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PubMed1985

Use of aztreonam in the treatment of serious infections due to multiresistant gram-negative organisms, including Pseudomonas aeruginosa.

Aztreonam is a novel antimicrobial agent belonging to the monobactam class of antibiotics. It inhibits both beta-lactamase-producing and non-beta-lactamase-producing aerobic gram-negative bacilli, but it has no activity against gram-positive species or against anaerobic species. The efficacy of aztreonam in the treatment of infection in 76 patients and its safety in 87 patients was evaluated. The majority (91 percent) of patients had significant underlying disease, and 47 percent were critically ill. Aztreonam produced an overall clinical response of 86 percent, with 10 of 11 cases of bacteremia cured, including four due to Pseudomonas aeruginosa, seven of eight cases of pneumonia, and seven of nine episodes of osteomyelitis. Infections due to bacteria resistant to ampicillin, carbenicillin, cefazolin, cefamandole, cefoxitin, and gentamicin were cured. Although 15 of 18 patients with exacerbations of pulmonary infection due to P. aeruginosa showed clinical improvement, bacteriologic cure was not achieved, as has been noted with other drugs. Similarly, patients with major underlying structural abnormalities of the urinary tract showed early relapses of bacteriuria. Aztreonam combined with antistaphylococcal, antistreptococcal, or antianaerobic agents provided an alternative to aminoglycoside use in these non-neutropenic patients. Administration of 1 or 2 g every eight hours yield serum bactericidal levels well in excess of 1:8 against all Enterobacteriaceae and some P. aeruginosa strains. There was a low incidence of adverse side effects, none serious. Overall, aztreonam is a useful alternative to the drugs available for use in hospital-acquired gram-negative infections and provides a chance for more directed therapy.

Adolescent↗

PubMed1990

Gram-negative bacillary pneumonia in the nosocomial setting. Role of aztreonam therapy.

Gram-negative bacterial pneumonia is the leading cause of fatal nosocomial infection in this country. Predisposing factors include altered upper respiratory tract flora and altered barriers that normally protect the sterile lower respiratory tract from invasion by pharyngeal bacteria. Aztreonam, which is highly active against most gram-negative pathogens and which does not cause nephrotoxicity, has been evaluated in the treatment of nosocomial pneumonia. In vitro and pharmacokinetic data on aztreonam indicate that this agent provides an alternative agent for use when resistance to cephalosporin and aminoglycoside antibiotics has developed. Data further suggest that aztreonam may interact synergistically with aminoglycosides against gram-negative pathogens. Clinical study supports the usefulness of aztreonam against gram-negative nosocomial pneumonia. Since aztreonam is inactive against gram-positive and anaerobic bacteria, it must be used in combination with other antibiotics when these pathogens are suspected.

Aztreonam↗

PubMed1987

Sex difference in responsiveness to Aztreonam of monooxygenase system in liver microsomes from rats.

Effect of successive administration of Aztreonam on microsomal monooxygenase system was investigated in male and female Sprague-Dawley rats. The activities of benzphetamine N-demethylase, aminopyrine N-demethylase, p-nitroanisole O-demethylase and aniline hydroxylase in liver microsomes from male rats were decreased dose-dependently by Aztreonam. On the contrary, the activities in liver microsomes from female rats were slightly increased rather than decreased by the administration of Aztreonam. In addition, Aztreonam was found to decrease the specific content of microsomal cytochrome P-450 in male rats but not in female rats. The decreases in the activities observed in male rats were accompanied by a parallel decrease in the specific content of cytochrome P-450. Furthermore, the results of quantitation of P-450 (M-1), one of the male specific forms of cytochrome P-450, indicated that the administration of Aztreonam resulted in a dose-dependent decrease in the content of P-450 (M-1) in liver microsomes from male rats.

Aminopyrine N-Demethylase↗

PubMedDate not supplied

Stability of aztreonam in AZACTAM.

