sy-5555 and Bacterial-Infections

Laboratory and clinical studies were performed on SY5555, the first penem oral antibiotic developed in Japan, in the pediatric field. The following results were obtained. 1. Antibacterial activities of the drug against 42 strains of Streptococcus pneumoniae clinically isolated in 1993 were compared to those of 13 other drugs mainly composed of beta-lactam preparations. Minimum inhibitory concentration (MIC) values of SY5555 were below 0.39 micrograms/ml for all strains examined, thus the drug showed an excellent activities against benzylpenicillin (PCG)-resistant strains as well. When the antibacterial effects of individual drugs were compared using MIC50 and MIC90 as indices, SY5555 was the most effective against PCG-sensitive strains and similar to cefazolin (CEZ), cefotaxime (CTX), cefuzonam (CZON), amoxicillin (AMPC) and imipenem (IPM). It also showed excellent antibacterial effects against moderately PCG-resistant strains, and the activities were similar to IPM. Activities of SY5555 on highly PCG-resistant strains were similar to those of CTX, CZON and IPM. 2. SY5555 at a dose of 5 mg/kg or 10 mg/kg was administered to 16 pediatric patients in the fasting state or after meal to examine its plasma concentration and urinary excretion rate. The fecal excretion was measured in 5 affected children treated with this drug. When the drug at a dose of 5 mg/kg was administered to 11 older children, 5 with ages 5-12 years and 6 with ages 10-13 years in the fasting state and after meal, respectively. Peak plasma levels were reached at 1 hour after administration in the two groups, and they were 0.93 +/- 0.25 and 2.44 +/- 1.25 micrograms/ml, respectively. The plasma levels then decreased gradually with half-lives of 1.95 +/- 1.09 and 0.72 +/- 0.21 hours, respectively. Urinary recovery rates in the first 6 hours after administration were 1.98 +/- 0.82 and 4.13 +/- 1.40%, respectively. In 3 cases (6-9 years) treated with the drug at a dose of 10 mg/kg after meal, a peak of 1.58 +/- 0.81 micrograms/ml appeared 1 hour after administration with a half-life of 1.08 +/- 0.30 hours and with the urinary recovery rate in the first 6 hours after administration of 3.46 +/- 1.03%. When the drug at a dose of 10 mg/kg was administered to 2 infants (2-3 months post partum) after meal, a peak plasma level of 3.74 micrograms/ml appeared 1 hour after administration with a half-life of 1.19 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Half-Life; Humans; Impetigo; Infant; Male; Microbial Sensitivity Tests; Patient Compliance; Respiratory Tract Infections; Urinary Tract Infections

Clinical studies on SY5555 dry syrup, a new oral penem antibiotic, were carried out in the field of pediatrics. The following results were obtained. 1. SY5555 was administered to 10 children with various bacterial infections (2 patients with acute tonsillitis, 2 with acute bronchitis, 1 with pharyngitis, 2 with scarlet fever, 1 with pertussis and 2 with urinary tract infections). The overall clinical efficacy rate was 90%. 2. Side effects or abnormal laboratory test values were not observed except for loose stool in 1 and eosinophilia in 1.

Topics: Administration, Oral; Bacterial Infections; Carbapenems; Child; Child, Preschool; Diarrhea; Eosinophilia; Female; Humans; Infant; Male; Respiratory Tract Infections; Scarlet Fever; Urinary Tract Infections

SY5555, a new oral penem, in the form of dry syrup (powder which is dissolved before use) was evaluated for its pharmacokinetics and clinical efficacy in pediatric patients. Oral administration of 5 mg/kg and 10 mg/kg of SY5555 in dry syrup resulted in respective maximum plasma concentrations of 1.08 +/- 0.38 micrograms/ml (n = 4) and 2.50 +/- 1.81 micrograms/ml (n = 4), half-lives (T 1/2) of 2.72 +/- 1.86 hours (n = 3) and 1.14 +/- 0.88 hours (n = 4), and urinary excretion until 6 hours of 4.7% (n = 1) and 3.86 +/- 2.01% (n = 4). Clinical efficacy was evaluable in 22 patients, and the overall efficacy rate was 100%. As for bacteriological efficacy, all 5 strains of pathogenic organisms identified were eradicated (eradication rate, 100%). No remarkable adverse reactions or abnormal laboratory values were observed.

