Methicillin-resistant penicillin

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. 

It is important to determine (1) whether the isolate is methicillin-susceptible or methicillin-resistant and (2) whether the patient has a prosthetic valve. For patients with no prosthetic material, methicillin-susceptible staphylococci treatment should consist of a penicillinase-resistant penicillin (e.g., nafcillin or oxacillin) with or without gentamicin, and for methicillin-resistant strains, therapy should consist of vancomycin (see Table 71-4). Combination therapy with aminoglycosides, when used in these patients, typically is given only during the first 3 to 5 days of therapy. In the absence of prosthetic material, some treatment guidelines do not recommend combination therapy against MRSA. However, many clinicians may combine either gentamicin or rifampin with vancomycin if the patient is unresponsive to monotherapy. 

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

In penicillin-allergic patients, oral or parenteral clindamycin may be used. Alternatively, a first-generation cephalosporin such as cefazolin (1 to 2 g IV every 6 to 8 hours) may be used cautiously for patients who have not experienced immediate or anaphylactic penicillin reactions and are penicillin skin test negative. In severe cases in which cephalosporins cannot be used because of documented methicillin resistance or severe allergic reactions to /1-lactam antibiotics, IV vancomycin should be administered. 

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. 

Severe staphylococcal Infections - Severe staphylococcal infections (including methicillin-resistant staphylococci) in patients who cannot receive or who have failed to respond to penicillins and cephalosporins, or who have infections with resistant staphylococci. Infections may include endocarditis, bone infections, lower respiratory tract infections, septicemia, and skin and skin structure infections. 

Nafcillin, oxacillin, cloxacillin, and dicloxacillin are more resistant to bacterial (3-lactamases than is penicillin G. Consequently, these antibiotics are effective against streptococci and most community-acquired penicillinase-producing staphylococci. Methicillin, which is no longer marketed in the United States, is another penicillinase-resistant antibiotic similar to nafcillin and oxacillin. For historical reasons, staphylococci resistant to oxacillin or nafcillin are labeled methicillin resistant. Many hospitals are reservoirs for MRSA and methi-cillin-resistant Staphylococcus epidermidis (MRSE). These nosocomial pathogens are resistant in vitro to all (3-lactam antibiotics. 

Altered target PBPs are the basis of methicillin resistance in staphylococci and of penicillin resistance in pneumococci and enterococci. These resistant... 

These semisynthetic penicillins are indicated for infection by 3-lactamase-producing staphylococci, although penicillin-susceptible strains of streptococci and pneumococci are also susceptible. Listeria, enterococci, and methicillin-resistant strains of staphylococci are resistant. In recent years the empirical use of these drugs has decreased substantially given increasing rates of methicillin-resistance in staphylococci. However, for infections caused by methicillin-susceptible strains of staphylococci these are considered the drugs of choice. 

Penicillins have been used in veterinary medicine for more than 30 years and still constimte the most important group of antibiotics. They can be classified in three distinct groups. The group of the natural penicillins includes penicillin G and penicillin V the group of the penicillinase-resistant penicillins includes methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and mecillinam the group of the broad-spectrum penicillins includes ampicillin, amoxicillin, and heta-cillin (Fig. 3.3.1)... 

Penicillin G [Bicillin, Wycillin, many others] Penicillin V [Beepen-VK, V-Cillin K, others] Penicillinase-resistant penicillins Cloxacillin [Cloxapen, Tegopen] Dicloxacillin [Dycill, Dynapen, Pathocil] Methicillin [Staphcillin]... 

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. 

---