Antibiotics Staph, aureus

Polyether antibiotic Staph, aureus ATCC No. 6538P Sarcina lutea 9341 Bacillus sp. E 27859 Bacillus suhtilis 558b Bacillus megaterium 8011 Bacillus sp. TA 27860 Mycobacterium phlei 355 Streptomyces cellulosae 3313 Paecilomyces varioti 26820... 

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. 

Mupirocin is a topical antibiotic that inhibits isoleucyl tRNA synthetase with the subsequent inhibition of protein synthesis. Mupirocin has become a mainstay in the treatment of Staph, aureus infection and colonization during hospital outbreaks, and it is in this organism that acquired resistance has arisen (Gilbart etal. 1993). 

It is a glycopeptide antibiotic and primarily active against gram positive bacteria, strains of Staph, aureus which are resistant to methicillin are inhibited by vancomycin. It is also effective against Strep, viridans, enterococcus, Clostridium dijficile and diphtheroids. 

Staph, aureus is responsible for a variety of skin infections which require therapeutic approaches different from those of streptococcal infections. Staphylococcal cellulitis is indistinguishable clinically from streptococcal cellulitis and responds to flucloxacillin, but generally fails to respond to penicillin owing to penicillinase (P-lactamase) production. Staph, aureus is an important cause of superficial, localized skin sepsis which varies from small pustules to boils and occasionally to a more deeply invasive, suppurative skin abscess known as a carbuncle. Antibiotics are generally not indicated for these conditions. Pustules and boils settle with antiseptic soaps or creams and often discharge spontaneously, whereas carbuncles frequently require surgical drainage. Staph, aureus may also... 

The problem of (3-lactamases became critical in 1960 when the widespread use of penicillin G led to an alarming increase of Staph, aureus infections. These problem strains had gained the lactamase enzyme and had thus gained resistance to the drug. At one point, 80 per cent of all Staph, aureus infections in hospitals were due to virulent, penicillin-resistant strains. Alarmingly, these strains were also resistant to all other available antibiotics. 

In the standard hospital test used here, dry swabs were used. Cells from these were transferred into 5 mL of broth containing 7% sodium chloride and incubated at 30 °C to selectively culture Staph, aureus. After overnight growth, a sub-sample was streaked out onto agar for antibiotic sensitivity testing. 

Up to this point, 30 C static incubation in antibiotic broth had been adopted to better fit in with the standard assay s conditions. In the light of the pre-trial work, this might have not allowed sufficient growth of Staph, aureus from the samples. Optimised growth conditions were therefore adopted with results shown under test set 3 in the Table. 

The intensive studies on the genetic code and on the proteins in recent years have led to a fairly good understanding of the mechanism of protein biosynthesis . The biosynthetic mechanism involved in the formation of peptides has not yet been studied in equal detail. Some physiologically active peptides like bradykinin and angiotensin are known to be derived from proteins by a specific enzymatic hydrolysis. Other peptides, like glutathione - , ophthalmic acid , the nucleotide-pentapeptide from Staph, aureus and y-polyglutamic acid have been shown to require for their synthesis only a soluble enzyme system. Their biosynthetic mechanism is therefore entirely different from that of the proteins. Such a different type of mechanism has also been demonstrated lately to be involved in the synthesis of peptide antibiotics. 

Kimura studied the sensitivity of micro-organisms to antibiotics, panfuran hydrochloride and acetyl panfuran. He used three strains of Staph, aureus, five strains of Shigella Jlexneri, and one strain of E. coli which were isolated from various clinical sources. All strains tested had remained highly sensitive to panfuran hydrochloride and acetylpanfuran but the sensitivity to antibiotics was markedly decreased. 

The sensitivity of the organisms to nitrofurantoin and five other antibiotics and chemotherapeutic agents was compared and, except for the greater sensitivity of Proteus to nalidixic acid, none of the test compounds surpassed the results achieved with nitrofurantoin. An interesting study by King proved that cultures of E. coli and Staph, aureus taken at the Cleveland Clinic in the U.S. between 1956 and 1961 showed increased sensitivity to nitrofurantoin but increased resistance to dihydrostreptomycin, chloramphenicol and neomycin. 

In an early report [48], it was stated that novobiocin inhibits the synthesis of the bacterial cytoplasmic membrane, as it decreased the crypticity of E. coli strain ML 35 and caused a loss of ribonucleic acid (RNA) into the surrounding medium. These effects were not induced in resting cells and indicated that the antibiotic interfered with the synthesis of new membrane material. Another early investigation had shown that novobiocin induced the loss of 260 nm absorbing material from washed suspensions of Staph, aureus [64]. 

A number of workers have shown that novobiocin inhibits protein synthesis in bacteria. For example, it inhibits /S-galactosidase synthesis in both Staph, aureus and E. coli [48, 64]. Although M-protein synthesis in a Group A streptococcus is not inhibited by novobiocin [70], the inhibition of protein synthesis in Strept. faecium has been attributed to the inhibition of tRNA synthesis [23]. Novobiocin inhibits protein synthesis in Staph, aureus [26], but as the inhibition of other macro-molecules also occurs to a similar extent, this effect may not be the primary action of the antibiotic. The antibiotic also inhibits protein synthesis in E. coli [33, 71] but this inhibition appears much later than the observed inhibition of deoxyribonucleic acid (DNA) synthesis. 

Earlier studies [48, 74] had shown that novobiocin induced a decrease in the DNA content of E. coli cells, but this was not regarded as being of primary importance. Wishnow, Strominger, Birge and Threnn [26] subsequently reported that novobiocin strongly inhibited the incorporation into Staph, aureus of radioactive lysine and of inorganic phosphate into nucleic acid, but the inhibition of inorganic phosphate also occurred in other macromolecular fractions of the cell, and the primary effect of the antibiotic was not defined. 

Nalidixic acid 4.33) binds heavy metals between the carboxylic- and the oxo-groups (Crumplin, Midgley and Smith, 1980). It is not known if this plays a part in its biological action, which is inhibition of the synthesis of DNA (Section 4.0.5, p. 136). The antibacterial action of kojic acid (77./7), a pyrone extracted from certain fungi, is enhanced by metallic cations (Weinberg, 1957). Bacitracin, a polypeptide antibiotic (Section 13.2), loses its antibacterial action against Staph, aureus in the presence of EDTA the action is restored by bivalent cations (Adler and Snoke, 1962). 

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