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PubMed1987

Pharmacokinetics and plasma bactericidal activity of aztreonam in low-birth-weight infants.

Aztreonam (30 mg/kg) was administered intravenously every 12 h during week 1 and every 8 h during weeks 2 to 4 of life to 26 low-birth-weight (less than 2,000 g) infants, and plasma concentration-time curves were measured on two occasions. The pharmacokinetics were described equally well by one-compartment and noncompartment models, and the values on day 1 were similar to those measured during the steady state on days 3 to 6. The mean peak plasma concentrations at completion of the 10-min infusion were from 65 to 83 micrograms/ml, the higher concentrations being seen in the larger infants. The half-lives of aztreonam ranged from 5.4 to 8.6 h and did not change significantly with birth weight. The median peak and trough plasma bactericidal titer against a strain of Escherichia coli (MBC, 10 micrograms/ml) was 1:16. Against a strain of Pseudomonas aeruginosa (MBC, 16 micrograms/ml), the median peak and trough bactericidal titers were 1:8 to 1:16 and 1:4, respectively. The urinary concentrations of aztreonam on day 1 of therapy were from 24 to 460.7 micrograms/ml (mean +/- 1 standard deviation, 254 +/- 113 micrograms/ml).

Aztreonam↗

PubMed1987

In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activity of aztreonam combined with tobramycin and with gentamicin was assessed in 78 clinical isolates of Pseudomonas aeruginosa and 11 clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis. Synergy was detected in 56.4% of P. aeruginosa isolates and 60% of P. cepacia isolates with the aztreonam-tobramycin combination and in 49.3% of P. aeruginosa isolates and 81.8% of P. cepacia isolates with the aztreonam-gentamicin combination. No antagonism was observed. These combinations merit clinical evaluation in the treatment of patients with cystic fibrosis.

Aztreonam↗

PubMed1991

Modulation of the intestinal flora of mice by treatment with aztreonam and tigemonam.

Oral and parenteral administration of aztreonam and oral administration of tigemonam to conventional mice caused a decrease in the number of aerobic gram-negative rods in the feces. Oral treatment with high doses of aztreonam (greater than or equal to 25 mg/kg/day) and tigemonam (100 mg/kg/day) adversely influenced colonization resistance, whereas oral treatment with lower doses of the monobactams or parenteral treatment with aztreonam did not.

Administration, Oral↗

PubMed1993

Aztreonam selective agar for gram positive bacteria.

Aztreonam blood agar, a new selective medium for Gram positive aerobic bacteria, was evaluated in comparison with conventional media for skin swabs. Aztreonam agar increased the number of isolates of Staphylococcus aureus by 17%. By producing purer growths on primary isolation, it significantly speeded up the identification and sensitivity testing of staphylococci and streptococci. All major Gram positive aerobic pathogens grow on this medium. Aztreonam agar is now an established addition to our culture media. It is used for swabs which are likely to have a mixed Gram positive and Gram negative flora, such as ears, burns, ulcers, and for the sputa of patients with cystic fibrosis.

Agar↗

PubMed1983

Review of single- and multiple-dose pharmacokinetics of the monobactam, aztreonam (SQ 26,776) in healthy subjects.

Aztreonam (SQ 26,776) is a new, completely synthetic, monocyclic beta-lactam antibiotic with potent activity against most aerobic gram-negative bacteria. The pharmacokinetics of single intravenous doses of 125-4,000 mg, single intramuscular doses of 250-1,000 mg, and multiple intravenous and intramuscular doses of 500 and 1,000 mg q.8 h during 7 days, were studied in 90 healthy male subjects. The half-life was 1.7, apparent volume of distribution 0.2 liters/kg, serum protein binding 56%, and urinary excretion 60-70% of the dose. No significant accumulation or change in pharmacokinetics of aztreonam was found during q.8 h dosing. Small amounts of the biologically inactive open beta-lactam ring metabolite, SQ 26,992, were found in the urine. Aztreonam level in serum and urine after 500- to 2,000-mg doses were potentially therapeutic for most Enterobacteriaceae and Pseudomonas aeruginosa.

Absorption↗

PubMed1985

Ro 17-2301: in vitro comparison with aztreonam, imipenem, ceftazidime, cefotaxime and netilmicin.

