group and control infants in terms of the LMOX plasma concentration at 30 minutes after injection revealed that the concentrations in the patients in this study were low.In terms of the half-life of the drug at the 2 dosage levels, both the mean and individual values in each of the age groups were longer than the half-lives in control infants.This tendency was especially marked in the case of infants 7 days of age or less.The values for the AUC also tended to be larger in the younger patient groups.
2. A good level of LMOX was detected in the urine during each of the 0-2, 2-4 and 4-6 hour periods following administration.When considering those patients for whom it was possible to determine the urinary concentration at each time, it was found that the maximum LMOX concentration occurred in the 0-2 hour period or the 2-4 hour period, in each of the age groups and regardless of the LMOX dosage level.The mean and individual values for the 6 hour urinary recovery rate were low in each of the age groups compared with the control infants, again regardless of the LMOX dosage level.However, there was a tendency for the recovery rate to increase in parallel with the age of the patient.
3. The clinical efficacy rate of the LMOX therapy was 64.7% in the 17 patients diagnosed as having various bacterial infections.With regard to the bacteriological effect of the LMOX, the causative microorganism was eradicated in 5 out of 6 of the patients, while no change occurred in the sixth patient.
4. A total of 52 patients was analyzed for side effects; these consisted of the 17 patients who were evaluated for the clinical efficacy of LMOX, plus 35 patients who were drop-outs from that clinical study.No cases of side effects were found to have developed in any of these patients.As abnormal laboratory test values, there were 4 cases (incidence: 10.3%) of eosinophilia, and 1 case of mild elevation of BUN.Otherwise, when consideration is given to the use of concomitant drugs and hemolysis of the test serum, it can be concluded that there were no other cases of laboratory test value abnormalities.

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Latamoxef (LMOX), a new oxacephem antibiotic, was studied for assessment of fundamental and clinical efficacy in 6 patients with neonatal surgical diseases, and in 1 with congenital bile duct atresia.The results were obtained as followings:
1. The serum levels of LMOX were 71.4-89.6μg/ml at 15-30 minutes following 20mg/kg intravenous one shot injection in postoperative neonatal surgical patients.The mean rate of urinary excretion was 29.1% for 6 hours following administration of LMOX.
2. The biliary levels of LMOX were 5.52-10.2μg/ml in maximum following 20mg/kg intravenous one shot injection in a patient with congenital bile duct atresia, but the excretion rate in bile was poor from liver disfunction. Also, the negative correlationship was obtained between bile and urine excretion rate.
3. LMOX was administered to 6 cases of neonatal surgical patients for prevention of the postoperative infection.The clinical results were good in 4, fair in 1 and not evaluated in 1 of these cases.No side effect was experienced.

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Latamoxef (LMOX) is a new oxacephem antibiotic with a broad spectrum of antimicrobial activity. In vivo transfer and therapeutic efficiency of this drug have studied in perinatal field.
The following results have been obtained.
1. Transfer of this drug to umbilical blood was higher than its MIC against majority of Gram-negative pathogens.
2. In the treatment of 5 cases of perinatal infection, the preparation showed excellent efficiency in 2 cases and good efficiency in 3 cases.
3. No side effect was evidenced in any of our patients.
In conclusion this drug has satisfactory fetal transfer as well as sufficient safety and excellent efficiency in treatment of perinatal infection cases.

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Pharmacokinetic studies and clinical evaluations of latamoxef (LMOX) were carried out in perinatal mothers and infants.
LMOX was promptly absorbed after intravenous injection and intravenous drip infusion in pregnant women, producing dose-related peak blood levels.
Placental transference to the fetus was favorable.After intravenous injection and intravenous drip infusion of 1.0-2.0g of LMOX, drug concentration of the cord blood, amniotic fluid and fetal blood exceeded MICs of the main pathogenic organisms. By administration of the dose of 1.0-2.0g twice a day, it is possible to successfully prevent or treat uterine infections.LMOX was effective in the prophylaxis or therapy of perinatal infections.Moreover, newborn infants delivered from mothers receiving LMOX treatment having drug concentrations exceeded MICs of main pathogenic organisms however not remained more than 12 hours after birth, and did not exhibit any laboratory test abnormalities.
The above results demonstrated that LMOX is a clinically useful antibiotic for the prophylaxis and treatment of perinatal infections.

