s-1108 and Bacterial-Infections

Excessive use of broad spectrum antibiotics is related to the spread of drug resistant bacterial strains in the community.. The effects of immediate testing for C reactive protein (CRP) and white blood cell count (WBC) on physicians' choices of antibiotic was investigated in patients with acute infection. Acutely febrile new outpatients were randomised into two groups: group 1 (147 patients) underwent CRP and WBC testing before initial consultation (advance testing). Prescriptions were compared with those in group 2 (no advance testing; 154 patients).. In non-pneumonic acute respiratory tract infections, 61 (58%) and 122 (91%) of group 1 and 2 patients were prescribed antibiotics, respectively. Cefcapene pivoxil (third generation cephalosporin) and amoxicillin were the most frequently chosen drugs for group 1 and 2, respectively. Total prescriptions of newer, extended spectrum antibiotics (cefcapene pivoxil and clarithromycin (advanced macrolide)) were reduced by 25% in group 1, although they increased in rate (41 (67%) v 55 (45%) prescriptions) because of the decreased prescription of amoxicillin. In group 1, cefcapene pivoxil was preferentially selected when WBC values were greater than 9 x 10(9)/litre. Prescription shifted to macrolides (mainly clarithromycin) in patients without leucocytosis. Patient treatment outcome did not significantly differ between the two groups.. The availability of CRP and WBC data during initial consultation greatly reduced prescription of amoxicillin, but had a lesser effect on newer, potent, broad spectrum antibiotics.

Topics: Acute Disease; Adult; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Cephalosporins; Clarithromycin; Fever; Humans; Japan; Leukocyte Count; Middle Aged; Outpatient Clinics, Hospital; Practice Patterns, Physicians'; Respiratory Tract Infections; Treatment Outcome

S-1108 in granules, a new oral cephem antibiotic, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained. 1. Pharmacokinetics S-1108 was administered at single doses of 2, 3, 4, 6 mg/kg orally and the following results were obtained on Cmax, T 1/2 and AUC, respectively: Cmax: 0.79, 1.03, 1.39, 1.06 micrograms/ml, T 1/2: 1.28 +/- 0.40, 1.27 +/- 0.65, 1.10 +/- 0.29, 1.83 hrs., AUC: 2.65 +/- 0.63, 3.99 +/- 2.77, 5.25 +/- 1.83, 5.15 micrograms.hr/ml. These values indicated a dose-dependent pharmacokinetic behavior. Urinary recovery rates were 12.5-30.0% in the first 8(6) hours after administration. 2. Clinical results The clinical efficacy of S-1108 was evaluated in 456 patients with various infections. S-1108 was administered at a dose of 2-4 mg/kg three time a day to most patients. The overall clinical efficacy rate was 95.0%. In 294 cases with identified causative pathogen, the clinical efficacy rate was 96.9%, and the bacteriological eradication rate was 89.0%. Side effects occurred in 18 (3.23%) of 558 patients subjected to safety analyses. The main side effect was diarrhea but those side effects were mild and reversible. Abnormal laboratory test results were observed in 25 cases, (eosinophilia and elevated GOT and GPT). These abnormalities were not dose-dependent and also seen with other cephems to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, S-1108 is considered to be very useful at a standard dose of 2-4 mg/kg t.i.d. against most infections encountered in the pediatric field out-patient clinic.

Topics: Administration, Oral; Adolescent; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Dosage Forms; Female; Humans; Infant; Male; Prodrugs

A clinical study in children has been performed on S-1108, a newly developed cephem antibiotic. S-1108 was given orally to 30 patients, at doses between 8 and 12 mg/kg/day in 3 divided doses for 2 to 10 days. Clinical evaluations were made on 26 patients consisting of 12 patients of pharyngitis, 5 of tonsillitis and of impetigo, one each of bronchitis, cystitis, lymphadenitis and cellulitis. Overall clinical effects were excellent in 10, good in 15, fair in 1 with an efficacy rate of 96%. As to adverse reactions, mild diarrhea (2 patients) and transients elevation of transaminases (one patient) were observed. These data suggest that S-1108 is a useful oral antibiotic for the treatment of bacterial infections in children.