The in vitro activity of the novel monobactam antibiotic, Ro 17-2301 has been compared with those of aztreonam, imipenem, ceftazidime, cefotaxime and netilmicin. A total of 438 clinical isolates of aerobic gram-negative rods were employed and an agar dilution method was used for measurement of MIC. Ro 17-2301 was highly active against a wide variety of Enterobacteriaceae species (MIC range less than or equal to 0.03-8, MIC50 less than or equal to 0.03, MIC90 0.06 mg/l). The activity of aztreonam parallelled that of Ro 17-2301 although the latter seemed to have more uniformly high activity against Klebsiella sp. The other agents showed generally high activity against Enterobacteriaceae except netilmicin against Providencia stuartii (MIC50 4, MIC90 greater than or equal to 16 mg/l). Activity against Pseudomonas aeruginosa. was more variable. Ro 17-2301 and aztreonam were moderately active (MIC50 2, MIC90 8 and 16 mg/l, respectively). Imipenem was the most active agent against Acinetobacter, whereas Ro 17-2301 was moderately active. In conclusion, Ro 17-2301 shows impressive activity against Enterobacteriaceae and moderate activity against Acinetobacter and P. aeruginosa. Ro 17-2301 may well prove to be a useful agent in the treatment of gram-negative infections.

Acinetobacter↗

PubMed1989

Aztreonam in the treatment of urinary tract infections: a multicenter trial.

A multicenter trial involving several urologic units in Italy provided pooled data on 1,427 patients with urinary tract infections to evaluate the efficacy and safety of aztreonam, a new monobactam antibiotic. Microbiologic and clinical data were collected methodically in all cases. A majority of the patients (79.9%) were hospitalized during the study period, an associated pathology was noted in 29.1%, and 16.7% were receiving additional therapy. Aztreonam was administered by different routes and in different dosages according to the severity of the pathology. At the end of treatment, 93.6% of the patients showed a positive microbiologic response. Eradication percentages of the 6 main pathogens determined from cultures taken within the seventh day after the end of treatment were as follows: 93.9% for Escherichia coli (n = 415), 86.3% for Pseudomonas sp. (n = 207), 91.6% for Proteus sp. (n = 192), 89.8% for Providencia sp. (n = 59), 96.2% for Klebsiella sp. (n = 56), and 98.1% for Serratia sp. (n = 56). Aztreonam was well tolerated. Of the 1,427 patients evaluated for safety, only 54 (3.8%) reported 55 adverse reactions, necessitating the withdrawal of therapy in 5 (0.2%) instances.

Adolescent↗

PubMed1989

The clinical use of aztreonam.

Aztreonam is the first monobactam antibiotic to be used clinically. It is highly resistant to beta-lactamases, and although its activity spectrum is similar to that of the aminoglycoside antibiotics, it has no effect on gram-positive bacteria. The current study was undertaken to determine the efficacy of aztreonam in treating gram-negative infections caused by multiresistant microorganisms in patients with known sensitivity to penicillins and cephalosporins. Sixty-six patients presented with urinary tract infection (UTI) and 30 with respiratory tract infection (RTI). All patients received aztreonam, between 4 and 6 g/day in divided doses for 10-14 days. Cure was achieved in 59 (89.3%) patients with UTI; in the group with RTI, 20 patients were cured and 4 improved with treatment. Tolerance to the drug was good in both groups, and in no instance did side effects necessitate modification of the dosing regimen.

Adult↗

PubMed1989

Successful response of severe neonatal gram-negative infection to treatment with aztreonam.

Aztreonam was administered to 25 neonates (16 term, 9 premature) with clinically and bacteriologically proved gram-negative infections. Ten patients had meningitis, 9 had septicemia and 6 had urinary tract infections. Patients were between 1 and 28 days of age. Aztreonam was administered intravenously in doses ranging from 40 to 120 mg/kg/day for 10-30 days, depending on the causative organism. All CSF, blood and urine cultures were sterile 48 h after drug treatment had begun. There was no incidence of bacteriologic relapse. Body temperature returned to normal in 96% of patients within 3-4 days of therapy. Aztreonam was well tolerated. One infant experience nausea and vomiting, but no patient was withdrawn from therapy due to adverse reactions.

Aztreonam↗

PubMed1994

Drug degradation during HPLC analysis of aztreonam: effect on pharmacokinetic parameter estimation.

