We evrluated clinical effects and toxicities of a combination treatment with cefminox (CMNX) and fosfomycin (FOM) for infections complicated with hematological disorders in 56 patients. Among those, 52 patients including 22 with malignant lymphoma, 19 with acute leukemia, and 11 with other hematological disorders were evaluable.
Excellent and good responses were obtained in 33 (63.5%) of the 52 patients. This treatment was also effective in 5 of 9 cases in which granulocyte counts were less than 500/mm3 through the course of administration.
Side effects were observed in only one patient. Mild nausea occurred but was not serious.
These results indicate that the combination of CMNX and FOM is an effective and safe regimen for the treatment of infections complicated in patients with hematological disorders.

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Results of the treatment of 5 cases of males with uncomplicated gonoccocal urethritis using levofloxacin (LVFX, DR-3355), the L-type optical isomer of ofloxacin (OFLX), were compared with those treated with OFLX itself. Three hundred mg/day of LVFX or 600mg/day of OFLX was given to each patient for 5 days. Both drugs showed excellent clinical results in all the patients. When MICs of the 2 drugs were compared against 57 isolated strains of Neisseria gonorrhoeae including 3 penicillinase-producing N. gonorrhoeae, it was found that MICs of LVFX were approximately one half of those of OFLX.

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MICs of 14 aminoglycoside antibiotics including 10 of those used clinically were determined against 50 strains of methicillin-resistant Staphylococcus aureus (MRSA) which had been isolated at a hospital in Osaka between 1986 and 1990. Arbekacin (ABK) inhibited the growth of all strains at≤0.20-6.25μg/ml, showing the most potent activities. Streptomycin showed good activities (1.56-6.25μg/ml) against all strains except one resistant strain (>100μg/ml). Based on susceptibilities to kanamycin (98% resistant), tobramycin (84%), gentamicin (62%), amikacin (36%) and ABK (0%), MRSA strains were classified into 5 types; type 0 producing no aminoglycosidemodifying enzyme, type 1a producing APH (3), type 1b producing AAD (4, 4), type 2a producing APH (2) /AAC (6) and APH (3), and type 2b producing APH (2) /AAC (6) and AAD (4, 4).
In addition to the aminoglycoside antibiotics, 13 known antibiotics including vancomycin (VCM) were found active against MRSA upon random screening. Taitomycin (0.013-0.050μg/ml) was the most potent, and griseoluteins A and B (each 0.10-0.39μg/ml), and macarbomycin (0.05-0.20μg/ml) were more active than VCM (0.39-1.56μg/ml). Novobiocin (≤0.20-0.78μg/ml) also showed good activities.

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Forty-three newborn and young infants including 13 low-birth-weight (LBW) infants were treated with flomoxef (FMOX) and the clinical efficacy and side effect were evaluated. The ages of the patients ranged from 0 to 99 days, and their body weights from 797 to 9,000 g. Dose levels were 10.5 to 48.5 mg/kg every 6 to 8 hours for 3 to 12 days. Those patients who responded to the FMOX treatment included 8 infans with sepsis, 14 with suspected sepsis, 6 with intrauterine infection, 2 with meningitis, 7 with pneumonia, 1 with staphylococcal scalded skin syndrome, 1 with epididymitis and 4 with urinary tract infections. The results were excellent in 17 and good in 22 patients. The drug was well tolerated, although diarrhea occurred in 2, slightly elevated serum concentrations of transaminases in 2, and eosinophilia and thrombocytosis in 1 patient each.
Pharmacokinetic studies on FMOX with 20 mg/kg dose were done in 19 patients including 8 LBW infants. Serum concentrations at 15 minutes after intravenous bolus injection in five 1-to 6-day-old LBW, five 1, to 6-day-old and four 8-to 19-day-old mature infants were 52.6, 52.7 and 58.0μg/ml, respectively, and those at 4 hours were 22.1, 13.3 and 5.2μg/ml, respectively. Serum half-lives of the drug were 3.93, 2.29 and 1.62 hours, respectively, and excretion rates of this drug into unne m the first 6 hours after administration were 30.4, 45.1 and 58.7%, respectively.
Mean serum concentrations just after intravenous 1-hour drip infusion in three 8-to 54-day-old LBW and two 8-and 10-day-old mature infants, were 31.5 and 18.9μg/ml, respectively, and those at 4 hours were 15.3 and 4.3μg/ml, respectively. Serum half-lives of the drug were 2.88 and 1.75 hours, respectively, and excretion rates of the drug into urine in the first 6 hours were 22.6 and 47.5%, respectively.
The cerebrospinal fiuid level at 3 hours after a dose was 7.09μg/ml on the second day of treatment in a patient with Staphylococcus aureus meningitis receiving 50 mg/kg of the drug every 6 hours per day. Its level at l hour after a dose was 3.52μg/ml on the 8th day of treatment in the same patlent.
The influence of FMOX on the fecal flora was studied in 7 patients. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium, the decrease or disappearance of Enterobacteriaceae and the preservation of Streptococcus. Antibiotic concentrations ranged from 41.6 to 238.4 (160.6±82.2) μg/g of wet feces in 5 patients. On the 2nd to 10th day after cessation of the drug administration, considerable numbers of Bifidobacteriumn and Entrobacteriaceae appeared in 4 patients tested.

