A dry syrup containing, per1g, 200mg(potency)of midecamycin acotate(MOM), a newly-doveloped demivative of midccamycin, was administered to 9 children rarging in age from 1 year and 2 months to 10 years and 9 months.The mean daily dosage administered to these subjects was 21.4mg/kg, Which was divided into 3 equal doses and given after the 3 moals in the day. The mean dumation of this drug administration was 12 days. The effect of this drug treatment on the bacterial flora of the irtostinal tmct was investigated.
In addition to this study, a second irvestigation was carried out;An MOM dry syrup containing 100 mg(potency)/1g(200mg(potecy)/g in the case of the 9 subjects studied for changes in the intestinal bacterial count)was administered to 162 pationts diagnosed as having mycoplasmal pneumonia. These patients ranged in age from 10 months to 16 ycars and 7 months.They had been outpatients, but were hospitalized in the authors department or in asgociatod hospitals during the 1-year-and-5-months period from June 1980 through October 1981.For comparison,an erythromycin dry syrup (other than EM estolate)was administered to 54 patients showing a similar age range and also diagnosed as having mycoPlasmal pneumonia.
These 2 drug treatment groups were then compared in terms of the clinical efficacy,the bacteriological efficacy,the usefulness and the occurrence of side effects.THe results were described as following. Of the 162 mycoplasmal pneumonia patients who were treated with MOM,it was possible to evaluate the clinical efficacy in 100 patients.The mean daily dosage in those patients was 21.8 mg/kg.The drug was divided into 3 equal doses and administred after meals in 90 of the patients, while the 3 doses were switched to 4 in 1 patient,and 9 patients were given the MOM dry syrup in 4 epual doses.The overwhelming majority of these patients thus took the drug in 3 daily doses.The mean duration of the MOM treatment was 12 days.Similarly,of the 54 mycoplasmal pneumonia patients treated with EM,it was possible to evaluate the clinical emcacy in 36.The mean daily dosage was 46.4mg/kg,and this was administered in 3 daily doses to 5 patients and in 4 daily doses to 31 patients.The mean duration of this EM dry syrup therapy was 12 days.
1.In order to determine the effect of the MOM dry syrup on the bacterial flora of the intestinal tract,samples were collected and studies were performed at 4 different times;prior to the start of the drug administration,on days 3-4 and 5-7 during the administration period,and on days 4-6 following the completion of the administration program.It was found that there was no effect on E.coli,which is representative of the Gram-negative bacilli.In 1 subject,K.oxytoca was isolated at 1.2×107cells/g on the 3rd day after the start of the MOM administrations,but the subject showed no symptoms of diarrhea and this bacterium could no longer be detected on day 5 of the administrations.Citrobacter sp.were compared before and after the MOM dosing Period:Most of the subjects yielded these microbes on days 3-4 and 5-7 during the administration period and days 4-6 after completing the dosings. The mean bacterial counts of these species at the 4 times of detection were 1.7×10⁹cells/g, 1.6×10¹⁰ cells/g5.6×10⁶cells/g and 2.4×10⁸cells/g,which shows that these bacteria increased.However,if we consider the enterobacteriaceae overall,there was no fixed pattrn at the 4 times of sampling.Within the Gram-positive cocci,Staphylococcus sp.showed findings similar to those for enterobacteriaceae.A comparison of the population of Streptocoms sp.before and after the MOM administrations showed that the count of these bacteria increased at each successive sampling time;however,the counts were still within the normal range of values for these species.

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After the fosfomycin(FOM) infusion, its levels in serum and cerebrospinal fluid (CSF) were repeatedly measured in 8 cases without meningitis.
1.The peak concentration of FOM in CSF was 15.5μg/ml with the average of 10.3μg/ml and was reached at 240 minutes with the average of 210 minutes after the infusion. The biological half life time of FOM in CSF was 2 to 6.5 hours.
2.The peak concentration in CSF was compared with it in serum. The average ratio was 4.3 per cent.Fitch area under the curve (AUC) of FOM concentration in CSF and serum was calculated and average of their ratio was 9.0 per cent.
3.In a case with middle cerebral artery aneurysm, FOM transferred into CSF with ease. The lowest diffusion into the CSF was shown in 2 cases of meningioma.In 3 cases of hypertensive intracerebral hemorrhage with intraventricular perforation, FOM moderately transfered into CSF.

