Staphylococcus aureus, penicillin resistance

The phenomenon of bacterial resistance to antibiotics was already known by the pioneers of the era of antibiotics, like Paul Ehrlich, who coined the term selective toxicity as the basic principle of antimicrobial therapeutics, as well as Gerhard Domagk, the inventor of the sulfonamide drugs, and Sir Alexander Fleming, the discoverer of the penicillins. When penicillin G was introduced into clinical practice in 1944, as many as 5% of the isolates of Staphylococcus aureus were resistant to penicillin, while 5 years later the percentage was 50%. 

Staphylococcus aures (penicillin-sensitive) Staphyloccocus aureus (penicillin-resistant) Streptococcus pyogenes Streptococcus pneumoniae Enterococcus faecalis ... 

In this way Staphylococcus aureus becomes resistant to penicillin in the clinic. Penicillin-resistant strains isolated from patients secrete the enzyme p-lactamase ( penicillinase ). This enzyme hydrolyses the drug to penicil-loic acid, which is biologically inert (see Section 12.i). Penicillinase-producing staphylococci are inherently quite sensitive to penicillin. Hence small inocula can be inhibited by low concentrations of the antibiotic. It is, in effect, a race between the speed with which penicillin can kill the bacteria and the speed with which they can produce enough of the enzyme to destroy the penicillin (Knox, 1962). Actually penicillin can be made to induce some strains of Staph, aureus to produce penicillinase. No permanently resistant population of this bacterium has arisen in this way, and the organisms return fairly rapidly to the uninduced susceptible state when the penicillin is withdrawn. Much of the detail of penicillinase-induction was first worked out in Bacillus cereus (Pollock and Ferret, 1951). 

Staphylococcus aureus cells can acquire large DNA fragments containing the mecA gene which encodes a complete new penicillin binding protein 2A (PBP 2A), as part of a transposon. PBP2A can substitute the natural set of penicillin-sensitive PBPs thereby mediating a complete cross resistance to all (3-lactam antibiotics. 

Methicillin-resistent staphylococci are strains of staphylococci, which show resistance to a wide variety of antibiotics. They are named for their resistance to methicillin, a (3 -lactamase-resistant penicillin. Methicil-lin-resistante Staphylococcus aureus (MRSA) has become a serious problem particularly in hospitals. 

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. 

Streptococcus pneumoniae Penicillin susceptible Penicillin intermediate Penicillin resistant Group B Streptococcus Staphylococcus aureus Methicillin susceptible Methicillin resistant Staphylococcus epidermidis Listeria monocytogenes... 

If Staphylococcus aureus is suspected, a penicillinase-resistant penicillin or first-generation cephalosporin should be used. 

Joint replacement S. aureus, S. epidermidis Cefazolin 1 gx 1 preoperatively, then every 8 hours x 2 more doses Vancomycin reserved for penicillin-allergic patients or where institutional prevalence of methicillin-resistant Staphylococcus aureus warrants use IA... 

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

The bacterium Staphylococcus aureus, which is a major cause of infection in the developed countries, is now resistant to most antibiotics. It is usually present on the skin, where it causes no problems, but it can invade the body through cuts and wounds, including those caused by surgery. These bacteria are now prevalent in many hospitals, so that infection is a major problem for the medical staff in hospitals. The resistant bacterium is known as methicillin-resistant Staphylococcus aureus (MRSA). It is also known in the mass media as the super bug . Penicillin kiUs bacteria because the P-lactam group in the antibiotic inhibits a reaction that is essential for bacterial ceU wall production. Consequently, the bacteria cannot proliferate. Resistance to penicillin in many bacteria is due to production of an enzyme, p-lactamase, that degrades P-lactams. The antibiotic methicillin is one of a group of semisynthetic penicillins in which the P-lactam group is not... 

An additional disadvantage with many penicillin and cephalosporin antibiotics is that bacteria have developed resistance to the drugs by producing enzymes capable of hydrolysing the P-lactam ring these enzymes are called P-lactamases. This type of resistance still poses serious problems. Indeed, methicillin is no longer used, and antibiotic-resistant strains of the most common infective bacterium Staphylococcus aureus are commonly referred to as MRSA (methicillin-resistant Staphylococcus aureus). The action of P-lactamase enzymes resembles simple base hydrolysis of an amide. 