OBJECTIVE: To assess the impact of degradation of aztreonam, a beta-lactam antibiotic, during HPLC analysis on pharmacokinetic parameter estimates. METHODS: The baseline (B) serum concentration-time data from a published pharmacokinetic study of aztreonam were degraded using first-order equations and a degradation rate constant (0.014 h-1) determined from a preliminary degradation study. Samples were mathematically degraded for autosampler run times of 8-13 h (D1) to approximate a normal work day and for autosampler run times of 16-17 h (D2) and compared with B data. It was assumed that B data were nondegraded and that changes in chromatography were the result of degradation of azetreonam and not to any changes in chromatographic conditions. A two-compartment model was used to fit the data and pharmacokinetic parameters were calculated using standard equations. Statistical significance between all pharmacokinetic parameters for B and D1 and B and D2 was determined using the paired, two-tailed Student's t-test. RESULTS: Increased variability was noted for all pharmacokinetic parameters for D1 and D2 compared with B. Statistically significant differences were found for clearance (B < D1, p = 0.0095 and B < D2, p = 0.0194), steady-state volume of distribution (B < D2, p = 0.0392), and area under the serum concentration-time curve (B > D1, p = 0.0497). CONCLUSIONS: Aztreonam degradation resulted in increased variability in pharmacokinetic parameter estimates. Investigators should be cognizant of this and preliminary studies should be performed to characterize degradation for the length of the expected autosampler run.

Aztreonam↗

PubMed1984

Clinical experience with aztreonam in urinary and respiratory tract infections.

Twenty patients with severe infection, 10 of the urinary tract and the other 10 of the respiratory tract, were enrolled in a clinical trial of aztreonam, a new monobactam antimicrobial agent. For the urinary tract infections, the mean duration of treatment was 7 days, with doses ranging from 0.25 to 1.0 g aztreonam intravenously twice daily. Sustained clinical and microbiological cure was achieved in 9 of the 10 patients. In the group with respiratory infections, the mean duration of treatment was 9.3 days, patients receiving 1 g aztreonam intravenously 3-times daily. Initial clinical cure was achieved in 9 of the patients, the tenth showing an incomplete response. However, bacteriological recurrence, related to the persistent nature of the underlying disease, occurred in 6 of the 10 patients during the 1-month follow-up period. The only side-effects were mild, transient biochemical abnormalities which did not require drug withdrawal in any patient.

Adult↗

PubMed1985

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.

Aztreonam↗

PubMed1999

Carbapenems and monobactams: imipenem, meropenem, and aztreonam.

Imipenem and meropenem, members of the carbapenem class of beta-lactam antibiotics, are among the most broadly active antibiotics available for systemic use in humans. They are active against streptococci, methicillin-sensitive staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas. Resistance to imipenem and meropenem may emerge during treatment of P. aeruginosa infections, as has occurred with other beta-lactam agents; Stenotrophomonas maltophilia is typically resistant to both imipenem and meropenem. Like the penicillins, the carbapenems have inhibitory activity against enterococci. In general, the in vitro activity of imipenem against aerobic gram-positive cocci is somewhat greater than that of meropenem, whereas the in vitro activity of meropenem against aerobic gram-negative bacilli is somewhat greater than that of imipenem. Daily dosages may range from 0.5 to 1 g every 6 to 8 hours in patients with normal renal function; the daily dose of meropenem, however, can be safely increased to 6 g. Infusion-related nausea and vomiting, as well as seizures, which have been the main toxic effects of imipenem, occur no more frequently during treatment with meropenem than during treatment with other beta-lactam antibiotics. The carbapenems should be considered for treatment of mixed bacterial infections and aerobic gram-negative bacteria that are not susceptible to other beta-lactam agents. Indiscriminate use of these drugs will promote resistance to them. Aztreonam, the first marketed monobactam, has activity against most aerobic gram-negative bacilli including P. aeruginosa. The drug is not nephrotoxic, is weakly immunogenic, and has not been associated with disorders of coagulation. Aztreonam may be administered intramuscularly or intravenously; the primary route of elimination is urinary excretion. In patients with normal renal function, the recommended dosing interval is every 8 hours. Patients with renal impairment require dosage adjustment. Aztreonam is used primarily as an alternative to aminoglycosides and for the treatment of aerobic gram-negative infections. It is often used in combination therapy for mixed aerobic and anaerobic infections. Approved indications for its use include infections of the urinary tract or lower respiratory tract, intra-abdominal and gynecologic infections, septicemia, and cutaneous infections caused by susceptible organisms. Concurrent initial therapy with other antimicrobial agents is recommended before the causative organism has been determined in patients who are seriously ill or at risk for gram-positive or anaerobic infection.

