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PubMed1979

[Ultrastructural and microbiological studies on the activity of azlocillin against Pseudomonas aeruginosa (author's transl)].

To examine the effect of 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) on the ultrastructure of Pseudomonas aeruginosa investigations were carried out by electron microscopy on thin sections and on negative-stained preparations. Depending on the concentration and the contact time of azlocillin the bacteria showed distinct alterations. The bacterial cells did not build septa and therefore only grew in length up to 100-fold that of untreated controls. The bacteria diameter remained unchanged. Survival curves showed that these bacterial filaments were unable to build colonies. They were irreversibly damaged.

Azlocillin↗
PubMed1989

[Pharmacokinetics of azlocillin in critical conditions: an individualized schedule of drug administration in relation to anatomo-physiologic and pathologic factors].

Azlocillin pharmacokinetics was studied after a single intravenous injection of the antibiotic in a dose of 4 g in 20 patients in critical state. To elucidate the causes of significant individual variability of the antibiotic pharmacokinetics observed in the patients, multiple correlation analysis of the main pharmacokinetic parameters i. e. the area under the concentration/time curve, total clearance, steady-state volume of distribution and mean residence time was performed in regard to the "patient factors" such as sex, age, the volumes of transfused liquid, blood, plasma and blood substitutes, hemoglobin levels, erythrocyte count and ESR. Adequate correspondence of the predicted by the "patient factor" values of the areas under the concentration/time curve and the total clearance to the actually determined values was observed. Correspondence of the predicted values to the steady-state volume of distribution and the mean residence time to the actually determined values was satisfactory. A procedure for design of azlocillin individual dosage regimens based on calculating individual clearance by the "patient factors" is described.

Azlocillin↗
PubMed1988

[The pharmacokinetics of azlocillin after single and multiple intravenous injections during the third trimester].

Examining serum level values and urinary concentrations taken from non-pregnant control persons and pregnant women suffering from urinary tract infections (UTI) during the III. trimenon, the pharmacokinetic dates after single and repeated applications of 4 g azlocillin have been evaluated. We used a computer program based on the two-compartment model. It is shown that during pregnancy complicated by UTI the elimination half-life time will be prolonged and returns after therapy nearly to normal values. The results, discussed with the dates given by literature, allow us to state that it is not necessary to change dosage and application interval of azlocillin during pregnancy.

Adult↗
PubMed1987

[Determination of azlocillin in the air].

A method for determination of air-borne azlocillin in production areas was developed. The method is based on redox reaction proceeding with reduction of the molybdenum blue heteropolycomplex. The reaction involves the antibiotic preliminarily hydrolyzed by alkali with heating. The blue solutions are photometered at 750 nm. The detection limit in the assay sample volume is 0.005 mg. The method may be useful in development of maximum permissible concentration of azlocillin and its control in ambient air of production areas.

Air Pollutants, Occupational↗
PubMed1986

Azlocillin and serum uric acid.

Uric acid levels in serum were observed to fall significantly in a group of 23 patients with cerebrovascular disease receiving azlocillin and vasodilators. Our findings suggest that the hypouricemic effect of azlocillin is dose-dependent and can be demonstrated mainly after the first 24 h of treatment.

Azlocillin↗
PubMed1979

[High pressure liquid chromatographic analysis of azlocillin and its penicilloate in urine].

A high-performance liquid chromatographic method has been developed for the determination of 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) and its major metabolite the azlocillin-penicilloic acid in human urine. The separation of the parent compound and its metabolite from the interfering material of the urine was performed by gradient elution technic using reversal-phase material as stationary phase. Urine was diluted with phosphate buffer, filtered through a micropore membrane and the filtrate was injected directly onto the chromatographic column.

Azlocillin↗
PubMed1979

Pharmacokinetics of azlocillin in children with cystic fibrosis.

6-E1(R)-2-(oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) was given in doses of 100 and 200 mg/kg body weight to children with cystic fibrosis. After intravenous bolus infections, the serum half-life was 0.82 +/- 0.12 h after the lower dose and 0.98 +/- 0.18 h after the higher dose. This was consequent to a dose limited elimination kinetics due to limitation in both renal and non-renal processes of elimination. Upon doubling of the dose from 100 to 200 mg/kg, the total body clearance dropped from 13.93 to 5.10 1/h. Evaluation of data presented in other publications indicate that a dose limited elimination kinetics is the normal situation for azlocillin. Besides, the serum concentrations of patients with cystic fibrosis were considerably lower than seen in the healthy state. The reason is faster elimination by the renal route in cystic fibrosis.

Adolescent↗
PubMed1979

Treatment with azlocillin in complicated urinary tract infections.

