Laboratory and clinical studies on norfloxacin in the pediatric field

In bacteriological, pharmacokinetic and clinical studies on norfloxacin (NFLX, AM-715), the following results were obtained: 1. Antibacterial activity of NFLX, nalidixic acid (NA), amoxicillin (AMPC), cefaclor (CCL), erythromycin (EM) and fosfomycin (FOM) against clinically isolated bacteria was examined, and it was found that MIC80 of NFLX against Staphylococcus aureus was 3.13 micrograms/ml, thus NFLX exhibited stronger antimicrobial activity than NA, AMPC, CCL, EM and FOM. NFLX also showed good activities to those strains of S. aureus which were resistance to NA, AMPC, CCL, EM and FOM. 2. MIC80 of NFLX against Escherichia coli was 0.05 micrograms/ml or lower, thus NFLX showed better activity than NA, AMPC, CCL, EM and FOM. 3. In single oral administration at fasting of NFLX at dose levels of 1.5-2.4 and 2.5-3.4 mg/kg in tablet form mean peak values of serum concentration were 0.32 micrograms/ml reached in 1 hour and 0.38 micrograms/ml in 2 hours, T1/2's obtained were 1.7-4.0 and 2.2-2.9 hours and AUC's were 1.54 +/- 0.52 and 2.02 +/- 0.93 micrograms.hr/ml, respectively. Urinary recovery rates of 11.6-46.9%, 13.8-35.4% in 6-8 hours were demonstrated with the 2 ranges of dose levels, respectively. 4. NFLX was administrated to 34 patients consisting of 8 cases of acute pneumonia, 3 cases of acute tonsillitis, 3 cases of bacterial colitis, 19 cases of urinary tract infections and 1 case of purulent parotitis. The clinical efficacy rate was 97.1% including 34 cases with excellent results in 28, good in 5 and fair in 1. 5. The bacterial eradication rate was 96.8% (30/31) with one exception of a Campylobacter jejuni strain. 6. NFLX was given to patients according to a dosing regimen with 4.5-21.4 mg/kg/day dose levels for 3 doses daily except 1 case of UTI where 2 daily doses were given daily. 7. No adverse reactions were observed. Abnormal laboratory test value was obtained in 1 case where eosinophilia was found. The above results have suggested that NFLX is a useful and safe antimicrobial agent against bacterial infections in children.     

Laboratory and clinical studies of norfloxacin in pediatric field

We have carried out laboratory and clinical studies on norfloxacin (NFLX, AM-715). The results are summarized as follows. NFLX was given through oral administration to one child each at dose levels of 1.7 mg/kg, 2.4 mg/kg and 3.2 mg/kg. After administration, peak serum levels of NFLX obtained for the 3 dose levels were 0.16 micrograms/ml at 1 hour, 0.69 micrograms/ml at 2 hours, 0.81 micrograms/ml at 1 hour, respectively, and half-lives were 2.5 hours, 1.8 hours and 2.7 hours, respectively. NFLX was given through oral administration to 2 children at a dose level of 4.4 mg/kg and to another child at a dose level of 4.8 mg/kg. After administration, mean peak serum levels of NFLX obtained were 1.17 +/- 0.48 micrograms/ml and half-lives were 3.0 +/- 0.5 hours. Urinary excretion rates of NFLX were 14.5% and 28.4% in the first 8 hours after administration of 1.7 mg/kg and 3.2 mg/kg, respectively, and 29.1% in the first 6 hours after administration of 2.4 mg/kg. Mean urinary excretion rates of NFLX were 38.5 +/- 13.0% in the first 8 hours after administration of 4.4 mg/kg and 4.8 mg/kg. Treatment with NFLX was made in 33 cases of pediatric bacterial infections including 5 cases of tonsillitis, 14 cases of enteritis, 10 cases of UTI and 1 case each of bronchitis, balanoposthitis, impetigo and pustulosis. Results obtained were excellent in 14 cases, good in 15 cases. No significant side effect due to the drug was observed in any cases.     