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Latamoxef (LMOX), a new semisynthetic beta-lactam antibiotic developed by Shionogi Research Laboratory, was evahlated basically and clinically in the perinatal period.
In basical study, concentrations of LMOX on maternal serum, mbilical card serum and axnniotic fluid. were measured by intravenous injection method, and that's placental transferences wele relatively favorable. The ratios of umbilical oord serum to maternal serum were 1/3-1/5 at early state after administration, 5-20 minutes, 2/3 at 1.5-1.75 hours. Umbilical serum concentrations were higher than maternal serum concentrations after about 2.5 hours of administration.
In 1 case, transferences into tissues of uterus and placenta were studied, that's values were 13.4 and 13.0μg/g at 1.75 hours after administration, respectively.
In clinical application, LMOX was administered to 4 cases (intrauterine infection 1 case, urinary tract infection 3 cases) at dose of 2.0g twice a day by intravenous drip infusion, intravenous injection and intramuscular injection method.
Excellent and good clinical response was observed in all 4 cases, and bacteriological response to causative organisms was satisfactory in 3 cases except S. faecalis of mixed infection case.
No side effect or abnormal laboratory values were noticed in the all cases.

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The concentrations of latamoxef (LMOX) in maternal serum, fetal cord serum and amniotic fluid were measured simultaneously at various times after administration to parturient women.
The drug concentrations in fetal cord serum taken from 11 minutes to 12 hours and 37 minutes after administration ranged from 1.1 to 16μg/ml.At the points from 3 to 5 hours after administration the maximum level of LMOX seems to be attained there.
LMOX in amniotic fluid was increasing graduatelly to be attained 21.0μg/ml as the peak concentration at 5 hours after administration.Thereafter, it began to decrease very slowly, 6.9μg/ml was still kept in amniotic fluid at 19 hours after. These findings lead expectation that the effective concentration to mainly recognized pathogens from obstetrical and gynecological infections was kept in amniotic fluid through 19 hours or more.
LMOX was given to each 4 peripartal and puerperal infections and 11 patients with premature rupture of the membranes for the purpose of prophylaxis.
All cases showed effective responses clinically and bacteriologically.
Neither noteworthy adverse reactions nor laboratory data abnormalities were caused throughout the studies.

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Fundamental and clinical studies on the perinatal use of latamoxef (LMOX) were performed, with the following results.
1. Concentration of LMOX was examined in maternal serum, umbilical cord serum and amniotic fluid after intravenous administration of 2 g dose.
Data were analyzed by the simulation curves using the two-compartment model.
The peak level of LMOX in maternal serum was 218.4μ and half-life of the β-phase was 1.9 hours.
The peak levels of LMOX in umbilical cord serum and amniotic fluid were 37.4μg/ml (1.4 hours) and 27.5 tug/ml (8.9 hours) after administration.
The concentration of LMOX in amniotic fluid decreased in amount after the peak, but it still remained 21.9μg/ml (16 hours) after administration.
Above these results, it was concluded that the transfer of LMOX to umbilical cord serum and to amniotic fluid was sufficient.
2. In clinical use, LMOX was administered to 30 pregnant patients with premature rupture of membrane. It showed excellent efficacy in preventing perinatal infection.
Seven patients with perinatal infections were treated with LMOX and all of them had excellent efficacy.
No side effects were observed in any of the cases studied.

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Latamoxef (LMOX), a new oxacephem antibiotic with high activity against Gram-negative bacteria has been investigated for use in No.of 58 mothers in perinatal period, and obtained following results.
1. Concentration of LMOX in maternal serum was 43.4μg/ml at the 1 hour after intravenous administration of 1g.In umbilical cord serum and amniotic fluid, LMOX showed good translation after intravenous administration of 1g into the mother, but no adverse effect appeared in the neonatus.
2. LMOX is highly useful antibiotic in perinatal infections, and the safe dose of LMOX to the mother in perinatal period is 1-2g per day considerably.

