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PubMed1990

Aztreonam.

Aztreonam, the first commercially available monobactam, has a wide range of activity against aerobic gram-negative bacilli. It can be administered two to three hours daily because its half-life is 1.6 to 2 hours. Excellent blood and tissue concentrations are attained. The MIC of aztreonam against most Enterobacteriaceae is less than or equal to 2 micrograms/ml and against P aeruginosa less than or equal to 16 micrograms g/ml. Aztreonam has been used in a wide array of infections of the urinary tract and respiratory tract, blood, intra-abdominal and gynecologic infections and infections of the skin, bones and joints. As empiric therapy, aztreonam is usually combined with another antimicrobial agent active against anaerobes and/or aerobic gram-positive cocci until culture results are available. One exception is empiric therapy for gram-negative urinary tract infections in which aztreonam can be used initially as monotherapy against susceptible gram-negative pathogens. In general, the efficacy of aztreonam is equal or superior to that of the aminoglycosides. Adverse reactions to aztreonam are unusual, and it as been shown to be a poor hapten, permitting its administration to patients with proven allergy to the penicillins and cephalosporins. Aztreonam is a useful addition to the available antibiotics for treatment of gram-negative infections.

Aztreonam↗

PubMed1995

Compatibility and stability of aztreonam and vancomycin hydrochloride.

The physical compatibility and chemical stability of aztreonam and vancomycin hydrochloride when combined at clinically used high and low concentrations were studied. Admixtures consisting of aztreonam 4 mg/mL and vancomycin 1 mg/mL (as the hydrochloride salt) in 5% dextrose injection, aztreonam 4 mg/mL and vancomycin 1 mg/mL in 0.9% sodium chloride injection, aztreonam 40 mg/mL and vancomycin 10 mg/mL in 5% dextrose injection, and aztreonam 40 mg/mL and vancomycin 10 mg/mL in 0.9% sodium chloride injection were prepared in triplicate in polyvinyl chloride containers. Three containers of each type of admixture were stored at 4, 23, and 32 degrees C. Samples were removed immediately and at various time points over 31 days. Compatibility was assessed by visual examination, with a turbidimeter, and with a particle sizer-counter. Stability was determined by stability-indicating high-performance liquid chromatography (HPLC). All the admixtures initially appeared clear to the unaided eye after the disappearance of a transient white swirl in the high-concentration admixtures (aztreonam 40 mg/mL and vancomycin 10 mg/mL). However, the high-concentration admixtures immediately developed unacceptable levels of a microcrystalline precipitate when viewed with a high-intensity fiber-optic light source. Easily visible gross turbidity and precipitation formed after various periods but often within 24 hours. HPLC showed aztreonam 4 mg/mL and vancomycin 1 mg/mL in 5% dextrose injection to be a stable combination for 7 days at 32 degrees C, 14 days at 23 degrees C, and 31 days at 4 degrees C. In 0.9% sodium chloride injection, the drugs in the low-concentration admixtures were stable for 7 days at 32 degrees C and for 31 days at 4 and 23 degrees C. Stability of the combination in the high-concentration admixtures was maintained for 3 days at 23 and 32 degrees C and for 14 days at 4 degrees C. Aztreonam and vancomycin hydrochloride were considerably less compatible and stable in the high-concentration admixtures than in the low-concentration ones.

Anti-Bacterial Agents↗

PubMedDate not supplied

Pharmacokinetics and extravascular penetration of aztreonam in patients with abdominal sepsis.

Patients with abdominal sepsis were enrolled in a clinical trial of aztreonam vs. tobramycin. All were given clindamycin concomitantly. The pharmacokinetics of aztreonam in 21 patients randomly assigned to receive treatment with aztreonam are reported. The mean age of these patients was 68 years; most had underlying disorders such as malnutrition and cardiac or pulmonary disease. Creatinine clearance (Clcr) ranged from 11.2 to 133.1 ml/min. The usual dose of aztreonam was 2.0 g every 8-12 hr. A single pharmacokinetic study was performed over one dosing interval after steady-state conditions were achieved. In approximately one-half of the patients, peritoneal fluid was collected during the interval between doses. Penetration of aztreonam, as expressed as the ratio of concentration in the peritoneal fluid to that in serum, was higher for aztreonam (0.95:1) than for tobramycin (0.46:1). The ratio of the concentration in peritoneal fluid to the minimum inhibitory concentration (MIC) of the infecting bacteria was also higher for aztreonam. Serum pharmacokinetic data were analyzed by both two-compartment and moment analysis. For both the steady-state volume of distribution (Vdss) and total body clearance (TBC), the values determined by both methods were highly correlated (r = .96, .99, respectively). Average values for Vdss and TBC were 0.28 liters/kg and 80 ml/min. TBC for aztreonam correlated strongly with CLcr and was described by the regression equation TBC = 1.1 (Clcr) + 1.6, r = .87, P less than .01.