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The authors have carried out the laboratory and clinical studies of cefmenoxime (CMX) andobtained the following results.
The antibacterial activities of CMX were measured by the plate dilution method against 27 strains of S. aureus, E. coli, K. pneumoniae, S. marcescens and P. aeruginosa respectively, and 14 of Proteus sp.
CMX inhibited the growth of all strains of S. aureus at concentrations less than 3.13μg/ml, and the peak of sensitivity distribution was obtained at 0.78μg/ml.
The peaks of sensitivity distribution of E. coli and K. pneumoniae were obtained at 0.1μg/ml or less than 0.1μg/ml respectively, and the growth of 85.2% of E. call was inhibited at concentration of less than 0.1 μg/ml.
The peak of sensitivity distribution of P. aeruginosa was obtained at 12.5 μg/ml. The growths of 70.4% of S. marcescens and 92.9% of Proteus were inhibited at concentration of less than 0.39 μg/ml and 0.2 μg/ml respectively.
CMX was given intravenously for 1 hour drip infusion and one shot infusion, at a single dose of 20 mg/kg.
The serum mean concentrations of CMX by one shot infusion were 26.7±11.1 μg/ml, 0.4±0.1 μg/ml at 15 minutes and 4 hours after injection respectively.
And the serum concentration at 6 hours after injection was 0.1μg/ml. Half-life time was 0.7 hours.
The serum mean concentration of CMX by drip infusion were 24.2±5.3 μg/ml at 30 minutes, 0.7±0.3 μg/ml at 4 hours after infusion. The serum mean concentration at 6 hours after infusion was less than 0.1 μg/ml. Half-life time was 0.6 hours.
Urinary excretion rate of CMX by 1 hour drip infusion was 45.9% up to 6 hours after administration.
CMX were given to 2 cases with tonsillitis, 1 case with bronchitis, 2 cases with pneumonia, 4 cases with UTI and 1 case with maxillary sinusitis, and 1 case with osteomyelitis and lung abscess, respectively.
A daily dose of 32-103.4 mg/kg of CMX was given tor 3-8 days.
Clinical results were obtained excellent and good resppns in all cases.
No side effects were observed except for 3 cases with elevation of transaminase.

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Clinical studies in the field of pediatrics have been carried out with cefrnenoxime (CMX), a new cephalosporin antibiotic and the following results were obtained.
1.CMX was administered intravenously by drip in1fusion in 23 patients with infectious diseases. These diseases consist of 10 pneumonia, 1 bronchitis, 6 upper respiratory tract infections, 2 acute pyelitis, 3 other urinary tract infections and 1 DOUGLAS abscess. CMX was effective in all cases except 1 case of pneumonia with pyothorax.
2.No sidey effects have been observed in all cases.As for abnormal laboratory findings, 2 eases of eosinophilia, slight elevations of GOT in 3 cases and GPT in 2 cases were seen.

