Aztreonam structure

In a second line of research, they prepared a new set of synthetic (3-lactam probes 62 around the monocyclic aztreonam structure (Fig. 28). Interestingly, none of these modified (3-lactam probes labeled any PBPs but had preference for other enzymes such as (3-ketoacyl acyl carrier protein III (KAS III), a (3-lactamase,... 

Breed J, Teras J, Gardovskis J, Maritz FJ, Vaasna T, Ross DP, Gioud-Paquet M, Dartois N, Ellis-Grosse EJ, Loh E. (2005) Safety and efficacy of tigecycline in treatment of skin and skin structure infections Results of a double-blind phase 3 comparison study with vancomycin-aztreonam. Antimicrob Agents Chemother 49 4658 666. 

Children Safety and efficacy of IV aztreonam have been established children 9 months to 16 years of age. Sufficient data are not available for pediatric patients younger than 9 months of age or for treatment of the following indications/pathogens Septicemia and skin and skin-structure infections (where the skin infection is caused by H. influenzae type b). In pediatric patients with cystic fibrosis, higher doses of aztreonam may be warranted. 

Aztreonam - intramuscular or intravenous - is excreted unchanged by glomerular filtration and renal tubular secretion. It lacks the allergenic tricyclic nuclear structure of penicillins, cephalosporins and carbapenem beta-lactams. 

There is cross-allergy between all the various forms of penicillin, probably due in part to their common structure, and in part to the degradation products common to them all. Partial cross-allergy exists between penicillins and cephalosporins (a maximum of 10%) which is of particular concern when the reaction to either group of antimicrobials has been angioedema or anaphylactic shock. Carba-penems (meropenem and imipenem-cilastatin) and the monobactam aztreonam apparently have a much lower risk of cross-reactivity. 

Figure 5. Schematic representation of the aztreonam 5 processing. Here, the reaction stops at the acylated stage and the deacylytion is hindered. The structure of the acylated state has been experimentally determined as shown in Fig. 6c.

The oxyacetic acid residue of the monoxacetams is bioisosteric with the sulfate moiety of the monosulfactams. In addition, the presence of the carboxylate moiety provided opportunity for the preparation of esters that could act as orally absorbed prodrugs. Based on structure-activity relationships, SQ 82,291 (45) [90898-90-1]y C12H15N506S, the nonacidic methoxime side chain of which was necessary to maintain oral absorption of the prodrugs, was prepared. SQ 82,291 has a high, specific affinity for the PBP-3 transpeptidase of gram-negative bacteria. However, it lacks the isobutyric acid moiety of aztreonam (17) on the oxime residue and whereas the activity of SQ 82,291 vs the Enterobacteriaceae was maintained, antipseudomonal activity was significandy diminished (37). 

The capacity to generate, and the amount of superoxide produced by a in vitro renal microsome system is dependent on the molecular structure of the specific P-lactam. Superoxide production is a function of exposure time and P-lactam concentration (Figure 5). The rank order of the magnitude of superoxide production by P-lactams in vitro is as follows cephaloridine > cefsulodin > mezlocillin > aztreonam > ceftazidime > cefotaxime [10]. 

The usual dose of aztreonam for severe infections is 2 g every 6 to 8 hours. This should be reduced in patients with renal insufficiency. Aztreonam has been used successfully for the therapy of a variety of infections. One of its notable features is little allergic cross-reactivity with P-lactam antibiotics, with the possible exception of ceftazidime with which it has considerable structural similarity. Aztreonam is therefore quite useful for treating Gramnegative infections that normally would be treated with a P-lactam antibiotic were it not for the history of a prior allergic reaction. 

Tigemonam. [S-iZ ]- f[l-(2-Amino-4-thiazolyi)-2-[[2,2-dimeihyl-4.0xo-l-(sutfooxy)-3-azetidinyl]amino]-2-ottoethylidene]amino]oxy]acetic acid [[[(Z)-(2-amino-4-thi-azolyl)[[(3S)-1 -hydroxy-2,2-dimethyl -4-OxO-3-azetidinyl]-carbamoyl]methylene]amino]oxy]aeetic acid hydrogen sulfate (ester). CI2H,jN-OA mol wt 437.40. C 32.95%, H 3.46%, N 16.01%, O 32.92%, S 14.66%. Orally active synthetic monosulfactam, structurally similar to the monobac-tam aztreonam, q.v. Prepn C. Yoshida et al, J. Antibiot. 38,... 

AZTREONAM Aztreonam (azactam) is a monocyclic /3-lactam. Its structural formula is ... 

Figure 7.10 Bacterial cell wall synthesis. 1) Alanine molecules are added to a carbohydrate tripeptide to form a "T" shaped cell wall precursor. This reaction is inhibited by D-cycloserine. 2) The precursor is transported across the plasma membrane by a carrier. Vancomycin inhibits the transport process. 3) The transporter is recycled to the inside of the cell to carry other precursors. Bacitracin inhibits this step. 4) The precursor is linked to the existing cell wall structure by transpeptidase. Penicillins, cephalosporins, imipenem and aztreonam inhibit the transpeptidase. Transpeptidase is one of several penicillin binding proteins and is not the only site of penicillin action.

These striking structures allow astonishing applications. The counterion x- used in the polypyrrole preparation becomes part of the polymer and can also be released, e.g. by applying a negative potential. Release can be specifically controlled, offering interesting possibilities for active counterions incorporated in the polypyrrole, e.g. those of medical interest (heparin, monobactam-aztreonam). ... 

Fig. 5.18 Structures of the monobactam aztreonam (a), oxazoUdine ring instead of the thiazolodine ring found in the carbapenems, imipenem (b) and meropenem (c), and peniciUins the clavam, clavulanic acid (d). Note that clavaras have an...

The monobactams have a single beta-lactam ring structure. The only clinically used monobactam is aztreonam. Replacement of the 1-sulfonic acids residue in monobactam with an Af-sulphonylated carbonyl amino moiety yields monocarbams [71, 72 ]. So far, however, no monocarbam derivative is on the market, probably because their antimicrobial moiety is not optimal. Since micro-organisms need iron for growth, some siderophore-conjugated monocarbams are now under evaluation [73 ]. It is reasonable to assume that it will take some time until they are marketed. One of the many problems not yet solved is the in vivo fate of the siderophore itself, since it may create some new adverse effects of its own. 

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