The influence of temperature and relative humidity on the stability of aztreonam in AZACTAM was investigated. Changes of the concentration of aztreonam were followed using the HPLC method with UV detection. The first-order rate constants of the reversible reaction of isomerization Z-aztreonam right harpoon over left harpoonE-aztreonam and the parallel reaction Z-aztreonam-->products were determined at RH=76.4% and T=313, 323, 333, 343 and 353 K, and at T=343 K and RH=50.9%, 60.5%, 66.5% and 76.4%. The thermodynamic parameters-energy, enthalpy and entropy of these reactions were calculated.

Aztreonam↗

PubMed2026

Aztreonam-avibactam Activity against Enterobacterales from Asia Pacific and Latin American Medical Centres: Summary of 5 years of Surveillance prior to Clinical Use (2020-2024).

OBJECTIVES: To assess the in vitro activity of aztreonam-avibactam against Enterobacterales from the Asia Pacific region (APAC) and Latin America (LATAM) during a 5-year period prior to its approval for clinical use in these regions. METHODS: 12,039 Enterobacterales isolates were consecutively collected in 2020-2024 from 17 medical centres in APAC (n=7,369) and 10 in LATAM (n=4,670) then susceptibility tested by broth microdilution. Carbapenem-resistant Enterobacterales (CRE) and isolates with elevated aztreonam-avibactam MICs (>4 mg/L) were submitted to whole genome sequencing. RESULTS: Aztreonam-avibactam was active against 99.9% of Enterobacterales from APAC and LATAM and exhibited potent activity against CRE isolates (MIC50/90, 0.25/2 mg/L; 97.3% susceptible in APAC and MIC50/90, 0.25/0.5 mg/L; 99.4% susceptible in LATAM). Cefiderocol was active against 91.2% of CREs from APAC and LATAM. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam showed limited activity against CRE isolates from LATAM (53.5% to 64.8% susceptibility) and APAC (27.3% to 38.8% susceptible). The occurrence of carbapenemases varied clearly among the countries evaluated. In general, metallo-β-lactamases (MBLs) prevailed in APAC and KPCs predominated in LATAM, but with great variability among countries within a region. Decreased susceptibility to aztreonam-avibactam was largely due to PBP3 alterations plus the production of CMY and/or CTX-M β-lactamases among Escherichia coli, and decreased membrane permeability associated with KPC production among Klebsiella pneumoniae. CONCLUSIONS: The results of this investigation provide a baseline for monitoring the activity of aztreonam-avibactam in APAC and LATAM and emphasize the importance of surveillance programs to monitor the emergence of resistance markers.

Aztreonam-avibactam↗

PubMed1991

Metabolic tolerance to arginine: implications for the safe use of arginine salt-aztreonam combination in the neonatal period.

Two similar cohorts of low birth weight infants whose size was appropriate for gestational age randomly received either aztreonam-arginine plus ampicillin (n = 15) or gentamicin plus ampicillin (n = 15) for empiric treatment of neonatal sepsis. The regimens were infused together with glucose at greater than 5 mg/kg per minute, and immediate (4 hours) and cumulative (3 days) effects were assessed. Serum arginine and insulin values rose immediately after administration of aztreonam (containing 0.15 mmol of arginine per kilogram), but there were no changes in the gentamicin-treated cohort; no differences occurred in either cohort in serum concentrations of glucose, ammonia, potassium, creatinine, and bilirubin. After 3 days of antibiotic therapy (n = 13), the baseline serum arginine concentration was almost twice as high in the aztreonam group and showed a similar further rise and fall during the 4 hours after infusion; arginine urinary fractional excretion (normalized to creatinine clearance) decreased in the gentamicin group. The indirect bilirubin concentration rose more (p less than 0.001) in the aztreonam-treated infants (5.1 to 11.5 mg/dl (87 to 196 mumol/L] than in the gentamicin-treated infants (5.5 to 8.1 mg/dl (94 to 138 mumol/L)). Thus a modest differential bilirubin response and modestly elevated baseline serum arginine level occurred after the 3-day low-arginine doses of this study; serum ammonia and glucose concentrations were not affected. Aztreonam-arginine in neonates was well tolerated metabolically, and we believe that it can be used safely in conjunction with attention to glucose and bilirubin metabolism.