Topics: Administration, Oral; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Diarrhea; Female; Humans; Infant; Male; Prodrugs

The effects of S-1108, an orally active cephem antibiotic newly synthesized by Shionogi Res. Lab., on pediatric bacterial infections was studied. S-1108 was administered orally at a daily dose between 9.3 and 12.4 mg/kg in three divided doses (after each meal) for 5 to 11 days to patients with pharyngitis (2), tonsillitis (1), bronchitis (3), pneumonia (1), lymphadenitis (1), enteritis (1) and cystitis (1). The clinical efficacy rate was 100% with excellent responses in 3, good in 6 and undetermined in 1. Bacteriological effects observed indicated that one strain each of Streptococcus pneumoniae, Streptococcus pyogenes, Klebsiella pneumoniae and two strains of Haemophilus influenzae were eradicated by the treatment. No clinical side effects and laboratory test abnormalities were observed at all in this study. These results suggested that S-1108 would be a useful antibiotic for the treatment of bacterial infections in the pediatric field.

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

1. S-1108 granules were administered to 22 children with bacterial infections (8 cases of bronchitis, 1 case of pneumonia, 3 cases of scarlet fever, 2 cases each of tonsillitis, pharyngitis, pertussis, purulent lymphadenitis and impetigo). 2. Clinical efficacies were excellent in 12 patients and good in 7, fair in 1, poor in 1 and unevaluable in 1 with an efficacy rate of 90.5%. 3. Neither side effects nor abnormal laboratory test values were observed. 4. There was no rejection of the drug during the therapy. From the above results, we consider S-1108 in granular form to be a useful and safe drug in the treatment of various bacterial infection in pediatric patients.

Topics: Administration, Oral; Adolescent; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Male; Prodrugs

S-1108 in a fine granular form was administered in 14 children and its safety and efficacy in bacterial infections were evaluated. Among them, 2 cases of cystitis and 1 case of pneumonia were considered unevaluable for the efficacy. The results obtained are summarized as follows. 1. The overall clinical efficacy rate was 81.8% in the eleven evaluable cases treated with S-1108 fine granules including 5 cases of pharyngitis, 2 cases each of tonsillitis, pertussis and cystitis. 2. Bacteriological efficacy of 100% was achieved against pathogens identified in 5 children including 1 case each of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae and 2 cases of Escherichia coli. 3. The only abnormal laboratory test results observed were eosinophilia and leukocytopenia in one case each. Diarrhea was recorded in 1 case. Judging from the above results, it appears that S-1108 in the fine granular form is an effective, useful and safe antibiotic of first choice for the treatment of infections in the pediatric field.

Topics: Administration, Oral; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Diarrhea; Female; Humans; Infant; Leukopenia; Male; Prodrugs