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Some fundamental and clinical evaluations of cefmenoxime (CMX) were made. and the following results were obtained.
1.Peaks of MIC distribution of this preparation with inoculation of 106/ml were 0.78 μg/ml for 14 strains of S.aureus and from 0.1to 0.2μg/ml for 42 strains of E.coli. The MIC distributions were almost the same with E.coli for Klebsiella, Salmonella and P.mirabilis, and less than 0.78 μg/ml for many strains ofindole-positive Proteus, Enterobagter, Citrobacter and S.marcescens. Peaks of 8 strains among 10 strains of P.aeruginosa, concentrate in a range of from 12.5 to 25μg/ml.And CMX rwas far superior to-cefitzolin for Gram-negative bacilli.
2.As for the passage of CMX in cerebrospinal fluid in meningitis rabbits, the CSF/serum ratio of AUC in meningitis caused by S.aureus Was 7.78% up to 2 hours and was not very satisfactory, but in csetlous meningitis caused by E, coli, the ratio was 31.8% and a very high passage efficiency was observed.
3.Blood concentrations after intravenous injection of about 20mg/kg of emx in 4 children were 18 to 39μg/mi, 4.5 to 11.8μg/ml, 1.56 to 4.3μg/ml, and 0.31 to 0.64μgiml in th order of after 1/2, 1, 2 and 4 hours, respectively. And the half lives were from 35.3 to 44.7 minutes.In urine of 1 of the children, 55.5% was recovered up to 6 hours.
4.This preparation was administered, in 19 cases. The diseases treated were tonsillitis, gingivitis, and pyothorax 1 case each, bronchitis, Cervical purulent lymphadenitis and pyelonephritis 2 cases each, pneumonia 7 cases and suspected sepsis 3 cases. Detected organisms were S.aureus 3 cases, S.pyogenes 1 case, S.pneumoniae 2 cases, H. influenzae 3 cases, H.parainfluenzae 1 case, E.coli 1 case, M.morganii 2 cases, and unknown ones 6 cases.The daily doses were.from 47.9 to 117.6mg/kg, and the frequencies of medication were 3 times in 18 cases and 4 times in 1 case.The methods of administration were intravenous injection: in 14 cases and 1 hour drip infusion in 5 cases.Among 19 cases, the effects were excellent in 8 cases, good in 8 cases, and poor in 3 cases;the overall efficacy rate was 84.2%.The. poor cases were pneumonia due to E.coli of a child with DOWN syndrotne, pyothorax due to S.pneumoniae, and suspected sepsis in a patient of acute rnyelogenous leukemia 1 case each.
5.As for side effects, diarrhea was observed in 1 case. And abnormal laboratory findings were an increase in the number of eosinophil, a rise in GOT, and a rise in BUN 1 case each.The side effect and the laboratory findings were all light and transient.
6.On, the basis of these results, it was concluded that the preparation is a potent new, antibiotic in the field of pediatrics.The recommended dose will be 10 to 20 mg/kg given 3 or 4 times daily by intravenous injection or intravenous drip infusion.

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Laboratory and clinical studies were performed on cefmenoxime (CMX), a new cephalosporin antibiotic, and the following results were obtained.
1.Susceptibility of clinically isolated bacteria to CMX and cefotiam (CTM) or cefazolin (CEZ)
Antimicrobial activity of CMX was compared with that of CTM and CEZ against S.aureus, S.epidermidis, S.pneumoniae, H.influenzae and E.coli.
CEZ and CTM were more active than CMX against S.aureus, S.epidermidis and S.pneumoniae. But CMX was found to be more active by 1-10 tubes than CEZ and CTM against H.influenzae and E.coli.
2.Clinical efficacy
CMX was intravenously administered to 19 patients: 3 with lacunar tonsillitis, 2 with acute bronchitis, 8 with bronchopneumonia, 3 with UTI, 1 with septicemia, 1 with acute panperitonitis, 1 with S.S.S.S.at daily doses of 30-115 mg/kg (64.6mg/kg on an average) t.i.d.or q.i.d.for 3-17 days (6.1days on an average).The overall efficacy rate was 94.7%, i.e., efficacy was excellent in 10 cases (52.6%), good in 8 cases (42.1%), and poor in 1 case (5.3%).Bacteriological efficacy was good, i.e.16 of the 19 strains disapeared.
Transient eosinophilia was observed in 1 patient, but no other laboratory abnormality was observed during treatment.
The above results suggest that CMX is 1 of the useful antibiotics in treatment of pediatric infections, especially due to Gram negative bacteria.