Topics: Administration, Oral; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Half-Life; Humans; Infant; Male; Respiratory Tract Infections; Urinary Tract Infections

Pharmacokinetic, bacteriological and clinical studies on SY5555 were performed in children. The results were as follows: 1. A total of 15 patients considered to have bacterial infections were treated with SY5555. Each dose, 5 mg/kg, was orally administered 3 times daily, for 4-11 days. Clinical efficacies of SY5555 in 13 patients with bacterial infections (1 with pneumonia, 2 with bronchitis, each 1 with maxillary sinusitis, 2 with otitis media, 5 with pharyngitis, 1 each with gastroenteritis and pyelonephritis) were evaluated as excellent in 10 patients and as good in 3 patients with an efficacy rate of 100%. Two patients with viral infection and malignant lymphoma were not evaluated. Thirteen causative strains in 7 species were found in 10 patients. Streptococcus pneumoniae in 1/3, Haemophilus influenzae in 2/2, Streptococcus pyogenes 4/4, Salmonella spp. in 1/1, Escherichia coli in 1/1 were eradicated. Only one patient developed mild diarrhea as an adverse reaction. Another patient showed elevated GPT (glutamate pyruvate transaminase). The abnormality was mild and the patient recovered after the cessation of SY5555 administration without specific treatment. 2. MICs of SY5555 were examined against 33 clinical isolates. SY5555 has low MICs against Enterococcus faecalis and other Gram-positive cocci. 3. Pharmacokinetic studies Peak plasma concentrations of SY5555 was 1.15 micrograms/ml at a dose level of 4.9 mg/kg orally administered at fasting. Based on the above results and the broad spectrum of the anti-bacterial activities, SY5555 appears to be a promising antibiotics that is usable as a single agent for the primary therapy of respiratory tract infections, skin soft tissue infections and urinary tract infections in children.

Topics: Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Respiratory Tract Infections; Urinary Tract Infections

Pharmacokinetic and clinical studies on SY5555, a new oral penem antibiotics, were performed in pediatric infections and the following results were obtained. 1. Pharmacokinetics studies Pharmacokinetics of SY5555 was studied in 5 children (5y1m-10y11m) using doses of 5 mg/kg (n = 3) and 10 mg/kg (n = 2). The average peak plasma levels were 0.65 microgram/ml at 1 or 2 hours after administration of 5 mg/kg and 2.12 micrograms/ml at 1 or 2 hours after administration of 10 mg/kg, and the plasma half-lives were 0.81 and 1.08 hours, respectively. Average cumulative urinary recovery rates at 0-6 hours were 2.97 and 3.96%, respectively. 2. Clinical studies SY5555 was administered to 45 patients with various infectious diseases (2 with acute pharyngitis, 8 with acute tonsillitis, 4 with lacunar tonsillitis, 3 each with acute bronchitis, pneumonia and pertussis, 7 with scarlet fever, 3 with impetigo contagiosa, 6 with acute urinary tract infections, 2 with balanoposthitis and 1 each with cervical lymphadenitis, S.S.S.S., vulvitis and acute colitis) at daily doses between 3.4-10 mg/kg, t.i.d., for 3-14 days. Clinical responses were excellent in 27 patients, good in 15 patients, fair in 1 patient, and poor in 2 patients, and the efficacy rate was 93.3%. Causative organisms were examined and 39 strains of 11 species were identified. The eradication rate was 78.9%. Side effects were observed in 1 patient with diarrhea. An abnormal laboratory test value was observed in 1 patient with elevation of eosinophils. The above results suggest that SY5555 may be a very useful and safe drug for the treatment of pediatric infection.

Topics: Administration, Oral; Adolescent; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Humans; Impetigo; Infant; Male; Respiratory Tract Infections; Scarlet Fever; Urinary Tract Infections

A new oral penem antibiotic, SY5555, was evaluated for its safety and efficacy in 35 children with various bacterial infections. SY5555 was effective in 100% of scarlet fever, pharyngotonsillitis, pneumonia, otitis media, bacterial diarrhea, urinary tract infections and skin and soft tissue infections. The etiologic bacteria were eradicated except Salmonella sp. Side effects were observed in 3.5% cases; one was diarrhea and Candida dermatitis, one was loose stool, and one was Candida dermatitis. From these data, SY5555 is thought to be a safe and effective antibiotic in the pediatric field. Regular dose of suspension preparation is 15 mg/kg/day in 3 divided dosages, and when needed the dose may be doubled.