Abdomen↗

PubMed1989

Safety and toxicity profile of aztreonam.

Aztreonam is the first monocyclic beta-lactam antibiotic released for clinical use. Extensive toxicity and safety data for aztreonam in animals, healthy volunteers and adult patients have been accumulated previously; recently these studies have been extended to children. Overall the incidence of adverse clinical reactions caused by aztreonam is similar to or lower than that caused by comparison drugs. There is no evidence that aztreonam causes significant ototoxicity or nephrotoxicity; biochemical and hematologic abnormalities are rarely significant. Compared with the broad spectrum cephalosporins, aztreonam causes less disruption of normal gastrointestinal flora and consequently a lower incidence of diarrhea. Aztreonam does not displace bilirubin from albumin and penetrates readily into cerebrospinal fluid. Because of negligible immunologic cross-reactivity with other beta-lactams, aztreonam has been safely administered to patients with IgE-mediated penicillin hypersensitivity. These data suggest that aztreonam should be safe and well-tolerated in infants and children with infections caused by susceptible Gram-negative bacteria.

Animals↗

PubMed1990

Comparative efficacies of aztreonam and chloramphenicol in children with typhoid fever.

We compared aztreonam with chloramphenicol in a randomized trial involving the treatment of 36 children with typhoid fever. Eighteen children were randomized to receive aztreonam, 150 mg/kg/day intravenously, and 18 to receive chloramphenicol, 100 mg/kg/day orally. On entry in the study the clinical characteristics of the two treatment groups were comparable. The duration of therapy was 14.9 +/- 3.6 days for the aztreonam group and 12.8 +/- 2.6 days for the chloramphenicol group. The mean duration of fever was 5.9 +/- 3.1 days and 4.05 +/- 2.1 days for aztreonam and chloramphenicol groups respectively (P greater than 0.05). Clinical cure was observed in all patients treated with aztreonam and in 17 of 18 children given chloramphenicol; one patient died in the latter group. There were no relapses in either group. We observed clinical adverse reactions during the treatment with aztreonam in 2 patients. All strains of Salmonella typhi were susceptible to aztreonam, 1 strain was resistant to chloramphenicol and 3 strains were resistant to ampicillin. Aztreonam appears to be a satisfactory alternative to chloramphenicol in cases of typhoid fever caused by resistant strains or when chloramphenicol is contraindicated.

Adolescent↗

PubMed1986

In vitro and in vivo studies of the effect of aztreonam on platelet function and coagulation in normal volunteers.

The in vitro effects of aztreonam on platelet aggregation were compared with those of cefotaxime, moxalactam, piperacillin, and carbenicillin. In addition, the in vivo effects of intravenously administered aztreonam on blood coagulation and platelet function were examined in 10 normal male volunteers in a randomized crossover study. In vitro, at concentrations of greater than 6.25 mM (2.7 mg/ml), aztreonam inhibited ADP-induced platelet aggregation in a dose-dependent manner. The effect was less than that produced by equimolar concentrations of cefotaxime, moxalactam, piperacillin, or carbenicillin. At all concentrations tested, aztreonam and cefotaxime inhibited epinephrine-induced aggregation least. All antibiotics inhibited collagen-induced aggregation, but only at inordinately high concentrations (25 mM). In vivo studies in 10 male subjects, randomly infused intravenously with 2 g of aztreonam or saline placebo every 6 h for 21 consecutive doses in a single-blind crossover study, revealed no evidence of bleeding or visible adverse side effects. Although plasma coagulation and platelet adhesion remained within normal limits in all subjects throughout the study, inhibition of ADP-induced platelet aggregation significantly (P less than 0.0001) increased on days 3 and 6, but still was below 40%. With the exception of one subject who had a mean template bleeding time of 7.3 min (normal, 2 to 7 min at 95% confidence limits) on day 6 of aztreonam administration, all volunteers exhibited bleeding times within the normal range. No abnormalities in platelet morphology were observed. Mean peak serum aztreonam concentrations on days 1 and 6 were 90.1 +/- 16.7 and 95.9 +/- 13.7 micrograms/ml, respectively; accumulation did not occur. Thus, in normal volunteers, aztreonam produced no significant recognizable abnormalities of hemostasis after 6 days of maximal recommended doses.

