Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers.

The common usage of extended spectrum beta-lactams co-administered with amikacin in everyday clinical practice for infections by multidrug-resistant isolates has created the need to search for pharmacokinetic interaction. Eighteen healthy volunteers were enrolled in the study; six were administered 1g of ceftazidime singly intravenously or combined with 0.5 g of amikacin; six received 0.5 g of imipenem singly or combined with 0.5 g of amikacin and six 1g of aztreonam singly or combined with 0.5 g of amikacin. Blood and urine samples were collected at regular time intervals and apparent serum levels were determined by a microbiological assay. Co-administration of ceftazidime and amikacin resulted in higher C(max) and AUC for amikacin than when administered alone. Co-administration of imipenem and amikacin resulted in higher C(max) for imipenem than when administered alone. The tested interactions did not affect plasma half-life (t(1/2)) and clearance rate of any antimicrobial compared with its single administration. All tested drugs were mainly eliminated by glomerular filtration. It is concluded that co-administration of ceftazidime, imipenem or aztreonam with amikacin in healthy volunteers might affect C(max) and AUC without influencing any other pharmacokinetic parameter. The probable clinical endpoint is that giving ceftazidime, imipenem or aztreonam with amikacin might result in a transient elevation of beta-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.

[Concentration of aztreonam in plasma, urine, and seminal fluid of patients with chronic prostatitis]. / Concentrazioni di aztreonam nel plasma, nell'urina e nel liquido seminale di soggetti affetti da prostatite cronica.

The authors consider the concentration of antibacterial drugs in the seminal fluid as a reliable experimental model for the study of pharmacokinetics in chronic prostatitis (c.p.). The study was conducted on 32 subjects, 20 of whom were affected by c.p. and 12 were normal controls. All subjects were treated with aztreonam at a dosage of 1 g.i.m. The assay was performed 1 hour after the injection, on seminal fluid, urine and serum samples. No difference was observed between normal subjects and patients with c.p. with regard to serum and urinary levels of the drug. There was a trend towards a higher concentration of the drug in the seminal fluid of patients with c.p. when compared to normal subjects, with mean values of 1.8 and 0.9 mcg/ml respectively. This difference was not statistically significant. Furthermore, the drug concentration of the drug in semen was below the sensitivity limits of the assay in 43% of normal subjects and in 10% of patients with c.p. In the latter group of patients the mean values of aztreonam concentration exceeded the minimal inhibitory concentrations for most aetiological agents causing c.p. In conclusion, it is suggested that aztreonam is likely to be effective in acute prostatitis, caused by Gram negative strains and may be indicated in selected cases for the treatment of c.p.

Aztreonam: clinical pharmacology.

Monocyclic beta-lactam antibiotics (monobactams) are structurally unique from the traditional bicyclic beta-lactams because of their single ring configuration. Aztreonam, the first of these monobactams, has been studied extensively in order to determine its pharmacologic and pharmacokinetic profile in adults and children with bacterial infections. It has been established, for example, that with intramuscular or intravenous dosing (30 to 50 mg/kg in children and 1 to 2 g in adults), serum concentrations above the minimum inhibitory concentrations of most aerobic Gram-negative bacteria can be maintained for up to 8 hours. Against a less susceptible pathogen such as Pseudomonas aeruginosa, every-6-hour dosing allows for preservation of the bactericidal effect, although longer intervals may be practical in low birth weight infants. The drug is primarily (80%) excreted by renal mechanisms and serum clearance varies with postnatal age. Distribution into body fluids is similar to that of other beta-lactams. For example in the presence of meningeal inflammation, cerebrospinal fluid concentrations are 17 to 33% of serum values. Urinary concentrations are high and prolonged with greater than 80% appearing as the active drug. Preliminary data from cystic fibrosis patients suggest that there are very minor pharmacokinetic differences in this population. The pharmacologic profile indicates that aztreonam may provide an appropriate alternative to traditional therapy for serious Gram-negative aerobic infections in infants and children.

Clinical-experimental research on aztreonam ampullar and ureteral concentrations.

After pointing out that, during urinary tract infections, bacteria can affect the peristalsis of the renal ampulla and of the ureter, the authors report the results of a trial on aztreonam concentrations in the upper urinary tract, performed in order to evaluate the concentrations of the drug in the ampullar and ureteral tissues. This study was carried out on bioptical specimens collected from 18 subjects (12 children and 6 adults), who underwent surgery for malformations of the urinary system. The authors report and discuss the results of the determinations performed on the samples of urinary tract tissue, serum and urine, 60 to 90 minutes after the i.m. administration of aztreonam.

Morphological studies of Escherichia coli in the urine of patients with acute simple cystitis treated with aztreonam.

The effects of aztreonam (AZT) on the morphology of Escherichia coli in the urine of 5 patients with acute simple cystitis were studied by differential interference contrast microscopy. The urine specimens were collected via catheter before, 5, 15 and 30 minutes after intravenous administration of 1.0 gm AZT. The minimum inhibitory concentration of E. coli against AZT was 0.05 microgram/ml. The mean urinary concentrations at 5, 15 and 30 minutes after administration of AZT were 481.6 micrograms/ml, 1168.2 micrograms/ml and 993.4 micrograms/ml, respectively. In 4 patients, the urinalysis became normal within 30 minutes after the administration. Filamentous cells were observed at low and high urinary concentrations of AZT. They had vacuole-like formations. These findings were characteristic morphological changes caused by AZT. In the other patient, spheroplasts and ovoid cells were observed. AZT in the urine of patients with acute simple cystitis is suggested to have a high affinity for penicillin-binding protein (PBP) 3 and moderate affinity for PBP 1a.