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PubMed1997

Characterization and amino acid sequence of the OXY-2 group beta-lactamase of pI 5.7 isolated from aztreonam-resistant Klebsiella oxytoca strain HB60.

Klebsiella oxytoca strain HB60 is highly resistant to cefoperazone and aztreonam (MICs = 128 mg/L). It produces a chromosomally encoded beta-lactamase of pI 5.7 which was highly efficient against penicillins, first-generation cephalosporins and cefoperazone, a non-oxyimino third-generation cephalosporin. Aztreonam and oxyimino broad-spectrum cephalosporins were less good substrates. The beta-lactamase activity was susceptible to inhibition by clavulanic acid (IC50 = 1 microM). The enzyme purified to homogeneity had a specific activity towards benzylpenicillin of 3670 U/mg. The 263 amino acid residues of the protein were sequenced by Edman degradation of proteolytic peptides. The beta-lactamase was shown to belong to the OXY-2 group as it had only one amino acid substitution (Asn for Asp at ABL position 197) compared with the beta-lactamase (pI 5.2) from the aztreonam-susceptible K. oxytoca strain SL911 and two substitutions (Ala223 for Val and Asp255 for Asn) compared with the beta-lactamase (pI 6.4) from the aztreonam-resistant K. oxytoca strain D488. These three OXY-2-group enzymes behave in the same way towards beta-lactam antibiotics. The variability in the resistance of these K. oxytoca strains would thus seem to be due to variation in the level of production of the beta-lactamases rather than to structural alteration of the enzymes.

Amino Acid Sequence↗

PubMed1995

Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in children.

An increase in the incidence of Salmonella typhi strains resistant to chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole causing enteric fever in Egyptian children stimulated the evaluation of alternative drugs. Children with positive blood cultures were treated with cefixime, ceftriaxone or aztreonam, and the efficacy, safety and cost of these regimens were evaluated and compared. Cefixime (7.5 mg/kg) was given orally twice daily to 50 children for 14 days, ceftriaxone (50 to 70 mg/kg) was given im once daily for 5 days to 43 children and aztreonam (50 to 70 mg/kg) was given im every 8 hours for 7 days to 31 children. Children in the 3 groups were comparable with regard to age, sex, duration and severity of illness before admission. All children were cured. A significant difference (P < 0.05) in duration of treatment before becoming afebrile seemed to favor ceftriaxone (3.9 days) over aztreonam (5.5 days) and cefixime (5.3 days). During the 4-week follow-up period relapses occurred in 3 (6%) children in the cefixime group, in 2 (5%) in the ceftriaxone group and in 2 (6%) in the aztreonam group. Safety and efficacy were comparable for all 3 drugs. Ceftriaxone was most cost-effective on an inpatient basis, because of a more rapid clinical cure, and cefixime was the most cost-effective on an outpatient basis, because of drug cost.

Adolescent↗

PubMed1985

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.

Adult↗

PubMed1987

Double-blind study comparing aztreonam with placebo for prophylaxis of infection following prostatic surgery.

In a prospective, randomised, double-blind study, 179 patients undergoing retropubic or transurethral prostatectomy were given pre-operatively either 1 g aztreonam or a placebo. In patients treated with aztreonam there was a significant reduction in the number with post-operative bacteriuria and in the number requiring treatment of post-operative bacteriuria. Other differences were not significant. The mean duration of post-operative hospital stay for patients receiving aztreonam was 7.1 days compared with 6.9 days for those receiving placebo. In patients treated with aztreonam there was no increase in the frequency of infections due to Gram-positive bacterial species.

Aztreonam↗

PubMed1984

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.

Animals↗

PubMed1984

Distribution of aztreonam into fetuses and milk of rats.

Subcutaneous administration of [14C]aztreonam (150 mg/kg) to pregnant rats was followed by the appearance of radioactive moieties in fetuses and amniotic fluid. Concentrations of both total radioactivity and unchanged aztreonam in maternal serum declined more rapidly than those in fetuses and amniotic fluid. [14C]aztreonam (150 mg/kg) was also administered subcutaneously to lactating rats. Radioactivity and unchanged aztreonam were found in the suckling pups and in the serum and milk of the dam. Results obtained by whole-body autoradiography were generally consistent with these obtained by measuring radioactivity present in the excised tissues. Autoradiographs of the pups showed detectable amounts of radioactivity in the brain; since no radioactivity was detectable in the brain of the dam, it appears that the blood-brain barrier was not fully developed in 7-day-old pups.

Amniotic Fluid↗

PubMed1984

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.

Age Factors↗

PubMed1984

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.

Adult↗

PubMed1985

Influence of four modes of administration on penetration of aztreonam, cefuroxime, and ampicillin into interstitial fluid and fibrin clots and on in vivo efficacy against Haemophilus influenzae.

