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PubMedDate not supplied

Selective decontamination of the digestive tract with oral aztreonam and temocillin.

Selective decontamination of the digestive tract by antimicrobial drugs with limited spectra of antibacterial activity has been reported to reduce the risk of superinfection and cross-infection in immunocompromised hosts by leaving the flora responsible for colonization resistance (largely anaerobic) intact. Aztreonam, a monobactam, and temocillin, a beta-lactam antibiotic, are possible candidates for use in selective decontamination of the digestive tract because of their specific activity against gram-negative bacteria. When these drugs were administered orally to mice, low dosages (0.016-1.13 mg per day) did not significantly affect colonization resistance. In volunteers, the indigenous flora either was not affected or was only minimally affected by orally administered aztreonam (20 mg and 100 mg every 8 hr). Intramuscular temocillin also was effective. However, in a small number of subjects inactivation (most likely enzymatic) of these antibiotics occurred in the bowel. Both drugs can be considered serious candidates for use in the selective decontamination of the digestive tract in granulocytopenic patients.

Animals↗

PubMedDate not supplied

Preservation of colonization resistance parameters during empiric therapy with aztreonam in the febrile neutropenic patient.

The role of the anaerobic intestinal flora in maintaining colonization resistance was examined in a study of empiric therapy in febrile neutropenic patients who received aztreonam plus tobramycin, aztreonam plus cloxacillin, or moxalactam plus tobramycin, regimens with differential effects on the anaerobic intestinal flora. Surveillance cultures showed that all regimens eradicated fecal carriage of enteric gram-negative bacilli but that fecal acquisition of fungi occurred in 4 (27%) of 15 aztreonam/tobramycin, 6 (43%) of 14 aztreonam/cloxacillin, and 13 (81%) of 16 moxalactam/tobramycin recipients. Fungi were acquired at 11 (22%) of 49 sites in aztreonam/tobramycin, 15 (31%) of 48 sites in aztreonam/cloxacillin, and 28 (54%) of 52 sites in moxalactam/tobramycin recipients. Aztreonam/tobramycin reduced fecal anaerobe counts by less than 1 log10; aztreonam/cloxacillin, by a mean of 2.5 log10; and moxalactam/tobramycin, by 5.1 log10 colony-forming units (cfu)/g of feces by day 10 +/- 3 of therapy. Elimination of the anaerobes was reflected by a reduction in concentrations of short-chain fatty acids (SCFAs) in fecal supernatants. Fecal specimens containing greater than or equal to 10(6) cfu of Bacteroides fragilis group organisms/g (dry weight) contained significantly higher concentrations of succinic, propionic, and isobutyric acids. Flat SCFA chromatograms were observed in 90% of fecal samples from which no anaerobes were recovered. Preservation of the anaerobic flora appears critical in the prevention of fungal acquisition in neutropenic patients.

Adolescent↗

PubMedDate not supplied

Clinical evaluation of aztreonam therapy for serious infections due to gram-negative bacteria.

Aztreonam--a new, synthetic, monocyclic beta-lactam antibiotic with excellent in vitro activity and beta-lactamase stability--was used for the treatment of 26 serious infections due to gram-negative bacteria in 23 patients: nine cases of bacteremia, one of endocarditis, one of pneumonia, one of septic arthritis, six of osteomyelitis, five of abscess or soft tissue infection, and three of meningitis. The majority of patients had serious underlying disease, and 18 were in critical or poor condition. The mean age of the patients was 62 years, and the mean duration of therapy was 19 days. The clinical condition of all 23 patients improved during therapy; 20 infections were cured according to clinical criteria. Three of the six instances of therapy failure were due to inadequate debridement. No superinfections, resistant pathogens, or significant adverse reactions were seen. Aztreonam was effective and safe for the treatment of serious gram-negative infections.

Abscess↗

PubMed1986

Pharmacokinetics of aztreonam in infected patients.