20 patients, aged 18-84 years, with complicated urinary tract infections admitted to hospital were treated with 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) for 5 to 10 days. Isolated bacteria were Pseudomonas aeruginosa (14), Proteus mirabilis (3), Escherichia coli (2) and Klebsiella spp. (1). Serum concentrations and urine recovery were measured on the fifth day of treatment. The mean serum half-life was 1.85 h and the mean value of the urine recovery 47% of the single dose. Tissue concentrations were analyzed in one patient. The samples were taken 3 h after the infusion. The azlocillin concentration of the renal cortex, 60 microgram/g, was six times higher than the corresponding serum concentration. On the 5th day of treatment the urine was sterile in 80% of the patients. In 12 patients (60%) the urine was still sterile when controlled 2-6 months later. Three patients were treated twice and bacteriologically cured after each period. No sign of sensitization was seen. Side-effects were not reported.

Adolescent↗
PubMed1984

[Pharmacokinetics of azlocillin in the burn patient].

Pharmacokinetic values of azlocillin were determined in burned patients during the exudation and repair periods. A single dose of 80 mg/kg was administered intravenously over 30 min. Pharmacokinetic constants were calculated using an open two-compartment model. During the exudation period the ultimate serum half-lives (t 1/2 beta) were 1.17 to 1.4 h, 1.73 to 1.78 h and 3.3 h respectively with creatinine clearances of 111-131, 60-94 and 14 ml/min/1.73 m2. Renal clearances varied from 30.9 to 128 ml/min/1.73 m2. During the repair period little change was observed in t 1/2 beta, but renal clearance increased from 36.6 to 116 ml/min/1.73 m2 in one patient. It is concluded that azlocillin behaves in burned patients as in patients with impaired renal function.

Adult↗
PubMed1981

[Degradation of Azlocillin and Mezlocillin / I. Behaviour in biological material and buffer (author's transl)].

The degradation of 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido] penicillanic acid Na-salt (azlocillin, Securopen) and 6-[(R)-2-[3-methylsulfonyl-2-oxoimidazolidine-1-carboxamido]-2-phenyl-acetamido ] penicillanic acid Na-salt (mezlocillin, Baypen), two chemically related acylureido penicillins, was tested in biological material (plasma and urine) and borate buffer at 37 degrees C over the time period of at least 6 h. In fresh human urine (pH 5.0) no degradation could be observed. In freshly prepared human plasma (pH 7.6) degradation was independent of the initial concentration and amounted to no more than 5%. No difference could be noted between the degradation in plasma or buffer, respectively, indicating that direct aminolysis did not play an important role in the degradation process. The extent of degradation could be demonstrated to be pH-dependent. After 8 h incubation at pH 9.0 azlocillin concentration was decreased to 70% and mezlocillin concentration to 50%, respectively, of the initial concentration. Since urinary pH values up to 8.5 are reported the urinary recovery of the substance could be influenced by alkaline pH.

Azlocillin↗
PubMed1983

[Pharmacokinetics after discontinuous intravenous administration of azlocillin].

In severe, sometimes life-threatening infections azlocillin (Securopen) is administered in single doses up to 10 g in order to increase therapeutic efficacy. Therefore the serum concentrations and urinary excretion of azlocillin were investigated in 2 healthy volunteers and in 11 patients after intravenous injection (5 min) of 2 g followed by intravenous infusion of 2 g/h over 4 h. The serum concentrations increased during infusion in patients up to a median concentration of 317 mg/l. The median serum concentrations decreased down to 94 mg/l at 2 h, 43 mg/l at 4 h and 11 mg/l at 6 h after the end of infusion. 24-h urinary excretion in patients was 54.3%. Serum half-life from the last five serum concentrations (6-10 hours after start of administration) calculated amounts to a median half life of 100 min (range 60-180 min). The study showed, that using this dose and kind of administration high serum concentrations can be maintained over many hours, sufficiently high also for life threatening and difficult-to-treat infections, if administered at intervals of 12 hours.

Adult↗
PubMed1981

Azlocillin and gentamicin in respiratory tract infections with Pseudomonas aeruginosa in patients with cystic fibrosis.

Azlocillin, 200 mg/kg bodyweight every 8 h, and gentamicin, 2.5-4 mg/kg bodyweight every 12 h, in combination were given intravenously to 10 patients with cystic fibrosis for at least 10 days. The patients were colonized with Pseudomonas aeruginosa and were hospitalized due to symptoms of lower respiratory tract infections. Using an agar well diffusion method the antibiotic concentrations were followed in serum and sputum. The individual sputum concentration of azlocillin varied during 4 h after administration from less than 1.5 to 38 micrograms/ml. The sputum concentration of gentamicin varied from 0.3 to 1.1 micrograms/ml. P. aeruginosa was apparently eliminated in 3 patients. The concentration of the antibiotics in sputum could not predict the outcome of treatment. All patients improved subjectively. No adverse effect was seen.

Adolescent↗
PubMed1986

In-vitro antibacterial activity of imipenem compared with four other beta-lactam antibiotics (ceftazidime, cefotaxime, piperacillin and azlocillin) against 828 separate clinical isolates from a Portuguese hospital.