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The therapeutic effects of cefmenoxime (CMX), a new synthetic cephalosporin antibiotic, were examined in the treatment of various pediatric infections.
Patients treated were infants and children ranging from one-month-old to 13-years-old suffering from pharyngitis in 2 cases, bronchopneumonia in 3 cases, cervical lymphadenitis in 2 cases, urinary tract infections in 7 cases, tympanitis in 2 cases, suppurative meningitis, sepsis, subcutaneous apostem, acute enteritis, chest wall apostem, phlegmon, staphylococcal scalded skin syndrome in 1 case each, a total of 23 cases.
As regards method of administration, CMX from a vial was dissolved in physiological saline or distilled water for injection, and the solution was administerd by 3 to 5 minutes one shot intravenous injection (14 cases), or CMX was diluted with large volume parenteral product and administered by 30 to 60 minutes drip infusion (9 cases).
The dosage of the drug was 30 to 200 mg/kg/day;103 mg/kg/day and under in 21 cases, 150 mg/kg/ day and 200 mg/kg/day in I case each.The administration was continued for 3 to 27 days.
As regards clinical efficacy, “good” or “excellent” results were obtained in all the cases except 2 cases, one was a-Streptococcus acute tympanitis supervening neuroblastoma, and the other was Pseudomonas urinary tract infection.The efficacy rate was 91.3% with excellent in 11 cases, good in 10 cases.
As regards bacteriological effects, of 13 strains of Gram-positive bacteria, 10 strains were eliminated and 3 strains were not changed, while of 10 strains of Gram-negative bacteria, 8 strains were eliminated and 2 strains were reduced; thus CMX showed better results against Gram-negative bacteria rather than against Gram-positive ones.
The antimicrobial activity of CMX against Gram-positive bacteria was inferior to those of CTM and CEZ, but CMX showed the highest antimicrobial activity against Gram-negative bacteria.
No clinical side effects nor abnormal laboratory findings obviously attributable to CMX were observed.

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Cefmenoxime (CMX) was intravenously administered to 20 children with the following bacterial infection;pneumonia in 14 cases, purulent meningitis in 2 cases, pyothorax in 2 cases, urinary tract infection in 1 case and brain abscess in 1 case.
The daily dosage administered in meningitis, pyothorax and brain abscess ranged from 145-311mg/kg/day, from 43-88 mg/kg/day in other bacterial infections.
The therapeutic efficacy was excellent in 15, good in 3, poor in 2 patients, efficacy rate being 90%.
Causative organisms were H. influenzae in 4 cases, S. aureus in 2 cases, Streptococcus sanguis in 1 case, E. coli in 1 case and unknown in 12 cases. All were eliminated with the exception of 2 strains of S. aureus after the administration of CMX.
As for side effect, transient eosinophilia was only observed in 1 ease.

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Cefmenoxime (CMX) was administered to 10 pediatric patients; by one shot intravenous injection at the dose of 10, 20 and 40 mg/kg in 3, 3 and 4 cases, respectively. CMX concentration in plasma was measured in all of the 10 cases, its concentration in urine and its urinary recovery in each group of 3 cases, and metabolites in plasma and urine in 3 cases with 40 mg/kg administration. CMX was also administered to 4 patients by one shot intravenous injection at the dose of 46.9 to 70.6mg/kg; 3 cases of bacterial meningitis, and 1 case of ventriculitis. CMX concentration was measured in plasma, cerebrospinal fluid and ventricular fluid. Further, this preparation was administered to 32 patients suffering various bacteriosis, by one shot intravenous injection 3 to 6 times daily, mostly 4times, at an average dose of 110.5mg/kg/day for an average period of 7days. CMX's clinical effects, bacteriological effects were examined in 32 cases and side effects in these cases as well as the dropped 23 cases; 55 cases in total. The results were as follows.
1. In each group of 3 cases given 10 or 20 mg/kg by one shot intravenous injection, CMX concentration in plasma reached the highest value 15 minutes after injection; the mean highest values of the groups were 21.6 and 52.1mcg/ml, and the mean half lives 0.68 and 0.83 hour, respectively.
2. For the 4 cases of 40 mg/kg by one shot intravenous injection, differing from the cases of 10 and 20mg/kg administration, CMX concentration in plasma was measured 5minutes after injection, when the concentration showed the peak value; the mean value was 262.0mcg/ml. After 15minutes, the mean value was 160.3mcg/ml. A clear relationship of dose response was observed for the groups with the varied doses, and the mean half life was 0.90 hour.
3. Urinary concentration showed the peak after 0 to 2hours for each dose group; the mean values were 803, 1,423 and 3,240 mcg/ml, for 10, 20 and 40mg/kg dose groups, respectively. Urinary recovery rates up to 6 hours were 39.9, 47.2 and 51.8%, respectively.
4. As the urinary recovery rates measured were low in corhparison with those of adult patients, for the 3 cases with 40mg/kg dose; metabolites in plasma and urine were measured, but no metabolites were detected.
5. CMX's transfer in cerebrospinal fluid, and ventricular fluid of the patients of bacterial meningitis or ventriculitis was satisfactory; the highest cerebrospinal fluid-plasma ratios of the cases were 40.5, 9.3 and 9.1%. However, concentration levels tended to drop towards convalescence.
6. The clinical efficacy rate for 32 cases of various microbism was 87.5%, and as to bacteriological effects, of 8 cases, causative organisms were eradicated in 6 cases, reduced in 1case, and unchanged in 1 case.
7. As to side effects in 55 cases including the dropped cases, there was 1 case of rash (1.8%). No abnormal findings were made in hematometry and urinalysis. When CMX's effects on liver and kidney were examined in terms of 6 items, abnormal rises in GOT, GOT and GPT, and LDH were observed in 2, 1 and 2 cases, respectively. Variations in Al-P, BUN and creatinine were within the normal ranges.

