Beta-lactam antibiotics cephalosporins

K. E. Price, D. N. McGregor, Basic Design of beta-Lactam Antibiotics - Cephalosporins , Scan. J. Infect. Dis. -Suppl. 1984, 42, 50-63. 

As with other beta-lactam antibiotics, cephalosporins can cause impaired hemostasis and bleeding by altering coagulation and platelet fnnction. 

Beta-lactam antibiotics are a second great class of antibacterials penicillins, cephalosporins, carbapenems, and monobactams. They act by inhibiting bacterial cell wall synthesis. 

Cephalosporins. These beta-lactam antibiotics share many features with the penicillins including mechanism, spectrum of action, distribution ans toxicity potential. At the present time, the cephalosporins are classified into three groups, designated as generations. 

There are many beta-lactamases and they can be classified differently by type of substrate, replacement of genes (chromosomes or plasmids), and place of production. A few of these enzymes directly hydrolyze penicillins (penicillinases), others hydrolyze cephalosporins (cephalosporinases), and others extend to a broad spectrum of substrates. A few bacteria have the ability to induce synthesis of beta-lactamase. Synthesis of beta-lactamase, which in a normal condition is suppressed, is induced in the presence of some beta-lactam antibiotics. 

Beta lactam antibiotics having a (3-lactam ring, which includes penicillin, in which a thiazolidine ring is attached to a betalactam ring that carries a secondary amino group. Other similar compounds are cephalosporins, monobactams and carbapenems. 

The cephalosporin drugs, which are also classified as beta-lactam antibiotics, exert their bactericidal effects in a manner similar to that of the penicillins (inhibition of PBPs, resulting in inadequate peptidoglycan production).56 Generally, the cephalosporins serve as alternative agents to penicillins if the penicillin drugs are ineffective or poorly tolerated by the patient. Cephalosporins may also be the drugs of choice in certain types of urinary tract infections (see Tables 33-5). 

A primary problem in using penicillins, cephalosporins, and other beta-lactam antibiotics is that certain bacteria produce enzymes known as beta-lactamases.26,70 These beta-lactamase enzymes bind to the beta-lactam drug and destroy it before it can exert an antibacterial... 

Petri WA. Penicillins, cephalosporins, and other beta-lactam antibiotics. In Brunton LL, et al, eds. The Pharmacological Basis of Therapeutics. 11th ed. New York McGraw-Hill 2006. 

The sulfur-free analogs of penicillins and cephalosporins have attracted much attention of both synthetic and medicinal chemists, since the successful development of new 1-oxacepham antibiotics by the Shionogi group17 . Namely, oxazoline-azeti-dinone derivatives 19 have been used as key intermediates in the synthetic chemistry of new beta-lactam antibiotics 18). The compounds 19 have usually been prepared by a two-step operation involving the reaction of 79 with chlorine or t-butylhypochlorite followed by treatment with a base. 

CA Bunnell, WD Luke, FM Perry. Industrial manufacture of cephalosporins. In SF Queener, Weber JA, SW Queener, eds. Beta-lactam Antibiotics for Clinical Use. New York Marcel Dekker, 1986, pp 255-284. 

Sinko PJ, Amidon GL. Characterization of the oral absorption of beta-lactam antibiotics. I. Cephalosporins determination of intrinsic membrane absorption parameters in the rat intestine in situ. Pharm Res 1988 5 645-650. 

So-called atypical bacteria such as Chlamydia pneumoniae and Mycoplasma pneumoniae are the next most important group of community-acquired pneumonia pathogens, accounting for around one case in every eight in hospitalised patients. Atypical bacteria are not sensitive to beta-lactam antibiotics such as penicillins and cephalosporins and the treatment of choice is a macrolide such as erythromycin. 

In situ methods involve the external perfusion of an isolated segment of intestinal tissne." The rat has been shown to be an excellent model for human intestinal permeability." One of the principle advantages of the in situ method is that the intact rat intestinal tissne maintains a normal complement of influx and efQux transporters. Cephalosporins and beta-lactam antibiotics are known to be absorbed by oligopeptide transporters in the GI tract. The rat in situ permeability method was used to determine the saturable Michaelis-Menten-type kinetics for this class of drug molecules. In like fashion, the permeabilities of thymidine anti-viral drugs, like AZT, involving the nncleoside transporter were determined in situ. ... 