The extravascular penetration and bactericidal activity of aztreonam, cefuroxime, and ampicillin against beta-lactamase-positive and -negative Haemophilus influenzae strains were compared in a rabbit model. All groups of animals received an identical total dose of 100 mg of either antibiotic per kg given by four different intravenous modes of administration including a single large injection, four intermittent injections, a continuous infusion, and an injection followed by an infusion. Aztreonam had a higher degree of penetration in interstitial fluid and fibrin clots and was the most effective agent against beta-lactamase-positive and -negative H. influenzae. A single large injection of either drug resulted in significantly higher peak levels and higher initial area under the curves of concentrations of drugs in serum, the interstitial fluid, and fibrin clots than those by other modes of administration. Continuous infusions of antibiotics resulted in poor in vivo bactericidal activity. Other modes of administration exhibited good antibacterial activity within the first 6 h of the study. Thereafter, a single large injection of aztreonam resulted in a much more rapid killing of H. influenzae than that by injection of the other drugs. Aztreonam and cefuroxime showed good in vivo stability to beta-lactamase produced by H. influenzae while ampicillin was rapidly hydrolyzed in vivo.

Ampicillin↗

PubMed1991

Aztreonam pharmacokinetics in burn patients.

The pharmacokinetics of aztreonam in eight adult patients with severe burn injuries (total body surface area burn, 49% +/- 21% [mean +/- standard deviation]) were studied. The time of initiation of study following burn injury was 7.0 +/- 1.4 days. Four patients at first dose and at steady state were studied. Aztreonam concentrations were measured by high-performance liquid chromatography, and a two-compartment model was used to fit the data. No significant differences in any pharmacokinetic parameters between first dose and steady state were observed. Volume of distribution of the central compartment after first dose (0.14 liters/kg) and volume of distribution at steady state (0.31 liters/kg) were approximately 30% higher than those reported for other patient populations. Total drug clearance and renal drug clearance when normalized to creatinine clearance (CLCR) were similar to those previously reported for other critically ill patients. CLCR was strongly correlated with renal drug clearance (r = 0.94) and total drug clearance (r = 0.95). The extent and degree of burn (percent second or third degree burn) were poorly correlated with all pharmacokinetic parameters with the exception of the volume of distribution at steady state, which was correlated with both total body surface area burn (r = 0.95) and percent second degree burn (r = 0.83). Aztreonam pharmacokinetics are altered as a result of thermal injury; however, CLCR can be used to assess the clearance of aztreonam in burn patients.

Adolescent↗

PubMed2005

Safety and efficacy of tigecycline in treatment of skin and skin structure infections: results of a double-blind phase 3 comparison study with vancomycin-aztreonam.

In a randomized, double-blind, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. The primary end point was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable (CE) populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed. Safety was assessed by physical examination, laboratory results, and adverse event reporting. Five hundred twenty patients were included in the c-mITT population (tigecycline group, n = 261; combination group, n = 259), and 436 were clinically evaluable (tigecycline group, n = 223; combination group, n = 213). The clinical responses in the tigecycline and the combination vancomycin and aztreonam groups were similar in the c-mITT population (84.3% versus 86.9%; difference, -2.6% [95% confidence interval, -9.0, 3.8]; P = 0.4755) and the CE population (89.7% versus 94.4%; difference, -4.7% [95% confidence interval, -10.2, 0.8]; P = 0.1015). Microbiologic eradication (documented or presumed) occurred in 84.8% of the patients receiving tigecycline and 93.2% of the patients receiving vancomycin and aztreonam (difference, -8.5 [95% confidence interval, -16.0, -1.0]; P = 0.0243). The numbers of patients reporting adverse events were similar in the two groups, with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the combination vancomycin and aztreonam group. Tigecycline was shown to be safe and effective for the treatment of complicated skin and skin structure infections.

Adult↗

PubMed2005

Pilot study for the development of a new campylobacter selective medium at 37 degrees C using aztreonam.

AIMS: To overcome contamination and temperature inhibition by isolating campylobacter at 37 degrees C. METHODS: The beta lactam antibiotic aztreonam was included in a selective medium because of its inhibitory activity against Gram negative organisms but not against Campylobacter jejuni. Vancomycin and amphotericin were added to inhibit Gram positive bacteria and yeasts. RESULTS: The aztreonam amphotericin vancomycin (AAV) experimental campylobacter selective medium showed growth microaerobically at 37 degrees C of C jejuni, C coli, C lari, C hyointestinalis, C fetus subsp. fetus, and C jejuni subsp. doylei after 24 to 48 hours of incubation. Six campylobacter NCTC strains demonstrated a minimum inhibitory concentration (MIC) > or = 256 mg/litre for vancomycin and aztreonam, whereas C upsaliensis and two "campylobacter-like" strains now reclassified under genus helicobacter--H cinaedi and H fennelliae--had a MIC of 4 mg/litre for vancomycin and aztreonam. In the pilot study (150 samples), AAV medium (37 degrees C) had a higher sensitivity for isolating campylobacters: 14 were isolated on AAV compared with 10 on modified CDA (43 degrees C) over three days, and nine were isolated on AAV medium compared with five on modified CDA (43 degrees C) after 24 hours of incubation. Contamination rates remained low. CONCLUSION: The medium was devised in a pilot study performed between 1990 and 1993; however, this is the first report of AAV medium used as a selective medium capable of growing six campylobacters of pathogenic importance at 37 degrees C. Further studies are indicated.