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A subacute (5-week) subcutaneous toxicity study of cefsulodin (CFS) was carried out using 9 3-week old juvenile Beagle dogs. The dogs were distributed to 3 groups, each of which was constituted of 3 animals. Dogs in group I, II and III were given physiological saline (control), 300 mg/kg of cefazolin (CEZ, control drug) and 300 mg/kg of CFS, respectively.
All animals used survived for 35 days of administration period. The changes, considered to be drug-related were histopathological changes at the sites of injection, which consisted inflammatory cellular infiltration and hyperplasia of fibroblast in subcutaneous tissue of skin. In terms of severity, CFS was less irritating than CEZ.
CFS-related changes were not observed in other tests.

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Clinical studies on cefsulodin (CFS) in 6 patients with Pseudomonas aeruginosa infection were carried out and the results as follows.
1. Among 4 patients administered CFS intravenously, 3 patients (urinary tract infection 1, acute purulent otitis media 1, aspiration pneumonia 1) responded well.
2. Two patients with respiratory infection were treated CFS by nebulization. One responded well and another fair.
3. No side effects were observed.

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A few studies on cefsulodin (CFS) were performed and the following results were obtained.
1.High blood concentration was obtained with intravenous drip infusion of this drug, but it did not last long.
2.In6to12hours after the conclusion of the infusion, 52-81% of the dose was excreted in active condition,
3.Pseudomonas aeruginosal abscess was completely cured by intravenous drip infusion of this drug.A decrease in Pseudomonas aeruginosa was noted in urine in the case of acute pyelonephritis and in sputum in the case of pneumonia.The minimum inhibitory concentrations of this drug against P.aeruginosa isolated from various materials were below12.5μg/ml for all strains,
4.In all the patients including 3-month-old infants to whom55-200mg/kg of this drug was intravenously drip infused for5days, systemic or topical adverte reactions were not recognized.Nor did this drug give any effect on general blood condition, and liver and kidney functions.We plan to futher study the clinical efficacy of this drug by adding more cases affected with P.aeruginosa in children.

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Cefsulodin (CFS) was evaluated for its safety and efficacy in 14 children with Pseudomonas aeruginosa infections. The diagnoses included pneumonia (4), sepsis (1), presumed sepsis (4), acute postoperative ascending cholangitis (1), acute postoperative peritonitis with wandering pneumonia (1), acute enterocolitis with acute UTI (1), recurrent UTI (1), and acute cystitis (1).CFS was administered intravenously with a daily dose of 93 to 299mg/kg in the cases with normal renal functions.CFS was effective in all but one case both clinically and bacteriologically.A case of pneumonia whose isolate was resistant to CFS responded poorly. Mild transient eosinophilia was observed in 3 cases, but no severe adverse reactions were encountered.Peak MIC values of 18 clinical isolates of P.aeruginosa were 1.56 mcg/ml, 0.39 to 0.78mcg/ml and 12.5mcg/ml for CFS, gentamicin, and sulbenicillin, respectively.
A half life of the serum CFS levels was 1.09 hours after intravenous bolus injection of 20 to 25 mg/kg of CFS (n=2).A cerebrospinal-fluid level and biliary levels measured in cases with inflamed meninges or with cholangitis were well above the MIC value.
From the present study, CFS appeared to be a safe and effective antibiotic when used in children with susceptible Pseudomonas infections.Combined use of another antibiotic should be considered in the case with polymicrobial infections because of the CFS's very narrow spectrum.

