Infections bacterial

Bacterial infections are a significant health risk for populations across the world. Bacteria pose a major treatment challenge because of their tendency to mutate and share mutations with other bacteria. Bacterial resistance to antibiotics is common, and new drugs are continuously being sought to replace those that have become less effective. 

As a class, antibiotics originate largely from natural products isolated from fungi or other bacteria. Consistent with the diversity of bacteria, antibiotics have a broad range of structures and are divided into numerous subclasses. Each division has strengths and weaknesses against various bacteria. Proper treatment of an infection often requires identification of the invading bacteria. 

Chemotherapy agents, such as DNA alkylators (see Chapter 6), have traditionally been administered intravenously because of their high chemical reactivity and low bioavailability. During the past decade, a new class of oral anticancer drug, the tyrosine kinase inhibitors, has been developed. These inhibitors bind membrane-bound tyrosine kinase-linked receptors (TKLR) (see Chapter 5). 

TKLRs have long been recognized as promising anticancer targets, but their breadth of cellular function poses a problem. Unless a specific TKLR can be bound with some 

FIGURE A.12 A prototypical TKLR and three approved drugs for CML 

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Much of the development of the chemistry of sulfanilamidoselenazole derivatives is a result of the important role played by sulfonamides in chemotherapy and more particularly the good activity of sulfathiazoie against bacterial infections. Backer and De Jonge (441 prepared these derivatives by reaction of 2-amino-4-methyl- and 2-aminO-4-phenyl-selenazoles with A -acetylsulfanilic acid chloride in pyridine.. Alkaline... 

Identification of the mechanism by which Pron tosil combats bacterial infections was an early triumph of pharmacology a branch of science at the interface... 

Because of its acidity phenol was known as carbolic acid when Joseph Lister intro duced It as an antiseptic in 1865 to prevent postopera tive bacterial infections that were then a life threatening hazard in even minor surgi cal procedures... 

IL-l radiation/cytotoxic injury bacterial infection rodent... 

NitrofuraZone. 2-[5-Nitro-2-furanyl)methylene]hydrazinecarboximide, the first nitrofiiran to be employed clinically, is prepared from 5-nitro-2-furancarboxaldehyde and semicarbazide (19). This product has seen clinical use topically as an antibacterial, for systemic appHcation for bacterial infections in poultry and swine, and also has been employed as a food additive. In rats, nitrofurazone is hydroxylated at the 4 position of the furan moiety (27). The involvement of nitrenium ions has also been postulated in the mechanism of action of nitrofurazone (38). 

During the most active period of investigation of sulfanilamide derivatives, 1935—1944, for systemic bacterial infections, the antimycobacterial activity of 4,4 -dianainodiphenylsulfone [80-08-8] (DDS, dapsone) was discovered (14). Although neither this compound nor its derivatives proved to be clinically usehil for human tuberculosis, it did evolve into the most important type of compound for leprosy (15). The diacetyl derivative has also... 

P-Lactams. AH 3-lactams are chemically characterized by having a 3-lactam ring. Substmcture groups are the penicillins, cephalosporias, carbapenems, monobactams, nocardicias, and clavulanic acid. Commercially this family is the most important group of antibiotics used to control bacterial infections. The 3-lactams act by inhibition of bacterial cell wall biosynthesis. 

P-lactam antibiotics, exert thek antibacterial effect by interfering with the synthesis of the bacterial cell wall. These antibiotics tend to be "kreversible" inhibitors of cell wall biosynthesis and they are usually bactericidal at concentrations close to thek bacteriostatic levels. Cephalospotins are widely used for treating bacterial infections. They are highly effective antibiotics and have low toxicity. 

Frequendy, the treatment of helminthic diseases requites adjunct medication. Allergic reactions are commonly seen as a result of tissue invasion by worms or as a consequence of anthelmintic therapy. Antihistamines and corticosteroids may be necessary adjuncts to therapy. Anemia, indigestion, and secondary bacterial infections can also occur and may requite concomitant therapy with hematopoietic drugs and appropriate antibiotics. 

The penicillins are a class of compound having the general structure (1). Because of their unique effectiveness in the treatment of bacterial infections in humans, these compounds have been investigated intensively from the chemical, microbiological and clinical points of view since about 1940. The early history of these developments (see especially B-80MI51100, B-49MI51100) contains the following pivotal studies ... 