S-1108 is a new oral esterified cephem antibiotic. Its active form, S-1006, has a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Furthermore, S-1006 is extremely stable against beta-lactamases with some exceptions. In the present study, we conducted laboratory and clinical evaluations of S-1108 granules in pediatrics. The obtained results are summarized as follows. 1. A drug sensitivity test revealed that MIC80 of the drug against 456 clinical isolates of Staphylococcus aureus that had been kept in our laboratory was 6.25 micrograms/ml, similar to those of cefaclor (CCL) and methicillin (DMPPC). The most frequent MIC was 1.56 micrograms/ml against 20 strains of S. aureus isolated from patients who received this drug, and this value was similar to those for CCL, amoxicillin (AMPC) and DMPPC. As regards to Streptococcus pyogenes, MIC of S-1006 was < or = 0.025 microgram/ml against 449 clinical isolates in our culture collection and 7 strains obtained from patients who received this drug, and these MICs are similar to those of cefteram (CFTM). MICs of S-1006 against 5 strains of Streptococcus pneumoniae obtained from patients who received this drug were < or = 0.025 microgram/ml, 0.10 microgram/ml or 0.39 microgram/ml which are similar to those of CFTM. MICs of S-1006 against 4 strains of Haemophilus influenzae obtained from patients who received this drug were 0.05 or 0.10 microgram/ml which are similar to those of CFTM. 2. When S-1108 granule preparation was administered to 1 patient at 4.0 mg/kg, the peak plasma concentration of S-1006 was 1.25 microgram/ml. S-1108 granule preparation was also administered to 2 patients at 6.0 mg/kg, and the peak plasma concentrations were 2.43 micrograms/ml and 2.23 micrograms/ml. Plasma half-lives were 1.11 hours after 4.0 mg/kg and 1.28 hours in both patients given 6.0 micrograms/ml. AUCs were 4.06, 8.37 and 7.73 micrograms.hr/ml, respectively. A dose-response relationship was observed between the two doses. 3. Urinary concentration was the highest during the 4-6-hour period for a patient given 4.0 mg/kg, and during the 0-2-hour or 4-6-hour period for 2 patients given 6.0 mg/kg. The peak concentrations were 258.0, 602.0 and 500.0 micrograms/ml, respectively, and urinary recovery rates during the 0-8-hour period were 38.9, 38.3 and 23.1%, respectively. 4. Clinical effects were excellent or good in 88 of 93 patients, showing a very high efficacy rate of 94.6%.(ABSTRACT TRUNCATED AT 40

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

To evaluate the efficacy, the safety and the usefulness of a novel and esterified cephem antibiotic for oral use, S-1108, in pediatric infections, a clinical trial was performed. The study subjects were 15 patients including 9 with acute pharyngitis, 1 with acute tonsillitis, 2 with acute bronchitis, 1 with chronic pyelonephritis, 1 with acute abscess of the skin and 1 with impetigo contagiosa. S-1108 was administered orally at a dose of 3.7 mg/kg to 12.5 mg/kg t.i.d. for 4 to 9 days. Clinical effects were excellent in 7 cases, good in 6, fair in 1 and poor in 1. The Overall efficacy rate was 86.7%. Bacteriologically, causative organisms were all eradicated in evaluable 4 cases. As to side effects, diarrhea was observed in 2 cases. No abnormal laboratory test values were obtained.

Topics: Adolescent; Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Diarrhea; Female; Humans; Infant; Male; Respiratory Tract Infections

As the post-marketing surveillance of cefpodoxime proxetil (Banan), MICs of cefpodoxime (CPDX, an active form of Banan) against 1090 clinical isolates of 22 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of oral cephem antibacterials, cefaclor, cefdinir, cefditoren, and cefcapene. In this study, remarkable change in the activity of CPDX was observed in Streptococcus pneumoniae and Haemophilus influenzae compared with the susceptibility in the studies before Banan was launched. This cause is considered to be the increase in the incidence of the following resistant strains: penicillin-intermediate S. pneumoniae (47.3%), penicillin-resistant S. pneumoniae (PRSP, 15.1%), and beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae (24.0%), which were scarcely isolated in 1989 when Banan was launched. Other tested drugs also exhibited low activity against these resistant strains. However, CPDX showed comparatively good activity with MIC90 of 2 micrograms/mL against PRSP. Against methicillin-susceptible Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, and Moraxella catarrhalis, CPDX also showed comparatively good activity with MIC90 of < or = 4 micrograms/mL, which was almost equal to that in the studies before its marketing. Against quinolones-resistant Neisseria gonorrhoeae, CPDX showed excellent activity with MIC90 of 0.5 microgram/mL. Against members of the family Enterobacteriaceae except for Citrobacter freundii, Enterobacter spp., Proteus vulgaris, and Morganella morganii, CPDX showed good activity. However, in Escherichia coli, Klebsiella spp. Proteus spp., and Providencia spp., there are some high-resistant strains to all tested drugs including CPDX. Against Peptostreptococcus spp., MIC90 of CPDX was 8 micrograms/mL and its MIC range was widely distributed from 0.03 to 32 micrograms/mL, which were similar to those in the studies before its marketing. In this study, CPDX showed the decrease in the activity against several species as did other drugs tested, but against most of species tested, CPDX maintained good activity. Furthermore, it is necessary to pay much attention to the trend of resistant strains.