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A new cephalosporin cefsulodin (CFS) was studied basically and clinically and the following results were obtained.
1.The serum levels of25mg/kg of CFS administered intravenously were39.5mcg/ml after30minutes, 22.6mcg/ml after1hour, 11.6mcg/ml after2hours, 6.0mcg/ml after4hours and2.1mcg/ml after6hours. The half life from serum was84minutes.
2.Clinical response on 4 cases of Pseudomonas aeruginosa infections were all good.
3.The slight elevations of GOT, GPT were observed by the drug administrations in1case. From the above results, CFS was effective drug to P.aeruginosa infections by intravenous administration of 25mg/kg of CFS.

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Experimental and clinical evaluation of cefsulodin (CFS), a newly developed injectable cephalosporin, was made and the following results were obtained.
1.Antimicrobial activity
Antimicrobial activity of CFS against P.aeruginosa was studied with the inoculum size of 10⁸ and 10⁶ CFU/ml. In case of108CFU/ml inoculum size, MIC distributed in the range of6.25to50tug/mland peak distribution was between6.25μg/mland12.5μg/ml.Growth of 76% P.aeruginosa wasinhibited by12.5tug/mlconcentration.
With10⁶CFU/ml inoculum size, MIC range was1.56to 25μg/ml, peak distribution was3.13aug/mland80% inhibitory concentration was6.25μg/ml
Irrespective of inoculum size, antimicrobial activity of CFS was1to2times superior to CPZ and PIPC, 4to 5times to CBPC and2times inferior to TOB.
2.Absorption and distribution
Ten, 15, 20mg/kg and50mg/kg CFS was administered by one-shot intravenous injection and15, 50mg/kg CFS by intravenous drip infusion.The peak serum level was noticed after30minutes of injection (initial serum collection) in one-shot cases with the amount of 34.5, 31.1, 53.4μg/ml and89.3μ/ml respectively and, in dri infusion cases, at the end of infusion with46.8, 102.2μg/mlrespectively. Half life time were1.21, 1.31, 1.64, 1.08, 1.21 hours and 1.30 hours respectively.
Urinary recovery rate until 6 hours from the start of injection in15, 20mg/kg and50mg/kg one-shot intravenous injection as well as15, 50mg/kg intravenous drip infusion cases were, 38.4-61.4, 51.7, 34.4-43.9, 37.0-40.0% and 35.8-74.3%respectively.
3.Clinical result
CFS was administered to 5 cases of bronchopneumonia, 2 of septicemia, 2of UTI, 2 of postoperative wound infection, 1of epididymitis and 1 of peritonitis, i.e. total13 cases with P.aeruginosa infection.
CFS was administered 65 to150mg/kg daily from 7 to 19 days and clinical result was excellent in1, good in 11 and poor in1case with the efficacy rate of92.3%. Ineffective case was septicemia in the terminal stage of leukemia accompanying ecthyma gangraenosum and posterior subperitoneal abscess.
As for bacteriological effect, P.aeruginosa was eradicated in 9 out of 13 cases and eradication rate wa 69.2%.
Side effect and abnormal change o laboratory findings to be caused by CFS administration have not been noticed.
As the result of the study above mentioned, CFS is considered to be the useful drug for the treatment of the infection caused by P. aeruginosa in the pediatric field.