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Clinical pharmacology and emcacy of flomoxef (FMOX) in neonates were investigated. And the following results were obtained.
1.Mean serum concentrations of FMOX at 30 minutes after administration were 24.3μg/ml, 47.6μg/ml, and 85.8μg/ml at doses of 10mg/kg, 20mg/kg, and 40mg/kg administered, respectiveiy.
2.Mean serum half-lives of FMOX were 3.4hours in 0-3 day-old neonates, and 2.6hours in 4 day-old or older subjects.
3.A dose response was evident among differentd ose groups given 10mg/kg, 20mg/kg, and 40mg/kg.
4.Urinary recovery rates of FMOX in the first 6 hours after administration ranged between 12.8 and 51.1%.
5.FMOX was effective in 7 out of 8 cases in which causative pathogens were identified.
6.Diarrhea was observed in 1 case as a side effect of the drug, but the symptom was relieved soon after the completion of the treatment. There was no case in which any abnormal laboratory results were observed.
7.FMOX has a broad spectrum of activities against Gram-positive and Gram-negative aerobes and anaerobJs. It is stable against most of β-lactamases. It was demonstrated to be highly effective in our study, and yet without any serious side efFects. FMOX is therefore considered to be one of the useful agents of the first choice for the treatment of bacterial infections such as sepsis and urinary tract infections in neonates and infants.

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Studiesw ere made on pharmacokinetics, c linicale ffectas nd influenceo n intestinabla cterialf lora in neonates upon administration of flomoxef (FMOX), and the results obtained are summarized as follows:
1.Serum concentrations of FMOX after intravenous administration of 20mg/kg/dose were 48.5μg/ml in 30 minutes, 33.0μg/ml in 1 hour and 7.3μg/ml in 6 hours. The T 1/2 was 2.7 hours. FMOX at adose of 40mg/kg was given to only one new born baby on the lst day after birth, and serum concentrations were 73.6μg/ml in 30 minutes, 55.9μg/ml in 1 hour and 16.9μg/ml in 6 hours. The T 1/2 was 4.60 hours.
2.FMOX was administered to 21 neonates between 0 and 32 days of age.
Clinical effects were evaluable in 8 of 21 cases. The results were excellent in 2 cases, good in 5 cases and poor in 1 case.
Of the 21 cases, diarrhea in 1 case, elevation of eosinophile in 2 cases (9.5%), elevation of plateletc ount in 3 cases (14.3%), and elevationo f GOT in 2 cases (9.5%) were recognized during treatment.
3.FMOX was detected in feces at levels of 0.84-44.4μg/g. Except for a slight decrease in numbers of anaerobes, little fluctuations of intestinal flora were observed during treatment.

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Studies on pharmacokinitics and clinicale ffectso f flomoxef (FMOX), a parenteral oxacephem antibioticw, e re carried out in nionates.
The resultso btained are summarized as follows.
1.Mean peak serum concentrations of FMOX upon single administrations at doses of 20 mg/kg and 40 mg/kg were 33.3±7.33μg/ml and 68.9μg/ml, respictivily.
2.Mean uinary recovery rates of FMOX in the first 6 hours after administration of the above dosis were 35.2%and 48.3%, respectively.
3.FMOX was admnistered to 4 cases including 1 prophylactic casi, 1 case each with aspiration pneumonia and sipsis, hypodermic abscess of the head, and itrauterine infection, at a dose of 20-30mg/kg 2 or 3 timis a day.
Clinically, excellent results were obtained in 3 cases including an methicillin-resistant Staphylococcus aureus case.
4.No side effects nor abnormal laboratory test results were observed.