Topics: Administration, Oral; Bacterial Infections; Carbapenems; Child; Child, Preschool; Diarrhea; Female; Humans; Infant; Male; Otitis Media; Respiratory Tract Infections; Urinary Tract Infections

Bacteriological, pharmacokinetic and clinical studies on SY5555 dry syrup (powder which is dissolved before use), a new penem antibiotic for oral use, were performed. The following results were obtained. 1. Antibacterial activities. MICs of SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN) were determined against clinically isolated Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli and Enterobacter cloacae at a dose of 10(6) CFU/ml. MICs of SY5555 against S. aureus, CNS, S. pneumoniae, S. pyogenes, H. influenzae, M. catarrhalis, E. coli and E. cloacae were 0.2, 0.2, 0.2, < or = 0.025, 0.78, 0.2, 0.78 and 3.13 micrograms/ml, respectively, showing excellent antibacterial effects on these pathogens. Although the effects of SY 5555 against H. influenzae and E. coli were slightly inferior to those of CPDX and CFDN, the drug showed the most excellent antibacterial effect on other strains as compared with the control drugs. 2. Absorption and excretion In this study, plasma concentrations and urinary recovery rates were examined after administration of SY5555 at doses of 5 and 10 mg/kg (potency) after meals. With both 5 and 10 mg/kg doses, peak plasma concentrations were reached 1 hour after administration, at 0.25-2.61 micrograms/ml (mean 1.47 micrograms/ml) and 1.08-2.17 micrograms/ml (mean 1.74 micrograms/ml), respectively. The plasma levels rapidly decreased to 0.06-0.19 micrograms/ml (0.12 micrograms/ml) and 0.0503-0.0637 micrograms/ml) after 6 hours. The half-lives 1.12 hours in the 5 mg/kg group and 1.0 hour in the 10 mg/kg group. The urinary recovery rates were determined in the first 8 hours after administration in the 5 mg/kg and 6 hours in the 10 mg/kg group, and the values were as low as 1.05-12.3% and 1.6-4.33%, respectively. 3. Clinical results The clinical responses were examined in a total of 73 cases including 4 acute pneumonia, 13 acute bronchitis, 11 tonsillitis, 3 pharyngitis, 12 scarlet fever, 2 pertussis, 6 urinary tract infection, 6 otitis media, 7 lymphadenitis, 2 staphylococcal scalded skin syndrome, 2 phlegmon, 4 impetigo and 1 purulent parotitis. The treatment was effective or better in 66 of 70 cases with an efficacy rate of 94.3% (3 undeterminable cases were excluded). Bacteriological effects were examined during the clinical course for detected or

Topics: Absorption; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Respiratory Tract Infections; Skin Diseases, Bacterial; Urinary Tract Infections

We assessed the in vitro antimicrobial activity and the clinical efficacy and safety of SY5555 in the field of pediatrics. The results obtained are summarized below. 1. In vitro antibacterial activities of SY5555 against 52 clinical isolates were compared with those of clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN). Against Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, SY5555 displayed antimicrobial activities superior or nearly equivalent to those of the reference agents used in the study. In cases of Gram-negative bacteria, the antimicrobial activity of SY5555 against Haemophilus influenzae was inferior to those of CPDX and CFDN. Against Klebsiella pneumoniae, the antimicrobial activity of SY5555 was less potent than that of CPDX. 2. Forty-seven children with infectious diseases were treated with SY5555 dry syrup (powder dissolved just before use). The clinical results were excellent in 24 and good in 16, with an efficacy rate of 85.1%. 3. Bacteriological screening identified 30 pathogenic organisms, and the eradication rate was 76.7%. 4. Side effects consisted of diarrhea in 12.5% (6 cases), loose stools in 4.2% (2 cases) and urticaria in 2.1% (1 case) of the patients. The only abnormal laboratory test value observed was an increase in eosinophil count in one child. 5. The palatability of SY5555 dry syrup was very good; it was very easily ingestable or easily ingestable by 32 of the 48 children. From the above results, SY5555 dry syrup appears to be a useful drug with a preferable safety profile in the treatment of pediatric patients with infectious diseases.

Topics: Administration, Oral; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Male; Microbial Sensitivity Tests

Clinical studies were carried out on SY5555, a new oral penem, in the field of pediatrics. The results obtained are summarized below. The clinical efficacies were examined in a total 31 patients consisting of 4 patients with pharyngitis, 10 with purulent tonsillitis, 4 with scarlet fever, 7 with impetigo, one with balanitis, one with cellulitis and 4 with UTI. The clinical efficacy rate was 96.8% (30/31). Bacteriological efficacies of SY5555 were examined on identified pathogens including 7 strains of Staphylococcus aureus, 6 of Streptococcus pyogenes, 3 of Enterococcus faecalis, 3 of Haemophilus influenzae, one of Escherichia coli and one of Citrobacter freundii. The bacteriological eradication rate was 81.0%. As for side effects, loose stool in one patient was noted. Abnormal laboratory findings test results included eosinophilia in 2 patients, eosinophilia and elevation of serum transaminase in one patient, and thrombocytosis in another.