The overwhelming majority of semisynthetic beta-lactam antibiotics, the penicillins and cephalosporin, currently available to physicians trace their origins to the intense research effort devoted to this field several decades ago. The emergence of pathogens resistant to those antibiotics has led some laboratories to revisit this field. The modified cephalosporin ceftobiprole (220), a compound with a rather complex extended side chain, has shown activity in the clinic against some strains of multidrug resistant bacteria. The synthesis starts with the well-precedented acylation of the of the cephalosporin (215), available in several steps from the commercially available 7-acetoxy cephalosporanic acid, with the activated... 

Beta-lactam antibiotics (pencillins, cephalosporins, and carbapenems) are excreted by the kidneys and hence the kidneys are targets of toxicity. These drugs can cause interstitial nephritis, tubular necrosis, and allergic angitis. Beta-lactams behave like haptens which are then... 

Altered platelet numbers and function Platelet dysfunction occurs dose-dependently with carbenicillin, ticarcillin, and, infrequently, other broad-spectrum penicillins (105), but the NMTT cephalosporin moxalactam has also been associated with altered platelet function in both healthy subjects and in patients treated with standard regimens (106-110). In contrast, clinical studies including cefotaxime, ceftizoxime, cefoperazone, and ceftracone did not show platelet dysfunction attributable to these compounds (109-111). There is evidence that beta-lactam-antibiotic-induced platelet dysfunction is at least partially irreversible (112). 

Gastrointestinal upsets, nausea, and vomiting have been observed with virtually all beta-lactam antibiotics, both oral and parenteral. Even when comparing analogous applications and doses, no particular risk can be clearly ascribed to a given compound. Acute hemorrhagic colitis without pseudomembrane formation has been described after treatment with various penicillins and cephalosporins (SEDA-21, 261). 

The cephalosporins represent a family of beta-lactam antibiotics originally derived from the naturally occurring cephalosporin C. Isolation of the cephalosporin C nucleus, 7-aminocephalosporanic acid, made it possible to introduce new groups into this molecule to obtain the current variety of compounds (1). Cephalosporins vary widely in their antibacterial properties, beta-lactamase stability, and pharmacokinetic behavior, but there is as yet no unequivocal classification (2). For reasons more practical than pharmacological, cephalosporins are often classified into first-, second-, third- and fourth-generation compounds, as shown in Table 1. 

As with all beta-lactam antibiotics, slight increases in serum transaminases and alkaline phosphatase have been reported with cephalosporins. However, in contrast to the isoxazolylpenicillins and co-amoxiclav, only very sporadic cases with more severe liver disease have occurred (94-98). Very prolonged cholestasis was reported in isolated cases with cefmenoxime (99) and ceftibuten (98). 

S. Selwyn, R. W. Lacey and M. Bakhtiar The Beta-Lactam Antibiotics Penicillins and Cephalosporins in Perspective , Hodder and Stoughton, London,... 

The beta-lactam antibiotics are commonly used because of their safety, efficacy, relatively low cost and the variety of dosage forms available. Both penicillins and cephalosporins have a four-membered beta-lactam ring that is responsible for the instability of these compounds. The penicillins are also relatively insoluble they are prepared as various salts by the substitution of the hydroxyl group or the hydrogen of the carboxyl group with sodium, potassium, benzathine or procaine. 

Cephalosporin (beta-lactam antibiotic) fermentation Cephalosporium... 

Other Beta-lactam Antibiotics - Several newer cephalosporins and cephamy-clns have been tested clinically in gonorrhea. Cefazolln, cefoxitin, cefu-roxime, cefamandole, and others are effective In vitro,10 21 but have given variable results in clinical trials.22-24 Cefuroxlme is the most effective, with cure rates in uncomplicated infection of 98-100% when 1.0-1.5 gm is given IM with probenecid 1.0 gm orally, and is effective against PPNG.25... 

The inhibitors of bacterial cell-wall synthesis are the beta lactam antibiotics (the penicillins and cephalosporins) (Figure V-l-l), the carbapenems, vancomycin, and aztreonam. 

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