Pharmacokinetics and clinical studies of norfloxacin in the pediatric field

Norfloxacin (NFLX) tablets with a potency of 50 mg/tablet or 100 mg/tablet were administered at doses of 1 to 4 tablets (1.5 to 6.1 mg/kg) orally 30 minutes before meals to 12 children with ages ranging from 8 years 9 months to 12 years 5 months, and serum/urinary NFLX levels and urinary recovery rates were determined. The drug sensitivity tests for NFLX and 10 other drugs were conducted against 128 strains of Shigella sonnei (10(6) CFU/ml) which had been isolated from pediatric patients with bacillary dysentery. In order to evaluate clinical and bacteriological effects of NFLX and its safety in the pediatric field, NFLX 50 mg tablets were administered t.i.d. (mean 8.3 mg/kg) for 5 days to 42 pediatric patients with bacillary dysentery. Similarly, this drug was administered in b.i.d. or t.i.d. (mean 6.7 mg/kg) for 4 days to 4 pediatric patients with urinary tract infections. The following results were obtained: 1. According to the dosage, the subjects were divided into 3 groups with dose levels 1.5-2.8 mg/kg, 3.1-4.7 mg/kg and 5.2-6.1 mg/kg. These groups had 5, 2 and 5 subjects, respectively. Mean serum drug concentrations for the 3 dosage groups were at peak levels of 0.27, 0.64 and 1.51 micrograms/ml at 4, 2 and 1 hour(s) after administration, respectively. Pharmacokinetic parameters for these dosage groups were as follows: Tmax values were 3.0, 3.0 and 1.2 hours; Cmax values were 0.32, 0.78 and 1.56 micrograms/ml; serum half-lives were 2.2, 2.4 and 2.3 hours; and AUCs were 1.65, 3.98 and 6.06 micrograms.hr/ml, respectively. Thus, dose-dependent responses were observed among the 3 dosage groups. 2. Mean peak urinary drug concentrations for the 3 dosage groups were 45.8, 109.2 and 215.1 micrograms/ml, respectively, and the peaks appeared 2-4 hours after administration. Mean recovery rates up to 8 hours after administration were 18.3%, 24.5% and 28.7%, respectively for the 3 dosages. 3. In a drug sensitivity test against 128 strains of S. sonnei, the most frequent MIC value of NFLX was 0.78 micrograms/ml against 65 strains, followed by 0.39 micrograms/ml for 56 strains. Together, these strains accounted for 94.5% of the strains tested. No resistant strain to this drug was observed and the antibacterial activity of this drug was second only to colistin, similar to that of ofloxacin, better than those of enoxacin and seven other drugs. 4. Clinical efficacy rate of NFLX against bacillary dysentery was 95.2% in 21 cases in which the evaluation was possible.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic, bacteriological and clinical studies in the pediatric field on norfloxacin

We have evaluated norfloxacin (NFLX), a fluoroquinolone agent, in tablet form for its efficacy and safety in the field of pediatrics. 1. Mean serum concentrations of NFLX following oral administration to 3 children at dose levels of 3.2 mg/kg, 3.7 mg/kg and 5.4 mg/kg were, respectively, 0.7 microgram/ml, 0.18 microgram/ml and 0.64 microgram/ml at 2-4 hours. Mean serum half-lives (T1/2) of NFLX were 2.5-2.9 hours and mean urinary recovery rates in the first 6 hours after administrations were 7.1-30.7%, depending on dose levels. 2. Antibacterial activities of NFLX against clinically isolated 30 organisms from children were determined. MIC of NFLX against Staphylococcus aureus was similar to that of ABPC, 0.39-25 micrograms/ml. MIC of NFLX against Escherichia coli was approximately less than or equal to 0.10 microgram/ml. This MIC value was lower than other antibiotics. MIC of NFLX against Vibrio parahaemolyticus was less than or equal to 0.10 microgram/ml. 3. NFLX was administered to 30 patients (7 patients with Salmonella enteritis, 7 patients with Campylobacter enteritis, 5 patients with other enteritis, 1 patient with bacillary dysentery, 8 patients with urinary tract infection, 2 patients with skin soft tissue infection). The clinical responses of these 30 patients were as follows; excellent: 24 patients, good: 4 patients. The efficacy rate was 93.3%. 4. The bacteriological efficacy rate of NFLX against clinically isolated 29 organisms from children was 75.9%, including 3 cases in which other antimicrobial agents had been ineffective. Especially against Salmonella spp. was superior to other agents tested. 5. Neither clinical adverse reaction nor abnormal laboratory data was found in any of these 33 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basic and clinical studies on ceftazidime in the pediatric field