Topics: Administration, Oral; Adolescent; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male

SY5555 dry syrup (powder to be dissolved before use) was clinically used in pediatric patients. The following results were obtained: 1. The subjects were 6 pediatric patients including 1 case each with pharyngitis, tonsillitis, lacunar tonsillitis and impetigo contagiosa and 2 cases with scarlet fever. The drug was administered at a daily dose of 14.5-29.0 mg/kg divided into 3 dosages. The clinical results were excellent in 5 cases and good in 1 case with an efficacy rate of 100%. 2. Identified bacteria included 3 strains of Haemophilus influenzae, 2 strains of Streptococcus pyogenes and 1 strain of Staphylococcus aureus. Five strains were eradicated but 1 strain still remained with an bacteriological eradication rate of 83.3%. 3. No side effects were observed throughout the study period. In laboratory test results, elevated eosinophil count was observed in only 1 case. 4. Patients' compliance was good in general. 5. Based on the results mentioned above, the drug was considered to be a useful new oral antibiotic in the pediatric field.

Topics: Administration, Oral; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Humans; Male

A clinical study was performed on SY5555, a newly developed penem antibiotic, in children. SY5555 was given orally to 14 patients at 19-29 mg/kg/day in 3 doses for 4 to 12 days. Clinical evaluations were made on the 14 patients including 4 with pharyngitis, 7 with tonsillitis, one with urinary tract infection, and 2 with impetigo. Overall clinical effects were excellent in 2, good in 12, with an efficacy rate of 100%. Causative organisms (Staphylococcus aureus and Streptococcus pyogenes) were all eradicated. As to adverse reactions, mild diarrhea was observed in 4 patients. These data suggest that SY5555 is a useful oral antibiotic for the treatment of bacterial infections in children.

Topics: Administration, Oral; Adolescent; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male; Staphylococcus aureus; Streptococcus pyogenes

1. SY5555 dry syrup (powder which is dissolved before use) was administered to 25 patients with bacterial infections (6 cases of bronchitis, 2 cases of bronchopneumonia, 1 case of pertussis, 3 cases of scarlet fever, 5 cases of tonsillitis, 3 cases of urinary tract infections, 2 cases of staphylococcal scalded skin syndrome, 1 case of impetigo, 2 cases of purulent lymphadenitis). 2. Clinical efficacies were excellent in 11 patients and good in 13, poor in 1 with an efficacy rate of 96.0%. As pathogenic organisms, 15 strains were identified and 14 of them were eradicated with eradication rate of 93.3%. 3. No side effects were observed. As for abnormal laboratory test results increase in eosinophiles in 2 cases, decrease in filamented neutrophiles in 1 case, elevation of GOT and GTP in 1 case and elevation of GPT and gamma-GTP were observed. 4. There was no rejection incidence of the drug during the therapy. From the above results, we consider SY5555 in dry syrup form to be a useful and safe drug in the treatment of various bacterial infections in pediatric patients.

Topics: Administration, Oral; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male

SY5555 in dry syrup (powder which is dissolved before use) or tablet form was given orally to 21 children with acute bacterial infections including 4 with acute pharyngitis, 5 with acute tonsillitis, 7 with acute bronchitis, 2 with acute gastroenteritis, 1 each with scarlet fever, acute lymphadenitis and urinary tract infection. Good to excellent clinical responses were obtained in all of the 21 patients and 8 of 11 strains found as causative organisms in these cases were eradicated and 3 strains were decreased. Loose stools were observed in 3 cases and eosinophilia was observed in 1 case. From the above clinical results, it appears that SY5555 is a useful antibiotic for the treatment of pediatric patients with various bacterial infections.