Amphotericin B↗

PubMed1988

Acute renal failure, skin rash, and eosinophilia associated with aztreonam.

A case of acute renal failure associated with aztreonam therapy is reported. A man, age 70, with infections due to Klebsiella pneumoniae and Enterobacter cloaca was treated for 9 days with aztreonam and presented with a generalized maculopapular rash, fever, eosinophilia, worsening renal function and increased IgE levels and eosinophiluria. Aztreonam was then discontinued and the patient was treated with supportive measures and steroids and his renal failure reversed over the course of 5 days. This appears to be one of the first cases of acute renal failure associated with aztreonam.

Acute Kidney Injury↗

PubMed1986

Beta-lactamase stability and in vitro activity of aztreonam, with a comparison to 9 other beta-lactam antibiotics and gentamicin.

The antibacterial activity of aztreonam, 9 other beta-lactam antibiotics and gentamicin was tested in vitro on 383 recently isolated bacteria. The activity of aztreonam against the gram-negative bacteria is similar to the activity of the 3rd generation cephalosporins and gentamicin. With regard to beta-lactamase stability only PSE-2 out of 14 plasmid mediated beta-lactamases and K-1 out of 2 chromosomally mediated beta-lactamases could hydrolyze aztreonam. With its beta-lactamase stability, high antibacterial activity and narrow-spectrum aztreonam seems to be a valuable addition to the antibiotic arsenal.

Anti-Bacterial Agents↗

PubMed1989

Multicenter comparative study of aztreonam and gentamicin in the treatment of renal and urinary tract infections.

A multicenter comparative study was carried out to evaluate the efficacy of aztreonam and gentamicin in 186 patients with symptomatic renal or urinary tract infections. Patients were divided randomly into two groups: 94 patients received aztreonam 1 g/day intramuscularly and 92 patients received gentamicin 80 mg i.m. twice daily. The clinical and microbiologic results found a single daily dose of aztreonam to be more effective than gentamicin b.i.d. Furthermore, no evidence of side effects was seen with aztreonam. Such results are generally thought to ensure better compliance in outpatients.

Adult↗

PubMed1988

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Aztreonam↗

PubMed1992

Toxic epidermal necrolysis possibly linked to aztreonam in bone marrow transplant patients.

OBJECTIVE AND SETTING: After instituting aztreonam as part of antibiotic prophylaxis in bone marrow transplant (BMT) patients at the Seattle Department of Veterans Affairs Medical Center, the first two cases of toxic epidermal necrolysis (TEN) occurred in more than 250 BMT patients at this center. We have examined the possible cause-and-effect relationship between aztreonam and TEN. PATIENTS: The first patient was a 23-year-old man with acute lymphocytic leukemia receiving a BMT from a related mismatched donor. He experienced profound conjunctivitis and superficial bulla covering 60 percent of his body surface area (BSA). The second patient, a 32-year-old man with lymphoma, received a BMT from a matched unrelated donor. He exhibited lymphocytosis, acute conjunctivitis, and bullous lesions covering 60 percent of his BSA. INTERVENTIONS: Aztreonam was discontinued in both patients. The first patient was treated with pigskin grafting and the second was treated with topical silver sulfadiazine. RESULTS: Despite stabilization of symptoms, both patients eventually died of infectious complications. CONCLUSIONS: Histological data in both patients were more consistent with TEN than graft-versus-host disease (GVHD) in that dermal infiltrates were sparse or absent. The onset of cutaneous symptoms was of more acute onset than acute GVHD, and ocular complaints are uncommon in acute GVHD. Furthermore, the onset of TEN bore a closer temporal relationship to aztreonam than to other drugs administered.

Adult↗

PubMed1987

Single intramuscular injection of aztreonam in the treatment of uncomplicated gonorrhoea in women.

A total of 225 female patients with uncomplicated gonorrhoea was treated at random with either a single intramuscular injection of 1 g aztreonam or with 2.4 mega units procaine penicillin intramuscularly plus 1 g probenacid orally. Patients were followed up at 1, 2 and 3 weeks for bacteriological tests. The success rate among 101 of 116 patients on aztreonam who attended at least 1 follow-up examination after treatment was 100%, including 11 cases with penicillinase-producing N. gonorrhoeae. The minimum inhibiting concentrations of aztreonam in vitro were very much lower than the serum concentration, all strains being sensitive at 0.5 micrograms/ml or less. In a comparative group of 109 women treated with penicillin, there were 11 failures (penicillinase-producing N. gonorrhoeae strains) in 98 women who were followed-up. Aztreonam was well tolerated and there were no side-effects.

Aztreonam↗