Pharmacokinetic parameters of aztreonam were determined in 22 patients with severe Gram-negative infections, treated with 0.5 or 1 g tid as an infusion of 30 min duration. Plasma concentrations were determined microbiologically. Most patients had various degrees of renal impairment and they showed a wide variety of age and body weight. The mean calculated volume of distribution was 17.31 or 260 ml/kg. The total plasma clearance correlated well with the creatinine clearance; the mean plasma clearance was 82 ml/min and the extrapolated extrarenal clearance was 9 ml/min. Actually measured half lives of aztreonam varied between 1 h 20 min, in a patient with normal renal function, and 9 h 40 min in a patient with severely impaired renal function. The results differ from predictions by other authors. Based on our results a dosage adjustment schedule for renal impairment is suggested.

Adult↗

PubMed1986

Ureidopenicillins, aztreonam, and thienamycin: efficacy as single-drug therapy of severe infections and potential as components of combined therapy.

The ureidopenicillins (piperacillin, mezlocillin, and azlocillin), aztreonam, and thienamycin are new broad-spectrum beta-lactams with more potent antibacterial activity than the older cephalosporins and penicillins. However, therapy of severe infections with the ureidopenicillins alone is limited by the potential for emergence of resistant organisms, while monotherapy with aztreonam does not provide adequate coverage for Gram-positive aerobic organisms and anaerobes. In combination therapy with the aminoglycosides, the ureidopenicillins may be preferred to carbenicillin or ticarcillin in the treatment of Pseudomonas aeruginosa infections and in institutions with a high prevalence of carbenicillin or ticarcillin-resistant organisms. Double beta-lactam therapy with piperacillin plus either latamoxef (moxalactam) or ceftazidime may be advantageous in patients for whom aminoglycoside toxicity is a concern. Thienamycin is the most promising of the new beta-lactams for single-agent therapy of severe infections but may also be associated with the emergence of resistant P. aeruginosa during monotherapy. In febrile granulocytopenic patients or other severely ill patients at risk of severe P. aeruginosa infections, thienamycin or another antipseudomonal beta-lactam should be combined with an aminoglycoside.

Aminoglycosides↗

PubMed1986

Pharmacokinetics of aztreonam in the aqueous humour.

Fifteen patients awaiting cataract extraction were given a 2 g intravenous bolus injection of aztreonam. The mean aztreonam concentrations in the aqueous humour. 1, 2 and 4 h after the injection were 1.22, 1.46 and 2.22 mg/l, respectively.

Aged↗

PubMed1989

Effect of Bacteroides fragilis on mortality induced by Escherichia coli in an experimental infection treated with cefotaxime, aztreonam or gentamicin.

The possibility that beta-lactamase-producing strains of Bacteroides fragilis can protect Escherichia coli from cefotaxime was studied in an in-vivo model of peritoneal infection in rats. The protective effect of cefotaxime, aztreonam and gentamicin in peritonitis induced by E. coli alone or combined with B. fragilis was evaluated by analysing mortality at 24 and 48 h after bacterial inoculation and treating the animals with two doses of each antibiotic. Comparisons, by drugs, at 24 and 48 h revealed that a statistically significant high mortality rate was obtained at 48 h when mixed infections were treated with cefotaxime, a drug very active in the infection caused by E. coli alone. Infections by mixed flora or E. coli alone treated with aztreonam or gentamicin did not show any significant difference in mortality rate analysed at 24 or 48 h. These in-vivo results confirm previous in-vitro studies and suggest that cefotaxime could be inactivated in mixed infections if a beta-lactamase-producing strain, such as B. fragilis, is involved in a clinical infection.

Animals↗

PubMed1989

The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients.

The pharmacokinetics of aztreonam were studied in ten critically ill intubated patients with lower respiratory tract infections. Serum and urinary concentrations of the drug and its penetration into bronchial secretions after a 2-g intravenous bolus were measured. Using a two-compartment linear model a terminal half-life of 1.87 + 0.46 h was determined. No interpatient differences were found for half-life values, AUC or volume of distribution, except in the case of one obese patient. The greatest variability was observed in the clearance values, and in particular the extrarenal clearance which ranged from 0.3 to 9.6 1/h. Maximum concentrations in bronchial secretions were reached very quickly in the 2 h after drug administration, with a range of 4.8-18.7 mg/l. No accumulation of aztreonam after repeated doses was detected.

Adolescent↗

PubMed1989

The penetration of aztreonam, a monobactam antibiotic, into intra-abdominal abscesses.