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Pharmacokinetic and clinical evaluations of cefsulodin (CFS) were made and the following results were obtained.
1.Pharmacokinetic study
Three hundred fifty grams of CFS (20mg/kg) was administered by30minutes intravenous drip infusion to 7years old child (17.5kg in weight).Serum concentrations of CFS at the end of the infusion and1, 1.5, 2.5, 6.5 hours thereafter were46.0, 44.9, 23.0, 11.9mcg/ml and0.6mcg/ml respectively.Urinary recovery rate until6hours from the start of infusion was66.2%.
2.Clinical study
CFS was administered to the case of bronchitis with cystic fibrosis of the pancreas and bronchiectasia (treatment was made2times), and each1case of pyelonephritis with renal calculus and measles pneumonia with infantile spasm.All infections were caused by P.aeruginosa and administration and dosage of CFS was47to86 mg/kg/day, 2to4times daily by intravenous injection or intravenous drip infusion for5to11days.Result was good in3infections (2cases) and fair in1case, i.e.measles pneumonia.Effectiveness rate was75.0%.Side effect as well as abnormal change of laboratory findings were not observed.Thus, CFS is considered to be the useful drug for the treatment of pediatric infection caused by P.aeruginosa.

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An anti-P.aeruginosa, cephalosporin, cefsulodin (CFS) was administered to2patients who were affected with inveterate urinary tract infection at ages of1year8months and2years, and another with pneumonia combined with lung fibrosis and bronchiectasia at3years. The clinical responses in3 cases were “good” in 2and “fair” in1.The bacteriological responses to3strains of P. aeruginosa isolated in thisclinical study were “eradicated” in1, “decreased” in1, and “unchanged” in1.
No side effects were observed.

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Pharmacokinetic and clinical studies of cefsulodin (CFS) were made and the fbllowing results were obtained.
1.Twenty or 50mg/kg of CFS was administered to 3 to 8 years old cases by one shot intravenous or 1 hour intravenous drip infusion, and serum level as well asurinary recovery rate was studied. Serum level ofCFS after 15, 30minutes, 1, 2, 4 hours and 6 hours, serum half life time and urinary recovery rate until 6 hours after injection was, in case of 20mg/kg one shot administration, 32.2, 27.2, 16.1, 9.5, 2.6μg/ml and O.6μg/ml, 1 hour and 49.6% respectively, and, incase of 50mg/kg one shot administration, 163.5, 101.9, 67.6, 32.7, 11.1μ9/ml and 3.9μg/ml, 1.29 hours and 64.7% respectively.In 1 hour intravenous dripinfusion case, serum level of CFS after 30 minutes, 1, 2, 4 hours and 6 hours from the start of infusion, serum half life time and urinary recovery rate until 6 hours after start of infusion was, in case of 20 mg/kg administration, 51.3, 60.4, 18.8, 4.5μg/nil and 1.4μg/ml, 1.07 hours and 87.7% respectively, and, in caseof 50 mg/kg administration 84.8, 149.5, 51.2, 13.5 tig/ml and 4.0μg/ml, 1.08 hours and 68.2% respectively. Metabolites of CFS were detected neither in serum nor urine.
2. Eighty to 117.6 mg/kg of CFS was administered to 4 cases of infection caused by P. aeruginosa, i.e. 2 of bronchopneumonia and each, 1 case of acute purulent otitis media and UTI. Clinical response was excellent in 2 and good in 2 cases, showing 100% effectiveness rate. Bacteriologically, P. aeruginosa was eradicated in 3 and decreased in 1 case. Side effect as well as abnormal change of laboratory findings were not observed. Thus, CFS is considered to be the useful drug for the treatment of infection caused by P. aeruginosa in pediatric field.

