Penicillin-resistant Staphylococcus aureus

The introduction of penicillin G more than 50 years ago was one of the milestones in the treatment of infectious diseases, leading to a drastic reduction in mortality from severe infections (283-285). Two years later the emergence of the first penicillin-resistant Staphylococcus aureus rapidly cooled clinicians enthusiasm. Since then microorganisms have developed various mechanisms to survive antibiotic pressure, including the following ... 

In the laboratory, chelating agents have been used to overcome resistance in bacteria. For example, ethylenediaminetetra-acetic acid (EDTA) restored susceptibility in polymyxin-resistant strains of Pseudomonas, presumably by removing calcium and magnesium from the plasma membrane (Brown and Richards, 1965). EDTA also restored susceptibility to hospital-isolated strains of penicillin-resistant Staphylococcus aureus (Rawal, 1969). Further, oxytetra-... 

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. 

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. 

The class of sugars or carbohydrates that contains one unit of the sugar. It is the simplest class of sugars, e.g. C6Hi2C>6, glucose. Methicillin-resistant Staphylococcus aureus (MRSA). Often called the hospital superbug because it is resistant to most of penicillin treatments. 

A further mode of /S-lactam resistance is due to an alteration in the PBP s structure, resulting in ineffective binding of the antibiotic. Notable examples of this mode of resistance include methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. 

Altered penicillin-binding proteins (PBPs) and methicillin-resistant Staphylococcus aureus... 

Steady-state peak and trough concentrations are chosen for the patient based on the site and severity of the infection, as well as the known or suspected pathogen and avoidance of potential side effects. Cmax.ss values of between 20 and 40 mg/L and C in.ss values of between 5 and 10 mg/L typically are used for patients with moderate to severe methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, or penicillin-resistant enterococcal infections. After appropriate steady-state concentrations are chosen, the dosage interval required to attain those concentrations is computed, and r is rounded to a clinically acceptable value (12, 18, 24, 36, 48, or 72 hours) r = (In Cmax.ss - In Cmin.ss)/ - Finally, the maintenance dose is computed for the patient using a one-compartment-model intravenous bolus equation at steady state, and the dose is rounded off to the nearest 100 to 250 mg ... 

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