We have studied the penetration of aztreonam into pus with a low mortality intra-abdominal abscess model in the Wistar rat. The mean peak serum concentration (standard error) of aztreonam was 74.6 +/- 9.88 mg/l at 30 min falling to 2.31 +/- 1.28 mg/l at 8 h. The mean concentration in pus was 17.04 +/- 2.01 mg/l at 2 h and was 14.47 +/- 2.23 mg/l at 8 h. These concentrations are in excess of the MICs of most Gram-negative aerobic bacilli commonly isolated from intra-abdominal abscesses.

Abdomen↗

PubMed1990

Beta-lactam antibiotics (aztreonam, ampicillin, cefazolin and ceftazidime) in the control and eradication of Salmonella typhimurium in naturally resistant and susceptible mice.

This study was undertaken to investigate the efficacy of different beta-lactam antibiotics in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c (Itys) and resistant CBA (Ityr) mice were used to investigate the efficacy of one monocyclic (aztreonam) and three bicyclic (ampicillin, cefazolin, ceftazidime) beta-lactam antibiotics in controlling systemic salmonella infections when given for brief or prolonged periods. The present study confirms and amplifies earlier reports on ampicillin therapy, demonstrates marked differences in the efficacy of the different antibiotics and shows that aztreonam is not only very effective but can completely eradicate the salmonellae from the RES when given early in the infection.

Ampicillin↗

PubMed1991

Synergy with cefsulodin or piperacillin and three aminoglycosides or aztreonam against aminoglycoside resistant strains of Pseudomonas aeruginosa.

Fifty-one strains of Pseudomonas aeruginosa, with resistance to one or more amino-glycosides, were tested for synergy with cefsulodin or piperacillin plus amikacin, tobramycin, gentamicin or aztreonam by the agar dilution technique. Cefsulodin plus any one of the three aminoglycosides regardless of the degree of resistance to the aminoglycoside was synergistic against P. aeruginosa for two thirds of the isolates. In contrast, synergy rates with piperacillin were much less uniform. The highest rate of synergy with piperacillin (90.0%) was observed with gentamicin for the gentamicin resistant strains. The lowest rate of synergy was observed with piperacillin plus amikacin (32.2%) for isolates with moderate resistance to amikacin. Synergy for strains with moderate resistance to amikacin was observed more commonly with cefsulodin than with piperacillin. Synergy for strains with a known mechanism of resistance to amikacin was more common with cefsulodin regardless of the mechanism of resistance. Cefsulodin or piperacillin in combination with aztreonam was rarely synergistic (less than 12%).

Aminoglycosides↗

PubMed1986

Treatment of acute pelvic inflammatory disease with aztreonam, a new monocyclic beta-lactam antibiotic, and clindamycin.

Forty-two patients with acute pelvic inflammatory disease were treated using aztreonam, a monobactam, and clindamycin. Sixty-four percent of protocol patients were culture positive for Neisseria gonorrhoeae, and 26% had positive endometrial cultures for other organisms. Fifty-one percent of patients had ultrasound findings consistent with a pelvic abscess. One patient with a tuboovarian abscess palpable to the umbilicus became afebrile and improved on treatment, but ultimately was treated surgically. All other protocol patients responded rapidly to the aztreonam-clindamycin regime, giving a 97.7% cure rate.

Adult↗

PubMed1988

Controlled trial of aztreonam vs. tobramycin and azlocillin for acute pulmonary exacerbations of cystic fibrosis.

The efficacy of aztreonam was compared to that of standard therapy consisting of tobramycin and azlocillin in the treatment of acute pulmonary exacerbations of cystic fibrosis in a randomized, open trial. Fifteen patients were randomized to each treatment. Responses were assessed based on changes in pulmonary and clinical scores, white blood cell counts, pulmonary function tests and quantitative bacteriology of sputum which were performed before, every 5 to 7 days during and on the last day of therapy. Patients in both groups responded to therapy and there were no statistically significant differences in changes in the above indicators of response with therapy between the two groups (P greater than 0.05). The incidence of detection of Pseudomonas aeruginosa isolates resistant to all three study antibiotics increased with therapy. Side effects were limited to transient elevations of liver enzymes (both groups) and rash and fever in one patient treated with azlocillin. Aztreonam represents effective therapy for pulmonary exacerbations of cystic fibrosis associated with susceptible pathogens.

