Aztreonam antibiotics

Lactam antibiotics, such as cephalosporins, and penicillins, such as ampicillin (11) and aztreonam, covalently modify their protein targets. Alkyne-functionalized versions of these antibiotics, for example, AmpN (12), were used to probe various penicillin-binding proteins in vitro and in vivo using CC-ABPP [36,37],... 

Nonabsorbable antibiotics are appealing because they have fewer systemic side effects and may be safer for children and pregnant women as well as in patients with renal and hepatic dysfunction. One such antibiotic, aztreonam, showed little effect on anaerobic flora in human volunteers, producing most of its effect on the aerobic flora [49, 50], A trial showed efficacy of aztreonam for traveler s diarrhea, where most pathogens are aerobes [51]. While there are no data on rates of AAD for nonabsorbable antibiotics and C. difficile, these would likely be decreased. Given the preservation of the anaerobic flora, another poorly absorbed antibiotic, bicozamycin, has efficacy in traveler s diarrhea with its major effect being on fecal aerobes [52],... 

There are two additional important variations on the theme of p-lactam antibiotics. These are the carbapenems, of which imipenem (Primaxin) is the outstanding example, and the monobactams, of which aztreonam (Azactam) is the outstanding example (see figure 23.2). 

Aztreonam (Azactam) Antibiotic Bacitracin (Bacitracin) Antibiotic... 

Aztreonam lysine (29 Cayston ) Aztreonam (29) Monobactam antibiotic NP-deiived Microbial Antibacterial Inhibits bacterial cell wall synhiesis 312-318... 

The first completely synthetic monocyclic beta-lactam antibiotic was aztreonam. The antimicrobial activity of this drug is exhibited mainly with respect to a broad spectrum of aerobic Gram-negative bacteria. It is resistant to beta-lactamases and does not induce their formation. The mechanism of its action is identical to that of other beta-lactam antibiotics with respect to Gram-negative bacteria. PBP are inactivated in the presence of aztreonam. 

Pharmacology Aztreonam, a synthetic bactericidal antibiotic, is the first of a class identified as monobactams. The monobactams have a monocyclic -lactam nucleus. Aztreonam s bactericidal action results from the inhibition of bacterial cell wall synthesis because of a high affinity of aztreonam for penicillin-binding protein 3 (PBP3). 

Drugs that may interact with aztreonam include other -lactamase-inducing antibiotics and aminoglycosides. 

Monobactams like aztreonam are monocyclic, as opposed to bicyclic, beta-lactam antibiotics. They are beta-lactamase-resistant. The monobactams are active against gram negative rods but lack activity against gram positive bacteria or against anaerobes. They are administered intravenously and they are rapidly excreted in the urine. 

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli. 

Aztreonam may be used as a substitute for an aminoglycoside in the treatment of infections caused by susceptible gram-negative organisms. Most of the adverse effects of aztreonam are local reactions at the site of injection. Interestingly, aztreonam rarely causes allergic reactions in patients with a history of type I hypersensitivity to other (3-lactam antibiotics. 

L B. The patient has complicated urinary tract infection and nonsevere sepsis syndrome caused by P. aeruginosa. Effective antibiotics for Pseudomonas spp. include mezlocillin, piperacillin, piperacillin-tazobactam, ticarcillin, and ticarciUin-clavulanate. The carbapenems (imipenem and meropenem) and the monobactam (aztreonam) are also active against P. aeruginosa. Ampicillin-sulbactam and cefazolin are ineffective against P. 

D. Marini, F. Balestrieri, and A. Sacchini, Characterization and assay of a new monobactamic antibiotic aztreonam, Boll. Chim. Farm., 724 218 (1985). 

R. B. Sykes and D. P. Bonner, "Monobactam Antibiotics History and Development," in J. D. Williams and P. Woods, Eds., Aztreonam, The Antibiotic Discovery for Gram-negative Infections, Royal Society Medicine International Congress Symposium Series No. 89, Royal Society Medicine, London, 1985, pp. 3-24. 

Koch C, Hjelt K, Pedersen SS, Jensen ET, Jensen T, Lanng S, Valerius NH, Pedersen M, Hoiby N. Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses. Rev Infect Dis 1991 13(Suppl 7) S608-11. 

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