A senior British government veterinarian stated in 1962 (3)> When penicillin was first used in treating mastitis only 2% of the strains of staphylococci recovered from cases of mastitis were resistant to penicillin. Today the figure is over 70%. Between 1958 and 1961, resistance to penicillin (PEN) increased from 62.0% to 70.6%. Resistance to streptomycin (STR), tetracycline and chloramphenicol also increased (. Antibiotic resistance increased for isolates of both mastitis staphylococci and streptococci in Canada between I960 and 1967 (5). In Belgium (6), Staphylococcus aureus strains isolated from cases of bovine mastitis showed increase in PEN resistance from 38% in 1971 to 78% in 1974> but then no further increase to 1980. The resistance situation was reported to remain stable in the Federal Republic of Germany between 1962 and 1975 (7), as also in Australia between 1974 and 1979 (8 ) and Denmark, at a very low level, for the period 1963 to 1978 (9). 

Levofloxacin (1), the levo-isomer or the (5)-enantiomer of ofloxacin, received FDA approval in 1996 (Fish, 2003 Hurst et al., 2002 Mascaretti, 2003 Norrby, 1999 North et al., 1998). The initial approval covered community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, uncomplicated skin and skin structure infections, acute pyelonephritis, and complicated urinary tract infections (North et al., 1998). Four years later, the levofloxacin indication list grew to include community-acquired pneumonia caused by penicillin-resistant Streptococcus pneumoniae. In addition, in 2002, nosocomial (hospital-acquired) pneumonia caused by methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Kliebsella pneumoniae, and Escherichia coli was added (Hurst et al., 2002). Finally in 2004, LVX was approved as a post-exposure treatment for individuals exposed to Bacillus anthracis, the microbe that causes anthrax, via inhalation (FDA, 2004). 

Some organisms, such as Staphylococcus aureus, Neisseria gonorrhoeae, and Haemophilus influenzae, may produce -lactamase and therefore be resistant to penicillin and its congeners. Testing for 3-lactamase production by isolates enables an early decision on the use of penicillin and congeners in treatment of the disease. 

Nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), or Streptococcus pneumoniae (penicillin-susceptible strains only). 

Staphylococcus aureus - [ANTIBIOTICS - BETA-LACTAMS - CEPHALOSPORINS] (Vol 3) - [DISINFECTANTS AND ANTISEPTICS] (Vol 8) - [ANTIBIOTICS - BETA-LACTAMS - BETA-LACTAMASE INHIBITORS] (Vol 3) - [ANTIBIOTICS - LINCOSAMINIDES] (Vol3) - [ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTHERS] (Vol 3) - [ANTIBIOTICS-AMINOGLYCOSIDES] (Vol2) - [ANTIBIOTICS - GLYCOPEPTIDES(DALBAHEPTIDES)] (Vol 2) -bacitracin resistance [ANTIBIOTICS - PEPTIDES] (Vol 3) -ethanol activity against [DISINFECTANTS AND ANTISEPTICS] (Vol 8) -inhibited by sorbates [SORBIC ACID] (Vol 22)... 

Staphylococcus aureus Abscesses bacteremia cellulitis endocarditis osteomyelitis pneumonia others If methicillin-sensitive nafcillin or oxacillin If methicillin-resistant vancomycin gentamicin or rifampin 1 st-generation cephalosporin clindamycin erythromycin trimethoprim-sulfamethoxazole a penicillin + a penicillinase inhibitor... 

LJ Frank, D Wisniewski, GG Hammond, J Hermes, A Marcy, PM Cameron. High-yield expression, refolding, and purification of penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus strain 27R. Prot Expr Purif 6 671-678, 1995. 

WP Lu, Y Sun, MD Bauer, S Paule, PM Koenigs, WG Kraft. Penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus, kinetic characteriza-... 

S Roychoudhury, JE Dotzlaf, S Ghag, WK Yeh. Purification, properties, and kinetics of enzymatic acylation with (3-lactams of soluble penicillin-binding protein 2a a major factor in methicillin-resistant Staphylococcus aureus. J Biol Chem 269 12067-12073, 1994. 

CYE Wu, J Hoskins, LC Blaszczak, DA Preston, PL Skatrud. Construction of a water-soluble form of penicillin-binding protein 2a from a methicillin-resistant Staphylococcus aureus isolate. Antimicrob Agents Chemother 36 533-539, 1992. 

CR Harrington, DM O Hara, PE Reynolds. Characterization of a monoclonal antibody and its use in the immunoaffinity purification of penicillin-binding protein 2 of methicillin-resistant Staphylococcus aureus. FEMS Microbiol Lett 53 143-147, 1989. 

S Roychoudhury, RE Kaiser, DN Brems, WK Yeh. Specific interaction between (3-lactams and soluble penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus development of a chromogenic assay. Antimicrob Agent Chemother 40 2075-2079, 1996. 

Staphylococcus aureus can cause serious blood poisoning when it enters a wound. It once was easily treated with penicillin, but the organism has now mutated to the point where it is totally resistant to penicillin. The next defense on the antibiotic ladder has been methicillin, but methicillin-resistant strains have become increasingly com-... 

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