Basic and clinical studies were made on ceftazidime (CAZ) in pediatric field, and the following results were obtained. The antibacterial activity of CAZ against clinically isolated and maintained strains was examined. CAZ was unequivocally more active than CEZ and CMZ against Gram-negative rods, with MIC distribution similar to that of CTX, except for that for P. aeruginosa. The MIC of CAZ was lower than that of CTX for P. aeruginosa. Compared with the MICs of CEZ, CMZ and CTX, CAZ showed slightly higher MICs for Gram-positive bacteria. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ were 64.9, 36.9, 28.3, 14.7, 4.92 and 2.42 micrograms/ml, respectively, with the half-life of 1.27 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 10 mg/kg of CAZ were 16.6, 24.5, 41.4, 17.1, 5.38 and 2.62 micrograms/ml, respectively, with the half-life of 1.28 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 20 mg/kg of CAZ were 73.1, 60.8, 39.3, 17.3, 8.23 and 4.45 micrograms/ml, respectively, with the half-life of 1.42 hours. The blood concentrations of CAZ, at 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 20 mg/kg of CAZ were 55.1, 69.0, 32.1, 11.4 and 4.56 micrograms/ml, respectively, with the half-life of 1.27 hours. Urinary recovery rate of CAZ during the first 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ was 86.7%. CAZ was administered to 17 children with infections, and the clinical response was excellent or good in 94%. CAZ was bacteriologically effective in 14 patients, all bacteria having been eradicated in them. The bacteria were E. coli in 10 patients, H. influenzae in 2, P. aeruginosa in 1 and S. pneumoniae in 1. As for side effects, slight elevation in GOT was observed in 1 case and eosinophilia, in another case.     

Basic and clinical studies on cefmenoxime in pediatric field

Basic and clinical studies were made on cefmenoxime (CMX) in pediatric field, and the following results were obtained. 1. The antibacterial activity of CMX against clinically isolated and maintained strains was examined. CMX had stronger antibacterial activity than CEZ against Escherichia coli, Salmonella, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens and Pseudomonas aeruginosa, but CEZ had stronger antibacterial activity against Staphylococcus aureus. 2. The blood concentrations of CMX, 0.5, 1, 2, 4 and 6 hours after a one-shot intravenous injection of 20 mg/kg of CMX were 33.6, 15.1, 4.5, 2.5 and 0.6 mcg/ml, respectively, with the half-life of 1.04 hours. 3. The blood concentrations of CMX, 0.5, 1, 2, 4 and 6 hours after a 1-hour intravenous drip infusion of 20 mg/kg of CMX were 32.0, 55.2, 8.4, 4.2 and 1.0 mcg/ml, respectively, with the half-lite of 0.96 hour. 4. A complete or partial clinical response to therapy with CMX was obtained in all 10 children with infectious diseases. 5. Bacteriological examination made on 3 patients showed that all bacteria had been eradicated, and that therapy was effective. The bacteria were E. coli in 2 patients and Proteus mirabilis in 1 patient. 6. The side effects produced were neutropenia, eosinophilia and skin eruption in 1 patient, and diarrhea in 1 patient.     