Topics: Adolescent; Adult; Bacteria; Bacterial Infections; Cefaclor; Cefdinir; Cefpodoxime; Cefpodoxime Proxetil; Ceftizoxime; Cephalosporins; Child; Drug Resistance, Bacterial; Humans; Japan; Product Surveillance, Postmarketing; Time Factors

We studied the transference of cefcapene pivoxil (CFPN-PI) into the maternal cubital blood, umbilical blood and amniotic fluid as well as its clinical usefulness. 58 pregnant women without complications who had a premature rupture of membranes after day 0 of the 36th week of pregnancy and delivered a child with a normal transvaginal labor were enrolled this study. As a result, we found that the maternal serum level of CFPN-PI reached a detectable level at 1 hr 15 min post dose, reached the maximum (Cmax) at 2 hr 30 min, and was maintained at 0.15-1.14 micrograms/ml until 4 hr 35 min. In the umbilical serum, the drug concentration reached a detectable level at 1 hr 45 min post dose, was maintained at Cmax of 0.40 microgram/ml from 3 hr 3 min until 4 hr 27 min, and showed a level as high as 0.14 microgram/ml at 7 hr 7 min. In the amniotic fluid, the drug concentration reached a detectable level of 0.09 microgram/ml at 2 hr 48 min post dose, reached Cmax at 3 hr 55 min, and was maintained at 0.15-0.61 microgram/ml until 13 hr 37 min. Concerning the prophylactic effects of CFPN-PI against infections, one case of puerperal intrauterine infection in the parent and two cases of neonatal infection were observed, showing an effectiveness of 95%. In terms of adverse events, neither abnormality in maternal laboratory test data suspected as due to CFPN-PI, nor abnormality in subjective and objective findings was observed. In the neonates, no abnormality suspected as due to CFPN-PI was detected, either, including growth retardation until the 3-month medical examination. We think that CFPN-PI can be a first choice drug for prophylaxis of infections in cases of premature rupture of membranes after the 36th week of pregnancy, because of convenience of oral administration, coupled with excellent safety and potent prophylactic effectiveness against infections resulting from a long term maintenance of high levels in the umbilical blood and amniotic fluid.

Topics: Adult; Amniotic Fluid; Bacterial Infections; Cephalosporins; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Pregnancy; Puerperal Infection

Topics: Bacterial Infections; Cephalosporins; Child; Community-Acquired Infections; Humans; Prodrugs; Skin Diseases; Urinary Tract Infections

Synthesis and biological activity of a series of 7 beta-[(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino]-3-cephe m-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice. Pivaloyloxymethyl 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-3- carbamoyloxymethyl-3-cephem-4-carboxylase hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation.

Topics: Administration, Oral; Animals; Bacterial Infections; Cephalosporins; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Intestinal Absorption; Intestine, Small; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Spectrophotometry, Infrared; Structure-Activity Relationship

This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol. 46, May, 1993. The Criteria Committee was organized in November 1991. Four meetings were held to establish the draft criteria. The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787. When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent". Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria. However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.

Topics: Bacterial Infections; Cefozopran; Cephalosporins; Child; Clinical Trials as Topic; Humans; Pediatrics

We performed laboratory and clinical evaluation of S-1108 granules, a new oral cephalosporin antibiotic, in the pediatric field. 1. Pharmacokinetics of S-1108 was examined with 6 patients, at a dose of 4 mg/kg that was orally ingested 30 minutes after meal. Mean plasma concentrations at 30 minutes, 1, 2, 4, 6 and 8 hours after dose were 0.35, 0.63, 0.86, 0.75, 0.37 and 0.09 microgram/ml, respectively, with a half life of 1.14 hours. The urinary recovery rate in the first 8 hours was 25.5%. 2. The clinical efficacy of S-1108 was evaluated in 31 patients with various infectious diseases. S-1108 was administered at doses ranging 2 to 4.2 mg/kg/dosage, 3 times a day for 1/3 to 10 days. Clinical effects were excellent in 19, good in 12, with an efficacy rate of 100%. Bacteriologically, all causative organisms except two of Staphylococcus aureus and Haemophilus influenzae were eradicated, with an eradication rate of 80%. As an adverse reaction, mild diarrhea was noted in 2 patients. Slight elevations of GOT and/or GPT were noted in 2 patients. Only 1 child had difficulty ingesting the antibiotic preparation. From the above results, we have concluded that S-1108 is a highly effective and safe for patients with various infectious diseases in the pediatric fields.

