hr-810 and Pneumonia

Topics: Cefpirome; Cephalosporins; Creatinine; Drug Interactions; Humans; Picrates; Pneumonia; Urea

Three hundred and forty-five clinical isolates from patients treated with cefpirome were studied using an MIC methodology to develop tentative breakpoints for cefpirome, and to correlate clinical success with in-vitro susceptibility. No relationship between elimination, persistence and MIC of potential pathogens was found. There was, however, a close relationship between clinical cure and improvement and eradication of causative organisms. Based on the data, tentative breakpoints of less than 4 mg/L for sensitive and greater than 16 mg/L for resistance, at a cefpirome dose of 2.0 g bid or 1.0 g bid for urinary tract infection, are suggested.

Topics: Bacteria; Cefpirome; Cephalosporins; Enterococcus; Escherichia coli; Humans; Klebsiella; Microbial Sensitivity Tests; Multicenter Studies as Topic; Pneumonia; Pseudomonas aeruginosa; Urinary Tract Infections

Bacteriological, pharmacokinetic and clinical studies on cefpirome (CPR, HR 810), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. Antibacterial activities of CPR against clinically isolated strains of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae and Haemophilus parainfluenzae were superior to those of ceftazidime. 2. Plasma concentrations and urinary excretion rates after intravenous bolus injection of CPR at doses of 10, 20 and 40 mg/kg for 5 minutes in 2 cases each were determined. Mean peak plasma concentrations of CPR at these dose levels were 33.9, 62.9 and 96.0 micrograms/ml at 15 minutes with plasma half-lives of 1.58, 1.69, and 2.13 hours, respectively. Mean cumulative urinary excretion rates in the first 8 hours after administration were 51.2, 78.0 and 74.9%, respectively. 3. Ten patients with bacterial infections (pneumonia 5 cases, urinary tract infection 5 cases) were treated with CPR at a daily dose of 16-79 mg/kg/day. The overall clinical efficacy and bacteriological eradication rates were both 100%. 4. No adverse reactions were observed except in 1 case of mild pain in blood vessels. Abnormal laboratory test results were also mild, slight elevation of GOT, GPT and thrombocytosis in 1 case and eosinophilia in 1 case.

Topics: Adolescent; Age Factors; Bacteria; Cefpirome; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Drug Resistance, Microbial; Female; Humans; Male; Pneumonia; Urinary Tract Infections

Cefpirome (CPR, HR 810) was given intravenously to 10 children with acute bacterial infections including 8 with acute pneumonia, 1 each with acute pleuritis and urinary tract infections. Good to excellent clinical responses were obtained in all of the 10 patients and bacterial eradication were obtained for all 8 strains found in these cases. Slight elevation of GOT, GPT and eosinophilia were observed in 1 case each. From the above clinical results, it appears that CPR is a useful antibiotic for treatment of pediatric patients with various bacterial infections.

Topics: Adolescent; Age Factors; Bacteria; Cefpirome; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Drug Resistance, Microbial; Female; Humans; Infant; Injections, Intravenous; Male; Pleurisy; Pneumonia; Urinary Tract Infections

Cefpirome (HR 810, CPR), a new cephem antibiotic, was investigated for its experimental and clinical studies in pediatrics. The results obtained are summarized as follows. 1. Plasma and urinary levels of CPR were determined in 2 children (age 5 and 7 years) after the one shot intravenous injection of the drug at 20 mg/kg. Average plasma levels of the drug were 44.7 micrograms/ml, 28.5 micrograms/ml, 10.5 micrograms/ml, 4.6 micrograms/ml and 1.5 micrograms/ml at 1/2 hour, 1 hour, 2 hours, 4 hours and 6 hours, respectively, and the average half life was 1.57 hours. Average urinary levels of the drug were 1,785 micrograms/ml, 545 micrograms/ml and 198 micrograms/ml at 0-2 hours, 2-4 hours, 4-6 hours, respectively and the average urinary elimination rate was 52.0%. The results were nearly equivalent to those in adults except for urinary elimination rate which tended to be slightly lower than that in adults. 2. Cerebrospinal fluid levels in 3 cases of purulent meningitis treated with CPR were investigated. Cerebrospinal fluid levels in a case of Neisseria meningitidis were 11.5-23.1 micrograms/ml at 1 hour and 0.94 microgram/ml at 5 hours after intravenous injection of 44.4 mg/kg, 4 times a day. Cerebrospinal fluid levels in a case of Streptococcus pneumoniae were 1.01-4.23 micrograms/ml at 1 hour after intravenous injection of 49.0 mg/kg, 6 times a day, and in the other case with Streptococcus pneumoniae, the levels were 16.8-37.1 micrograms/ml at 1 hour, 11.3 and 3.60 micrograms/ml at 3 and 4 hours after intravenous injection 52.2 mg/kg, 6 times a day. These results are not inferior to those with cefotaxime or ceftriaxone. These levels appear to be higher than MIC90 values against Escherichia coli, Streptococcus agalactiae, S. pneumoniae or Haemophilus influenzae which are the major pathogens of these diseases. 3. CPR was given to 62 patients and clinical efficacy, bacteriological response and adverse reactions were evaluated. Evaluated cases for clinical efficacy included 3 cases of purulent meningitis, 1 case of acute purulent otitis media, 2 cases of acute purulent tonsillitis, 1 case of acute bronchitis, 49 cases of acute pneumoniae, 1 case of scarlet fever, 1 case of acute osteomyelitis, 1 case of acute enterocolitis, and 2 cases of acute UTI, totalling 61 cases. Clinical efficacies were excellent in 38 cases, good in 22 cases and fair in 1 case with an efficacy rete of 98.4% (excellent + good).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acute Disease; Adolescent; Bacterial Infections; Bronchitis; Cefpirome; Cephalosporins; Child; Child, Preschool; Enterocolitis; Female; Humans; Infant; Male; Meningitis; Osteomyelitis; Otitis Media; Pneumonia; Scarlet Fever; Tonsillitis; Urinary Tract Infections