Basic and clinical studies of ceftizoxime suppositories in the pediatric field

A bacteriological and clinical study of ceftizoxime suppositories (CZX-S) let to the following results. The CZX serum concentration 10 minutes after insertion of one 250 mg suppository (i.e. 5.7-15.2 mg CZX per kg body weight) ranged from 1.64 to 6.53 micrograms/ml (average: 4.41 micrograms/ml). In one child the concentration 7 minutes after insertion was 4.13 micrograms/ml. Therapeutic responsiveness was recorded as "effective" in 8 (88.9%) of the 9 children who were broken down into 6 with tonsillitis, 1 with pharyngitis, and 2 with UTI. Bacteriological studies conducted in 5 children have confirmed eradication in 4 children, one of whom showing appearance of another strain. The rate of discharge of the suppository within 10 minutes after insertion was 20.4%. Reddening and erosion of the anus were observed in 1 child.     

Basic and clinical studies on imipenem/cilastatin sodium in the pediatric field

Basic and clinical studies have been performed on imipenem/cilastatin sodium (MK-0787/MK-0791) in the pediatric field. Antibacterial activities of MK-0787 against 14 clinical isolates of S. aureus and 67 isolates of E. coli were determined. The MIC of MK-0787 was 0.10 microgram/ml or less against all 14 strains of S. aureus. The MIC of MK-0787 was 0.39 microgram/ml or less against all 67 strains of E. coli. The pharmacokinetics of MK-0787/MK-0791 was studied at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg. The peak serum levels of MK-0787 achieved approximately 1 hour after the administration of 10 mg/10 mg/kg and 20 mg/20 mg/kg doses were 38.6 micrograms/ml and 36.2 micrograms/ml, respectively. The serum half-lives were 0.8 hour and 0.9 hour, respectively. The total 6-hour urinary excretions were 82.1% and 66.7%, respectively. The MK-0787/MK-0791 was administered to 13 children with bacterial infections. The clinical results were excellent or good in all cases. The overall efficacy rate was 100%. As a side effect, diarrhea was observed in 1 patient. Abnormalities in laboratory findings observed were elevation of direct bilirubin in 1 patient, thrombocytosis in 2, and a prolonged prothrombin time in 1 patient. Based on the above results, it can be concluded that MK-0787/MK-0791 is a safe and effective drug to use for the treatment of pediatric infections.     

Bacteriological and clinical studies on norfloxacin in the field of pediatrics

Bacteriological and clinical studies on norfloxacin (NFLX) were carried out in the field of pediatrics, and the results obtained are summarized as follows: 1. The MICs of NFLX against clinically isolated organisms were determined to compare with MICs of nalidixic acid, amoxicillin, cefaclor, erythromycin and fosfomycin. NFLX had low MICs against both Gram-positive and Gram-negative bacteria and, particularly, showed higher antimicrobial activity to Escherichia coli, Salmonella sp., Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae and Campylobacter jejuni than any other drugs tested. 2. Seventeen pediatric patients (11 cases of enteritis, 4 cases of urinary tract infections, 1 case of tonsillitis and 1 case of pyoderma) were treated orally with NFLX in daily doses ranging from 3.1 to 16.7 mg/kg t.i.d. for 6-14 days. Rates of clinical effectiveness and bacterial elimination were 94.1% and 58.8%, respectively. 3. None of the treated children showed clinical symptoms indicating the occurrence of side effects nor abnormal laboratory findings except 1 patient with eosinophilia. These results indicate the usefulness of NFLX in the treatment of bacterial infections in the pediatric field.     

