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PubMed1992

Nephrotoxicity and ototoxicity of aztreonam versus aminoglycoside therapy in seriously ill nonneutropenic patients.

A randomized double-blind clinical trial was done of aztreonam versus aminoglycoside therapy for the empiric treatment of seriously ill nonneutropenic patients suspected of aerobic gram-negative bacterial infection. Each patient was treated for greater than or equal to 72 h with the study drug. Nephrotoxicity, defined by greater than or equal to 50% increase in baseline serum creatinine, occurred in 12 (15%) of 92 patients receiving aminoglycoside therapy and 1 (1%) of 92 patients receiving aztreonam (P less than .004). More severe nephrotoxicity, defined by greater than or equal to 100% increase in baseline serum creatinine, occurred in 6 (6.5%) of 92 patients receiving aminoglycoside therapy and in 1 of 92 receiving aztreonam (P less than .11). Patients with an elevated baseline total bilirubin level were most likely to develop nephrotoxicity. Auditory toxicity occurred in 2 (7%) of 28 evaluatable patients receiving aminoglycoside therapy and in 1 (3%) of 33 receiving aztreonam (P less than .58). One patient, who received aminoglycoside, developed vestibular toxicity. In nonneutropenic patients believed to be at increased risk for renal dysfunction, aztreonam is a less toxic alternative to aminoglycoside therapy for treatment of suspected aerobic gram-negative infection.

Aminoglycosides↗

PubMed1988

Enhanced susceptibility of gram-negative bacteria to phagocytic killing by human polymorphonuclear leucocytes after brief exposure to aztreonam.

Brief exposure of Escherichia coli, Serratia marcescens, Klebsiella pneumoniae and Salmonella typhimurium to supra-inhibitory concentrations of aztreonam enhanced their susceptibility to phagocytic killing by human polymorphonuclear leucocytes. The effect was independent of the continuous presence of the antibiotic and required the presence of serum opsonins. Phagocytic killing of Pseudomonas aeruginosa was enhanced by prior exposure to subminimal inhibitory concentrations, and killing, relative to control bacteria, was not increased with increasing concentrations of aztreonam above minimal inhibitory concentrations. The degree of sensitization, and the range of bacteria susceptible to antibiotic modulation varied between antibiotics. Under the conditions of these experiments, gentamicin sensitized pseudomonas, but failed to sensitize E. coli, while cefotaxime failed to sensitize serratia, and varied in it's activity against E. coli and pseudomonas. Enhanced killing of aztreonam-pretreated bacteria was associated with an increase in uptake by leucocytes. Aztreonam exposure decreased the liability of the bacteria to hydrophilic interactions in an aqueous two-phase partitioning system. These observations indicate that exposure of Gram-negative bacteria to aztreonam enhances phagocytic killing through modification of cell surface structures. This may be mediated through an increase in surface hydrophobicity which enhances bacterial association with leucocyte membranes with subsequent phagocytosis and intracellular killing.

Aztreonam↗

PubMed1990

Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis.

The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.

Aztreonam↗

PubMed1993

Comparison of imipenem/cilastatin with the combination of aztreonam and clindamycin in the treatment of intra-abdominal infections.

The clinical safety and efficacy of imipenem/cilastatin in the treatment of intra-abdominal infections was compared with the combination of aztreonam and clindamycin in a randomized prospective trial. The severity of illness was determined by means of the Apache II score and a fixed outcome reporting scheme was used. One hundred and four patients were entered into the study, of whom 80 were evaluable. Forty-two patients were treated with imipenem/cilastatin (500 + 500 mg qds) and 38 with aztreonam (600 tds) and clindamycin (1000 mg tds). The study groups were comparable for age and sex. The imipenem/cilastatin group differed from the aztreonam and clindamycin group in having significantly more patients with the diagnosis of acute appendicitis (P < 0.01) and a significantly lower mean Apache score (P < 0.05). The predominate microorganisms isolated in both groups were Escherichia coli and Bacteroides fragilis. Treatment with imipenem/cilastatin proved successful in 71% and failed in 24%, and initial success only was seen in 5%. The numbers in the group treated with aztreonam and clindamycin were 64%, 29% and 7% respectively. Severity of illness, as measured by Apache II score, had no influence on the study outcome. Imipenem/cilastatin as well as the combination of aztreonam and clindamycin were effective in the treatment of abdominal infections and no major adverse reactions were seen.

