Clinical evaluation of cefuzonam in pediatrics and a study on the penetration into cerebrospinal fluid

Studies were carried out on the penetration of cefuzonam (L-105, CZON), a new synthetic cephalosporin antibiotic, into cerebrospinal fluid, and on the clinical efficacy against bacterial infections. The results are summarized as follows: Concentrations of CZON in cerebrospinal fluid at 1 hour after intravenous administration of 100 mg/kg in cases of furunculosis of the external canal, encephalitis and mumps meningitis were 0.56 micrograms/ml, 1.44 micrograms/ml and 0.33 micrograms/ml, respectively. Concentrations of CZON in cerebrospinal fluid at 1 hour after intravenous administration of 100 mg/kg in 3 cases of purulent meningitis were 2.80-6.40 micrograms/ml at the acute stage and 0.56-1.45 micrograms/ml even at the recovering stage. Sensitivities of clinically isolated strains to CZON were determined and expressed as MIC. MICs of CZON on Haemophilus influenzae, Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae were similar to MIC's of cefmenoxime (CMX), and lower than those of cefoperazone (CPZ), cefmetazole (CMZ), cefatiam (CTM) and Cefazolin (CEZ). The MIC of CZON on Staphylococcus aureus was similar to those of CEZ, CMZ and CTM, and lower than those of CMX and CPZ. Clinical responses of CZON were good in 2 cases of purulent meningitis, good in 2 cases of pyothorax, excellent in 1 case of septicemia, excellent in 3 cases of urinary tract infections, excellent in 7 cases and good in 3 cases out of 10 cases of pneumonia. Clinical responses of other diseases were excellent in 4 cases of bronchitis, good in 1 case of furunculosis of the external canal, excellent in 1 case of tonsillitis. No side effects nor abnormal laboratory findings were observed except 2 cases of mild diarrhea out of 24 cases.     

Clinical evaluation of flomoxef in pediatrics and a study on the penetration into cerebrospinal fluid

The transfer to cerebrospinal fluid of a new oxacephem antibiotic flomoxef (FMOX, 6315-S) and its clinical efficacy against bacterial infections were investigated. 1. In 3 cases of purulent meningitis, cerebrospinal fluid concentrations of FMOX after one shot intravenous injection of 100 mg/kg during the acute stage of infections were 5.12-6.32 micrograms/ml and ratios of FMOX in cerebrospinal fluid in serum were about 5%. During the recovery stage, cerebrospinal fluid concentrations were about 3.8 micrograms/ml and cerebrospinal fluid/serum ratios were about 3.5%. 2. In 1 case of purulent meningitis, the treatment with FMOX was clinically effective but this case was classified as "unevaluable" because other drug was used concomitantly. FMOX was rated effective in other 2 cases of purulent meningitis. Of 9 cases of pneumonia, FMOX was rated very effective in 8 cases and it was rated only effective in the other. Of 4 cases of bronchitis, the drug was rated very effective in 3 cases and only effective in the other. FMOX was rated very effective against 2 cases of tonsillitis, also. 3. As side effects, thrombocytosis was observed in 3 of 20 cases examined. All cases, however, were deemed unrelated to the FMOX treatment and the side effect was only transient as are often found in courses of recovery from infections.     

Clinical evaluation of cefpirome in pediatrics and a study on the penetration into cerebrospinal fluid

Cefpirome (CPR, HR 810), a new cephem antibiotic, was investigated for its penetration into cerebrospinal fluid (CSF), and its clinical efficacy against bacterial infections. 1. CSF concentrations of CPR following intravenous injection was investigated in 2 patients with purulent meningitis. In one of them, the concentrations were 2.11 micrograms/ml and 1.31 micrograms/ml on 3 and 8 days, respectively, after start of administration. In the other patient, they were 24.2 micrograms/ml, and 1.35 micrograms/ml on 2 days and 7 days after administration, respectively. 2. Antibacterial activities of CPR against clinical isolates, Escherichia coli, Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae, except those against Pseudomonas aeruginosa, were clearly superior to those of ceftazidime. 3. Clinical efficacies evaluated in 15 patients were "excellent" in 9, "good" in 5 and "unknown" in 1. The overall efficacy rate was 93.0%. 4. Clinical efficacies were "excellent" in 1 patient with bacteremia, "excellent" in 6 and "good" in one of 7 patients with pneumonia, and "good" in both of the 2 patients with purulent meningitis. Clinical efficacies against other diseases were "excellent" or "good", in 1 patient with pyothorax, 1 patient with purulent lymphadenitis, and 2 patients with facial cellulitis. In 1 patient with biliary tract infection, the results of treatment with CPR were "unknown" due to insufficient clinical data. 5. No adverse reactions were observed except in 1 patient who showed an increase in platelet count.     