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Antimicrobial, pharmacokinetic and clinical evaluation of cefsulodin (CFS) was made and the following results were obtained.
1.Antimicrobial activity of CFS against P. aeruginosa was similar to a little lower than that of GM. Antimicrobial activity of CFS against S.aureus was similar to that of SBPC and against E.coil CFS showed lower antimicrobial activity.
2.Twenty or 50 mg/kg CFS was administered by 1 hour intravenous drip infusion. Average serum levels at the completion of the infusion were 35.1±8.0, 114.5±36.1μg/ml and 1.6±0.7, 4.5±3.2μg/ml at 6 hours after ward with the half life imes of 1.50, 1.29 hours respectively.In case of 12.1 mg/kg 1 hour intravenous drip infusion, peak serum level was 13.4 μg/ml at the completion of infusion, and the concentration in the sputum was 1.0μg/ml at 5 hours after completion of infusion.
Average serum levels of CFS by one shot infusion of 20 mg/kg were 58.4±6.8μg/ml, 2.7±2.5μg/ml at 15 minutes and 6 hours after injection respectively.Half-life time was 1.54 hours.
Average urinary excretion rates of CFS were 64.4%, 64.2% and 48.9% up to 6 hours after 1 hour intravenous drip infusion of 20mg/kg, 50mg/kg CFS and one shot intravenous of 20mg/kg CFS respectively.
3.CFS was administered to 2 pneumonia cases caused by P.aeruginosa, i.e.one was 15 years and 11 months old male accompanying bronchial asthma and the another 4 years old male with LENNOX syndrome. Neither bacteriological nor clinical efficacy was, however, observed.Side effect as well as bacterial superinfection were not observed.

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Our investigation of cefsulodin in pediatric Pseudomonas infect ion produced the following results.
1.Cefsulodin (CFS) was administered intravenousl by one shot or drip infusion in3patients with Pseudomonas infections. These diseases consisted of pneumonia with IgA deficiency, ALL with opportunistic infection, UTI with paraplegia due to spina bifida.CFS was effective in all cases.
2.Transient eosinophilia was observed in1case.But other side effect was not noted in any cases.

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The basic and clinical studies were performed on a new antibiotic, cefsulodin (CFS), and the following results were obtained.
1. The MICs of CFS against clinically isolated 68 strains of P. aeruginosa were distributed from 0.78 to> 100 mcg/ml, and the peak MIC was 1.56 mcg/ml in 10⁶ cells/ml inoculum size, with 7 strains being over 100 mcg/ml. This drug was not inferior to GM, AMK and NTL.
2. After intravenous injection of 100 mg/kg of CFS to 5 rabbits with staphylococcal meningitis, the mean peak level in cerebrospinal fluid (CSF) was 7.22±3.14 mcg/ml, even when 1 rabbit showing on extremely high peak was included. The CSF/serum ratios at peak levels and in AUC up to 2 hours were 3.57% and 4.44%, respectively. The ratio of CSF to serum in half-life (T 1/2) was 2.05.
3. The mean serum levels in 2 children intravenously administered with approximately 20 mg/kg of CFS were 43.75 mcg/ml after 30 minutes, 14.8 mcg/ml after 2 hours, 7.15 mcg/ml after 4 hours. T 1/2 was 1.57 hours and 1.16 hours in each child. The urine recovery for 6 hours was 94.2% in 1 child and the urine level was more than 1,000 mcg/ml in 4 hours. In an immature baby with meningitis, the serum levels after an intravenous injection of 48.4 mg/kg of CFS were 97 mcg/ml after 30 minutes and 48 mcg/ml after 6 hours. T 1/2 was, extremely long i. e. 6.35 hours. CSF levels of the drug were determined 6 times in this baby, but it was not detectable in 3 occasions while in the remaining occasions it ranged from 0.27 to 1.01 mcg/ml. In another meningitic child, CSF level was measured once at 1 hour after intravenous injection of 50 mg/kg of CFS, but CFS was not detectable also.
4. CFS was administered intravenous by to 6 cases with pyelonephritis at a daily dose of 62.5 to 90.4 mg/kg t. i. d. The responses were “excellent” in 3 and “good” in the remaining 3 cases.
5. Side effects and abnormal laboratory findings due to CFS were not observed in the 7 cases even when the immature baby on a daily dose of 177.2 mg/kg for 14 days who was excluded from efficacy evaluation was added.
6. From the above results, it is considered that CFS is a highly useful antibiotic against infections caused by P. aeruginosa in children. However, the results obtained so far suggest that the transfer of CFS into CSF is not very good. More careful studies have to be carried out to determine the usefulness of CFS against meningitis.

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