Abdomen↗

PubMed1989

The use of aztreonam in the cystic fibrosis patient.

Eradication of pulmonary infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients has long presented a significant challenge to the medical community. Many antimicrobial agents have proved incompletely effective against this persistent pathogen, and even the aminoglycosides, which represent the traditional therapy for such infections, have been associated with considerable toxicity and resistance. The monobactam antibacterial agent aztreonam is used both as single-agent therapy and in combination with other drugs. Several controlled, clinical trials have demonstrated the efficacy of aztreonam in the treatment of CF patients with pulmonary exacerbations caused by P. aeruginosa. The only side effect of aztreonam therapy commonly encountered in these studies was elevation of hepatic transaminase concentrations; this effect was of uncertain significance. It was concluded that aztreonam may offer clinical efficacy comparable to that provided by the combination of tobramycin plus azlocillin. Further, there does not seem to be any appreciable difference in the development of resistance to aztreonam compared with traditional therapies.

Aztreonam↗

PubMed1989

[Selective decontamination of intestinal flora with oral aztreonam in compromised children].

Effects of oral aztreonam on fecal flora were studied in 6 compromised children. Their ages ranged from 4 to 14 years. Daily doses of aztreonam were 10 to 30 mg/kg. The stool specimens were obtained before the treatment, on day 5 to 7 of aztreonam use and 2 to 5 days after the cessation of treatment. The counts of enterobacteria decreased from 10(7.7) to 10(4.4) per gram of wet feces (p less than 0.01), and bifidobacteria also decreased from 10(10.2) to 10(8.4) per gram of wet feces (p less than 0.01) during aztreonam administration. Those of streptococci increased from 10(2.9) to 10(9.4) per gram of wet feces (p less than 0.001). The other anaerobic organisms showed no marked change. Based upon the above results, we conclude that oral administration of aztreonam may be useful for selective decontamination of intestinal flora in compromised hosts.

Administration, Oral↗

PubMed1984

Serum bactericidal activity of aztreonam, cefoperazone, and amikacin, alone or in combination, against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa.

Serum samples from volunteers receiving (per kilogram) 20 mg of aztreonam, 20 mg of cefoperazone, 7.5 mg of amikacin, 20 mg of cefoperazone plus 20 mg of aztreonam, or 20 mg of aztreonam plus 7.5 mg of amikacin were evaluated for bactericidal activity against Escherichia coli, Klebsiella pneumonia, Serratia marcescens, and Pseudomonas aeruginosa. Serum bactericidal activities were similar for aztreonam alone or in combination but were lower for amikacin and cefoperazone alone, especially against S. marcescens and P. aeruginosa. Killing studies, performed with serum samples diluted 1:8, demonstrated a high killing rate for aztreonam plus amikacin, especially against P. aeruginosa.

Amikacin↗

PubMed1984

Effect of aztreonam on throat and stool flora of cancer patients.

Eighteen patients with hematological malignancies received aztreonam in one of two dosing regimens, 1 or 2 g every 8 h for a total of 7 to 9 days. Throat and stool cultures were obtained before and during treatment with aztreonam. Aztreonam had little effect on the predominant throat flora. In contrast, facultatively anaerobic gram-negative bacilli were markedly decreased in stools during the administration of aztreonam. Strict anaerobes in the stool were variably affected by aztreonam.

Adolescent↗

PubMed1985

Pharmacokinetics of aztreonam in patients with gram-negative infections.