In systemic and local infections, the therapeutic efficacy of cefpirome was compared to that of imipenem and cefotaxime. Murine septicemia induced with methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains responded well to cefpirome and imipenem therapy, the ED50 values ranged from 0.8 to 28.40 mg/kg and 0.5 to 15.58 mg/kg, respectively. The carbapenem also displayed high efficacy against Enterococci and was more potent than cefpirome. Cefotaxime, however, exhibited lower activity or proved to be inactive against these strains. With ED50 values of 0.03 to 31.33 mg/kg, cefpirome was the most active of the three antibiotics in protecting mice challenged with Enterobacteriaceae. The corresponding ED50 values of imipenem and cefotaxime ranged from 0.72 to 70.95 mg/kg and 0.06 to 66.30 mg/kg, respectively. Despite distinctly lower in vitro activity against the infecting organism, cefpirome showed efficacy similar to imipenem in the treatment of subcutaneous S. aureus abscesses in mice. It was more effective than imipenem and cefotaxime against experimental Klebsiella pneumonia in mice and the Escherichia coli infected granuloma pouch in rats.

Topics: Abscess; Animals; Bacterial Infections; Cefotaxime; Cefpirome; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Granuloma; Imipenem; Male; Mice; Mice, Hairless; Mice, Inbred C3H; Pneumonia; Rats; Rats, Inbred Strains; Sepsis; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections

Sixty adult patients with suspected systemic bacterial infections were treated with cefpirome 1 g or 2 g twice daily for 5-22 days. Forty-seven patients were evaluable for clinical efficacy. Diagnoses in evaluable patients were urinary tract infections (20), pneumonia (10), soft tissue infections (17), and bone and joint infections (4); four patients had two infections each. Nine patients were bacteraemic and all were cured; the responsible bacteria were Escherichia coli (6), Streptococcus pneumoniae (1), Pseudomonas aeruginosa (1), and Haemophilus influenzae (1). One patient with a soft tissue infection failed to respond clinically to cefpirome. Bacteriologically, 41 of 48 isolated pathogens (85%) were eradicated. In wound cultures, three strains of Staphylococcus aureus and one each of Ps. aeruginosa and Str. faecalis persisted. One Enterobacter sp. relapsed in urine. Of isolated strains, only Str. faecalis and methicillin resistant Staph, epidermidis were resistant to cefpirome. Staph, aureus strains were inhibited in vitro by 0.25 to 2 mg/l of cefpirome in agar dilution. Adverse effects, probably or possibly related to cefpirome, were skin reactions (3), fever (1), Clostridium difficile diarrhoea (2), and disturbed taste sensation (1). Tolerance was good. Cefpirome is suitable for large-scale comparative trials.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Cefpirome; Cephalosporins; Drug Evaluation; Female; Humans; Male; Middle Aged; Pneumonia; Urinary Tract Infections

The chemotherapeutic efficacy of cefpirome (HR 810), a new polar aminothiazolylcephalosporin and that of ceftazidime, cefotaxime, cefoperazone, latamoxef and cefodizime were examined against experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. When compared in terms of MIC values against the infecting organism and the pharmacokinetic pattern, cefpirome showed equal activity and a similar pharmacokinetic behavior to ceftazidime and cefotaxime in mice. Trials to assess the bactericidal activity in vivo, however, showed that cefpirome displayed a more marked bactericidal effect in pneumonic mice than the other cephalosporins tested. Only cefodizime, a cephalosporin with extremely high and prolonged blood and tissue levels in experimental animals exerted chemotherapeutic effects similar to cefpirome. After cefpirome or cefodizime medication (50 mg/kg), the viable counts in the lungs of experimental animals fell steadily to 1/10,000 of the pretreatment level and, in contrast to the reference compounds, no regrowth of the challenge organisms could be observed with both drugs. Moreover, with ED50s ranging from 1.1 to 59.1 mg/kg in treatment studies, cefpirome as well as cefodizime were two to ten times more effective than ceftazidime and cefotaxime, whereas cefoperazone and latamoxef were considerably less effective.

Topics: Animals; Cefpirome; Cephalosporins; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Mice; Mice, Inbred Strains; Pneumonia