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Pharmacokinetics and clinical studies on the perinatal use of latamoxef (LMOX, Shiomarin), a new parenteral oxacephem antibiotic, were carried out and the results obtained were as follows:
1. After LMOX was intravenously given to mother at a dose of 1g, the umbilical cord serum concentration of LMOX reached to peak with 18.4μg/ml in 1 hour 20 minutes and its concentration was higher than the maternal serum after 2 hours 25 minutes and decreased gradually (T1/2β=1.61 hours).The materno-fetal transfer of LMOX was 71.0%.LMOX showed the good transfer as well as other cephalosporins.
2. After LMOX was intravenously administered to mother at a dose of 1g, LMOX concentration in milk wasn't detectable up to 12 hours.
3. LMOX was intravenously administered to 18 cases with premature rupture of membrane, at a daily dose of 2g for 3-6 days.The prophylactic effects were observed in all cases, both mother and neonate. 4. No adverse effects were observed in mother except for 1 case with low grade abnormality of S-GPT, transiently.We observed 3 neonates with jaundice (total bilirubin>17.0mg/dl) probably not related to LMOX.
It is concluded that LMOX is less toxic, safe and clinically useful antibiotic for the treatment of perinatal infections.

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Clinical study on cefotetan (CTT), a new cephamycin antibiotic, was carried out and the following results were obtained.
1. CTT was intravenously administered at a daily dose of 2 to 4g to 24 cases including 10 cases with intrauterine infection, 2 cases with adnexitis, 6 cases with intrapelvic infection and 6 cases with extragenital infection.Marked response was seen in 8 cases, moderate response in 15 and no response in 1.
2. Neither side effects nor abnormal values in clinical laboratory tests were observed.

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Fundamental and clinical studies on gynecological use of cefotetan (CTT), a new cephamycin antibiotic, were performed with following results.
1. Following the intravenous administration of 2.0g of CTT, T 1/2β in serum was 3.1 hours and longer than the previous cephamycin antibiotics. The yields of CTT from serum to various uterine tissues and discharge from retroperitoneum were about 30-50%.
2. In clinical use, 14 patients with gynecological infections were administrated CTT, and it showed excellent or good efficacy in all patients. No side effects were noted except 1 transient disturbance inliver function.

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A new cephamycin antibiotic, cefotetan, was administered intramuscularly to 45 patients with female genital infections including 2 cases with abscess of BARTHOLINGSL and, 14 cases with endometritis, 23 cases with adnexitis and 6 cases with pelvic peritonitis.
The daily doses of the drug were 1 to 3 g, with 2 g daily being the most frequent regimen. The treatment was given twice daily in most patients.
All cases responded to the drug, and marked response was seen in 22 cases and moderate response in 23.
The eradication rate for causative organisms was 64.3%.
In 16 cases of S. faecalis, it was rather low at 37.5%.
Neither side effects nor abnormalities in clinical laboratory findings attributable to the drug were seen.

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Fundamental and clinical studies on a new cephamycin antibiotic, cefotetan (CTT), was carried out under a joint study programme, in order to evaluate the usefulness of the drug in treating infections of the female genital organs.The results obtained were as follows.
1. CTT was readily transported to female genital organ tissues, and the concentrations of the drug exceeded 20μg/g in various organ tissues in about 1 hour, following intravenous injection of 1g.A level of more than 1μg/g was maintained even 12 hours after the injection.
2. The transport of CTT to various tissues was also studied following intravenous drip of 1g in 30 minutes or 1 hour.The results were similar to those following intravenous injection.
3. The peak concentration of the drug in the dead space exudate tended to appear slightly later than those in the organ tissues.However, the concentration reached a level of more than 10μg/ml following intravenous injection of 1g.
4. Clinical effects of CTT were analyzed in 225 patients, including 65 cases with intrauterine infection, 60 cases with intrapelvic infection, 22 cases with external genital infection, 55 cases with adnexitis, 8 cases with mastitis, 8 cases with postoperative wound infection and 7 cases with other infections.Excellent response was seen in 53 (23.6%), moderate response in 150 (66.7%), and no response in 22 (9.8%).The rate of response was calculated as 90.2%.
5. Safety of the drug was analyzed in 273 patients, and side effects occurred in 11 (4.0%) patients. Of these 11 patients, rash was seen in 4 patients, rash accompanying edema in 1, rash accompanying diarrhea in 1, chest discomfort in 2 and feeling of general fatigue in 2.
Abnormal values in clinical laboratory findings were seen in 10 patiens.Elevations of transaminase were seen in 7 patients, and no other changes of particular note appeared.