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To evaluate pharmacokinetics and clinical effcacy of flomoxef (6315-S, FMOX) in neonates, FMOX was administered to 21 neonates.
With 20 mg/kg and 40 mg/kg of intravenous drip-infusion of FMOX 60 minutes, half lives (T1/2's) were 64.9 minutes and 130.3 minutes, respectively, and when 20 mg/kg of FMOX was infused intravenously to 2 cases, half lives were 70.8minutes and 110.1minutes, respectively.
When 45-100 mg/kg of FMOX was administered to 17 neonates with infections (pneumonia 8, sepsis 1, sepsis suspected 2, intrauterine infection 2, urinary tract infection 2, omphalitis 2), the efficacy rate was 88.2% (15 of 17). No adverse reactions were observed clinically in the 21 neollates. Transient elevation of eosinophilia was observed in 1 case and transient elevation of S-GOT and S-GPT 1 in another.
These results suggest that FMOX is an effective and safe antibiotic to use in neonates.

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Flomoxef sodium (FMOX) was evalurted experimentallya nd clinicalliyn neonates.
1. Serum concentrations and urinary excretions of the drug were examined after a bolus intravenous injection at 20mg/kg to 22 neonrtes 1-30 days after birth (durations of pregnancy 31-43 weeks, weights at birth 1,650-4,040g) and 5 infants 50-95 days after birth (duralions of pregnrncy 33-40 weeks, weights at birth 1,720-3,308g).
Serum concentrrtions were 10.8-67.6μg/ml (mean 32.7±2.8μg/ml) and 25.1-52.0μg/ml (mean 38.9±4.3μg/ml) in the neonates and the iffrnts, respectively, at their peaks (0.5 hour value), decreased thereafter with half-lives of 0.96-5.59 hours (mean 2.20±0.26 hours value), and 0.97-1.54 hours (mean 1.22±0.12 hours value), respectively. Serum levels decreased to 0.2-17.1μg/ml (mern 2.9±0.6μg/ml) and N.D.-1.1μg/ml (mean 0.4±0.2μg/ml) after 8 hours, respectively.
The urinary recoyery rates of the drug in the first 8 hours after adminislralion were 15.0-96.0% (mean 53.7±4.9%) and 29.9-73.3% (mean 62.4±9.4%) in the neonates and in the infants, respectively.
2. FMOX was administered to 78 neonates (duralions of pregnancy 31-42 weeks, weights at birth 1,420-3,860g) in whom bacterial infcliofs were estrblished or suspected, and clinical, bacteriological, and side efcts were evrluated.
In 47 neonates examined (1 with sepsis, 3 with acute upper respiratory infections, 18 with acute pneumonir, 1 with umbilical infction, 1 with impetigo, 4 with acute urifary tract infclions, 1 with acute otitis extema, 1 with periproctal abscess, and 17 with intrruterine infclions), the trealment was markedly efctive in 41, and eflive in 6, with an overall efficacy rate of 100%. The bacterilogicrl effects of the drug on 3 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 1 strain of Streotococcus agalactiae, 9 strains of Escherichia coli, and 2 strains of Haemophilus influenzae which were responsible for these infctiofs were all rated as “eradicated”. Moreover, the drug, administered with or without prophylactic intentions showed complete prophylactic effects in all 27 crses tesled.
No side effects were observed in any of the patients.
Conceming abnoral clinical laborrtory results, increrses in GOT were noted in 2, eosinophilia in 1, and thrombocytosis in 1, but these abnormalities were invrriably mild and the noralized in 1 patient without treatment.
The resulls suggest that FMOX is useful and safe also in neonrtes.