Aztreonam pharmacokinetics were assessed in seven patients treated for urinary (n = 6) or lower respiratory (n = 1) tract infections. Each patient was studied twice, at the beginning and end of therapy (7 to 10 days). The patients enrolled had normal to moderately impaired renal function; a good correlation (r2 = 0.90) between serum aztreonam clearance (CL) and creatinine clearance (CLCR) was observed (mean CL/CLCR ratio = 1.11). CL ranged from 21.6 to 121 ml/min per 70 kg, and the half-life ranged from 1.6 to 8.9 h. The mean steady-state volume of distribution (0.16 +/- 0.05 [standard deviation] liter/kg) approximated the extracellular fluid volume. Protein binding of aztreonam in serum (mean, 30%) was lower than that reported in healthy adults. CL increased significantly from the first to the last day of the study, probably reflecting increasing renal function. After multiple dosing (1 g every 8 h), no significant accumulation of aztreonam was observed. Overall, the disposition of aztreonam is comparable in infected and noninfected subjects, and dosing adjustments in patients with renal impairment should be facilitated by the good correlation between CL and CLCR.

Adult↗

PubMed1985

Efficacy and safety of aztreonam-clindamycin versus tobramycin-clindamycin in the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli.

A total of 80 patients were randomized to receive either aztreonam or tobramycin for the treatment of lower respiratory tract infections caused by gram-negative bacilli; all these patients received clindamycin concomitantly. A total of 53 patients were randomized to receive aztreonam-clindamycin; of these, 46 were clinically evaluable and 39 were bacteriologically evaluable. Of the 46 clinically evaluable patients, 41 were considered cured, 3 failed to be cured, and 2 died during the study period of unrelated causes. Of the 39 bacteriologically evaluable patients, 36 were considered cured, and 3 failed to be cured. There were 26 clinically evaluable patients in the group randomized to receive tobramycin-clindamycin. Of them, 22 patients were considered cured, 3 failed to be cured, and 1 died of unrelated causes during the study period. There were 18 bacteriologically evaluable patients in the tobramycin-clindamycin group; 17 were cured, and 1 failed to be cured. The most common pathogens isolated from the patients were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. All of the isolated organisms were susceptible to both tested antibiotics, except for a strain of Pseudomonas cepacia resistant to both tested antimicrobial agents and a strain of Enterobacter aerogenes and one of P. aeruginosa that were resistant to aztreonam. Very few adverse reactions related to the antibiotics were seen. These effects, when present, were transient and comparable in both studied groups, except for renal-function tests, which were altered in 7.7% of the patients randomized to receive tobramycin-clindamycin and in none of the patients randomized to receive aztreonam-clindamycin. Aztreonam-clindamycin is safe and effective for the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli when the organisms are susceptible.

Aged↗

PubMed1986

Penetration of aztreonam into cerebrospinal fluid of patients with bacterial meningitis.

The penetration of aztreonam into the cerebrospinal fluid was determined in 16 patients with bacterial meningitis undergoing treatment with other antibiotics. Three aztreonam doses of 30 mg/kg were infused intravenously over 30 to 45 min at 8-h intervals, first between days 2 and 4 and again between days 11 and 20 after onset of the disease. Concentrations of aztreonam in serum and cerebrospinal fluid samples obtained at 60, 90, 120, and 240 min after the third aztreonam dose were measured by high-pressure liquid chromatography. The concentrations of aztreonam in cerebrospinal fluid ranged from 3.5 to 62 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. These concentrations were equal to or higher than the MICs for most of the gram-negative bacilli (including Pseudomonas aeruginosa).

Adult↗

PubMed1989

Comparison of aztreonam plus clindamycin with tobramycin plus clindamycin in the treatment of intra-abdominal infections.