Basic and clinical studies of sulbactam/cefoperazone in pediatric field

We conducted several studies using a combination of sulbactam (SBT) and cefoperazone (CPZ) in a ratio of 1:1 with the following results. Serum and cerebrospinal fluid (CSF) concentrations of the drugs were determined in 2 rabbits with meningitis caused by S. aureus. Following intravenous injection, serum concentrations of CPZ were higher than those of SBT in both rabbits whereas CSF concentrations were much higher with sulbactam than with CPZ indicating good penetrability of SBT into CSF. The serum concentration of SBT at 1/2, 1, 2 and 4 hours after an intravenous administration of 9.8 mg/kg of the combination to a child were 3.5, 1.4, 0.3 and 0.1 microgram/ml and those of CPZ 19.0, 13.0, 6.7 and 2.9 micrograms/ml, respectively. The half-lives were 0.705 hours for SBT and 1.31 hours for CPZ. An intravenous dose of this combination (19.6 mg/kg) was given 3 times a day to 13-year-old girl with decreased neutrophil chemotaxis due to periblepharal abscess caused by S. aureus. The therapeutic effect was excellent. Though very slight transient eosinophilia was noted, no adverse reaction was found. The susceptibility of the isolated organism to this drug was not determined, but it was found to be resistant to the CTX using the disc method.     

Basic and clinical studies of cefotiam in pediatric field (author's transl)

The basic and clinical studies of cefotiam (CTM) in pediatric infections were carried out, and the following results were obtained: 1. The antibacterial activity of CTM against S. aureus was equal or slightly less than that of cefazolin (CEZ). Those of CTM against E. coli and K. pneumoniae were eight times more active than those of CEZ. 2. CTM 20 mg/kg was administered wither by 30 minutes or 1 hour intravenous drip infusion. The peak serum levels were obtained at the end of each drip infusion, with the mean peak levels being 44.8 and 41.4 mcg/ml respectively. The serum levels at 1.5 and 2 hours after drip infusion were 2.8 and 2.2 mcg/ml respectively, and at 3.5 and 4 hours after drip and 4 hours after drip infusion were 0.3 and 0.7 mcg/ml respectively. The half lives were 0.62 and 1.15 hours, respectively. The mean urinary excretion over 6 hours were 52.8% in ;the 30 minutes drip infusion group and 42.6% in the 1 hour drip infusion group. 3. Clinical efficacy was evaluated in sixteen cases suffering from tonsillitis (4 cases), pneumonia (4), bronchitis (2), cervical lymphadenitis (2), purulent meningitis (2), suppurative arthritis (1) and suspected sepsis (1). Good and excellent responses were obtained in 15 of 16 cases (93.8%). Bacteriological response in the form of eradication was noted in 4 of 6 cases. Side effect observed was rash in 1 case, and laboratory abnormalities were elevation of BUN in 1 case and elevation of GPT in 2 cases.     

Pharmacokinetic and clinical studies on flomoxef in the pediatric field

The new antibiotic flomoxef (FMOX, 6315-S) was administered to 38 children. The results obtained are summarized as follows. 1. In 3 cases of children administered with FMOX (20 mg/kg) by intravenous drip infusion for 30 minutes, the mean T1/2 (beta) was 0.96 hour and the mean 6-hour urinary excretion was 95.5%. 2. The antibiotic was administered to a total of 38 patients with bronchopneumonia, lacunar tonsillitis, upper respiratory tract infection complicated with brain tumor, otitis media, urinary tract infection, purulent meningitis, subcutaneous and hyponychial abscess, cervical lymphadenitis, or bacterial enteritis. The treatment was markedly effective in 24 cases, effective in 13, fair in 1, and ineffective in none. The efficacy rate was 97.4%. From our results, this drug appears to be particularly effective to bronchopneumonia, upper respiratory tract infection and urinary tract infection. 3. None of the children showed clinical symptoms indicating side effects of the drug. These results showed that FMOX is a drug that can be safely used in the pediatric field as well as for adults.     