Ammonia↗

PubMed1995

Aztreonam.

Aztreonam is a monocyclic beta-lactam antibiotic that is active exclusively against the aerobic gram-negative bacilli. It is not ototoxic or nephrotoxic and so is used as an alternative to aminoglycosides in a variety of clinical situations. In polymicrobial infections or when used for empiric therapy, aztreonam must be combined with other antimicrobial agents active against gram-positive and anaerobic species. Aztreonam is often effective against resistant strains of gram-negative organisms, which are often involved in nosocomial infections. Overuse of aztreonam should be avoided to prevent the emergence of resistant P. aeruginosa strains. Except in the treatment of P. aeruginosa infections, aztreonam should not be added to beta-lactam regimens for additional gram-negative coverage.

Aztreonam↗

PubMed1999

Pharmacokinetics and pharmacodynamics of aztreonam administered by continuous intravenous infusion.

The pharmacodynamic parameter that appears to correlate best with a successful therapeutic outcome with beta-lactam antibiotics is the length of time the serum antibiotic concentration remains above the minimum inhibitory concentration (MIC) for the infecting pathogen. By maximizing this parameter, continuous administration of beta-lactam and related antibiotics by intravenous infusion could represent the optimal mode of drug administration. The pharmacokinetic and pharmacodynamic properties of ceftazidime administered by continuous intravenous infusion have been evaluated previously. Aztreonam is a monobactam antibiotic with similar pharmacokinetic and microbiologic activity to that of ceftazidime. This study evaluated the pharmacokinetic and pharmacodynamic characteristics of aztreonam administered as a continuous intravenous infusion in healthy volunteers against multiple clinical isolates. Five men and 3 women received 6 g of aztreonam administered by continuous intravenous infusion over 24 hours. Blood samples were collected before the infusion and at 0.5, 1 through 8, 12, 18, and 24 hours after the start of the infusion. Pharmacokinetic parameters were determined by standard equations. In vitro susceptibility testing was performed using National Committee for Clinical Laboratory Standards guidelines for 4 clinical isolates of gram-negative bacteria (2 each of Escherichia coli and Pseudomonas aeruginosa). Serum inhibitory titers (SITs) were determined in duplicate for each clinical isolate at 0 and 24 hours. The subjects' mean (+/- SD) age was 29.3+/-4.4 years; mean weight, 74.6+/-14.0 kg; and calculated mean creatinine clearance, 107+/-13 mL/min. For the pharmacokinetic parameters, mean (+/- SD) values were as follows: steady-state serum concentration, 40.9+/-8.8 microg/L; half-life, 1.5+/-0.4 hours; elimination rate constant, 0.50+/-0.13 hours(-1); steady-state volume of distribution, 0.18+/-0.04 L/kg; and total body clearance, 6.1+/-1.2 L/h. The MICs were 0.0625 and 0.125 microg/mL against the 2 E coli isolates and 4 microg/mL against both P aeruginosa isolates. The median SITs against the E. coli isolates were 1:256 and 1:512, and against the P. aeruginosa isolates were 1:8 and 1:16. At steady state, II subjects had serum concentrations of aztreonam > or =4 times the MIC for each organism. These findings suggest that further clinical study of the administration of aztreonam by continuous intravenous infusion is warranted.

Adolescent↗

PubMed1997

The use of aztreonam as an alternate therapy for multi-resistant Pseudomonas aeruginosa.