Topics: Absorption; Alanine Transaminase; Aspartate Aminotransferases; Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Diarrhea; Drug Evaluation; Female; Humans; Infant; Male; Respiratory Tract Infections; Urinary Tract Infections

Clinical studies on S-1108, a new oral cephem antibiotic, were carried out in the field of pediatrics. The following results were obtained. 1. The peak plasma level of S-1006 when administered after meal at a dose of 4 mg/kg was 2.47 micrograms/ml at an hour, and the serum half-life was 0.81 hour. The 4 hours urinary excretion rate of S-1006 was 35.7%. 2. S-1108 was administered to 15 children with various infections (3 patients with pneumonia, 3 with acute bronchitis, 4 with scarlet fever, 2 with acute tonsillitis, 1 with phlegmon and 2 with urinary tract infections). The overall clinical efficacy rate was 100%. 3. Side effects or abnormal laboratory test values were not observed except for diarrhea in 1 and eosinophilia in 1.

Topics: Absorption; Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male

We administered S-1108 to 16 children with ages ranging from 7 month to 15 years at doses between 1.8 and 6.0 mg/kg x 3/day for 3 to 13 days. We evaluated the efficacy and safety of S-1108 in 11 children with respiratory tract infections, 3 urinary tract infections, and 2 skin infections. The efficacy rate of S-1108 was 100% and bacteriological eradication rate was 83.3%. No adverse effects were observed. These results suggested that S-1108 could be used safely in children.

Topics: Adolescent; Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Respiratory Tract Infections; Skin Diseases, Bacterial; Urinary Tract Infections

Nine pediatric patients with bacterial infections (5 cases of tonsillitis, 3 cases of impetigo and 1 case of UTI) were treated with S-1108, and the efficacy and the safety were evaluated. The clinical responses to S-1108 treatment were excellent in 7 cases and good in 2. The efficacy rate was 100%. Bacteriologically, the causative organisms (Streptococcus pyogenes, Staphylococcus aureus, Haemophilus parainfluenzae and Escherichia coli) were eradicated. No clinical side effects were observed. Elevation of CK in 2 cases and eosinophilia in 1 case were noted.

Topics: Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Creatine Kinase; Drug Evaluation; Eosinophilia; Female; Humans; Infant; Male; Microbial Sensitivity Tests

Pharmacokinetic, bacteriological and clinical studies on S-1108 were performed in children. The results were as follows: 1. A total of 11 patients were treated with S-1108. Each dose was 3 mg/kg, orally administered 3 times daily for 4-14 days. The clinical efficacies of S-1108 in 10 patients with bacterial infections (1 with bacteremia, 4 with pneumonia, 1 with acute maxillary sinusitis, 1 with scarlet fever and 2 with streptococcal pharyngitis) were evaluated as excellent in 8 patients and as good in 2 patients with an efficacy rate of 100%. Only one patient with staphylococcal scalded skin syndrome due to methicillin resistant Staphylococcus aureus (MRSA) who received gamma-globulin was not evaluated. Fourteen causative strains of 5 species were found in 10 patients. Three strains of Streptococcus pneumoniae out of 5, 2 of 3 Branhamella catarrhalis strains, none of Staphylococcus aureus and all 3 strains of Streptococcus pyogenes were eradicated. No adverse reaction was observed in any of the 11 patients. 2. MICs of S-1108 against 5 clinically isolated S. pneumoniae from cases of infections were examined. All of them were relatively highly resistant to penicillins. S-1108 was compared with cefteram pivoxil, cefpodoxime proxetil, cefaclor and cefixime, and it showed better antibacterial activity or than other cephems. 3. Double peaks were obtained in plasma levels of S-1108 orally administered at a dose of 3 mg/kg at 30 minutes after meal and were 1.03 microgram/ml and 0.74 microgram/ml at 1 and 4 hours after administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Streptococcus pneumoniae

