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PubMed1983

Pharmacology of aztreonam after intravenous infusion.

The pharmacokinetics of aztreonam, a monocyclic beta-lactam which inhibits most members of the family Enterobacteriaceae at concentrations of less than 1 microgram/ml and most Pseudomonas aeruginosa isolates at concentrations of less than 16 micrograms/ml, were examined in healthy male volunteers after 30-min intravenous infusions of 0.5, 1, and 2 g of the drug. Mean peak levels of the drug in serum at the end of infusion were 65.5, 164, 255 micrograms/ml after 0.5 1, and 2 g, respectively, with levels of the drug in serum of 1.8, 3, and 8.5 micrograms/ml at 8.5 h for the three doses, respectively. The half-life was approximately 2 h for all three doses. The total serum clearance averaged 1 ml/min per kg. The apparent volume of distribution averaged 0.17 liter/kg for the three doses. Overall excretion of the drug in urine was 61%, with mean levels in urine of 23, 52, and 109 micrograms/ml at 8.5 to 12.5 h after 0.5, 1, and 2 g of aztreonam, respectively. Concentrations of the drug in serum after a 1-g dose exceeded the minimal inhibitory concentration for 90% of the members of the Enterobacteriaceae by four- to eightfold for 8 h and exceeded the minimal inhibitory concentration for P. aeruginosa isolates for 4 h.

Adult↗

PubMed1983

In vitro activity and beta-lactamase stability of a monobactam, SQ 26,917, compared with those of aztreonam and other agents.

SQ 26,917 is a monobactam antibiotic. Its in vitro activity was compared with those of aztreonam, cefotaxime, ceftazidime, and moxalactam. SQ 26,917, which contains a beta-methyl configuration on the beta-lactam ring, was similar in activity to aztreonam with the exception of greater activity against Pseudomonas aeruginosa isolates. SQ 26,917 had no activity against gram-positive isolates or anaerobic bacteria. It was not hydrolyzed by common plasmid and chromosomal beta-lactamases.

Anti-Bacterial Agents↗

PubMed1984

Biliary excretion of aztreonam in patients with biliary tract disease.

The biliary excretion of aztreonam was studied in 10 post-cholecystectomy patients with T-tube biliary drainage (group A) and four other subjects with obstructive biliary tract disease who had recent placement of external biliary drainage (group B). Maximum biliary levels ranged from 9.7 to 88.2 micrograms/ml (mean, 42.9 +/- 7.9 micrograms/ml) and occurred 2.4 h after injection of a single 1-g dose intravenously. Peak biliary levels observed in group B patients were approximately one-third those in group A. Cumulative 12-h biliary excretion (group B) accounted for 0.18 +/- 0.06% of the total dose. In the same period, urinary excretion accounted for 65 to 72% of the total dose. The lower biliary levels of aztreonam observed in group B patients relative to those in group A suggest that in patients with total biliary tract obstruction the liver may not recover full secretory capacity, at least within 3 to 7 days after biliary decompression.

Adult↗

PubMed1984

Efficacy of aztreonam in treatment of experimental syphilis in rabbits.

The efficacy of aztreonam (SQ 26,776) in the therapy of active syphilis infection was evaluated in the rabbit model. Aztreonam was effective in treating active syphilis at a dose of 25 mg/kg given intramuscularly twice daily for 10 days; doses of 2.5 and 0.25 mg/kg were not effective.

Animals↗

PubMed1984

Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up.

Aztreonam at doses of 1 or 2 g given intramuscularly or intravenously every 8 h for 7 to 42 days was given to 55 patients, most of them suffering from difficult-to-treat infections either because the isolated pathogens were multiresistant or because of the location of the infection. Infections included: urinary tract (23 cases), deep soft tissue phlegmon (12 cases), chronic osteomyelitis in exacerbation (7 cases), abscesses (7 cases), pneumonia (4 cases), and external otitis (2 cases). In culture specimens, Pseudomonas aeruginosa (24 isolates) and various Enterobacteriaceae species (37 isolates) were isolated with MICs ranging from 0.25 to 16 micrograms/ml. Clinically, at the completion of treatment and after a 6-week posttreatment follow-up, 45 (81.6%) patients were cured, 4 (7.2%) improved, 3 (5.6%) relapsed, and 3 (5.6%) failed to respond to therapy. Bacteriologically, at the end of treatment, the pathogen was eradicated in 50 patients (91%) and persisted in 5 (9%). After a 6-week follow-up, cultures remained sterile in 33 patients (60.0%), 16 (29.1%) relapsed, in 6 (10.9%) bacteria persisted, and superinfection was reported in 4 (7.3%) patients. No appreciable adverse effects or toxicity was observed. From the reported results, it is concluded that aztreonam is a valuable addition to the field of antimicrobial chemotherapy that can be used effectively and safely in the treatment of a variety of gram-negative infections.