An agar dilution technique was used to determine the MIC50 and MIC90 of imipenem in comparison with ceftazidime, cefotaxime, piperacillin and azlocillin. Eight hundred and eighteen of the 828 (98.8%) unselected Gram-positive cocci and Gram-negative bacilli were inhibited by imipenem at a concentration of 8 mg/l or less. Imipenem was shown to be superior to the other four beta-lactam antibiotics against Acinetobacter calcoaceticus (40 strains), all the Staphylococcus aureus (80 strains, 10 of them penicillin- and methicillin-resistant), Streptococcus faecalis (20 strains) and Salmonella spp. (50 strains). Imipenem and cefotaxime were the most active against Str. pneumoniae (20 strains). Against Escherichia coli (52 strains) the activity of imipenem was similar to that of ceftadizime and superior to the other three antibiotics. Imipenem was two-fold inferior to cefotaxime and four-fold inferior to ceftazidime against Serratia marcescens (52 strains) and superior to piperacillin and azlocillin. Against Pseudomonas aeruginosa (300 strains), Ps. cepacia (104 strains) and indole positive Proteus (52 strains), only ceftazidime was better than imipenem. This study confirms published results that point to the impressive spectrum of activity offered by imipenem.

Anti-Bacterial Agents↗
PubMed1979

Mezlocillin and azlocillin: an evaluation of two new beta-lactam antibiotics.

Mezlocillin and azlocillin are broad spectrum penicillins for parenteral administration. In this study it was shown that they were very active against a wide range of pathogenic bacteria. Thirty-five patients were treated with mezlocillin, and 5 patients were treated with azlocillin (in combination with cefoxitin in 3 cases). The serum, bile and CSF levels of the drugs were measured. Both antibiotics would appear to be safe and efficacious in treating serious infections by sensitive pathogens. Infections caused by unknown pathogens could be treated by one of these agents in combination with a broad spectrum beta-lactamase stable cephalosporin or cephamycin.

Adolescent↗
PubMed1979

[The biliary excretion of azlocillin].

The excretion of azlocillin into the human biliary tract was investigated in 8 patients with a T-tube in the common bile duct after intravenous injection of 2 g. Samples of serum and common duct bile were assayed from 15 min to 12 hours after injection. Biliary tract levels generally run parallel to serum levels but were about 15 times higher than those. Peak levels in T-tube bile averaged 1137 mg/l 60 to 90 min after administration. 12 hours after administration there were still mean concentrations of 13 mg/l to be found. It is concluded that azlocillin concentrations in bile exceed for a long time the minimum inhibitory concentrations for gram-negative and gram-positive causative organisms (above all E. coli, enterococci, Klebsiella spp., Proteus spp., staphylococci) of biliary tract-infections.

Bile↗
PubMed1982

Pseudomonas aeruginosa meningitis treated with an azlocillin combination.

Pseudomonas aeruginosa meningitis following trauma or surgery is associated with a high mortality rate. This high rate is explained both by tissue damage which leads to infection and by the failure of antibacterial therapy. The latter is due to the relatively resistant microorganism and the insufficient penetration of antibiotics into the CSF. We are reporting the successful therapy of a case of postoperative P. aeruginosa meningitis treated with the combination of azlocillin and gentamicin administered systemically together with intraventricular gentamicin.

Adolescent↗
PubMed1988

Evaluation of the Cobas Bact automated system for susceptibility testing of Enterobacteriaceae, Pseudomonas aeruginosa, and Enterococcus faecalis to azlocillin, mezlocillin, and ciprofloxacin compared to NCCLS and DIN standards.

The aim of automated susceptibility testing systems like the Cobas Bact is to provide the clinicians with rapid and reliable results for the care of patients and to decrease the work load in microbiological laboratories. Because data about accuracy on mezlocillin, azlocillin and ciprofloxacin were lacking, we investigated 184 bacterial strains and compared the results of the Cobas Bact susceptibility testing to standardized agar dilution and agar diffusion methods. Essential correlations for all methods compared exceeded 90% for the three chemotherapeutics and all species investigated, with the exception of Pseudomonas aeruginosa. On an average only 1.5% very major errors were observed with the several species of Enterobacteriaceae, whereas P. aeruginosa and Enterococcus faecalis were characterized by the complete absence of very major errors when Cobas Bact was correlated to NCCLS agar diffusion.

Autoanalysis↗
PubMed1984

Systemic treatment of septicaemia caused by P. aeruginosa with special reference to azlocillin.

Of the pathogens causing septicaemia due to Gram-negative bacteria at Zentrum der Inneren Medizin, Frankfurt, over a 7-year period (1974-80), 16.8 per cent were due to P. aeruginosa. Analysis of all septicaemias over this period, however, shows a decrease from 13 per cent in the 3-year period 1974-76 to 8 per cent in 1977-79 and 5 per cent P. aeruginosa septicaemia in 1980. The overall mortality rate was 66 per cent, most of the patients dying within 24 hours. Azlocillin and Piperacillin are at present the drugs of choice for systemic therapy of pseudomonas infections, preferably in combination with an aminoglycoside.

Anti-Bacterial Agents↗