The importance of the penicillins as a class of heterocyclic compounds derives primarily from their effectiveness in the treatment of bacterial infections in mammals (especially humans). It has been estimated that, in 1980, the worldwide production of antibiotics was 25 000 tons and, of this, approximately 17 000 tons were penicillins (81MI51103). The Food and Drug Administration has estimated that, in 1979 in the U.S.A., 30.1 x 10 prescriptions of penicillin V and 44.3 x 10 prescriptions of ampicillin/amoxicillin were dispensed. This level of usage indicates that, compared to other methods of dealing with bacterial infection, the cost-benefit properties of penicillin therapy are particularly favorable. Stated differently, penicillin treatment leads to the elimination of the pathogen in a relatively high percentage of cases of bacterial infection at a relatively low cost to the patient in terms of toxic reactions and financial resources. 

Respiratory tract (nose and throat) problems Increase in bacterial infection. Resistance to throat, nose, and lung infection is increased, due to the breakdown of the proicctive mechanism,s in the body. 

Just as fflnides are more stable than esters, lactfflns are more stable than lactones. Thus, although p-lactones are rare (Section 19.15), p-lactfflns are fflnong the best known products of the phaiinaceutical industry. The penicillin and cephalosporin antibiotics, which are so useful in treating bacterial infections, are p-lactfflns and are customarily refeired to as (3-lactam antibiotics. 

Recently, a variety of natural peptides that form transmembrane channels have been identified and characterized. Melittin (Figure 10.35) is a bee venom toxin peptide of 26 residues. The cecropins are peptides induced in Hyalophora cecropia (Figure 10.36) and other related silkworms when challenged by bacterial infections. These peptides are thought to form m-helical aggregates in mem-... 

The large importance of the sulfonamides for chemotherapeutics, and specially the high activity of sulfathiazole toward bacterial infections, indicated that sulfonamido derivatives of selenazole should also be investigated. Backer and de Jonge used for this purpose 2-amino-... 

More then a dozen representatives of the above ring systems were introduced into the human therapy. Actisomide (2) and trequinsin (3) are used as antiarrhytmic and antihypertensive agents, respectively. Sunepitron (4), a a 2-adrenoceptor antagonist, is under clinical trials for the treatment of anxiety and depression. Representatives of the third generation of antibacterial quinolone-3-carboxylic acids the blockbluster ofloxacin (5), its levorotatory enantiomer, levofloxacin (6), and rufloxacin (7) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (8) is under development. Praziquantel (9) is widely applied for the treatment of schistosomes- and cestode-caused infection in both veterinary and human therapies (Scheme 4). 

Although the advent of the antibiotics revolutionized the treatment of bacterial infections, tuberculosis has proven unusually resistant to chemotherapeutic attack. Although many antibiotics are effective to some extent in arresting the progress of... 

Cleanliness and good housekeeping in machine shops do much to avoid bacterial infection, and their importance cannot be overstressed. Various techniques such as heat treatment, centrifuging and filtration can be used to advantage, although economic considerations may restrict their use to systems containing large volumes of soluble oil. Chemical sterilization with bactericides can be more convenient. 

Chloramphenicol, a powerful antibiotic isolated in 1949 from the Streptomyces venezuelae bacterium, is active against a broad spectrum of bacterial infections and is particularly valuable against typhoid fever. Assign R,S configurations to the chirality centers in chloramphenicol. 

Penicillin (MM = 356 g/md), an antibiotic often used to treat bacterial infections, is a weak acid. ItsfQis 1.7 X 10-3. Calculate [H+] in solutions prepared by adding enough water to the following to make 725 ml.. 

Chemotherapy is the control and treatment of disease by synthetic drugs. Most of these are organic compounds, often of remarkably simple structure. Sulfanilamide is one example of an organic compound synthesized by chemists for the treatment of bacterial infections. 

The discovery and production of antibiotics has been of tremendous importance to human and animal health care. Prior to their discovery about half a century ago, many bacterial infections caused debilitating diseases and fatalities were high. The discovery of antibiotics was a major step in the treatment of infectious diseases, especially those caused by bacteria. Today about 50,000 tonnes of antibiotics are produced annually. About a third of this consists of penicillins, whilst tetracyclines make up about a quarter of the market. 

Tetracycline and its derivative doxycycline are antibiotics widely used in the treatment of bacterial infections. They also exert an antimalarial activity. Tetracyclines inhibit the binding of aminoacyl-tRNA to the ribosome during protein synthesis. 

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