Adolescent↗

PubMed1990

Evaluation of aztreonam and ampicillin vs. amikacin and ampicillin for treatment of neonatal bacterial infections.

In a prospective randomized, open study we evaluated aztreonam (AZ) for treatment of neonatal bacterial infections. There were 147 patients enrolled in the study; 75 received AZ and ampicillin (AMP) and 72 amikacin (AM) and AMP (conventional therapy). Twenty-eight AZ/AMP-treated patients and 32 conventionally treated patients had bacteriologically documented infections caused by gram-negative enteric bacilli or Pseudomonas species. Treatment groups were comparable in age, clinical status, and type and severity of underlying disease at the time of enrollment. Bronchopneumonia and infections caused by Pseudomonas species occurred significantly more often in AM/AMP-treated patients compared with patients given AZ/AMP. Sepsis was documented in 83% of patients in each treatment group and Gram-negative enteric bacilli and Pseudomonas species were the principal pathogens. Median peak serum bactericidal titers against the etiologic agent were 1:64 for the AZ/AMP and 1:16 for AM/AMP-treated patients. Case fatality rates resulting from the primary infection were 7 and 22% (P = 0.011), superinfection occurred in 39% and 34% and treatment failure occurred in 7 and 28% (P = 0.036) of the AZ/AMP and AM/AMP-treated patients, respectively. No clinical adverse reactions were observed in either group. Based on these results aztreonam appears to be at least as effective as and possibly more effective than amikacin when used initially with ampicillin for empiric treatment of neonatal bacterial infections.

Amikacin↗

PubMed1985

Pharmacokinetics of aztreonam in elderly male volunteers.

The pharmacokinetics of aztreonam were studied in 12 healthy male volunteers aged 65 to 75 years who received 1 g of the antibiotic intravenously. Data were fitted to a two-compartment open model to yield the following parameters: t 1/2, lambda 1, 0.15 h; t 1/2,z, 2.06 h; area under the 24-h serum concentration-time curve, 231.8 micrograms ml-1 h; Cmax, 120.1 micrograms/ml; V1 area, 0.16 l/kg; and serum clearance, 0.94 ml min-1 kg. Twenty-four hour urinary elimination reached 63.1% of dose as aztreonam and 3.1% as the open ring metabolite SQ 26,992. These data were similar to those obtained for healthy males aged 18 to 35 years. Thus, age per se is not a major therapeutic consideration in treating elderly patients, and other factors, primarily the parameters of renal function, should serve as the basis for any dose reduction.

Age Factors↗

PubMed1990

A comparative efficacy and safety study of teicoplanin plus aztreonam versus gentamicin plus piperacillin in haematology oncology patients with clinically diagnosed septicaemia.

Infections due to Gram-positive bacteria, especially coagulase-negative staphylococci, have been increasing in immunocompromised patients during the last 5 years because of an increased use of Hickman catheters and oral gut decontamination with quinolones. Teicoplanin, a new glycopeptide antibiotic, has a long plasma half-life which allows once-a-day bolus administration, making it a 'user friendly' agent. A randomized comparative evaluation of teicoplanin plus aztreonam versus gentamicin plus piperacillin in leukaemic patients with a clinical diagnosis of septicaemia was undertaken. The objectives of this study were (1) to evaluate the efficacy and safety of teicoplanin and aztreonam in comparison to a 'standard antibiotic' regimen and (2) to assess the local and systemic tolerance of these drugs. Results of the study in more than 70 patients to date are presented, and the role of anti-Gram-positive antibiotics in the management of severe sepsis in immunocompromised patients is discussed.

Adult↗

PubMed1993

Urticaria caused by sensitization to aztreonam.

A 72-year-old woman presented with generalized urticaria after receiving an injection of aztreonam. After successive in vitro and in vivo studies, allergy to aztreonam with a good tolerance of the other beta-lactams was diagnosed.

Aged↗

PubMed1989

Effects of acute and chronic administration of two antibiotics, aztreonam and gentamicin, alone or in combination, on "open-field test" in mice.

A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test. Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.

Animals↗