Laboratory and clinical studies on cefodizime in the pediatric field

Laboratory and clinical studies on cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, were done. The results obtained are summarized as follows: 1. Absorption and elimination were examined in a total of 5 cases including a case of 10 mg/kg intravenous drip infusion for 30 minutes, 2 cases of 20 mg/kg rapid intravenous injection and 2 cases of 40 mg/kg drip infusion for 30 minutes. Maximum serum levels were attained immediately after drip infusion or rapid injection. Cmax's were 119.2 micrograms/ml for 10 mg/kg, 374.9 micrograms/ml or 255.7 micrograms/ml for 20 mg/kg, and 321.3 micrograms/ml or 431.8 micrograms/ml for 40 mg/kg. These values were determined using an high performance liquid chromatography (HPLC) method. In general, values using the bioassay were higher than those with the HPLC method. T 1/2 (beta)'s were between 1.74 and 1.93 hours using HPLC, and between 1.77 and 2.24 hours using bioassay. Urinary recovery rates were examined in 3 out of 5 cases. Cumulative urinary recovery rates were 57.9-90.6% with HPLC method and 50.4-88.0% with bioassay in a period of 0-8 hours after administration. 2. Clinical efficacy was evaluated in a total of 22 cases including 14 cases of respiratory tract infections, 5 cases of urinary tract infections and 3 cases of cellulitis. Clinical efficacy rate was 95.2%. Bacteriologically, pathogenic organisms were eradicated in 90.0%. As adverse reactions, 1 angular stomatitis, 1 diarrhea and 1 loose stool were noted. Abnormal laboratory test values detected were 1 case of increased GPT and 1 case of increased GOT and GPT.     

Laboratory and clinical studies on cefminox in the pediatric field

Laboratory and clinical studies were performed as follows on cefminox (CMNX, MT-141), a new cephamycin antibiotic. Pharmacokinetics Serum concentrations of CMNX were measured in 4 patients given CMNX for prophylactic purpose during cardiac catheterization. In 2 patients given 20 mg/kg of CMNX by intravenous bolus injection, the average of peak serum concentration was 178.9 micrograms/ml at 15 minutes. The mean urinary recoveries in these 2 cases was 66.9% within 6 hours after injection. In 2 patients given 20 mg/kg of this drug by 1 hour drip infusion, the peak serum concentration was obtained at the time drip was completed, and the average value was 68.3 micrograms/ml. Clinical efficacy CMNX was administrated intravenously to 13 patients in dose of 52.9 approximately 96.0 mg/kg t.i.d. or q.i.d. for 4 approximately 7 days; 3 with tonsillitis, 6 with bronchitis, 1 with bronchopneumonia, 1 with UTI, 1 with lymphadenitis and 1 with enterocolitis. The overall efficacy rate was 92.3%, i.e., efficacy was excellent in 12, and poor in 1. Bacteriological efficacy was excellent, i.e., 3 of 3 strains disappeared. Side effects were observed in 3 cases, i.e., 1 case of eruption, 1 case of diarrhea and 1 case of transient eosinophilia. The above results suggest that CMNX is a useful antibiotic for treating pediatric bacterial infections.     

Laboratory and clinical studies on aztreonam in the pediatric field

Laboratory and clinical studies were performed as follows on aztreonam (AZT), a new monobactam antibiotic. Pharmacokinetics Serum concentrations of AZT were measured in 1 patient given 20 mg/kg by intravenous bolus injection. The peak concentration was 100 micrograms/ml at 15 minutes, and T 1/2 was 1.85 hours. Clinical efficacy AZT was administrated intravenously to 10 patients in doses of 59.2-170.7 mg/kg (average 76.1 mg/kg) t.i.d. for 3-8 days (average 5.3 days); 5 with pneumonia, 1 with bronchitis, 1 with lymphadenitis, 1 with sepsis (suspected) and 2 with urinary tract infections. The overall efficacy rate was 80%, i.e., efficacy was excellent in 5, good in 3, fair in 1 and poor in 1. Bacteriological efficacy was excellent, i.e., 4 of 4 Gram-negative strains disappeared. Any clinical side effects and laboratory abnormalities were not observed. The above results suggest that AZT is a useful antibiotic for treating pediatric bacterial infections, especially due to Gram-negative bacteria.     