A new oral cephem antibiotic, S-1108, was evaluated for its clinical efficacy and safety in children. S-1108 was effective in 95% of the 59 examined cases of respiratory, middle ear, skin and urinary tract infections. S-1108 was highly effective in infections of Streptococcus pyogenes, Haemophilus influenzae and Escherichia coli, but was less effective in penicillin-resistant Streptococcus pneumoniae and Staphylococcus aureus infections. The serum half-life was 1.26 +/- 0.36 hours upon after meal administration of 4 mg/kg. No severe adverse reaction was encountered. From these data, S-1108 appears to be safe and effective in children with susceptible bacterial infections.

Topics: Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pyogenes; Urinary Tract Infections

Pharmacokinetic and clinical studies on S-1108, a new oral cephem antibiotic, were performed in pediatric infections and the following results were obtained. 1. Pharmacokinetics studies Pharmacokinetics of S-1108 was studied in 4 children (3 y 7 m-11 y 1 m) using doses of 2 mg/kg (n = 2) and 4 mg/kg (n = 2). The average peak plasma level was 0.88 microgram/ml at 2 hours after administration of 2 mg/kg and 2.00 micrograms/ml at 3 hours after administration of 4 mg/kg, and plasma half-lives were 1.45 and 0.96 hours, respectively. Average cumulative urinary recovery rates at 0-6 hours were 30.0 and 34.8%, respectively. 2. Clinical studies S-1108 was administered to 32 patients with various infectious diseases (6 with acute tonsillitis, 2 each with pertussis and acute bronchitis, 3 with pneumonia, 4 with scarlet fever, 5 with impetigo contagiosa, 6 with acute urinary infection and 1 each with subcutaneous abscess, impetigo, vulvitis and urethritis) at daily doses between 6-12 mg/kg/day, t.i.d., for 5-12 days. Clinical responses were excellent in 17 patients, good in 13, and poor in 2, and the efficacy rate was 93.8%. Bacteria were identified and 33 strains of 12 species were found. The eradication rate was 93.9%. No side effects were observed in 43 patients. Abnormal laboratory test values were observed in 2 patients, 1 with elevation of eosin. and the other with elevations of GOT and GPT. The results suggest that S-1108 may be a very useful and safe drug for the treatment of pediatric infections.

Topics: Administration, Oral; Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Microbial Sensitivity Tests

Laboratory and Clinical Studies on S-1108, a new oral cephem antibiotic, were carried out to evaluate its usefulness at a dose between 2 and 4 mg/kg a day for 7 to 14 days in the pediatric field. 1) Pharmacokinetic studies S-1108 at a dose of 2 mg/kg was administered to evaluate the pharmacokinetic parameters in 1 subject. Cmax, T1/2 and AUC were 0.69 hour, 1.42 hours and 2.15 micrograms.hr/ml, respectively. 2) Antimicrobial activities MICs against various clinically isolated organisms (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Branhamella catarrhalis, Escherichia coli and Haemophilus influenzae) were determined. The MIC values of S-1006 were similar to those of cefteram, the MICs against S. pyogenes, and H. influenzae were < or = 0.025 and 0.10 microgram/ml, respectively. 3) Clinical studies S-1108 was administered to patients with various pediatrics infections in 34 cases (upper respiratory tract infections: 12 cases, lower respiratory tract infections: 5 cases, urinary tract infections: 9 cases, skin and soft tissue infection: 6 cases, otitis media: 2 cases). Clinical efficacy rate was evaluated according to "Standard of clinical evaluation in pediatrics field". The responses were all good or excellent. 4) Side reactions There were no serious adverse reactions in any cases. The above results suggest that S-1108 is potent effective and safe agent in the pediatric field at a dose between 2-4 mg/kg (t.i.d.) a day.

