Drugs 8-lactam antibiotics

Isothiazole substituents have been attached to /3-lactam antibiotics and to macrocyclic antibiotics such as erythromycin. The sulfa drug, Sulfasomizole (244) also has good antibacterial activity. Thiosemicarbazones of 5-formyl- and 5-acetylisothiazoles show high activity against the pox group of viruses (65AHC(4)107). 

Lactam Antibiotics Microbial Resistance to Drugs Quinolones... 

Over the past few years there have been an increasing number of reports of diseases that are becoming resistant to previously effective drug treatments. This resistance is often due to the presence of enzymes that bring about chemical modification of the drug to an inactive form, e.g. /S-lactamase enzymes deactivate (6-lactam antibiotics by their conversion to penicillanic acid. 

Once the organism has been identified and sensitivities are known, drug selection should be adjusted to reflect the susceptibilities of the organism. Streptococcal, staphylococcal, and enterococcal species sensitive to P-lactam antibiotics should be treated with continuous IP dosing to increase efficacy and minimize resistance.49 Peritonitis caused by S. aureus or P. aeruginosa are often associated with catheter-related... 

Hypersensitivity reactions with P-lactam antibiotics, especially penicillin, may encompass any of the type I through IV Gell-Coombs classifications. The most common reactions are maculopapular and urticarial eruptions.7 While rare (less than 0.05%), anaphylaxis to penicillins causes the greatest concern because they are responsible for the majority of drug-induced anaphylaxis deaths in patients, accounting for 75% of all ana-i phylaxis cases in the United States.5,8 The treatment of ana-I phylaxis is given in Table 51-2.9... 

The P-lactam antibiotic cephalosporin is one of the most important drugs for the treatment of bacterial infections. Recently, several new compounds such as ce-fadroxil (2-161), cephalexin (2-162), cefixime (2-163), and cefzil (2-167) have been isolated, which contain an alkyl or alkenyl substituent instead of an acetoxymethyl group at C-3 (Scheme 2.37 and 2.38) [88]. 

The classification of antibiotics and the most popular antibiotic in its class are given in Table 6. Usually, the antibiotics excreted are partially metabolized and end up in sewage system. Some of the most commonly used antibiotics (e.g., sulfa drugs and p-lactam antibiotics) are difficult to biodegrade because of their complex structure, which protect them from the attack of wastewater biocoenosis. Moreover, the difficulty in biodegradation is also due to the lack of significant microorganism... 

Like with primary amides (see Sect. 4.2.1), bacterial amidases can be useful for the transformation of secondary amides in drug synthesis. Bacterial amidases have been extensively studied in the presence of penicillins and other [i-lactam antibiotics, for which two hydrolysis reactions are possible. One of these is carried out by enzymes known as penicillinases or /3-lactamases that open the /3-lactam ring this aspect will be discussed in Chapt. 5. The second type of hydrolysis involves cleavage of the side-chain amide bond (4.47 to 4.48) and is carried out by an enzyme called penicillinacylase (penicillin amidohydrolase, EC 3.5.1.11). Both types of hydrolysis inactivate the antibiotic [29-31],... 

There have been sustained efforts in recent years to use the carrier systems of the brush-border membrane of intestinal mucosa to increase absorption of orally administered drugs [29] [30]. One system of particular interest is the intestinal peptide carrier (hPEPTl) whose physiological function is the absorption of di- and tripeptides and whose xenobiotic substrates include /3-lactam antibiotics, renin inhibitors, and angiotensin-converting enzyme (ACE) inhibitors [31]. 

Following the sulfa drugs, a second discovery of the greatest importance for infectious bacterial disease was made penicillin. Penicillin is the first of the p-lactam antibiotics, so named because each of these molecules contains a four-membered lactam ring ... 

Other miscellaneous assays for penicillin or other 3-lactams in milk is the Penzyme Test which uses cell wall enzjrmes inhibited by 3-lactam drugs in a kinetic assay. This test system is purported to be able to detect 0.005 units penicillin/mL and requires approximately 30 min to complete. It, like many other assays, detects 3-lactam antibiotics only. 

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