Fundamental and clinical studies on cefuzoname in the pediatric field

Cefuzoname (CZON) one of the aminothiazolyloxyiminoacetamido cephalosporins, was studied for its antibacterial activity, absorption and excretion, concentration in the cerebrospinal fluid (CSF) and the penetration, and clinical efficacy. The following are a summary of the results: 1. Antibacterial activity; The antibacterial activity of CZON was studied on clinically isolated Staphylococcus aureus (cefazolin (CEZ)-susceptible and CEZ-tolerant strains), Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis. Compared with CZON were cefmenoxime (CMX), latamoxef (LMOX), cefoperazone, cefmetazol (CMZ), cefotiam and CEZ, but for S. aureus cefamandole (CMD) was replaced for CPZ. Activities of CZON against S. aureus, both CEZ-susceptible and CEZ-tolerant strains, were superior to those of 6 control drugs. The distribution of MICs for the CEZ-susceptible strains was 0.10-12.5 micrograms/ml, and for the CEZ-tolerant strains 0.20-greater than 100 micrograms/ml. MIC peaks were 0.39 micrograms/ml and 0.78-1.56 micrograms/ml for CEZ-susceptible and CEZ-tolerant strains, respectively. Against both susceptible and tolerant strains, CZON showed superiority to CMZ and CMD, which are used prevalently and used for Methicillin-resistant S. aureus also. Distributions of MICs of CZON (and the peak of MICs) on E. coli, K. pneumoniae, and P. mirabilis were less than or equal to 0.025-1.56 (less than or equal to 0.025), less than or equal to 0.025-25 (less than or equal to 0.025-0.05), less than or equal to 0.025-25 (less than or equal to 0.025) micrograms/ml, respectively, showing CZON's similar antibacterial activity to those of cephalosporins, CMX and LMOX, which are 5th group. 2. Absorption and excretion: Eight patients, aged 10 months to 15 years, were administered with CZON 20 mg/kg, one shot intravenously. Serum concentrations somewhat varied from patient to patient, but the mean value was 48.7 micrograms/ml after 30 minutes of administration which decreased rapidly to 13.3 micrograms/ml after 1 hour, to 3.4 micrograms/ml after 2 hours, to 1.14 micrograms/ml after 4 hours, and to 0.15 microgram/ml after 6 hours. Half-lives were 0.67-1.47 hours, with the mean of 0.87 hour. Urinary recovery rates were 24.7-55.9%, with the mean of 45.1%, in 6 hours after administration. 3. CSF concentration and penetration rate: To 4 pediatric patients with purulent meningitis, CZON 25 mg/kg or 50 mg/kg was administered and the concentration in CSF was measured.(ABSTRACT TRUNCATED AT 400 WORDS)     