Topics: Administration, Oral; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male; Powders; Tablets

Clinical effects of SY5555 dry syrup, a new oral penem antibiotic, were analysed in 20 children with various bacterial infections. Ages of the patients varied from 8 months to 14 years. Doses of SY5555 were varied from 12.8 mg/kg/day to 30.5 mg/kg/day, and it was administered in 3 divided dosages. Clinical efficacy rates were as follows; 6/7 in acute bronchitis, 5/5 in pharyngotonsillitis, 3/3 in acute otitis media and 2/2 in cystitis and 3/3 in impetigo contagiosa. The overall rate was 95.0% (19/20). Bacteriologically, eradications were obtained with 1/2 strains of Streptococcus pyogenes, 3/3 of Staphylococcus aureus, 1/1 of Haemophilus influenzae, and each of Staphylococcus epidermidis, Haemophilus parainfluenzae, coagulase-negative staphylococci and Serratia marcescens. Diarrhea was observed in 1 patient. And elevated eosinophiles or GPT was observed in one patient each. In vivo pharmacokinetics of SY5555 was examined in 2 cases. Peak plasma levels were observed at 1 hour after dosage in one patient and at 2 hours in another upon oral administration of 8.3 mg/kg of SY5555, and peak levels were 2.44 and 1.38 micrograms/ml respectively. Half-lives of SY5555 were 1.39 and 0.59 hr. Concentrations of SY5555 in urine after administration were 70.2 (2-4 hrs.) to 91.0 (0-5 hrs.) micrograms/ml, respectively. SY5555 dry syrup is considered as an useful and safe antibiotic in treating the infectious diseases in children.

Topics: Administration, Oral; Adolescent; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male

Pharmacokinetic, bacteriological and clinical studies on SY5555, a new oral penem, were carried out, and the following results were obtained. 1. MICs were determined for 6 drugs, SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefaclor (CCL), cefotiam (CTM), cefpodoxime (CPDX), cefdinir (CFDN) against 20 strains of bacteria isolated from patients who were subsequently treated with SY5555. MICs of SY5555 for Gram-positive cocci ranged from 0.05 to 0.10 microgram/ml against 10 strains of Staphylococcus aureus. The MIC was < or = 0.025 microgram/ml against one strain of Streptococcus pyogenes, and MICs were from < or = 0.025 to 0.39 microgram/ml against Streptococcus pneumoniae. These MIC values were equivalent or superior to those of the other 5 drugs. MICs of SY5555 for Gram-negative bacilli were 0.39 and 6.25 micrograms/ml against Haemophilus influenzae, and these values were equivalent to those of the other drugs, except CPDX. The MIC of SY5555 was 0.39 microgram/ml against 2 strains of Escherichia coli, and this value was equivalent or superior to those of CVA/AMPC and CCL, similar or inferior to those of CPDX and CFDN, and inferior to that of CTM. The MICs of several drugs were determined for 10 strains of Bordetella pertussis and 30 strains of Campylobacter jejuni isolated from patients before this clinical study. The MICs of SY5555 against the 10 strains of B. pertussis were compared with those of 7 drugs, CCL, CTM, CPDX, ampicillin (ABPC), piperacillin (PIPC), imipenem (IPM) and erythromycin (EM). The MIC of SY5555 was 0.78 microgram/ml against all of the strains. This value was superior to those of CCL, CTM and CPDX, similar or inferior to that of IPM and inferior to those of PIPC and EM. The MICs of SY5555 against the 30 strains of C. jejuni were compared with those of 7 drugs. CCL, CTM, CPDX, CFDN, ABPC, IPM and EM, and the MIC of SY5555 was < or = 0.025 microgram/ml or 0.05 microgram/ml and these values were equivalent or superior to those of the 7 reference drugs. 2. SY5555 dry syrup was administered orally at 30 min. after meals, to a total of 5 patients, at doses of 5.0 and 10.0 mg/kg to 2 patients each and at a dose of 15.0 mg/kg to one patient and the plasma concentrations were determined. Peak concentrations were detected 1 to 3 hours after administration in all patients and the peak concentrations were 0.93 and 1.21 micrograms/ml at the 5.0 mg/kg dose, 2.85 and 5.49 micrograms/ml at the 10.0 mg/kg dose and 5.79 micrograms/ml at the 15.0 m

Topics: Administration, Oral; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male; Powders