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The clinical evaluation for cefsulodin (CFS) against P.aeruginosa was studied in postoperative infections of chronic otitis media by means of washing the middle ear with the drug, and the following results were obtained;
CFS treatment was given to 5 cases, and the clinical responses were excellent in 4 and good in 1 case. P.aeruginosa in otorrhea was eradicated within several days, and otorrhea disappeared in all the cases.No side effect was observed in all cases.

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Cefadroxil (CDX), a new semisynthetic cephalosporin derivative, was administered to 20 patients with acute or chronic otolaryngological infections and following results were obtained.
Of 11 cases with acute infections such as acute otitis media, acute otitis externa and postoperative maxillary cyst, excellent, good and fair results were obtained in 10 cases, the efficacy ratio being 91%, while the efficacy ratio in 9 cases with chronic infections such as chronic pharyngolaryngitis and chronic otitis media was 56%. CDX is, therefore, extremely effective for acute otolaryngological infections.
No severe side effect was observed, although there were 2 cases with minor adverse effects, one with drug induced eruption and the other with stomatitis.

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Twenty patients suffering from severe infections (9 with respiratory tract infection, 9 with urinary tract infection, 2 with pharyngitis, 1 with enteritis and 4 with fever of unknown origin (FUO)) were treated by intravenous infusing CTX 2g over 30 to 40 minutes 2 or 3 times daily for 4 to 10 days.Other antibiotics were concomitantly used in 9 cases.
Response to CTX was proved good in 15 cases (75%), fair in 3 cases and poor in 2 cases.
No adverse reactions were observed.

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Cefroxadine was administered at dose level of 750mg/day to 21 cases of superficial suppurative diseases and the following results were obtained:
1. The effective rate determined by the treating doctor was 9/21 (42.9%).
2. The effective rate by the evaluation standard was 12/21 (57.1%).
3. The negative-conversion rate was 11/11 (100%) in the 11 cases in which bacteriological effects were clarified.
4. No side effects were observed in all of the 21 cases.

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Cefroxadine (CXD), an orally active cephalosporin antibiotic, has a broad spectrum and a bactericidal action.
The efficacy of CXD in the surgical field was investigated and the following results were obtained.
1. CXD was administered to 31 cases in all; 13 cases with mastitis, 9 with wound infection, 4 with infected atheroma, 3 with periproctal abscess and 2 with phlegmon, respectively.
2. The daily dose was ranged from 750 mg to 1,500 mg.
3. Clinical effects were good in 27 cases and fair in 4 cases, and the effective rate was 87.1%.
4. As to side effects, a slight diarrhea was observed in 1 case, but the symptom was disappeared after 2 days without a special treatment.

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Clinical effect and excretion into wound exudate of a new semisynthetic cephalosporin cefroxadine (CXD), were studied.
CXD was given in 25 cases of surgical infections; 6 cases of wound infection, 9 cases of abscess, 9 cases of infected atheroma and 1 case of furuncle. CXD was orally administered in daily dose of 750 to 1,500mg.
Clinical results were excellent in 1 case, good in 18 cases, fair in 3 cases and poor in 3 cases. The overall clinical efficacy rate was 76.0%.
Clinical efficacy classified by diagnosis was 66.7% in wound infection, 66.7% in abscess, 88.9% in infected atheroma, and 100% in furuncle. Side effects were not observed in all cases among 25 patients in CXD trials.
Studies of excretion into wound exudate of CXD were performed in 1 postoperative case of mamma carcinoma after oral administration of 500mg of CXD. The concentration of CXD in exudate was 1.12μg/ml in 2 hours, 3.48μg/ml in 3 hours, 4.13μg/ml in 4 hours, 5.56μg/ml in 5 hours and 4.41μg/ml in 6 hours after administration, which was observed that CXD was excreted in wound exudate in high concentration.