Fundamental and clinical studies on aztreonam in the pediatric field

Fundamental and clinical studies on aztreonam (AZT), a new monobactam antibiotic, were performed in the pediatric field. The MICs of AZT were assessed against the clinically isolated strains in the pediatric infections. AZT showed an excellent antibacterial activity against Gram-negative bacteria, i.e., against E. coli (20 strains), K. pneumoniae (9), P. mirabilis (16), P. vulgaris (5), P. aeruginosa (10), S. typhimurium (4) and H. influenzae (11); the MICs of AZT against the above strains were less than 0.39 microgram/ml, 0.10 microgram/ml, 0.024 microgram/ml, 0.024 microgram/ml, 6.25 micrograms/ml, 0.10 microgram/ml and 0.10 microgram/ml, respectively. However, antibacterial activity of AZT against Gram-positive bacteria was inferior to that against Gram-negative bacteria, i.e., against the strains of S. aureus (16) and S. pyogenes (4), those MICs were more than 400 micrograms/ml and 3.13 micrograms/ml, respectively. Serum concentrations and urinary excretion of AZT were measured in 2 children aged 7 and 11 years after a single intravenous injection at the dose of 20 mg/kg. The mean serum concentration of AZT followed by the injection 62.5 micrograms/ml at 1/4 hour, 28.5 micrograms/ml at 1/2 hour, 16.5 micrograms/ml at 1 hour, 12.0 micrograms/ml at 2 hours, 3.6 micrograms/ml at 4 hours and 1.1 micrograms/ml at 6 hours, respectively. The mean half-life (beta-phase) was 1.24 hours. The mean urinary concentrations after the injection were 5,000 micrograms/ml in 0-2 hours, 1,650 micrograms/ml in 2-4 hours and 611 micrograms/ml in 4-6 hours and the mean urinary recovery rate up to 6 hours was 61.2%. These results in our studies were considered to be comparable with those reported in adults. In our clinical studies, AZT was administered to a total of 14 cases, i.e., acute pneumonia (4 cases), acute pyelonephritis (4), acute enteritis (5) and acute sppurative cholangitis (1). Clinical effect of AZT was excellent or good in 13 cases except fair in 1 case with acute enteritis and the efficacy rate (excellent and good) was 92.9%. With regard to bacteriological effect, all the strains of H. influenzae (3), E. coli (2), P. mirabilis (1) and P. vulgaris (1) were eradicated, but, S. typhimurium (4) was not eradicated. Neither side effect nor abnormal laboratory findings were observed during the study.     

Pharmacokinetic and clinical studies on cefuzonam in the pediatric field

A multi-center open study was conducted to investigate cefuzonam (L-105, CZON), a newly developed cephalosporin from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows. Serum concentrations and urinary excretion. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg, via one shot intravenous injection or intravenous drip infusion over 1 hour. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after one shot intravenous injections were: 52.8 micrograms/ml with the dosage of 10 mg/kg, 135 micrograms/ml with 20 mg/kg, and 317 micrograms/ml with 40 mg/kg, and T1/2 beta's for the 3 dosages were 1.07 hours, 0.91 hour, and 1.01 hours, respectively. With 1-hour intravenous drip infusion, mean serum concentrations at the end of infusion were: 22.4 micrograms/ml with 10 mg/kg, 46.3 micrograms/ml with 20 mg/kg, 72.5 micrograms/ml with 40 mg/kg, and 69.2 micrograms/ml with 50 mg/kg, and T1/2 beta's for these dosages were 1.31 hours, 1.45 hours, 0.84 hour, and 0.66 hour, respectively. In 6 hours after administration of CZON, urinary excretion rates were 43.5-51.4% for one shot intravenous injections of 10-40 mg/kg, and 42.7-58.6% for 10-50 mg/kg drip infusions. Concentrations in cerebrospinal fluid Penetrations into cerebrospinal fluids in patients with purulent meningitis achieved levels of 2.80-6.40 micrograms/ml with the administration of CZON at 100 mg/kg in acute cases of within 6 days after onset. When the administration of the drug was done at the earlier stage, the greater penetration occurred. However, rates of penetration were 3.10% to 5.03% within 4 days after a drug administration, thus, the penetration was not thought to be as good as other beta-lactam agents which achieve higher penetration rates. Clinical results Of 407 cases treated with CZON, 18 cases were excluded from the statistical analysis. The remaining 389 cases plus 8 cases each of which had 2 complicated diseases, with a total of 397, were statistically analyzed for the clinical effectiveness of this drug against various infections. The efficacy was evaluated as "good" or "excellent" in 248 out of 266 cases from which pathogens were isolated, for an efficacy rate of 93.2%. The efficacy rate was 88.5% for 131 cases for which pathogens were unidentified, thus no statistically significant difference was noted between the 2 groups.(ABSTRACT TRUNCATED AT 400 WORDS)