The emergence of multi-resistant Gram-negative bacteria has created a most alarming clinical situation. The armamentarium of antibiotics used against this group of organisms is rapidly being depleted. Our routine therapeutic approach to control and prevent these Gram-negative bacteria from gaining a foothold was the empirical use of an aminoglycoside combined with piperacillin. However, aminoglycoside resistance is now routine rather than unusual. We evaluated the role of the monobactam aztreonam in burn wound infections and compared it to the aminoglycosides amikacin and gentamicin as well as piperacillin for the Enterobacteriacae and Pseudomonas aeruginosa. A total of 1274 Gram-negative isolates including P. aeruginosa were evaluated for susceptibility to the above-mentioned antibiotics from January 1995 to August 1995 (Table I). Among the Enterobacteriacae, aztreonam was more effective than amikacin and piperacillin (58.4 per cent vs. 45.8 per cent, respectively). However, it still fluctuated among the Enterobacteriacae as did the aminoglycosides. One major significant finding was that while susceptibility to aztreonam was variable for the Enterobacteriacae, P. aeruginosa remained 90 per cent susceptible to aztreonam and 90 per cent susceptible to piperacillin, whereas it was 79 per cent resistant to the aminoglycosides. Consequently, when choosing an antimicrobial in a suspected P. aeruginosa burn wound infection, aztreonam and piperacillin should be considered as the first line of defense.

Aminoglycosides↗

PubMed1989

Single-dose pharmacokinetics of aztreonam in healthy volunteers and renal failure patients.

The pharmacokinetics of aztreonam were studied in 6 healthy male volunteers and 12 male patients with various degrees of chronic renal failure after intravenous bolus injection of 1g of the drug. Serum pharmacokinetics of aztreonam were described by an open, two-compartment kinetic model. The serum levels of aztreonam exceeded the reported minimum inhibitory concentration (MIC)90 for Enterobacteriaceae for 8 hours and up to 24 hours, in healthy volunteers and renal failure patients, respectively. However, the serum levels of the drug exceeded the MIC50 for Pseudomonas aeruginosa for only 4 hours and 12 hours in healthy volunteers and patients, respectively. The half-life of elimination (t 1/2/beta) increased significantly (P less than 0.001) from 1.8 +/- 0.14 h in healthy volunteers and to 4.9 +/- 1.1 h in patients with renal failure. The total serum clearance of aztreonam decreased significantly (P less than 0.001) from 84.2 +/- 7.8 ml/h/kg in healthy volunteers to 30.2 + 9.2 ml/h/kg in patients with renal failure. A linear correlation (r = 0.971, P less than 0.001) was found between creatinine clearance and the total serum clearance of aztreonam. The AUC0-infinity increased significantly (P less than 0.001) from 137.5 +/- 12.2 micrograms/h/ml in healthy volunteers to 464 +/- 114.5 micrograms/h/ml in patients with renal failure.

Adult↗

PubMedDate not supplied

Clinical experience with aztreonam for treatment of infections in children.

The in vitro activity, pharmacokinetics, bactericidal activity, and tissue penetration of aztreonam suggest that it may play a role in therapy for serious gram-negative bacterial infections in children. Several thousand children throughout the world received aztreonam during open or comparative clinical trials for treatment of infections including pyelonephritis, bacteremia, meningitis, skeletal infection, pneumonia, and peritonitis. Cure rates have ranged from 92% to 100%, with relapses seen mainly in children with obstructive renal lesions and those with infections caused by Salmonella. A comparative trial of aztreonam for treatment of neonatal sepsis showed it to be at least as effective as amikacin for this infection. Aztreonam yielded clinical results comparable to those of conventional combined therapy for pulmonary infection in patients with cystic fibrosis. Adverse effects in pediatric trials have been uncommon; fever, diarrhea, or rash occurred in less than 2% of treated children. Reversible laboratory abnormalities have occasionally been noted. On the basis of these data, aztreonam is considered an appropriate alternative agent for the treatment of serious gram-negative bacterial infections in neonates and children. Further comparative clinical trials will delineate specific indications.

Aztreonam↗

PubMedDate not supplied

Safety of aztreonam in patients with cystic fibrosis and allergy to beta-lactam antibiotics.