Adult↗

PubMed1984

Enterococcal superinfection and colonization with aztreonam therapy.

Patients were given aztreonam (SQ 26,776) parenterally for the treatment of various gram-negative infections. During or shortly after therapy, 8 (17.8%) of 45 patients became infected with or colonized by enterococcus. These eight cases included eight urinary tract isolates; one of these cases subsequently developed bacteremia. Five patients required further antimicrobial therapy directed against enterococcus. Patients receiving aztreonam are at risk for the development of enterococcal superinfection or colonization.

Anti-Bacterial Agents↗

PubMed1984

Effect of aztreonam in combination with azlocillin or piperacillin on Pseudomonas aeruginosa.

Aztreonam, a synthetic monobactam antimicrobial agent specifically active against aerobic, gram-negative microorganisms, was studied in combination with the extended-spectrum penicillins azlocillin and piperacillin against 46 strains of Pseudomonas aeruginosa. Of these strains, 4.3% were synergistically inhibited, and 19.7% showed evidence for an additive effect of the antibiotics. All other strains showed indifference. The addition of cefoxitin to these combinations increased the MICs of azlocillin and piperacillin by two to three tubes, whereas zero- to one-tube increases were noted for aztreonam MICs. Attempts to block cefoxitin-induced beta-lactamase production by using clindamycin were unsuccessful even at high clindamycin concentrations.

Anti-Bacterial Agents↗

PubMed1985

Penetration of aztreonam into human bronchial secretions.

Nine intubated patients were given a single, 2-g intravenous dose of aztreonam over 5 min. Samples of serum and bronchial secretion were obtained 2, 4, and 8 h after administration and assayed for aztreonam content. The mean concentrations in bronchial secretion ranged from 1.9 to 5.2 micrograms/ml and tended to be highest at 4 h. The concentrations in bronchial secretion varied from patient to patient, but each patient had one or more bronchial secretion samples that contained at least 2.7 micrograms of drug per ml.

Adult↗

PubMed1985

Aztreonam therapy in experimental meningitis due to Haemophilus influenzae type b and Escherichia coli K1.

The penetration of aztreonam into cerebrospinal fluid was 7 to 15% and 9 to 25%, respectively, in experimental Haemophilus influenzae type b and Escherichia coli K1 meningitis. Aztreonam was effective in reducing the number of organisms in cerebrospinal fluid after single-dose and continuous infusion administration, and the median bactericidal titers in cerebrospinal fluid were 1:32 against both meningeal pathogens.

Animals↗

PubMed1985

In vitro activities of enoxacin, ticarcillin plus clavulanic acid, aztreonam, piperacillin, and imipenem and comparison with commonly used antimicrobial agents.

A total of 745 gram-negative and 313 gram-positive clinical isolates were tested against enoxacin, ticarcillin plus clavulanic acid, aztreonam, imipenem, and piperacillin and compared with commonly used antimicrobial agents. Ticarcillin plus clavulanic acid, imipenem, and piperacillin were active against Pseudomonas aeruginosa and Acinetobacter spp. and most Pseudomonas spp. Aztreonam was active against members of the family Enterobacteriaceae but was less effective against the nonfermenters. Enoxacin was active against the Enterobacteriaceae, P. aeruginosa, the staphylococci, and most Acinetobacter spp. but was less active against Pseudomonas spp. and streptococci. Imipenem was very active against all gram-positive and -negative organisms tested except for Pseudomonas maltophilia.

Anti-Bacterial Agents↗

PubMed1986

Aztreonam treatment of gram-negative septicemia.

Seventy-five aztreonam treatment courses in 74 patients with gram-negative septicemia resulted in 56 clinical cures (75%), 12 partial clinical cures (16%), and 7 clinical failures (9%). Eradication of the original pathogen from the blood was obtained in all patients but two, who had relapses 1 and 4 days, respectively, after treatment. In nine patients (12%) a superinfection was reported. Significant adverse reactions were limited to one transient urticarial rash. Aztreonam may prove to be an effective alternative for the treatment of gram-negative septicemia, but superinfections should be carefully monitored.

Adolescent↗

PubMed1986

Aztreonam in the treatment of severe urinary tract infections in pediatric patients.