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Cefroxadine (CXD) was studied in the field of obstetrics and gynecology and the following results were obtained.
1. MIC values of CXD against 55 clinical isolates were investigated, from 6.25 to 12.5μg/ml for 8 strains of E.coli, 6.25μg/ml for 3 strains of K. pneumoniae and from 0.39 to 3.13μg/ml for 9 strains of anaerobes such as Peptostreptococcus and Peptococcus in 106cells/ml.
2. Transfer of CXD into intrapelvic organ such as uterus, uterine tube and ovary after the oral administration of 500mg was investigated.The concentrations in the tissues of genitalia ranged from 5.84 to 7.44μg/g about 2 hours later after the administration.
3. CXD was orally given to 18 patients with infections of genital organs at daily dose of 1,500mg (500 mg 3 times a day).The clinical response was good, and efficacy rate was 88.9%. No remarkable side effects were observed.

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Cefroxadine (CXD), an oral cephalosporin antibiotic was studied in the field of obstetrics and gynecology and the following results were obtained.
CXD was orally given to 22 cases at daily dose of 1,500mg 3 times a day.CXD administration was given to 22 cases in all;4 with cervicitis, 6 with endometritis, 2 with puerperal fever, 4 with bartholinitis, 5 with adnexitis and 1 with vulvitis, respectively.Overall efficacy rate was 77.3% (17/22)(excellent 4, good 13, fair 5).As for side effects, a slight diarrhea was observed.CXD was considered to be a useful antibiotic in the field of obstetrics and gynecology by above the results.

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Clinical study of cefroxadine (CXD), an orally active cephalosporin, for the treatment of infections in the field of obstetrics and gynecology was carried out and the following results were obtained.
1. Fifteen strains were isolated in present study.These isolates were mainly E.coli and anaerobes (Peptococcus sp., Peptostreptococcus sp.).The distribution of susceptibilities to CXD of E.coli was between 6.25-12.5μg/ml and that of anaerobes was between 0.39-1.56μg/ml. These results were similar to those of CEX.
2. CXD was used in the treatment of 11 patients (endometritis 1 case, adnexitis 3 cases, bartholinitis 7 cases).In overall clinical efficacies, patients evaluated as better than good were 10 out of 11 (90.9%).
3. Skin eruption was observed in 2 cases.No abnormality in laboratory findings was recognized.

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Clinical studies of cefroxadine (CXD), a new orally active of cephalosporin, in obstetrical and gynecological field were performed, and the results were summarized as follows.
1. CXD was orally administered to 16 cases of obstetrical and gynecological infections in daily dose 750-1,500mg.
2. Clinical efficacy was 88.9% in endometritis (9 cases), 100% in cervicitis (2 cases), 75% in adnexitis (4 cases) and 100% in suppurative haematoma vulva (1 case), respectively.
Overall efficacy was 87.5% (14/16).
3. Clinical efficacy classified by caused organisms was 83.3% (10/12) overall, and bacteriological effect was 91.7% (11/12).
4. Neither side effects nor abnormalities in laboratory findings caused by this drug were observed.
5. Based on these results, CXD should be considered a very safe and useful drug for treating obstetrical and gynecological infections.