Clinical study and trial of penetration to the cerebrospinal fluid of aspoxicillin in the pediatric field

Penetration of aspoxicillin (ASPC), a new semisynthetic penicillin, to cerebrospinal fluid (CSF) and clinical studies against bacterial infections were carried out and the following results were obtained. The concentration of ASPC in CSF was below 1 microgram/ml at 1 hour after intravenous administration of about 50 mg/kg dose to 2 cases of aseptic meningitis on the acute stage. The concentration of ASPC in CSF was above 10 micrograms/ml at 1 hour after intravenous administration of about 80 mg/kg dose to 3 cases of purulent meningitis on the acute stage, and was above 2 micrograms/ml even on the recovering stage. On each stage, its concentration was more than minimum inhibitory concentration of H. influenzae (less than or equal to 0.05 microgram/ml; at inoculum size of 10(6) cells/ml). Clinical efficacy of ASPC was good in all 3 cases of purulent meningitis, excellent in 3 cases, good in 3 cases and poor in 1 case out of 7 cases of septicemia, good in 2 cases and poor in 1 case out of 3 cases of gastroenteritis, respectively. And clinical efficacy of other diseases were excellent or good, that were 2 cases of tonsillitis, 2 cases of soft tissue abscess, 1 case of purulent lymphadenitis and 1 case of urinary tract infection, respectively. Side effects were mild eosinophilia in only 2 cases out of 22 cases.     

Fluconazole penetration into cerebrospinal fluid in humans

One hour after intravenous doses of 50 mg/d fluconazole for 6 days or 100 mg/d for seven days to healthy subjects, the cerebrospinal fluid concentrations of fluconazole were 1.26 mg/L and 2.74 mg/L, respectively. These values were approximately 52% and 62% those of serum. Four patients with an initial clinical diagnosis of meningitis also had significant concentrations of fluconazole in the cerebrospinal fluid.     

Clinical experience with aztreonam in the pediatric field

Aztreonam (AZT) was given intravenously to 20 children with the following acute bacterial infections: 13 cases of bronchopneumonia, 5 cases of urinary tract infection, 1 case of cervical lymphadenitis with acute tonsillitis and 1 case of acute enteritis. Clinical effectiveness was obtained in 17 cases of 20 cases and bacteriological effectiveness in 10 strains out of 11 strains. No side effect was observed except for 2 cases with eruption, 1 case with slight elevation of GPT, 1 case with slight elevation of GOT and 1 case with slight elevation of GOT and GPT. From the above clinical results, it is apparent that AZT is a useful antibiotic for treating pediatric patients with various kinds of bacterial infections.     

Clinical evaluation of aztreonam against pediatric purulent meningitis

A monotherapy of aztreonam (AZT) was applied to 9 male and 3 female pediatric patients of ages ranging from 2 months to 8 years and 11 months with serious purulent meningitis. The results are summarized as follows: 1. Daily dosages of 134 to 400 mg/kg were given 3 to 4 times a day for 10 to 28 days. 2. The isolated pathogens were Neisseria meningitidis in 2 cases, Escherichia coli in 3 cases, Haemophilus influenzae in 6 cases, but the pathogen of the last case was unknown. In this case, the patient had myelomeningocele and suffered from recurrent purulent meningitis. 3. Clinical effect was "excellent" in 5 of 12 cases, "good" in 7 cases and efficacy rate was 100%. Microbiological tests were performed on 9 cases during the course of treatment and bacterial elimination rate was 100%. All the pathogens were eliminated in 72 hours. 4. One case of diarrhea was observed, but the diarrhea started before the administration of AZT and was stopped after the AZT treatment. A slight elevation of GOT value was observed in 1 case but the value returned to the initial level promptly after the treatment was completed. It is considered that AZT is highly useful for purulent meningitis caused by Gram-negative pathogens such as H. influenzae, E. coli and N. meningitidis.     

Clinical experience of latamoxef in the field of neurosurgery on the penetration into the cerebrospinal fluid in the patients with postoperative meningitis

Latamoxef (LMOX) at a dose of 2 g was intravenously administered to 12 cases with postoperative meningitis and the concentrations in serum and cerebrospinal fluid (CSF) were examined up to 2 hours and the results obtained were as follows; The average serum and CSF concentrations of LMOX were 125.0 micrograms/ml, 4.33 micrograms/ml at 0.5 hour, 80.7 micrograms/ml, 4.64 micrograms/ml at 1 hour and 45.8 micrograms/ml, 3.82 micrograms/ml at 2 hours, respectively. The clinical responses of LMOX against postoperative meningitis were revealed excellent in 4 cases and good in 8 cases. No side effects were observed. LMOX was thought to be effective agent in the treatment of the postoperative meningitis.     