Aztreonam was administered to 30 patients, ages 0.03 to 15.4 years, with severe and in 21 cases complicated urinary tract infections caused by members of the family Enterobacteriaceae and Pseudomonas aeruginosa which were resistant to ampicillin and susceptible to the study drug in vitro. A mean dose of 47.7 mg/kg was given intramuscularly every 12 h to 26 patients. In four patients with renal insufficiency, the dose was reduced according to pharmacokinetic data. Permanent urine sterilization and clinical cure were achieved in 22 patients, 13 of whom had urological malformations. In two patients with P. aeruginosa and Proteus mirabilis infections, the treatment failed. Another patient had an Escherichia coli reinfection 21 days after the end of therapy. Four patients with various urological abnormalities had gram-positive superinfections, and two patients had gram-negative superinfections during and at the end of therapy: all six had indwelling ureteric splints or pyelostomy as predisposing conditions. No adverse clinical effects were observed. Some transient and slight or moderate alterations were observed at the end of treatment: eosinophilia (nine cases), elevation of hepatic enzymes (eight cases), prolongation of prothrombin time (three cases), and neutropenia (one case). A pharmacokinetic study was performed in six patients with normal renal function and in seven patients with various degrees of renal insufficiency. The elimination half-life of the drug was inversely correlated with the glomerular filtration rate. At the dosage used, aztreonam proved effective for severe urinary tract infections caused by members of the family Enterobacteriaceae in pediatric patients.

Adolescent↗

PubMed1987

In vitro activities of aztreonam, imipenem, and amoxycillin-clavulanate against ampicillin-resistant Haemophilus influenzae.

Two hundred and fifty-seven ampicillin-resistant clinical isolates of Haemophilus influenzae were tested by disk diffusion and MIC determination for susceptibility to aztreonam, imipenem, and amoxycillin combined with clavulanate. The modal MICs and MICs for 50 and 90% of isolates of all three antimicrobial agents for the 157 beta-lactamase-positive strains did not differ significantly from figures obtained with 2,201 ampicillin-susceptible H. influenzae by the same methods. Aztreonam and amoxycillin-clavulanate were less active, as reflected by an increase in these parameters, against 38 beta-lactamase-negative isolates requiring greater than or equal to 4 micrograms of ampicillin per ml for inhibition and 62 strains considered to have an intermediate degree of nonenzymic (intrinsic) resistance to ampicillin (zone diameters of less than 20 mm with 2-micrograms ampicillin disks and MICs of 1 or 2 micrograms/ml). There was no detectable difference in imipenem activity against these 100 strains compared with that observed against the ampicillin-susceptible group. Of the 24 strains requiring at least 4 micrograms of imipenem per ml for inhibition, 13 also showed reduced susceptibility to ampicillin (5 beta-lactamase-positive and 8 beta-lactamase-negative isolates). A lack of correlation between reduced susceptibility to imipenem and the other beta-lactams was observed.

Amoxicillin↗

PubMed1989

Novel plasmid-mediated beta-lactamase (TEM-10) conferring selective resistance to ceftazidime and aztreonam in clinical isolates of Klebsiella pneumoniae.

Two clinical isolates of Klebsiella pneumoniae from seriously ill patients in Chicago, Ill., have been identified as resistant to ceftazidime and aztreonam but susceptible to other cephalosporins. This unusual antibiogram was shown to be due to a novel plasmid-mediated beta-lactamase which readily hydrolyzed ceftazidime and aztreonam in addition to penicillins such as piperacillin and carbenicillin. This enzyme and its attendant resistance were transferred to Escherichia coli by conjugation on a 50-kilobase plasmid. Isoelectric focusing revealed a single beta-lactamase band with a molecular weight of 29,000 and an isoelectric point of 5.57 in the resistant isolates and transconjugants. The beta-lactamase inhibitors clavulanic acid and sulbactam restored beta-lactam susceptibility in the resistant isolates. Fifty percent inhibitory concentrations of clavulanic acid and sulbactam were 4.4 and 940 nM, respectively. DNA hybridization studies indicated that this enzyme, designated TEM-10, is related to well-established TEM-type beta-lactamases. However, the TEM-10 enzyme was inhibited by p-chloromercuribenzoate, in contrast to TEM-2 beta-lactamase. On the basis of substrate and inhibition profiles, the TEM-10 enzyme could be easily discriminated from TEM-5 and RHH-I beta-lactamases.

Anti-Bacterial Agents↗

PubMed1991

Pharmacokinetics and renal tolerance of aztreonam in premature infants.

