Penicillins, bacterial infections

Microbe Penicillin Bacterial infections (/S-lactam antibiotic)... 

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. 

In general, penicillins exert thek biological effect, as do the other -lactams, by inhibiting the synthesis of essential structural components of the bacterial cell wall. These components are absent in mammalian cells so that inhibition of the synthesis of the bacterial cell wall stmcture occurs with Htde or no effect on mammalian cell metaboHsm. Additionally, penicillins tend to be kreversible inhibitors of bacterial cell-wall synthesis and are generally bactericidal at concentrations close to thek bacteriostatic levels. Consequently penicillins have become widely used for the treatment of bacterial infections and are regarded as one of the safest and most efficacious classes of 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. 

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. 

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.. 

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. 

As with all drugs, the specific side effects of the quinolones must be considered when they are chosen for treatment of bacterial infections [5]. Reactions of the gastrointestinal tract and the central neivous system are the most often observed adverse effects during therapy with quinolones. It should be underlined, however, that compared with many other antimicrobials, diarrhea is less frequently observed during quinolone treatment. Antibiotic-associated colitis has been observed rarely during quinolone therapy. Similarly, hypersensitivity reactions, as observed during therapy with penicillins and other (3-lactams, is less frequently caused by quinolones. Some other risks of quinolone therapy have been defined and must be considered if a drug from this class is chosen for treatment of bacterial infections. 

Because the natural penicillins have been used for many years, drug-resistant strains of microorganisms have developed, making the natural penicillins less effective than some of the newer antibiotics in treating a broad range of infections. Bacterial resistance has occurred within tire penicillins. Bacterial resistance is the ability of bacteria to produce substances that inactivate or destroy the penicillin. One example of bacterial resistance is tiie ability of certain bacteria to produce penicillinase, an enzyme that inactivates penicillin. The penicillinase-resistant penicillins were developed to combat this problem. 

The natural and semi ynthetic penicillins are used in tire treatment of bacterial infections due to susceptible microorganisms. Fbnicillins may be used to treat infections such as urinary tract infections, septicemia, meningitis, intra-abdominal infection, gonorrhea, syphilis, pneumonia, and other respiratory infections. Examples of infectious microorganisms (bacteria) that may respond to penicillin therapy include gonococci, staphylococci,... 

The anthrax bioterrorist attacks that followed the events of September 11th 2001 resulted in a renewed interest BadUus anthracis, the causative agent of this disease. Research has focused on the development of better vaccines than the one currently available. It has been estimated that the aerosolized release of 100 kg of anthrax spores upwind of Washington DC would cause mortalities of 130,000-3,000,000 [63]. Nonetheless, wild-type Bacillus anthracis is susceptible to conventional antibiotics, including penicillin, oxyfloxacin and ciprofloxacin. The problem lies not with the bacterial infection itself, but with three proteins released by the bacteria - protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa) and edema factor (EF, 89 kDa) -known as anthrax toxins [63]. 

The answer is d. (Hardman, p 989.) Both trimethoprim-sulfamethoxazole and pentamidine are effective in pneumonia caused by E carinii. This protozoal disease usually occurs in immunodeficient patients, such as those with AIDS. Nifurtimox is effective in trypanosomiasis and metronidazole in amebiasis and leishmaniasis, as well as in anaerobic bacterial infections. Penicillins are not considered drugs of choice for this particular disease state. 

Much information on the mechanism of action and cross-resistance of purine analogues has been obtained in bacteria, some of which are quite sensitive to certain of these compounds in vitro. There is a great deal of variation in response of the various bacteria to a particular agent and of a particular bacterium to the various cytotoxic purine analogues. Some, if not most, of these differences are probably due to differences in the anabolism of the various compounds. Despite the fact that certain purine analogues have quite a spectrum of antibacterial activity in vitro, none has been useful in the treatment of bacterial infections in vivo because their toxicity is not selective—the metabolic events whose blockade is responsible for their antibacterial activity are also blocked in mammalian cells and thus inhibition of bacterial growth can only be attained at the cost of prohibitive host toxicity. In contrast, the sulpha drugs and antibiotics such as penicillin act on metabolic events peculiar to bacteria. 

Mastitis is nearly always caused by bacterial infection. The introduction of benzyl penicillin for the treatment of intramammary infections (IMI) caused by Gram positive bacteria, followed by products containing other antimicrobial agents, was a major advance in... 

Since 1969, the Food and Drug Administration s Center for Veterinary Medicine (formerly the Bureau of Veterinary Medicine) has had cause for concern that the subtherapeutic use of antibiotics in animal feeds may cause bacteria in animals to become resistant to antibiotics. This resistance to antibiotics is said by many knowledgeable scientists to be transferred to bacteria in humans, thus making these antibiotics ineffective in treating human bacterial infections due to compromise of therapy. For this reason, FDA proposed in 1977 to withdraw the use of penicillin in animal feed and restrict the use of the tetracyclines (chlortetracycline and oxytetracycline) to certain uses in animal feed. This talk will focus on FDA s efforts to finalize its review of the issue and present an update on the current status of the 1977 proposals. 

Antibiotics. The history of antibiotics is one of remarkable success in saving lives. Penicillin, although discovered earlier, began to be manufactured for sale as a drug in 1942. Tetracycline followed in 1955 and amoxicillin in 1981. These, other variants developed over the years, and some new recent classes of antibiotics treat bacterial infections by killing the bacteria or preventing them from multiplying. In the process, they save lives and speed recovery. Except for some products sold for external use, antibiotics require a prescription. 

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. 

In the 1860s, Louis Pasteur (1822-1895) confirmed the germ theory of disease with his discovery of bacteria. This led to the discovery of the antiseptic properties of phenol and related compounds, which, as discussed in Chapter 12, could be used to prevent bacterial infection. The first major advance toward curing bacterial diseases was not made until the 1930s, however, when sulfur-containing compounds known as sulfa drugs were developed. Next came penicillin,... 

The development of antibacterial chemotherapy during the past 75 years has spearheaded the successful use of today s drugs to combat bacterial infections. Studies in (3-lactam chemistry were stimulated when (3-lactam ring, the four membered heterocycle, was recognized as a key structural feature as well as a key therapeutic feature of the bicyclic (3-lactam antibiotics such as penicillins, cephalosporins, and other classical antibiotics. The last two decades have registered the discovery of several nonclassical bicyclic (3-lactam antibiotics, e.g., thienamycin and carba-penems of natural origin like olivanic acids, carpetimycin, pluracidomycin, and aspareomycins. 

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