Adult↗

PubMed1993

Efficacy of ceftazidime and aztreonam alone or in combination with amikacin in experimental left-sided Pseudomonas aeruginosa endocarditis.

The in vivo efficacies of ceftazidime, aztreonam, and the combinations of ceftazidime with amikacin and aztreonam with amikacin were studied in the rabbit left-sided endocarditis model by using two strains of Pseudomonas aeruginosa, one multisusceptible and one multiresistant, in a total of 156 animals. Antibiotics were given intramuscularly for 10 days, as follows: amikacin, 7 mg/kg of body weight every 8 h, and ceftazidime and aztreonam, 50 mg/kg every 8 h. All regimens except amikacin alone significantly reduced the number of CFU per gram of vegetation (P < or = 0.008), but only for the multisusceptible strain for which sterile vegetations were obtained in 20, 25, 21, 75, and 53% of the groups treated with amikacin, ceftazidime, aztreonam, and the combination groups ceftazidime-amikacin and aztreonam-amikacin, respectively (ceftazidime plus amikacin versus controls, P = 0.001). Regarding the decrease in the numbers of colonies in vegetations, (i) all regimens significantly reduced the number of CFU per gram of vegetation (P < 0.001), (ii) results with ceftazidime-amikacin compared with those with monotherapy were significantly different (P < or = 0.007), and (iii) results with aztreonam-amikacin, although better than those with monotherapy, were marginally not statistically significant. At 1 h postdose, mean amikacin, aztreonam, and ceftazidime levels in serum were 35 +/- 19.4, 89.6 +/- 8.16, and 92.61 +/- 11.52 micrograms/ml, respectively. It was concluded that the combination of ceftazidime, and possibly aztreonam, with amikacin given at high doses and short intervals could have a place in the therapy of patients with left-sided endocarditis caused by P. aeruginosa.

Amikacin↗

PubMedDate not supplied

Pharmacokinetics of aztreonam and imipenem in critically ill patients with pneumonia.

STUDY OBJECTIVE: To evaluate the pharmacokinetic profiles of aztreonam and imipenem in critically ill trauma patients with pneumonia. METHODS: Trauma patients in intensive care units who were intubated within 3 days of hospital admission were eligible for the study. Patients with the clinical diagnosis of pneumonia were consecutively randomized to receive either aztreonam plus vancomycin or imipenem-cilastatin. Serial blood samples were taken and sputum was collected to determine aztreonam and imipenem concentrations after 2-3 days and 7-8 days of therapy. Pharmacokinetics of both agents were estimated and compared with estimates from healthy volunteers. RESULTS: Twenty patients were enrolled in the study, 10 patients received imipenem-cilastatin, and 10 received aztreonam plus vancomycin. Steady-state volume of distribution (Vss) for aztreonam at 2-3 days and 7-8 days was significantly greater in patients than in historical controls, whereas the Vss for imipenem was greater at 2-3 days. The beta-half-life for aztreonam at both sampling periods was significantly greater in patients than in controls. No significant changes in pharmacokinetics occurred over time for either antibiotic. Sputum concentrations of aztreonam and imipenem were highly variable when sampled 2 hours after the infusion. CONCLUSION: Larger volumes of distribution were observed for both aztreonam and imipenem in trauma patients than in volunteers, suggesting that standard initial dosages of the antibiotics may result in lower concentrations in these critically ill patients. Both antibiotics penetrated into the sputum of most patients; however, the degree of penetration was highly variable in relation to serum concentrations.

Adolescent↗

PubMedDate not supplied

Single-dose pharmacokinetics of aztreonam in children with cystic fibrosis.

The single-dose pharmacokinetics of aztreonam was evaluated in 10 clinically stable subjects with cystic fibrosis. Each child received 30 mg aztreonam/kg intravenously over 2 to 3 minutes. Multiple timed blood samples were obtained over 8 hours for determination of aztreonam elimination kinetics; all urine excreted for 24 hours was collected in timed aliquots for the determination of aztreonam and its microbiologically inactive metabolite, SQ 26,992. Aztreonam pharmacokinetic parameters were determined by model-independent methods. Mean t1/2, steady-state volume distribution, and body clearance were 1.3 hr, 0.25 L/kg, and 127.2 ml/min/1.73m2, respectively. In 9 of the 10 subjects, two-compartment pharmacokinetic analysis was possible and compared favorably with model-independent parameter estimates. Twenty-four-hour urinary recovery of aztreonam was 76.3% of the administered dose; 2.6% was recovered as the metabolite SQ 26,992. The renal clearance of aztreonam averaged 92.5 ml/min/1.73m2. When these data are combined with in vitro susceptibility data for aztreonam against Pseudomonas aeruginosa isolated from the sputum of patients with cystic fibrosis, a dose of 200 mg aztreonam/kg/day divided six hourly would be predicted to maintain serum concentrations above the minimum inhibitory concentration (MIC) for these organisms for the majority of the dosing interval.

