Bacteria, penicillin-resistant

Promoting Optimal Response to Therapy The results of a culture and sensitivity test take several days because time must be allowed for the bacteria to grow on the culture media However, infections are treated as soon as possible In a few instances, the primary health care provider may determine that a penicillin is the treatment of choice until the results of the culture and sensitivity tests are known. In many instances, the primary health care provider selects a broad-spectrum antibiotic (ie, an antibiotic that is effective against many types or strains of bacteria) for initial treatment because of the many penicillin-resistant strains of microorganisms. 

Kanamycin (a complex of three antibiotics. A, B and C) is active in low concentrations against various Gram-positive (including penicillin-resistant staphylococci) and Gram-negative bacteria. It is a recognized second-line dmg in the treatment of tuberculosis. 

Bacterial resistance to antibiotics has been recognized since the first drugs were introduced for clinical use. The sulphonamides were introduced in 1935 and approximately 10 years later 20% of clinical isolates of Neisseria gonorrhoeae had become resistant. Similar increases in sulphonamide resistance were found in streptococci, coliforms and other bacteria. Penicillin was first used in 1941, when less than 1 % of Staphylococcus aureus strains were resistant to its action. By 1947,3 8% of hospital strains had acquired resistance and currently over 90% of Staph, aureus isolates are resistant to penicillin. Increasing resistance to antibiotics is a consequence of selective pressure, but the actual incidence of resistance varies between different bacterial species. For example, ampicillin resistance inEscherichia coli, presumably under similar selective pressure as Staph, aureus with penicillin, has remained at a level of 30-40% for mai years with a slow rate of increase. Streptococcus pyogenes, another major pathogen, has remained susceptible to penicillin since its introduction, with no reports of resistance in the scientific literature. Equally, it is well recognized that certain bacteria are unaffected by specific antibiotics. In other words, these bacteria have always been antibiotic-resistant. 

The emergence of multidrug-resistant Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci... 

Benzylpenicillin or penicillin G has a narrow antimicrobial spectrum. It is active with respect to Gram-positive bacteria (staphylococcus, streptococcus, and pneumococci), causative agent of diphtheria, and anthrax bacillus. Gram-negative bacteria are resistant to it. Benzylpenicillin is broken down by stomach acid and destroyed by staphylococcus penicillinase. 

It shares with penicillin extremely low toxicity but some danger of allergic reactions. Other semisynthetic penicillins are resistant to P-lactamases, enzymes produced by penicillin-resistant bacteria which cleave the four-membered (i-lactam ring of natural penicillins and inactivate them. 

Several classes of (3-lactamases, often encoded in transmissible plasmids, have spread worldwide rapidly among bacteria, seriously decreasing the effectivenss of penicillins and other (3-lactam anti-biotics.t y Most (3-lactamases (classes A and C) contain an active site serine and are thought to have evolved from the dd transpeptidases, but the B typey has a catalytic Zn2+. The latter, as well as a recently discovered type A enzyme,2 hydrolyze imipenem, currently one of the antibiotics of last resort used to treat infections by penicillin-resistant bacteria. Some (3-lactam antibiotics are also powerful inhibitors of (3-lactamases.U/aa/bb These antibiotics may also have uses in inhibition of serine proteasesCC/dd such as elastase. Some antibiotic-resistant staphylococci produce an extra penicillin-binding protein that protects them from beta lactams.ee Because of antibiotic resistance the isolation of antibiotics from mixed populations of microbes from soil, swamps, and lakes continues. Renewed efforts are being... 

One would think that by now questions about the medicinal efficacy of peyote and mescaline would be settled, but so far there haven t been good controlled studies of comprehensive scope. One constituent in peyote— peyocactin, which is also called hordonine—has been shown by James McCleary and his colleagues at California State University, Fullerton, to be an antibiotic active against a wide spectrum of bacteria, having an inhibitory action against at least eighteen strains of penicillin-resistant Staphylococcus... 

For an example with a four-membered ring, we go back to (3-lactams. A serious problem with [3-lactam antibiotics is that bacteria develop resistance by evolving enzymes called [3-lactamases, which break open the four-membered ring. In 1984, a team from Beechams reported the exciting discovery of some very simple inhibitors of these enzymes all based on the core structure named clavulanic acid. This too was a [3-lactam but a much simpler one than the penicillins we saw earlier. 

Drug inactivation or modification, for example the enzymatic deactivation of penicillin G in some penicillin-resistant bacteria, through the production of -lactamases. 

Thus, unfortunately, bacteria become resistant to drugs and new drugs have to be produced. In the case of penicillin it seems that some bacteria have developed the ability to break down the penicillin molecule by producing an enzyme to do this (penicillinase or P-lactamase). This necessitated the design by chemists of other drugs which were resistant to this enzyme such as flucloxaciUin, or which inhibited it such as clavulanic acid. In time bacteria will become resistant to these too and new drugs again have to be developed. 

Some streptococci have developed a different mechanism of acquired resistance to penicillin drugs. These bacteria have altered transpeptidases (also known as penicillin-binding proteins) that no longer bind penicillin, and thus peptidoglycan synthesis is not disrupted. This mechanism of resistance is found in Streptococcus pneumoniae. Estimates of penicillin-resistant S. pneumoniae in the United States range from 25% to 66%, including strains recovered from ocular and periocular infections. Many isolates of penicillin-resistant S.pneumoniae also are resistant to the cephalosporins, macrolides, and the older fluoroquinolones. Use of alternative antibiotics such as vancomycin is necessary for infections caused by penicillin-resistant isolates. 

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