Clinical evaluation of aztreonam in the field of obstetrics and gynecology

Aztreonam (AZT), a new monobactam antibiotic was evaluated on clinical efficacy and bacteriological response in gynecological and obstetrical infections, and the following results were obtained. AZT was given to 22 cases with obstetrical and gynecological infections at a dose of 1 g X 2 times daily and 86.4% of clinical efficacy, 45.5% of eradicated rate on diagnosis, 52.5% of bacteriological response on isolated organisms and 83.3% of bacteriological effect on cases isolated Gram-negative bacteria were assessed. Side effect incidence was very low.     

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 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.     

Laboratory and clinical studies of aztreonam in the pediatric field

The authors have carried out the laboratory and clinical studies of aztreonam (AZT) and obtained the following results. The antibacterial activities of AZT against the clinical isolates of E. coli, K. pneumoniae and P. aeruginosa were measured by the agar dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of E. coli to AZT ranged from 0.025 or lower to 1.56 microgram/ml, and the peak of distribution was 0.05 microgram/ml. The peak of susceptibility distribution of K. pneumoniae was 0.025 microgram/ml or lower, and the distribution of P. aeruginosa ranged from 0.1 to 100 micrograms/ml higher and the peak of distribution was 3.13 micrograms/ml. After intravenous bolus injection of 20 mg of AZT in 4 children, the mean peak serum level was 117 +/- 35.1 micrograms/ml at 15 minutes after injection, and half-life time was 1.42 hours. The mean urinary excretion rates was 63.2 +/- 30.6% up to 6 hours after bolus injection of 20 mg/kg of AZT. AZT was given 11 cases with bacterial injection. Daily doses of AZT were from 41.7 to 94.9 mg/kg. Clinical results obtained were excellent and good responses in 8 of 11 cases (72.7%). No side effect was observed.     

Clinical study on cefdinir in pediatric field

We studied pharmacokinetics and clinical effects of cefdinir (CFDN), a newly developed oral cephalosporin, and the following results were obtained. 1. Pharmacokinetics of CFDN in 2 patients were investigated. The 2 patients with ages of 8 years (36.5 kg, body weight) and 6 years (26.5 kg, body weight) were administered with 3 mg/kg of fine granules of CFDN on empty stomachs. Peak plasma levels of CFDN were 0.85 microgram/ml in one patient and 0.56 microgram/ml in the other. The 8-hour urinary recovery rate was 21.6% of the administered dose in one and was not calculable in the other. 2. Clinical effects of CFDN were studied in 25 children with various infectious diseases: 11 with acute pharyngitis, 1 with acute tonsillitis, 2 with acute laryngitis, 3 with acute bronchitis, 2 with acute bronchopneumonia, 4 with scarlet fever, 1 with acute otitis media, 1 with acute lymphadenitis. The efficacy rate was 96% (24/25), and the bacteriological eradication rate was 83.3% (10/12). 3. No side effects were noted. Clinical laboratory test values were investigated in 14 patients. There were no seriously abnormal laboratory test findings except a slight elevation of eosinophile and GPT.     

Clinical study on aztreonam in pediatrics

Efficacy and safety of aztreonam (AZT) for 31 cases of infections of children were studied with the following results. Clinical efficacy of AZT for 22 respiratory tract infections, 5 urinary tract infections and 2 gastrointestinal infections was "excellent" for 19 cases (65.5%), "good" for 9 cases (31.0%) and "poor" for 1 case (3.4%) with an overall effective rate of 96.6%. Microbiological effect of AZT for 19 isolated strains (15 cases) was 100% in disappearance of the Gram-negative bacteria and 89.5% on the whole. With regard to side effect of AZT in 31 cases, there was a slight elevation of GPT in 1 case and eosinophilia in 2 cases. It was considered from the above results that AZT is a useful and safe antibiotic for infections of children.     