Adolescent↗

PubMed1985

Aztreonam: worldwide overview of the treatment of patients with gram-negative infections.

Multicenter trials were conducted to determine the safety and efficacy of aztreonam in the treatment of patients with gram-negative bacterial infections. A total of 2,821 patients were treated; 2,117 received aztreonam and 704 received control antibiotics. All patients were evaluated for safety and 1,180 of those treated with aztreonam and 428 treated with the control drugs met the criteria for efficacy evaluation. The number of patients treated with aztreonam who were evaluable for efficacy and their microbiologic response rates were: urinary tract infections, 443 (82 percent); lower respiratory tract infections, 217 (79 percent); septicemia, 63 (98 percent); skin/skin structure infections, 136 (88 percent); intra-abdominal infections, 47 (85 percent); postpartum/gynecologic infections, 21 (100 percent); bone and joint infections, 12 (100 percent); acute uncomplicated gonorrhea, 209 (97 percent); and acute uncomplicated cystitis, 56 (84 percent). Adverse reactions were qualitatively similar to those reported for beta-lactam antibiotics, i.e., mild gastrointestinal upset, rash, eosinophilia, or transient increase in hepatic enzyme parameters. There was an apparent lack of adverse effects on kidney, inner ear, and blood coagulation system. The most frequent adverse effect was phlebitis at infusion site (2.4 percent of patients). Superinfections and colonization with new organisms occurred in 9.4 percent of aztreonam-treated patients and in 7.4 percent of control drug-treated patients; only 40 percent of patients in each group, approximately 4 percent of all patients receiving aztreonam and 3 percent of those receiving control antibiotics, required specific therapy for the superinfection. Overall, results indicated that aztreonam is a safe and effective antibiotic in the treatment of aerobic gram-negative infections, when used either as monotherapy or in combination with other antibiotics.

Abdomen↗

PubMed1990

Aztreonam in the prevention and treatment of infection in neutropenic cancer patients.

The treatment of bacterial infections in neutropenic cancer patients presents a serious challenge to physicians. Although gram-positive infections have become more common in recent years, most infections in this population are caused by gram-negative bacilli. No single regimen has been found to be optimal, and most commonly used regimens are associated with significant disadvantages. Extensive investigation is therefore under way to evaluate the potential of several promising newer antimicrobial agents. Aztreonam, for example, is active against most gram-negative pathogenic bacteria and has been evaluated in several clinical trials in neutropenic patients. As the only agent with gram-negative activity or in combination either with aminoglycosides or with other beta-lactam antibiotics, aztreonam proved useful in the treatment of gram-negative infections in this population. Combination with an aminoglycoside, however, was not found to improve efficacy over aztreonam alone. In fact, since aminoglycosides may potentiate ototoxicity and nephrotoxicity, it may be more appropriate to replace the aminoglycoside component of a combination regimen with aztreonam, as indicated by data from a study of aztreonam plus cefoperazone. Aztreonam selectively inhibits the aerobic gram-negative intestinal flora with only minimal disruption of anaerobic flora, and may be useful for infection prevention, but the importance of anaerobic preservation is not clear. It was concluded that aztreonam appears to be a useful agent for the treatment of febrile neutropenic patients, but further study is recommended.

Agranulocytosis↗

PubMed1993

Prevention of radiation-induced bacteraemia by post-treatment with OK-432 and aztreonam.

