Concentrations Of Aztreonam Research Articles

Effect of aztreonam on the colon microflora in patients undergoing colorectal surgery.

Aztreonam was given intravenously at a dose of 1 g at induction of anaesthesia, followed by subsequent doses of 1 g at eight hour intervals during 48 hours to 20 patients undergoing colorectal surgery. A series of serum and faecal specimens were taken for analysis of aztreonam concentrations. Tissue samples from the gut wall were taken at surgery. The maximum serum concentrations (mean value 114.7 mg/l) during surgery were reached 15 minutes after aztreonam administration. The aztreonam concentration in the tissue samples varied from 4.1-28.3 mg/kg and the concentration in the faecal samples from 0.4-34.4 mg/kg. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Enterobacteria were suppressed significantly during the prophylaxis period and there was a significant increase of staphylococci in ten of the patients. Three of these patients developed postoperative wound infections with staphylococci. Among the anaerobic bacteria, only minor changes were observed during the same period. After two weeks, the microflora was normalized in all patients. Five postoperative infections including an anastomose dehiscence in one patient occurred.

Aztreonam in human serum and breast milk.

Serum and milk concentrations of aztreonam were studied in 12 lactating, healthy subjects over the 8 h period after the administration of a single intramuscular or intravenous 1 g dose. Milk concentrations of aztreonam were found to be much lower than serum concentrations at all time points after both routes of injection. Peak milk concentrations of aztreonam averaged less than 1% of peak serum concentrations. Times to peak concentrations averaged 6 and 10 times longer in milk than in serum after intramuscular and intravenous injections, respectively. The low milk levels, as well as the previously determined poor oral absorption of aztreonam, suggest a low risk of untoward effects in the nursing infant.

Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology

Fundamental and clinical studies on aztreonam (AZT), a new synthetic monobactam antibiotic, were performed and following results were obtained. Concentration of AZT was examined in serum, internal genital tissues and retroperitoneal fluid after a single intravenous administration of 1 g dose. The venous serum level of AZT was 114.0 micrograms/ml at 10 minutes after the administration, then decreased to 7.0 micrograms/ml at 3 hours. Since concentration of AZT in examined tissues showed wide variation, it was irrelevant to calculate transfer ratio. Concentration in retroperitoneal fluid made the peak of 40.0 +/- 22.6 micrograms/ml at 1 hour after the administration, then slowly decreased to 13.4 +/- 3.2 micrograms/ml at 6 hours. Judging from above data, the transfer of AZT to retroperitoneal fluid was favorable. In clinical trial, AZT was given to 17 cases with obstetrical and gynecological infections such as endometritis, uterine adnexitis, pelvic peritonitis, parametritis and lymphocystitis. The efficacy was evaluated as excellent in 2 cases, good in 12 and poor in 3, and efficacy rate was 82.4%. No side effects were observed in any of the cases. In laboratory findings, transient elevation of liver function in 2 cases and eosinophilia in 1 case were noticed.

Pharmacokinetics of aztreonam in patients with chronic renal failure.

The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given.

The use of aztreonam in the treatment of uncomplicated gonorrhoea.

A total of 57 men and 26 women with uncomplicated gonorrhoea was treated with 1 g aztreonam intramuscularly. The cure rate was 96% and included successful treatment of 4 infections due to beta-lactamase producing organisms and 8 patients with pharyngeal involvement. The minimum inhibitory concentrations of aztreonam in vitro were lower than those of penicillin and similar to cefuroxime, and side-effects were minimal. It is concluded that aztreonam is effective against Neisseria gonorrhoeae in vivo and in vitro.

The intrarenal distribution of aztreonam in healthy and diseased kidneys: clinical therapeutic implications.

Using a healthy canine model, we evaluated the influence of renal physiological activity on the stability, intrarenal distribution, and clearance of aztreonam and compared the results with the concentrations of aztreonam that can be achieved in the scarred devitalized renal tissues of patients with end-stage kidney disease. Renal physiological activity significantly modulates the intrarenal distribution of aztreonam. During the production of maximally acid-concentrated urine, urinary aztreonam levels, clearance rates, and inner zone renal tissue concentrations are increased. Aztreonam concentrations in the parenchyma of severely diseased kidneys are significantly reduced in comparison with healthy tissues; nonetheless, the values are similar to concurrent serum drug levels, a result suggesting that treatment may provide adequate coverage for aztreonam-susceptible organisms.

Penetration of aztreonam into cerebrospinal fluid of patients with and without inflamed meninges.

Aztreonam was administered as a single, 2-g intravenous dose to 25 patients with noninflamed meninges and to 9 patients with inflamed meninges. It was well tolerated and was detected in the cerebrospinal fluid at the initial sampling period at 1 h after the end of infusion. Aztreonam levels in the cerebrospinal fluid of patients with inflamed meninges were four times higher than those recorded for the same time period in patients with noninflamed meninges. Aztreonam concentrations in cerebrospinal fluid in the presence of normal and inflamed meninges exceeded the inhibitory and bactericidal concentrations for most gram-negative bacteria. Thus, a multiple-dose treatment regimen with 2-g intravenous doses every 6 h appears to be appropriate for clinical trials of aztreonam for the treatment of gram-negative bacillary meningitis which is caused by susceptible organisms.

Selective decontamination of the digestive tract with aztreonam: a study of 10 healthy volunteers.