The activity of aztreonam (a beta-lactam antibiotic with specific activity against gram-negative bacteria) was evaluated and compared with that of tobramycin in hospitalized patients with severe intra-abdominal infections due to gram-negative pathogens, either alone or in association with other bacteria. Of a total study population of 156 patients, 76 were assigned to treatment with aztreonam + clindamycin, and the remaining 80 were treated with tobramycin + clindamycin. Patients underwent a variety of surgical procedures involving the peritoneal cavity. The final clinical evaluation revealed similar percentages of satisfactory results: 86.8% for the patients in the aztreonam-treated group and 86.2% for the tobramycin-treated patients. Among the patients who had a poor therapeutic result, gram-negative bacteria, either alone or associated with gram-positive pathogens, were considered responsible for 50% of the infections in the aztreonam group; the percentage increased to 82% among those treated with tobramycin. The incidence of side effects and laboratory alterations was not significant and was similar in both groups. The results of this study suggest that aztreonam may be an effective and safe drug for the treatment of bacterial infections due to gram-negative pathogens.

Abdomen↗

PubMed1991

Aztreonam-induced myelosuppression during treatment of Pseudomonas aeruginosa pneumonia.

Aztreonam is a synthetic, monobactam antibiotic structurally related to the beta-lactam class of drugs. It has inhibitory activity against many aerobic gram-negative bacteria, although it does not inhibit gram-positive or anaerobic bacteria. Administration of aztreonam occasionally is associated with minimal and transient adverse effects. This case report describes a patient we believe experienced bone marrow suppression approximately ten days after aztreonam was given for treatment of pneumonia caused by Pseudomonas aeruginosa. This untoward effect primarily was manifested as neutropenia, although normochromic, normocytic anemia and thrombocytopenia were noted as well. One week after aztreonam was discontinued, the patient's bone marrow suppression resolved spontaneously. Although the mechanism responsible for myelosuppression is unclear, aztreonam may be implicated as the offending agent based on the temporal relationship between the development of neutropenia and its administration, and the resolution of neutropenia upon its discontinuation.

Aztreonam↗

PubMed2003

Aztreonam treatment of Pasteurella multocida cellulitis and bacteremia.

OBJECTIVE: To report a case of Pasteurella multocida cellulitis and bacteremia treated successfully with aztreonam. CASE SUMMARY: An 81-year-old white man with multiple antibiotic allergies was admitted with severe cellulitis of the left arm and bacteremia due to P. multocida. The patient was treated for 14 days with aztreonam and had complete resolution of the infection. DISCUSSION: To our knowledge, this is the first published case describing successful treatment of P. multocida cellulitis and bacteremia with aztreonam. Antimicrobials recommended for use in P. multocida infections include penicillin, ampicillin, amoxicillin, second- and third-generation cephalosporins, tetracyclines, fluoroquinolones, and trimethoprim/sulfamethoxazole. There is very little information in the current literature regarding the activity of aztreonam toward P. multocida. CONCLUSIONS: This case demonstrates the potential use of aztreonam for P. multocida cellulitis and bacteremia in those instances where antibiotics of choice cannot be given.

Aged↗

PubMed1994

Clinical pharmacokinetics of aztreonam. An update.

Plasma concentrations of aztreonam follow a 2-compartment open model with a distribution half-life of 0.20 hours after intravenous injection. The volume of distribution at steady-state (Vss) after intravenous and intramuscular injection is about 0.16 L/kg (0.42 L/kg for free drug). After intramuscular injection, absorption is almost complete. Absorption after intraperitoneal administration in patients with peritonitis is 92%. Over a large dosage range, plasma concentrations increase dose proportionally. In healthy individuals, about 56% of the drug is plasma protein bound. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma aztreonam concentration seems to depend mainly on tissue composition. Aztreonam penetrates into cerebrospinal fluid (CSF) more rapidly in patients with inflamed meninges than in those with noninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breastmilk. Aztreonam is predominantly eliminated by the kidney, partly by active tubular excretion. Extrarenal clearance appears to be through hepatic excretion. Metabolism occurs to a very limited extent. Total plasma clearance (CLp) in healthy adults is about 5.6 L/h and the terminal elimination half-life is 1.7 to 2.0 hours. CLp is similar in both children and adults when expressed as a function of bodyweight. However, in neonates, especially in low birthweight infants, CLp is lower. In various disease states, the Vss of aztreonam is not appreciably different from that found in healthy individuals. However, patients with low serum albumin levels (e.g. burn patients, critically ill patients and those with cirrhosis of the liver) generally have an increased volume of distribution. The elimination half-life of the drug is dependent on renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1992

A comparison of aztreonam and ceftazidime in the treatment of respiratory infections in adults with cystic fibrosis.