SY5555 is a new oral penem antibiotic. Pharmacokinetic and clinical studies using SY5555 dry syrup (powder which is dissolved before use) were performed in pediatric patients. 1. Pharmacokinetic investigation Peak plasma concentrations of SY5555 after dose of 5 mg/kg, 10 mg/kg and 15 mg/kg were, respectively, 1.58 +/- 0.37 micrograms/ml, 2.78 +/- 0.54 micrograms/ml and 5.28 micrograms/ml at 1 hour. The average half-life with 5 mg/kg administration was 0.94 +/- 0.05 hours, that with 10 mg/kg was 1.46 +/- 0.31 hours and that with 15 mg/kg was 0.88 hours. 2. Clinical investigation Enrolled in the study were 15 patients including 5 with acute otitis media, 5 with urinary tract infections and 1 each with pharyngitis, tonsillitis, bronchitis, pneumonia and subcutaneous abscess. Responses were excellent in 4 patients, good in 8 patients, fair in 2 patients and poor in 1 patient. In the assessment of the bacteriological efficacy, 8 out of 10 strains of organism identified previous to treatment were eradicated and 2 strains were unchanged, hence the eradication rate was 80.0%. 3. No adverse reactions attributable to the drug were observed and good drug compliance were obtained. From the above results, it has been concluded that SY5555 is a highly effective and safe agent for mild to moderate respiratory and urinary tract infections in children.

Topics: Administration, Oral; Bacterial Infections; Carbapenems; Child; Child, Preschool; Female; Humans; Infant; Male

SY5555, a new oral penem, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics Pharmacokinetics of SY5555 dry syrup (powder which is dissolved before use) was investigated in 64 children. At a dose level of 3 mg (potency)/kg, Cmax and T1/2 were 0.33 micrograms/ml and 0.95 hours (n = 1), respectively, in the non-fasting state. At a dose level of 5 mg/kg Cmax and T1/2 were 2.09 +/- 1.25 micrograms/ml and 1.20 +/- 1.07 hours, respectively, in the fasting state, and were 1.21 +/- 0.70 micrograms/ml and 1.33 +/- 0.90 hours, respectively, in the non-fasting state. At a dose level of 10 mg/kg, Cmax and T1/2 were 2.96 +/- 1.89 micrograms/ml and 0.89 +/- 0.43 hours, respectively, in the fasting state, and were 2.45 +/- 1.37 micrograms/ml and 1.17 +/- 0.53 hours, respectively, in the non-fasting state. At a dose level of 15 mg/kg, Cmax and T1/2 were 4.30 +/- 2.15 micrograms/ml and 0.82 +/- 0.09 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that plasma concentration of the drug depended on dose levels. Urinary recovery rates in the first 6 hours were 1.71% (n = 1) in the non-fasting state at a dose level of 3 mg/kg, 4.13 +/- 1.40% in the fasting state and 4.17 +/- 3.29% in the fasting and the non-fasting state, respectively at a dose level of 5 mg/kg, and 6.02% (n = 1) and 4.64 +/- 2.81%, respectively, at a dose level of 10 mg/kg. At a dose level of 15 mg/kg, urinary recovery rate in the first 6 hours was 7.97% (n = 2) in the non-fasting state. 2. Clinical results 1) Dry syrup The clinical efficacy of the SY5555 dry syrup was evaluated in 506 cases. SY5555 was administered at daily doses of 15-30 mg/kg divided into 3 equal doses to most patients. Daily doses of 12- < 18 mg/kg were given to 46.6% of the patients. The overall clinical efficacy rate was 92.9%, and this drug was effective in 93.0% of the 301 patients for whom the causative pathogens were identified, and in 92.7% of the 205 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of 12 - < 18 mg/kg was 94.5% similar to those obtained at daily doses of 18- < 27 mg/kg (91.7%) or 27- < 33 mg/kg (91.3%). The bacteriological eradication rate was 82.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Absorption; Adolescent; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Dosage Forms; Female; Half-Life; Humans; Infant; Japan; Male; Tablets

The in vitro activity of the new penem derivative ALP-201 against 226 aerobic and 350 anaerobic clinical bacterial isolates was determined using agar dilution techniques. For comparison amoxicillin, cefaclor, ceftazidime, doxycycline, erythromycin, imipenem and trimethoprim/sulfamethoxazole were also tested with aerobic bacteria, and cefoxitin, chloramphenicol, clindamycin, imipenem, metronidazole and piperacillin with anaerobic bacteria. ALP-201 was found to be highly active against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, Branhamella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, anaerobic cocci, Propioni-bacterium acnes, Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria. Pseudomonas aeruginosa and Clostridium difficile were resistant to ALP-201. When tested against aerobic bacteria using a high inoculum or using the broth dilution technique, the activity of ALP-201 showed little dependence on inoculum size and the bactericidal activity was similar to the inhibitory activity. Further investigations are warranted with ALP-201, which is absorbed from the gastrointestinal tract after oral administration.

Topics: Administration, Oral; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Humans; In Vitro Techniques; Microbial Sensitivity Tests