The effects of combined treatment with OK-432, an immunomodulator prepared from Streptococcus haemolyticus, and aztreonam, a monobactum antibiotic, in the prevention of radiation-induced bacteraemia and mortality were examined in ICR-MCH mice irradiated with 9.5 Gy. The organisms recovered from the irradiated mice were Streptococcus faecalis and Proteus mirabilis. Treatment with aztreonam reduced the incidence of mice infected with Proteus mirabilis (p < 0.01), but it showed no efficacy on Streptococcus faecalis. OK-432 could reduce the frequency of bacteraemia attributed to both organisms (p < 0.05). Combined treatment with OK-432 and aztreonam further decreased the incidence of bacteraemia by both organisms; no organisms were recovered at 14 days following irradiation. The survival rate at 30 days following irradiation was 80% in mice treated with OK-432 plus aztreonam and 55% with OK-432 alone, while it was 0% in the groups treated with aztreonam or saline alone. These results indicated that combined treatment with OK-432 and a suitable antibiotic such as aztreonam is more effective than OK-432 or aztreonam alone.

Animals↗

PubMed1997

Pharmacokinetics of aztreonam in critically ill surgical patients.

The pharmacokinetics of aztreonam in critically ill surgical patients with serious gram-negative infections were studied. Blood samples were taken before and at 30 minutes, 2.5 hours, and 5 hours after a dose of aztreonam 2 g i.v. every six hours. All patients had received at least two aztreonam doses before the dosage interval being studied. Aztreonam concentrations were measured by high-performance liquid chromatography. Aztreonam's pharmacokinetics, the severity of illness, and patient outcomes were examined. A total of 28 patients with 111 serum aztreonam concentrations were included in the analysis. The patients were young (mean age, 35 years) and predominantly male. The mean APACHE II score was 19.3, and 22 patients had sepsis. Four patients died. The mean volume of distribution (V) of 0.35 L/ kg was nearly twice the previously reported steady-state value for healthy volunteers (0.18 L/kg) and was highly variable. A slightly higher than normal mean V, 0.22 L/ kg, was seen in a subset of six patients whose infection occurred earlier in their intensive care and who had lower APACHE II scores. While with some antibiotics the elevated V would imply difficulty in achieving therapeutic drug levels, 99 (89%) of the 111 concentrations were at or above the in vitro susceptibility breakpoint of 8 micrograms/mL. Despite observations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually sufficient to maintain adequate serum drug levels.

Adolescent↗

PubMed1989

Randomized clinical trial of aztreonam and aminoglycoside antibiotics in the treatment of serious infections caused by gram-negative bacilli.

Aztreonam was compared with aminoglycoside antibiotics (tobramycin and amikacin) in a randomized, prospective, clinical trial in serious infections caused by gram-negative bacilli (GNB). A total of 43 evaluable patients with 47 infected sites were treated with aztreonam, and 41 evaluable patients were treated with aminoglycosides for 43 infections. Of patients treated with aztreonam, 17 were bacteremic, as were 12 of those treated with aminoglycosides. Clinical and microbiologic response rates were similar, except that only 5 of 11 patients with pneumonia were considered to be clinically cured with aminoglycoside therapy, while 5 of 6 patients with pneumonia treated with aztreonam were cured. Renal impairment was observed in 9 of 54 patients who received aminoglycoside antibiotics, but in only 2 of 53 patients treated with aztreonam. Hearing impairment developed in one patient treated with tobramycin. Transient elevations of serum transaminase levels occurred in 9 of 53 patients treated with aztreonam and in only 2 of 54 aminoglycoside-treated patients. Diarrhea and superinfection occurred with equal frequency in both groups. Serum concentrations of bactericidal activity could not be correlated with the outcome of therapy. Aztreonam appears to have comparable clinical efficacy with aminoglycoside antibiotics for the treatment of serious infections caused by aerobic and facultative GNB. Its use as a single agent for the treatment of serious lower respiratory infections caused by GNB warrants further evaluation.

Adult↗

PubMed1990

Characteristics of aztreonam as a substrate, inhibitor and inducer for beta-lactamases.

Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined beta-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of beta-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A beta-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range. However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A beta-lactamases. Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the beta-lactamase. While the MICs of aztreonam in the cases of the constitutive producers of class C beta-lactamases were evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable beta-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of beta-lactamases.

Amdinocillin↗

PubMed1992

Oral aztreonam, a poorly absorbed yet effective therapy for bacterial diarrhea in US travelers to Mexico.