Aztreonam, a minimally absorbable monobactam antibiotic that is active primarily against gram-negative bacilli, was given orally to 10 healthy volunteers in three regimens: 60 mg, 300 mg, and 1,500 mg daily for five days. The regimens were administered at least two weeks apart so that the flora could return to normal. Aztreonam had no effect on oropharyngeal flora cultured every other day. Fecal cultures from volunteers receiving the 300-mg regimen yielded no gram-negative bacilli after an average of 4.4 days of treatment. Administration of the highest dose gave similar results, albeit after a shorter interval (3.0 days). None of the regimens appreciably influenced total microscopic (anaerobic) bacterial counts in the feces. However, during administration of the 1,500-mg regimen, fecal counts of enterococci increased from an average of approximately 10(4)/g to greater than 10(7)/g, and fecal counts of yeasts tended to increase by the end of the five-day treatment period. Fecal concentrations of aztreonam increased as the dose increased in eight volunteers. No aztreonam was recovered from the feces of two volunteers, perhaps because of drug inactivation.

Single-dose pharmacokinetics of aztreonam in pediatric patients.

Single intravenous doses (30 mg/kg) of aztreonam, a novel monobactam antibiotic, were administered to 29 children from 2 days to 11 years old. Serum, urine, and, when possible, cerebrospinal fluid samples were analyzed by high-pressure liquid chromatography and microbiological methods. The concentration of aztreonam in serum 15 min after drug administration was approximately 100 micrograms/ml in all age groups. The elimination half-life varied inversely, and the clearance from serum varied directly, with age. Aztreonam pharmacokinetics in 2- to 12-year-olds were similar to those in adults. The concentration in urine was high and prolonged, with potentially therapeutic concentrations still present 12 to 24 h after infusion in all age groups. Penetration into cerebrospinal fluid averaged 17.3% in children with inflamed meninges. Standard clinical and laboratory measurements revealed no untoward reactions. The 30-mg/kg dose of aztreonam produced potentially therapeutic concentrations in serum, urine, and cerebrospinal fluid. A dosage schedule of every 6 to 8 h in older children and every 8 to 12 h in neonates is suggested for multiple-dose clinical trials.

Distribution of [14C]aztreonam in rat tissue.

[14C]aztreonam was administered intramuscularly (50 mg/kg) to male and female rats. Groups of 10 rats (five male and five female) were sacrificed at 0.25, 2, 6, and 24 h after dosing. Blood and various tissues were removed from six rats (three male and three female) in each group for determination of total radioactivity and unchanged aztreonam by liquid scintillation counting and thin-layer radiochromatography. The remaining rats were prepared for whole-body autoradiography. Radioactivity was distributed rapidly to most tissues and was rapidly eliminated from blood into urine and bile. Concentrations of total radioactivity in kidney, liver, small and large intestines and their contents, and urinary bladder were higher than those in serum at all the times examined. Concentrations of unchanged aztreonam in serum, kidney, liver, and lung declined at about the same rate as did that of total radioactivity in the same tissues. The results of whole-body autoradiography essentially confirmed the results of the distribution of [14C]aztreonam as determined by liquid scintillation counting. No major differences between males and females were observed when concentrations in organs common to both were compared.

Aztreonam concentrations in human prostatic tissue.

The concentrations of aztreonam in human prostatic tissue specimens obtained by transurethral resection were measured in nine patients after the intramuscular administration of a single 1-g dose. The average concentration of aztreonam was 7.8 microgram/g of prostate between 50 and 180 min after dosage. The average ratio of the drug concentration in prostate to that in serum was 0.25. The concentrations of aztreonam achieved were significantly higher than the MICs for most members of the family Enterobacteriaceae implicated in chronic prostatitis.

Pharmacokinetic Interaction of Aztreonam with Other Antibiotics

The pharmacokinetic interaction of the monobactam antibiotic aztreonam with cephradine, clindamycin, gentamicin, metronidazole, and nafcillin was investigated in five separate studies in 48 healthy male volunteers. All drugs were administered by 30-minute intravenous infusions in single-dose, three-way balanced cross-over studies. Drug levels were measured in serum, protein-free filtrate of serum, and urine. Small changes of no clinical significance were seen when aztreonam was given simultaneously with another antibiotic as compared with each drug alone. Maximum serum concentrations of aztreonam were reduced by 12.6 and 9.8 per cent when it was given with gentamicin and metronidazole, respectively. The percentage of serum aztreonam bound to protein fell by a maximum of 5.0 per cent when the monobactam was given in conjunction with nafcillin and rose by 5.1 per cent when accompanied by cephradine. Twenty-four-hour cumulative urinary excretion of aztreonam and clindamycin rose by 5.2 and 10.9 per cent, respectively, when they were administered simultaneously.

Prediction of aztreonam pharmacokinetics in humans based on data from animals.

Interspecies correlations of pharmacokinetic parameters obtained in animals were used to predict human pharmacokinetics in order to design the first clinical study of an investigational drug. The serum pharmacokinetics of aztreonam, a novel monocyclic beta-lactam antibiotic, were described for mice, rats, rabbits, and monkeys, using serum clearance and apparent volume of distribution. A one-compartment pharmacokinetic model yielded predictions for aztreonam clinical pharmacokinetics that were very helpful in choosing doses and serum sampling times for the first kinetic study in healthy male volunteers. Predicted serum aztreonam concentrations agreed well with subsequently measured values in man.