Topics: Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Respiratory Tract Infections; Urinary Tract Infections

Pharmacokinetic and clinical studies on S-1108, a new oral cephem antibiotic, were performed in the field pediatrics. The following results were obtained. 1) Antibacterial activities Antibacterial activities of S-1006, the active form of S-1108, were studied against clinically isolated strains of (Staphylococcus aureus (n = 5), Streptococcus pneumoniae (n = 6), Streptococcus pyogenes (n = 3), Haemophilus influenzae (n = 8), Branhamella catarrhalis (n = 5) and Haemophilus parainfluenzae (n = 2). MIC values ranged < or = 0.025-1.56 for GPC and < or = 0.025-0.78 microgram/ml for GNR. 2) Absorption and excretion Blood concentrations and urinary excretion rates of S-1108 were measured upon administration of S-1108 after meal at dose of 3 mg/kg (n = 4), 4 mg/kg (n = 1) and 6 mg/kg (n = 1). The peak blood concentrations of S-1006 at a dose of 3 mg/kg (n = 4), ranged from 0.57 to 1.82 micrograms/ml at 1, 2 and 4 hours after dosing. Mean pharmacokinetic parameters T1/2 and AUC were 1.29 +/- 0.69 hours and 4.47 +/- 2.25 micrograms.hr/ml, respectively. At a dose of 4 mg/kg and 6 mg/kg, peak concentrations were 1.79 and 1.27 micrograms/ml at 2 and 3 hours after treatment. T1/2 and AUC were 1.34 and 1.11 hours, and 8.19 and 5.65 micrograms.hr/ml, respectively. Urinary recovery rates ranged from 13.0 to 37.2% for the first 8 hours after administration. 3) Clinical studies Clinical efficacies were examined in 32 cases of various pediatric infections including 5 cases of acute pneumonia, 11 cases of bronchitis, 2 cases of scarlet fever, 8 cases of tonsillitis, 1 case of pharyngitis, 2 cases of otitis media and 3 cases of UTI. Clinical efficacy rate was 96.9% (31/32) and bacteriological eradication rate was 87.1% (27/31). There were no side effects and abnormal laboratory test values except 1 case (Eosino. 2-->10%) in the 32 cases.

Topics: Absorption; Bacteria; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Microbial Sensitivity Tests

The metabolism and clinical safety of the pivalic acid-containing antibiotic S-1108, an orally active pro-drug cephalosporin, were investigated to assess the clinical effects, with special emphasis on the influence of carnitine consumption in 15 patients with various infectious diseases receiving S-1108 three times a day at a 300- or 600-mg total daily dose for 3 to 7 days. The free carnitine concentrations in plasma were greatly reduced to approximately 65% of pretreatment levels, and the plasma pivaloylcarnitine (the main metabolite of pivaloyloxymethyl ester) concentrations were increased during the 200-mg (three times a day) regimens but returned to the pretreatment levels within 3 to 5 days after the cessation of treatment. In three elderly patients with declining renal function (creatinine clearance rate, 31 to 50 ml/min), the acylcarnitine/free carnitine ratio increased from 0.1 to 0.4 up to 0.7 to 1.5 at day 5 during the 7-day treatment, showed a tendency to decrease, and then returned to the pretreatment ratio 4 days after discontinuation of the drug. The degree of free carnitine reduction and increase of the acylcarnitine/free carnitine ratio depended mostly on the dose and the duration of S-1108 treatment. The increased acylcarnitine/free carnitine ratio in elderly patients was due to reduction of the free carnitine concentration in plasma and mainly to the retardation of nontoxic pivaloylcarnitine excretion. This study indicated that there was a decrease in free carnitine levels in plasma, but there were no clinical symptoms or adverse effects associated with carnitine reduction in patients during the 7-day multiple administration of S-1108.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Bacterial Infections; Carnitine; Cephalosporins; Female; Humans; Kidney Diseases; Male; Middle Aged; Pentanoic Acids; Prodrugs