Aztreonam (30 mg/kg of body weight) was administered intravenously over 3 min every 12 h to 30 preterm neonates divided into two groups according to gestational age (mean age for group A was less than 30 weeks and mean age for group B was greater than 30 weeks) and birth weight (mean weight for group A was less than 1,500 g and mean weight for group B was greater than 1,500 g). Blood and urine samples were analyzed by microbiological assay. The pharmacokinetics were described by one-compartment and noncompartment models. The mean half-life and clearance for premature infants weighing less than 1,500 g were 5.33 +/- 3.61 h and 1.52 +/- 1.33 ml/min/kg, respectively; for those weighing more than 1,500 g, the values were 4.08 +/- 2.28 h and 2.41 +/- 2.10 ml/min/kg, respectively. The mean urinary concentration of aztreonam in 15 premature infants during the first 6 h of therapy was 242.72 +/- 188.19 micrograms/ml, with a mean percentage of elimination of 13.29%. Urinary excretion of N-acetyl-beta-D-glucosaminidase (a specific and sensitive test for the detection of drug-induced renal tubule damage) did not show significant differences in our group of premature infants compared with that in a control group. The dose of 30 mg/kg and a dosage interval of 8 to 12 h could be recommended for the treatment of suitable bacterial infections in all premature infants.

Acetylglucosaminidase↗

PubMed1993

Novel, plasmid-encoded, TEM-derived extended-spectrum beta-lactamase in Klebsiella pneumoniae conferring higher resistance to aztreonam than to extended-spectrum cephalosporins.

A clinical isolate of Klebsiella pneumoniae was more resistant to aztreonam than to cefotaxime and ceftazidime. It produced a clavulanate-susceptible beta-lactamase with an isoelectric point of 6.3 which readily hydrolyzed penicillins, cefotaxime, and ceftazidime, but which hydrolyzed aztreonam poorly. The enzyme was encoded by a gene on a 15-kb plasmid; the gene hybridized with an intragenic DNA probe of blaTEM.

Anti-Bacterial Agents↗

PubMed1998

Can results obtained with commercially available MicroScan microdilution panels serve as an indicator of beta-lactamase production among escherichia coli and Klebsiella isolates with hidden resistance to expanded-spectrum cephalosporins and aztreonam?

Among clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca, there is an ever-increasing prevalence of beta-lactamases that may confer resistance to newer beta-lactam antibiotics that is not detectable by conventional procedures. Therefore, 75 isolates of these species producing well-characterized beta-lactamases were studied using two MicroScan conventional microdilution panels, Gram Negative Urine MIC 7 (NU7) and Gram Negative MIC Plus 2 (N+2), to determine if results could be utilized to provide an accurate indication of beta-lactamase production in the absence of frank resistance to expanded-spectrum cephalosporins and aztreonam. The enzymes studied included Bush groups 1 (AmpC), 2b (TEM-1, TEM-2, and SHV-1), 2be (extended spectrum beta-lactamases [ESBLs] and K1), and 2br, alone and in various combinations. In tests with E. coli and K. pneumoniae and the NU7 panel, cefpodoxime MICs of >/=2 microg/ml were obtained only for isolates producing ESBLs or AmpC beta-lactamases. Cefoxitin MICs of >16 microg/ml were obtained for all strains producing AmpC beta-lactamase and only 1 of 33 strains producing ESBLs. For the N+2 panel, ceftazidime MICs of >/=4 microg/ml correctly identified 90% of ESBL producers and 100% of AmpC producers among isolates of E. coli and K. pneumoniae. Cefotetan MICs of >/= 8 microg/ml were obtained for seven of eight producers of AmpC beta-lactamase and no ESBL producers. For tests performed with either panel and isolates of K. oxytoca, MICs of ceftazidime, cefotaxime, and ceftizoxime were elevated for strains producing ESBLs, while ceftriaxone and aztreonam MICs separated low-level K1 from high-level K1 producers within this species. These results suggest that microdilution panels can be used by clinical laboratories as an indicator of certain beta-lactamases that may produce hidden but clinically significant resistance among isolates of E. coli, K. pneumoniae, and K. oxytoca. Although it may not always be possible to differentiate between strains that produce ESBLs and those that produce AmpC, this differentiation is not critical since therapeutic options for patients infected with such organisms are similarly limited.

Aztreonam↗

PubMed1986

Treatment of uncomplicated gonorrhoea with single dose aztreonam.

Infection with Neisseria gonorrhoeae was cleared in 61 men and 26 women at all sites (except in the pharynx of one male bisexual patient with urethral and pharyngeal gonorrhoea) after treatment with aztreonam as a single 1 g intramuscular injection. Aztreonam was well tolerated with no adverse effects. This monobactam antibiotic was effective against both penicillin sensitive and resistant strains.

Adult↗