A randomised double blind 2-week trial of monotherapy with ceftazidime and aztreonam was completed in 22 adults with cystic fibrosis. 26 courses of treatment were initiated and 22 courses were completed. Within groups, both ceftazidime and aztreonam demonstrated a significant improvement in FEV1 at 2 weeks (ceftazidime p less than 0.05; aztreonam p less than 0.01) and a decline in sputum weight at 2 weeks (ceftazidime p less than 0.05; aztreonam p less than 0.05). Between groups, for spirometry and sputum weight the only change was a slower decline in FEV1 in the aztreonam group at 42 days (p less than 0.05).

Adolescent↗

PubMedDate not supplied

Compatibility and stability of linezolid injection admixed with aztreonam or piperacillin sodium.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with aztreonam (Azactam-Squibb) 2 grams and separately with piperacillin sodium (Pipracil-Lederle) 3 grams over 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test samples were prepared by adding the required amount of aztreonam or piperacillin sodium to separate bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical compatibility and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C. RESULTS: All of the linezolid admixtures with aztreonam and with piperacillin sodium were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change throughout the study at both storage temperatures. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Aztreonam in the linezolid admixtures was stable for 7 days, exhibiting less than 5% loss at 4 degrees C and 9% loss at 23 degrees C. Piperacillin sodium in the linezolid admixtures was stable for 7 days at 4 degrees C, exhibiting no loss, but was stable for only 3 days at 23 degrees C with losses of about 5%. Losses had increased to 9% to 12% after 5 days of storage at room temperature. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with aztreonam 2 grams or piperacillin sodium 3 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C and for 7 days or 3 days, respectively, at 23 degrees C.

Acetamides↗

PubMed1988

[Aztreonam treatment of severe infections caused by gram-negative aerobic bacilli].

Twenty nine patients of an intensive care unit (9 women and 20 men), aged 63.9 +/- 15.8 years, with a mean body weight of 62.5 +/- 11.8 kg were treated during 9.4 +/- 2.1 days by aztreonam (2 x 1 g/24 h) administered by short infusion (30 min) for a severe infection due to a Gram-negative bacilli. The primary (n = 25) or nosocomial (n = 4) infection sites were a peritonitis (14), a septicaemia (6), a cholecystitis (6), a pyelonephritis (5), a cholangitis (2), a subphrenic abscess (1) or a pneumonia (2). The isolated Gram-negative bacilli were all susceptible to aztreonam, their MIC being less than or equal to 0.5 micrograms/ml, except for a Pseudomonas aeruginosa (MIC = 4 micrograms/ml). Aztreonam was administered as a single therapy to 7 patients and in association with metronidazole (18) and/or penicillin G (14) to 22 patients; in fact, anaerobes were isolated in ten patients. The mean serum concentrations of aztreonam, as measured by HPLC, before and after the 7th administration respectively were 83.2 +/- 17.5 and 6.1 +/- 5.5 micrograms/ml for peak and through levels. The treatment of the 29 infections was a success in all the cases. No complication occurred due to the presence of Gram positive cocci (n = 4) in the first bacteriological sample, or due to the emergence (n = 12) of Gram positive cocci, except for one case of sepsis of the abdominal wall by Staphylococcus aureus. Aztreonam (2 x 1 g/24 h) may be a suitable alternative for the treatment of severe infections of intensive care units, mostly due to Gram-negative bacilli.

Aged↗