In an open clinical trial, aztreonam was administered repeatedly to 15 cystic fibrosis patients who were chronically infected with Pseudomonas aeruginosa and had previously had severe hypersensitivity reactions to other beta-lactam antibiotics, including anaphylactic shock, generalized urticaria, and drug-associated fever. After negative results in a skin-prick test and a lack of reaction to an intravenous test dose of aztreonam, the patients were treated with aztreonam (150 mg/[kg.d]) in combination with tobramycin (10-20 mg/[kg.d]) for 14-day periods at 3- to 4-month intervals. To date, a total of 56 course of aztreonam have been administered to these patients (three to six courses per patient), and no type 1 hypersensitivity reactions have occurred. However, as a result of drug-associated fever, the administration of aztreonam had to be discontinued in two of 15 cases. The remaining 13 patients have tolerated treatment well.

Adolescent↗

PubMedDate not supplied

Efficacy of aztreonam in the treatment of skeletal infections due to Pseudomonas aeruginosa.

Twenty-eight patients with skeletal infections due to Pseudomonas aeruginosa were treated with aztreonam during two open, noncomparative, multicenter clinical trials. Ten patients with septic arthritis received 2 g of aztreonam three times a day (modal) for 30 days (mean). The mean follow-up period was 4 weeks. Microbiologic cure was achieved in all 10 patients; complete clinical cure, in eight; and partial clinical cure, in two. Eighteen cases of osteomyelitis were treated with 2 g of aztreonam three times a day (modal) for 40 days (mean), with a mean follow-up period of 6 months. Microbiologic cure was achieved in 17 patients. Relapse occurred 1 month after therapy in one patient. Complete clinical cure was achieved in 13 and partial clinical cure was achieved in five patients. The most common adverse reactions to aztreonam were a transient elevation in levels of hepatic enzymes and transient eosinophilia. Three superinfections and one subsequent infection occurred. These results support use of aztreonam for the treatment of skeletal infections due to P. aeruginosa.

Adolescent↗

PubMedDate not supplied

Efficacy and safety of low-dose aztreonam in the treatment of moderate to severe infections due to gram-negative bacilli.

One hundred fifty-three patients with moderate to severe infections due to gram-negative bacilli, including septicemia (60 cases), lower respiratory tract infection (32 cases), intraabdominal infection (40 cases), and urinary tract infection (21 cases), were treated with aztreonam (1 g every 12 h). This dosage is lower than usual. Criteria for inclusion in the study included documented infection due to gram-negative bacilli and a measurement of severity of disease of less than 12 (as defined by a Simplified Acute Physiology Score for the 115 cases of community-acquired infection). Other than aztreonam, no antibiotic active against gram-negative bacilli was allowed to be used for treatment. Seventy-one patients in whom gram-positive or anaerobic organisms were detected or suspected were given additional agents effective against the organisms. One hundred forty-one patients (92.2%) were cured; the mean duration of treatment was 10.9 +/- 4.0 days. None of the gram-negative bacilli initially isolated became resistant to aztreonam. Colonization, generally by a gram-positive organism, was observed in 27 patients and superinfection was observed in five. Aztreonam was well tolerated. This study suggests that a dosage of 2 g daily of aztreonam should be appropriate in the treatment of moderate to severe infections due to susceptible gram-negative bacilli.

Abdomen↗

PubMedDate not supplied

Safety of aztreonam and SQ 26,992 in elderly patients with renal insufficiency.

Aztreonam is hydrolyzed (2%-7%) in vivo to a noncyclic compound, SQ 26,992, which has a serum half-life of 26 hr in healthy volunteers. In a study of whether SQ 26,992 accumulates to potentially toxic levels in patients with renal insufficiency, serum concentrations were measured daily in nine elderly patients (average age, 72 years) with diminished renal function and urinary tract infections. The dosage of aztreonam (1.5, 3.0, or 6.0 g per day) was selected according to the creatinine clearance rate (5-49 ml/min) and the severity of infection. Trough levels of aztreonam for eight patients averaged 34.2 micrograms/ml before the third or fourth dose and 32.7 micrograms/ml on the fifth day of therapy (P = .77). Trough levels of SQ 26,992 at the same times averaged 3.2 and 9.1 micrograms/ml, respectively (P = .04). In the one patient who was undergoing hemodialysis, trough levels of aztreonam averaged 55 micrograms/ml for seven days, and trough levels of SQ 26,992 increased progressively from 2.6 to 38.2 micrograms/ml. For all nine patients, the ratio of the SQ 26,992 concentration on day 5 to that on day 1 was inversely related to the creatinine clearance rate (r = -.89). No adverse clinical reactions or laboratory test abnormalities were detected during therapy. Thus, aztreonam should prove to be safe in elderly patients with diminished renal function.

