Although it is less potent than cephalothin against Gram-positive bacteria and cefamandole against most of the Enterobacteriaceae, cefoxitin is effective against certain strains of Gram-negative bacilli The activity of cefoxitin and cephamycins, in general, against resistant bacterial strains is because of their resistance to hydrolysis by β-lactamases conferred by the 7α-methoxyl substituent. The pharmacokinetic properties of cefoxitin resemble those of cefamandole. Because its half-life is relatively short, cefoxitin must be administered 3 or 4 times daily.

Cefotaxime Sodium, Sterile Cefotaxime (Claforan) was the first third- generation cephalosporin to be introduced. It possesses excellent broad-spectrum activity against Gram-positive and Gramnegative. aerobic and anaerobic bacteria. It is more active than moxalactam against Gram-positive organisms.

It is β-lactamases inhibition due to alkoximino group also contain polar group,acyl group. The syn-isomer of cefotaxime is significantly more active than the anti-isomer against β-lactamase– producing bacteria. This potency difference is, in part, because of greater resistance of the syn-isomer to the action of β- lactamases. The higher affinity of the syn-isomer for PBPs, however, may also be a factor. The parent drug reaches the cerebrospinal fluid in sufficient concentration to be effective in the treatment of meningitis.

NEWER CEPHALOSPORINS

Cephalosporins currently undergoing clinical trials or recently being marketed in the United States fall into two categories: (a) orally active β-lactamase–resistant cephalosporins (b) parenteral β-lactamase–resistant antipseudomonal cephalosporins. The status of some of these compounds awaits more extensive clinical evaluation. Nonetheless, it appears that any advances they represent will be relatively modest. Cefpirome, Cefepime, Ceftibuten

Ceftibuten Ceftibuten (Cedax) is a recently introduced, chemically novel analog of the oximino cephalosporins in which an olefinic methylene group (C=CHCH2-) with Z stereochemistry has replaced the syn(Cis) oximino (C=NO-) group. This isosteric replacement yields a compound that retains resistance to hydrolysis catalyzed by many β- lactamases, has enhanced chemical stability, and is orally active. Oral absorption is rapid and nearly complete. It has the highest oral bioavailability of the third-generation cephalosporins.

Ceftibuten possesses excellent potency against most members of the Enterobacteriaceae family. Ceftibuten is recommended in the management of community-acquired respiratory tract, urinary tract, and gynecological infections.

Monobactams: like Sulfazecin

The development of useful monobactam antibiotics began with the independent isolation of sulfazecin and other monocyclic β-lactam antibiotics from saprophytic soil bacteria in Japan100 and the United States. Sulfazecin was found to be weakly active as an antibacterial agent but highly resistant to β-lactamases.

SAR Extensive SAR studies eventually led to the development of aztreonam, which has useful properties as an antibacterial agent. Early work established that the 3-methoxy group, which was in part responsible for β-lactamase stability(resistance in cephalosporins) here it contributes to the low antibacterial potency, and poor chemical stability of these antibiotics (not active orally). The carbon no 4 (CH2) if one (H) substituted by methyl (CH3) increased stability to β-lactamases and activity against Gram-negative bacteria and decrease activity against G+ve bacteria. 4,4-gem-dimethyl substitution confers to oral administration and decreases antibiotic activity.

Products Tigemonam Tigemonam is a newer monobactam that is orally active. It is highly resistant to β- lactamases. Tigemonam is not particularly active against Gram-positive or anaerobic bacteria and is inactive against P. aeruginosa.

the oral absorption of tigemonam is excellent. It could become a valuable agent for the oral treatment of urinary tract infections and other non–life-threatening infections caused by β- lactamase–producing Gram-negative bacteria.

Aminoglycosides

Contain sugar moiety their structures amino sugars linked glycosidically The discovery of streptomycin, the first aminoglycoside antibiotic to be used in chemotherapy, was begun in This success stimulated worldwide searches for antibiotics from the actinomycetes and, particularly, from the genus Streptomyces.