Aztreonam↗

PubMed1999

[Transfer of resistance to 3rd generation cephalosporins and aztreonam in strains of Klebsiella pneumoniae producing extended spectrum beta-lactamases].

The authors demonstrated the transferability of antibiotic resistance genes in nosocomial strains of Klebsiella pneumoniae, isolated from newborn children at the Paediatric University Hospital in Bratislava. Strains were resistant to cefotaxime, ceftazidime and aztreonam. The determinants of resistance (carbenicillin, cephaloridine, cefotaxime, ceftazidime and aztreonam) were transferred to recipient strains of Escherichia coli K-12 and Proteus mirabilis P-38. The transfer of resistance determinant from donor strains was demonstrated by the analysis of the resistance spectrum in transconjugant clones of recipient strains by the method of indirect selection. The ability of production of extended spectrum beta-lactamases (ESBL) was demonstrated by the double disc diffusion test. Synergy between clavulanate and cefotaxime, clavulanate and ceftazidime and/or clavulanate and aztreonam indicated production of ESBL by these strains.

Aztreonam↗

PubMed1992

Stability of ranitidine hydrochloride with aztreonam, ceftazidime, or piperacillin sodium during simulated Y-site administration.

The stability of ranitidine hydrochloride after being mixed with commonly used i.v. beta-lactam antibiotics and administered by simulated Y-site injection was studied. Solutions of ranitidine 1 mg/mL (as the hydrochloride salt), aztreonam 16.7 mg/mL, ceftazidime 20 mg/mL (with sodium carbonate), and piperacillin 30 mg/mL (as the sodium salt) were prepared by reconstitution in i.v. mini-bags. To simulate Y-site injection, 2 mL of ranitidine hydrochloride was mixed with 2 mL of each antibiotic in glass test tubes. These admixtures were prepared in triplicate and stored at room temperature under fluorescent light. Concentrations of each drug in each admixture were determined by stability-indicating high-performance liquid chromatography immediately and after one, two, and four hours. Aztreonam, ceftazidime, and piperacillin each retained more than 95% of the original concentration for at least four hours when mixed 1:1 with ranitidine. Ranitidine retained more than 90% of its original concentration for at least four hours when combined with each of the other drugs. Ranitidine 1 mg/mL (as the hydrochloride salt) and aztreonam 16.7 mg/mL, ceftazidime 20 mg/mL (with sodium carbonate), or piperacillin 30 mg/mL (as the sodium salt) were stable for at least four hours during simulated Y-site administration.

Anti-Bacterial Agents↗

PubMed1992

Aztreonam compared to chloramphenicol in the treatment of enteric fevers.

Fifty-seven patients, twenty-six males and thirty-one females, aged 6 to 50 years (mean 12.6 years) with proven Salmonella typhi or S. paratyphi A septicaemia, were treated in an open randomized parallel study with either aztreonam or chloramphenicol. Aztreonam was given intramuscularly at a level of 50 to 80 mg/kg body weight per dose every 8 h for 7 days to thirty patients. Chloramphenicol was given orally in a dose of 50 to 70 mg/kg body weight every 6 h for 12 days to twenty-seven patients. All patients responded rapidly to treatment, becoming afebrile and asymptomatic within 5.5 to 6.4 days. Only one patient on aztreonam relapsed following treatment, whereas three patients relapsed after chloramphenicol treatment. There were no serious side effects with either drug.

Administration, Oral↗

PubMed1992

Purification of beta-lactamases and enzyme kinetic studies on aztreonam.

Standard beta-lactamases K1, P99, TEM-1, SHV-1 and beta-lactamase K-CAZ purified using FPLC through ion-exchange chromatography and filtration chromatography, were identified by determination of isoelectric points, molecular weights and substrate profiles. The results showed that the beta-lactamase stability of domestic aztreonam was very similar to that of cefotaxime, ceftazidime and much better than that of cefoperazone. Aztreonam showed a high affinity to chromosomal-mediated cephalosporinase P99, its Ki for inhibition of P99 with cephaloridine as substrate was 0.0159 microns. Aztreonam and the three third generation cephalosporins tested were not stable to beta-lactamase K-CAZ, which hydrolysed them in different degrees.

Aztreonam↗

PubMed1992

[Concentration of aztreonam in plasma, urine, and seminal fluid of patients with chronic prostatitis].

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.

Adult↗