Aged↗

PubMedDate not supplied

Comparative evaluation of aztreonam in therapy for experimental bacterial meningitis and cerebritis.

Aztreonam (SQ 26,776), a new monocyclic beta-lactam agent, was compared with several frequently used antibiotics in therapy for three types of experimental meningitis in rabbits and for experimental Escherichia coli cerebritis in rats. Aztreonam was highly active against common gram-negative meningeal pathogens in vitro (all minimal bactericidal concentrations less than or equal to 0.125 microgram/ml), including ampicillin-sensitive and ampicillin-resistant strains of Haemophilus influenzae, E. coli, and meningococci. In both rabbits and rats, serum concentrations of all antibiotics evaluated closely approximated concentrations found in humans receiving standard parenteral regimens. The percent penetration of aztreonam into purulent rabbit cerebrospinal fluid was 23%. In experimental meningitis, aztreonam was more rapidly bactericidal than ampicillin in meningitis due to ampicillin-sensitive H. influenzae, than ampicillin or chloramphenicol in meningitis due to ampicillin-resistant H. influenzae, and than gentamicin in meningitis due to E. coli. Aztreonam also reduced concentrations of E. coli in rat brain as rapidly as did gentamicin during therapy for experimental cerebritis, the early stage of brain abscess formation.

Ampicillin↗

PubMedDate not supplied

Overall clinical experience with aztreonam in the treatment of obstetric-gynecologic infections.

Gynecologic infections (primarily endometritis and pelvic inflammatory disease) in 73 women were evaluated for clinical and microbiologic response to treatment with aztreonam plus clindamycin or a control regimen. The dosage of aztreonam used most frequently was 1 g three times daily. For 72 of the 73 women, a microbiologic cure and a satisfactory clinical response were achieved. Twenty-three of the 73 patients were treated with aztreonam in an open study; all experienced a microbiologic cure and a favorable clinical response. Fifty of the 73 patients treated with aztreonam plus clindamycin were entered into a comparative study that included 38 patients who received gentamicin (3-5 mg/kg per day) plus clindamycin (600 mg three times a day). In 49 (98%) of the aztreonam-treated patients and in 36 (95%) of the gentamicin-treated patients, the causative organism was eradicated, and in 98% and 89% of the patients, respectively, a favorable clinical response was achieved.

Adolescent↗

PubMed1984

Lack of cross-reactivity between aztreonam , a monobactam antibiotic, and penicillin in penicillin-allergic subjects.

Monobactam antibiotics are a new class of beta-lactam antibiotics. In contrast to penicillins or cephalosporins, monobactams possess a monocyclic beta-lactam structure. IgE or immediate hypersensitivity cross-reactivity between aztreonam (a monobactam) and penicillin was investigated, since this will be an important consideration when therapy is chosen. The maximum concentration of aztreonam reagents not giving false-positive skin tests was determined in normal subjects who were not allergic to penicillin. Subsequently, 41 subjects with IgE antibody to one or more penicillin moieties, as determined by positive skin reactions, were tested with the aztreonam reagents. Thirty-seven of these persons showed no reactivity while four showed equivocal tests. Repeat tests in those four persons were negative to the aztreonam reagents, while their penicillin tests remained unchanged. These in vivo data suggest that there is no cross-reactivity between IgE antibodies to penicillin and aztreonam and provide a basis for investigating the therapeutic use of monobactams in patients who are allergic to penicillin.

Adult↗