Common Gram-positive Cocci

In Gram-positive bacteria, resistance to β-lactam antibiotics may be associated either with a decrease in the affinity of PBP (penicillin binding protein) for the antibiotic or with a change in the amount of PBP produced by the bacterium. In S. aureus and E. faecum, additional PBPs may be inducible and those have a lower affinity for β-lactam antibiotics (Opal et al., 2000).

β-lactam antibiotics inhibit bacteria by binding covalently to PBPs in the cytoplasmic membrane. These target proteins catalyze the synthesis of

peptidoglcan that forms the cell wall of bacteria. Alteration of PBPs can lead to β-lactam antibiotic resistance (Malouin anf Bryan, 1986).

2.2.1 Staphylococcus aureus:
Staphylococcus aureus is the leading cause of surgical wound infections and the second most frequent cause of bacteremia in the hospital setting (Boyce, 1997).

Methicillin-resistant S. aureus (MRSA) remains the most prevalent nosocomial pathogen in the United States (Emori and Gaynes, 1993).

Furthermore, the percentage of MRSA among all hospitals in the National Nosocomial Infection Surveillance (NNIS) system rise from 2.1% in 1975 to 29% in 1991 and to 35% in 1996. In New York City and surrounding countries, ~13, 550 patients hospitalized in 1995 had S. aureus infections; MRSA accounted for 29% of these infections and 50% of associated deaths (Roberts et al., 1998).

2.2.2 Coagulase-Negative Staphylococci:
Multi resistant Coagulase-Negative Staphylococci (CoNS) also commonly colonize the skin of hospitalized patients and hospital personnel Archer, (1991). Widespread skin colonization servers as a potential reservoir for multiresistant isolates that can cause infections, particularly infections of in dwelling intravascular devices. In addition, these colonizing
isolates serve as a reservoir for antibiotic resistance genes that can transfer among CoNS and be acquired by S. aureus (McDonnell et al., 1983).

The widespread distribution of vancomycin resistance among enterococci Eliopoulos, (1997) and the detection of vancomycin-resistant S. haemolyticus emphasize the importance of using vancomycin selectively and appropriately (Schwalble et al., 1987).

As with S. aureus, from 80 to 90% of CoNS produce an inducible beta-
lactamase, although the substrate profile and genetic basis for enzyme
production have been little studied (Archer and Scott, 1991).

However, the most important mechanism for resistance to beta- lactams is production of a low affinity penicillin-binding protein, PBP2 a. This resistance, designated methicillin or oxacillin resistance, effectively precludes therapy with any of the currently available beta-lactam antibiotics (Chambers, 1988; Gradelski et al., 2001).

2.2.3 Enterococci:
Recent attention has focused on enterococci not only because of their
increasing role in nosocomial infections but also because of their remarkable and increasing resistance to antimicrobial agents (Jett et al., 1994).

Antimicrbial resistance markers may be either intrinsic (inherent) or acquired. In intrinsic resistance traits are present in all most of the strains
and therefore appears to be chromosomaly encoded. Acquired resistance markers result from rather mutation in existing DNA or acquisition of new
DNA found in plasmid or transposons (Hodel – Christian and Murray, 1992).

Bacterial pathogens have become increasingly resistant to a variety of antibiotics. The high usage level of antimicrobial drugs in hospitals provides an atmosphere in which resistant organisms can flourish. For this reason, Gram-positive cocci have become predominant causes of infection (Hambraeus, 1995).

The pattern of micro-organisms responsible for nosocomial infections has changed over the last few decades Lee and Bishop, (1997). In the1920s,
Streptococcus pyogenes was the most important feared microbes in hospitals. In the 1940s, Staphylococcus aureus had replaced the Streptococci as the dominant cause of hospital acquired infections (HAI). In the early 1960s, strains of methicillin - resistant Staphylococcus aureus (MRSA) appeared. Since then MRSA has been responsible for numerous epidemics in hospitals and is still a major concern in hospital infection control. Gram-negative rods especially E. coli, Pseudomonas spp., Klebsiella spp., and to a lesser extent species of proteus, Enterobacter and other enteric bacteria have always played a prominent role in hospital acquired infections (HAI). The dominance of Gram-positive species is due to the abundant number of currently available antibiotics that affect Gram negative species. Increased use of these antimicrobial agents has encouraged the selection of antibiotic-resistant strains of the offending organisms (Speller and Humphreys, 1998).