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To evaluate the efficacy, safety, and utility of cefroxadine (CXD) for the treatment of complicated urinary tract infections, a double blind study comparing CXD with cephalexin (CEX) was carried out.Patient received either 1,500mg/day of CXD 3 times a day, or 2,000mg/day of CEX 4 times a day for 5 days by oral route, and the following results were obtained.
1. Of the 305 patients, clinical efficacies were evaluated in.220 cases (CXD 105 cases, CEX 115 cases) except that excluded or dropped out.Side effect was evaluated in 301 cases (CXD 150 cases, CEX 151 cases). There was no statistically significant difference in the back ground characteristics between the 2 groups.
2. Overall clinical assessment by the committee according to the “Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on Urinary Tract Infection” patients evaluated as better than “good” were 64 of 105 (61.0%) for CXD and 75 of 115 (65.2%) for CEX.The difference between the 2 groups was not statistically significant.In effect on pyuria, patients evaluated as better than “decreased” were 58 of 105 (55.2%) for CXD and 69 of 115 (60.0%) for CEX.The difference between the 2 groups was not statistically significant. In effect of bacteriuria, patients evaluated as better than “decreased” were 57 of 105 (54.3%) for CXD and 69 of 115 (60.0%) for CEX.The difference between the 2 groups was not statistically significant.Analyses were stratified according to classification by the type of infection, diagnosis, degree of pyuria before treatment, and bacterial count before treatment.There were no statistically significant differences between the 2 treatment groups as to any item.
3.In evaluation by attending physician, patients evaluated as better than “good” were 81 of 140 (57.9%) for CXD, and 85 of 141 (60.3%) for CEX.Statistically significant difference was not observed between the 2 groups.In drug usefulness by attending physician, patients evaluated as better than “usefulness” were 106 of 140 (75.7%) for CXD, and 109 of 141 (77.3%) for CEX.The difference between the 2 groups was not statistically significant.
4. In evaluation of the infections with sensitive species to both CXD and CEX by the committee according to Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on Urinary Tract Infections, overall clinical efficacies were evaluated in 102 (CXD 48 cases, CEX 54 cases) which were infected with sensitive species. There was no statistically significant difference in the back ground characteristics between the 2 treatment groups. In overall clinical efficacy by the committee, patients evaluated as better than “good” were 43 of 48 (89.6%) for CXD and 45 of 54 (83.3%) for CEX.The difference between the 2 groups was not statistically significant. In effect pyuria, patients evaluated as better than “decreased” were 36 of 48 (75.0%) for CXD and 43 of 54 (79.6%) for CEX.In effect on bacteriuria, patients evaluated as better than “decreased” were 38 of 48 (79.2%) for CXD and 40 of 54 (74.1%) for CEX.The difference between the 2 groups was not statistically significant as to any item.
5. Side effect was observed 1 case in the CEX group but none in the CXD group.No significant difference was observed between the 2 groups.No severe change in laboratory findings was observed.
In conclusion, CXD 1,500mg/day was considered to be as effective as CEX 2,000mg/day against complicated urinary tract infections (patients without indwelling catheter) and to be useful judging from evaluation on safety.

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A double-blind controlled trial of cefroxadine (CXD) 250 mg t.i.d.was undertaken to objectively evaluate its safety and effectiveness in the treatment of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media, using cephalexin (CEX) 250 mg q.i.d.as a control drug, and the following results were obtained.
1. In the treatment of acute suppurative otitis media, the 2 drugs produced almost equal outcomes, showing no significant difference in assessments of both overall effects and usefulness.
2. In the treatment of acute exacerbation of chronic suppurative otitis media, the 2 drugs exhibited no significant difference as well in overall effects by WiLcoxoN's two-sample test. However, the CEX group had significantly more nonresponsive patients, i.e.35.5% as compared with 9.7% of the CXD group (X2-test, P<0.05).In the assessment of clinical usefulness as well, no significant difference was observed between the 2 groups.
3. In the assessment of overall effects based on the patients whose isolated organisms were sensitive to the drugs, CEX group had more patients not responding to the treatment of acute exacerbation of chronic suppurative otitis media (x²-test, P<0.05).
4. Bacteriological effects were not significantly different between the 2 drugs in both acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media.
5. Overall safety rating was not significantly different between the 2 drugs.Side effects occurred as the symptoms of digestive organ in 2 patients each in both groups (equally an incidence of 2.6%).
6. As for the improvement of each symptom after treatment (assessed on day 3), CXD was superior in the improvement rate of otorrhea volume as the main symptom of acute exacerbation of chronic suppurative otitis media, while CEX was superior in that of otoobstruction feeling.
From the above findings, it is presumed that CXD is a safe drug which can exhibit equal or superior therapeutic effects to CEX in the treatment of acute suppurative otitis media and acute exacerbation ofchronic suppurative otitis media, at 3/4 of the CEX dose level.

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[in Japanese]

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