sy-5555 and Respiratory-Tract-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

Furopenem is a novel orally active penem. In this study, furopenem was highly active in vitro against Streptococcus pneumoniae (MIC90 0.03 mg/L), Haemophilus influenzae (MIC90, 2 mg/L), and Moraxella catarrhalls (MIC90, 0.5 mg/L). Its activity was not reduced by a variety of beta-lactamase enzymes, however beta -lactam resistance by other mechanisms was associated with higher MICs.

Topics: Bacteria; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cephalosporins; Haemophilus influenzae; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Streptococcus pneumoniae