Clinical evaluation of aztreonam in children

Clinical usage of aztreonam (AZT), a newly synthesized antibiotic which belongs to monobactam, was evaluated for its efficacy and safety in 22 patients aged from 1 month-old to 13 year-5 month-old with bacterial infections and the following results were obtained. AZT was administered to 4 patients with pyelonephritis and 10 patients with tonsillitis at a daily dosage of 40.4-120.9 mg/kg and to 5 patients with clinical sepsis associated with agranulocytosis caused by intensive antileukemic therapy at a daily dosage of 142.4-171.4 mg/kg, divided into 3 or 4, by intravenous injection or by 30 minutes drip infusion. The clinical results of these 19 evaluable patients were as follows: excellent; 10 cases, good; 5 cases, fair; 2 cases, poor; 2 cases. The over all efficacy rate was 78.9% and that of pyelonephritis and tonsillitis was 100.0%. No clinical side effects were observed in any 23 patients, including a patient who proved to be suffering from Mycoplasma pneumoniae infection, and no abnormal laboratory findings caused by AZT was noticed. The MICs of AZT against 9 strains isolated from patients with pyelonephritis and those with tonsillitis were as follows: MICs against all of 3 strains of K. pneumoniae were less than 0.05 microgram/ml. MICs against 2 out of 4 strains of H. influenzae were less than 0.05 microgram/ml and those of the remaining 2 strains were 0.10 microgram/ml. MIC against 1 strain of S. aureus was 1.56 microgram/ml. MIC against 1 strain of S. epidermidis was more than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of cefdinir in pediatric field

We studied the clinical efficacy of cefdinir (CFDN), a new oral cephalosporin, in 18 children with ages 2 years and 4 months to 11 years and 4 months with pediatric infections. The diagnoses consisted of respiratory tract infections in 15 cases, impetigo in 2 and balanoposthitis in 1. Clinical efficacies were excellent in 11 patients and good in 7, with an efficacy rate of 100%. Bacteriologically, 9 (64.3%) of the 14 strains of clinical isolates were eradicated. No side effects nor abnormal laboratory findings were observed. We have concluded that CFDN is a useful antibiotic for the treatment of mild to moderate pediatric infections.     

Clinical evaluation of cefpirome in pediatric field

Cefpirome (CPR), a new synthetic cephalosporin antibiotic, was administered to 10 patients with infectious diseases. The patients included 5 boys and 5 girls from 1 month to 5 years of age. They were given the drug intravenously at dosages ranging 53-100 mg/kg/day for 4 to 10 days. Clinical efficacy was evaluated in 9 patients: excellent in 2 patients, good in 6 patients and fair in 1 patient. The overall efficacy rate was 88.9%. No adverse effects were observed except in one patient who showed a slight increase of serum GOT and GPT.     

The penetration of cefoperazone into the cerebrospinal fluid in patients on acute or chronic stage

Cefoperazone (CPZ) was administered to 10 patients with cerebrovascular disturbances at acute and chronic phases to investigate its passage into the cerebrospinal fluid. The antibiotic was administered at dosages of 1 g and 2 g to patients in the acute phase to examine the dose-dependency. The results obtained are summarized as follows: 1. Serum concentrations Peak values of CPZ were 46.9 +/- 4.42 microgram/ml in acute phase patients in 1 g dosage group (acute group 1), 253.1 +/- 63.2 micrograms/ml in acute phase patients in 2 g dosage group (acute group 2), and 197.9 +/- 15.7 micrograms/ml in chronic phase patients in 2 g dosage group (chronic group 2) at 1 hour after CPZ administration. Concentrations of CPZ varied about 5-fold between the 1 g dosage group and the 2 g dosage groups. The acute group 2 showed generally higher values of CPZ concentrations than the chronic group 2. 2. Cerebrospinal fluid concentrations. Peak values were 0.96 +/- 0.30 microgram/ml (at 3 hours) in acute group 1, 4.55 +/- 3.41 micrograms/ml (at 1 hour, except 1 case) in acute group 2, and 1.29 +/- 1.28 micrograms/ml (at 1 hour) in chronic group 2. Acute group 2 showed generally higher values than chronic group 2. 3. CPZ was considered useful for the prevention of postoperative infections in the field of brain surgery.     

Clinical study on meropenem in pediatric field]

We studied clinical effects of meropenem (MEPM, SM-7338), a newly developed parenteral carbapenem beta-lactam drug, and following results were obtained. The patients were administered with 16-20 mg/kg of MEPM every 8 hours using 1 hour drip infusion. 1. Clinical effects of MEPM were studied in 10 children with various infectious diseases: 1 with acute bronchitis, and 2 each with acute tonsillitis, acute bronchopneumonia, acute pneumonia, acute urinary infection, and 1 with pertussis pneumonia. The case of pertussis pneumonia later developed bronchiolitis obliterans, hence a steroid and gamma-globulin were used. This case was excluded from the clinical evaluation. The efficacy rate was 100% (9/9), and the bacteriological eradication rate was 100% (6/6). 2. No side effects were noted. Clinical laboratory test values were investigated in 10 patients. There was a case of abnormal laboratory test findings with mild elevations of liver functions such as GOT, GPT, and gamma-GTP. These abnormalities disappeared in 1 week after the end of therapy.