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Serum concentraeions, urinary excretion and clinical responset of flomoxef (FMOX) were seudied. The results are summarized as follows.
1.Serum concentrations of FMOX were 17.4μg/ml 1-hour after intravenous injection on the average in 5 cases who received approximately 10mg/kg, 41.8μg/ml in 2 cates given 20mg/kg, and 69.6μg/ml in 2 cases given 40mg/kg, indicating that serum concentrations of FMOX changed in a dose-dependent manner in thit range.
Average serum half-1ife (T1/2) in 4 mature babies was 2.48 hours and that in 6 premature babies wat 3.17 hourt, indicating that elimination rates in premature cases tend to be slower than those in mature cates.
Urinary recovery rates averaged 39.2% in the first 6 hours in 5 cases examined.
2.Five newborns or premature babies received FMOX 33.1-80.2mg/kg (b. i. d. or t. i. d.) viaintravenous route fbr 5 to 8 days.
FMOX showed excellent or good clinical effectiveness in the treatment of all patients including 1 case each of sepsis with urinary infection, furunclal otitis, impetigo, uterogenic fetus infection and urinary infection.
Bacteriological responses were also studied, and eradication of identified organisms (Escherichia coli 3 strains and Staphylococcus aureus 2 strains) was obtained upon the FMOX treatment, but in 1 strain of S. aureus showed only a decrease.
No adverse reactions were observed in any cases, but a slight elevation of eosinophil was noted in 1 patient receiving a dose of 210mg a day.
From the results obtained in these tests, FMOX appears to be very usefull and safe fbr the treatment of some infectious diseases in neonates.

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Phamacokinetic and clinical studies of nomoxef (FMOX) in neonates and premature infants were conducted, and the results obtained are summarized below.
1.Plasma concentrations of FMOX at 15 minutes after one shot intravenous injection of 20 mg/kg to 6 cases were in a rang of 33.0-69.9μg/ml and half-1ives (T 1/2's) were between 0.68 and 4.89 hours.
The plasma concentration of FMOX at 15 minutes after one shot intravenous inlection of 40 mg/kg to 1 case was 79.9μg/ml and the half-life (T 1/2) was 2.45 hours.
Drug concentrations in plasma upon 1-hour intravenous drip infusion were 71.1-114.0μg/ml and T 1/2's were 1.64-3.41 hours.
T 1/2 tended to be couse shorter as ages of babies increased.
2.Urinary excretion rates in the first 6 hours after one shot intravenous inlection of FMOX 20 mg/kg to l case and 1-hour intravenous drip infusion of FMOX 40mg/kg to 2 cases were 60.4%, and 27.2 and 55.3%, respectively.
3.Clinical effects of FMOX against 12 cases of bacterial infections were excellent in 6 cases, good in 5 cases and poor in 1 case, thus the clinical emcacy rate was 91.7%.
FMOX was also given to 6 cases fbr prophylaxis and prophylactic effects were observed in all the cases.
4.No adverse effects were observed in the 21 cases examined, but elevations of S-GOT and S-GPT were fbund in 1 case. The abnormal laboratory test results were probably due to this drug.

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Flomoxef (FMOX), a new broad spectrum oxacephem antibioticw, a s studied in the neonatal fielda nd the pharmacokinetic resultso btained are summarized below.
1.Serum aoncentrations of FMOX after dosages of 20mg/kg via 1 hour drip infusion were 21.8±7.59μg/ml, 15.4±4.35μg/ml, 4.3±2.88μg/ml at 1, 2 and 5 hours after admini Stration, respeatively, and T 2/1 (β) averaged 2.08±1.01hours.
2.Urinary excretion rates were 53.38±16.94% in the first 7 hours after administration.

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Basic and clinicaslt udieso f flomoxef (6315-S, FMOX) were performed in the pediatrics urgical field. The results obtained are summarized as follows:
1.FMOX was administered to 7 pediatric patients with biliary atresia (FMOX 20mg/kg, i.v.d.). Peak biliaryl evels of FMOX were obtained at 1 hour after finishinag dministrationb y drip infusion, a nd were higher than those in blood 1 hours afterf inishinga dministrationb y drip infusion.
2. Urinary excretion was excellent, and urinary recovery rates were 57.8-97.8%.
3. FMOX was administeredt o 5 patientsi n the pediatrics urgicalf ield. One case was phlegmon, and other 4 cases were premature babiesf or postoperativper ophylactiucs e. Clinical resultwse re excellenitn 1 case, g ood in 4 cases, w ith an overalel fficacrya teo f 100%. No clinical and laboratorsy idee ffectdsu e to the administration FMOX were observed.
It was concluded that FMOX was a safe and effective antibiotic in the pediatric surgical field.

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