OBJECTIVE: To evaluate a poorly absorbed antimicrobial with in vitro activity against all major bacterial enteropathogens in oral therapy for bacterial diarrhea. DESIGN: One hundred ninety-one US students with diarrhea acquired in Mexico received 100 mg of aztreonam or matching placebo three times a day for 5 days. Stools were cultured for bacterial enteropathogens before and after therapy. SETTING: We studied US students who acquired diarrhea in Mexico (travelers' diarrhea) in view of the high frequency of bacterial agents in this setting. MAIN OUTCOME MEASURE: We examined time of clinical recovery, treatment failures, adverse experiences, and microbiologic eradication from stool of the etiologic agent in subjects randomized to receive aztreonam or placebo. RESULTS: Aztreonam reduced the average duration of diarrhea compared with the placebo: for all cases, by 40 hours (P much less than .01); for those with enterotoxigenic Escherichia coli diarrhea, by 50 hours (P less than .01); for those with shigellosis, by 90 hours (P, not significant [small sample size]); for all bacterial agents, by 57 hours (P much less than .01). Clinical failures during the 5 days of therapy were seen in six patients (6%) receiving aztreonam and 25 (27%) receiving placebo (P less than .01). Pathogen eradication occurred in 95% of those receiving aztreonam and in 70% of those receiving the placebo (P less than .01). All bacterial enteropathogens were susceptible in vitro to aztreonam. The drug was well tolerated. CONCLUSIONS: Oral aztreonam, which is poorly absorbed, was well tolerated and was an effective therapy for bacterial diarrhea in US adults in Mexico.

Administration, Oral↗

PubMed1990

How and why aztreonam works.

Aztreonam is the first monocyclic beta-lactam antibiotic (monobactam) to be tested clinically. Its synthetic structure determines specific areas of activity, including enhanced activity against Pseudomonas species, exceptional activity against gram-negative bacteria, stability to beta-lactamases and lack of activity against gram-positive bacteria--all of which can be directly related to its chemical composition. Aztreonam has a high affinity for the protein-binding protein 3 (PBP-3) of aerobic gram-negative bacteria. Most of these organisms are inhibited and killed at low concentrations of the drug. Aztreonam binds poorly to PBP sites of the aerobic gram-positive and anaerobic bacteria and consequently has relatively poor inhibitory effects against these bacteria. In vitro, minimum inhibition concentration (MIC) values against almost all of the Enterobacteriaceae and against Neisseria and Haemophilus strains are typically below 1 microgram per milliliter. MIC values against Pseudomonas aeruginosa of 8 micrograms per milliliter are comparable with those of other antipseudomonal beta-lactams and the acylureidopenicillins. As combination therapy with amino-glycosides, aztreonam acts in synergy against P. aeruginosa, Acinetobacter and gentamicin-resistant gram-negative rods. Aztreonam is widely distributed in the body tissues and fluids, and the average elimination half-life is 1.7 hours. Intramuscular dosing results in peak serum levels in approximately one hour, while intravenous dosing results in peak levels within five minutes. After a 2 gram dose given intravenously, MIC90 values for most of the Enterobacteriaceae are exceeded for eight hours, and those for P. aeruginosa, for almost six hours. The steady-state volume of distribution is approximately 0.18 liter per kilogram. Concentrations above the MIC90 for most gram-negative bacteria are also present within bone, prostate and cerebrospinal fluid. Between 60 and 70 per cent of the drug is excreted unchanged in the urine, resulting in concentrations approximating 3,000 micrograms per milliliter two hours after a 1 gram dose given intravenously. Serum clearance of aztreonam is directly proportional to creatinine clearance. Dosage adjustment must, therefore, be made in the presence of reduced clearance. Dosing varies between 0.5 and 2.0 grams every six to 12 hours, depending on the severity of the infection. The characteristics of aztreonam suggest that it is a useful nonnephrotoxic drug for treatment of aerobic gram-negative infection.

Aztreonam↗

PubMed1986

Stability of intravenous admixtures containing aztreonam and cefazolin.

The stability of aztreonam and cefazolin in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride containers: aztreonam 20 mg/mL and cefazolin 20 mg/mL (as the sodium salt); aztreonam 10 mg/mL and cefazolin 5 mg/mL; aztreonam 20 mg/mL and cefazolin 5 mg/mL; and aztreonam 10 mg/mL and cefazolin 20 mg/mL. One of each of these admixtures was stored at 23-25 degrees C for 48 hours and at 4-5 degrees C for seven days. At various storage times the admixtures were inspected for visual changes, and 1-mL samples were tested for pH and assayed using a stability-indicating high-performance liquid chromatographic assay. No visual changes were observed, and changes in pH were negligible. Concentrations of aztreonam and cefazolin under both storage conditions decreased by less than 3%. Intravenous admixtures of aztreonam and cefazolin at the concentrations studied are stable for at least 48 hours at 23-25 degrees C and for seven days at 4-5 degrees C.

Aztreonam↗