easier to treat. Infections at other body sites are difficult to document, because VRE isolated
from other sites frequently represent colonization and not infection (32,33).
METHICILLIN-RESISTANTS. AUREUS
Types of MRSA
HA-MRSA
HA-MRSA first appeared in the United States in 1968 (2). It has spread across the country over
the last three-and-a-half decades by lateral transfer among hospital patients, by transfer of
patients between hospitals, and between hospitals and long-term care facilities. Most
circulating strains of HA-MRSA appear to have originated from two or three clones of
MRSA (34,35).
Methicillin resistance and resistance to allb-lactam antibiotics are conferred by the
staphylococcal cassette chromosomemec(SCCmec), which carries themecAgene that encodes a
protein designated “penicillin-binding protein 2a” or “penicillin-binding protein 2^0 .” These
altered penicillin-binding proteins bind b-lactam antibiotics poorly, permitting cell wall
synthesis to continue in the presence of these antimicrobial agents.
There are three types of SCCmecin HA-MRSA: types I, II and III (4,36). Type I contains no
additional resistance determinants, but types II and III contain resistance determinants in
addition tomecA; these additional genetic elements account for the antimicrobial resistance to
many antibiotics in addition to theb-lactam agents. The three SCCmectypes contained in HA-
MRSA have an identical chromosomal integration site and cassette chromosome recombinase
genes, which are responsible for horizontal transfer of SCCmec(4). Thus, HA-MRSA are
resistant to many antibiotics and have a selective advantage as they are spread among patients
by the hands of personnel and contaminated environmental surfaces. The presence of
underlying diseases and multiple types of instrumentation and procedures predisposes
patients to colonization and infection by the multiply resistant strains of HA-MRSA.
CA-MRSA.CA-MRSA have appeared gradually over about the last 15 years. Early on there
was uncertainty about the origin of CA-MRSA, and it was unclear whether CA-MRSA were
different from HA-MRSA. Some investigators believed that most of the CA-MRSA infections
could be traced back to some previous contact with the health care system. More recently, it has
become clear that these infections occur in young healthy persons with no recent health care
contacts and no risk factors for HA-MRSA. It has also become clear that CA-MRSA have evolved
in the community through an evolutionary pathway entirely separate from HA-MRSA.
It appears that all four of the SCCmectypes have risen fromStaphylococcus sciuri, the most
ubiquitous and ancient species ofStaphylococcus(37). Because of their large size, SCCmectypes I,
II, and III have rarely been transferred to the cells of methicillin-susceptibleS. aureus(MSSA).
On the contrary, CA-MRSA has an SCCmectype IV that is small enough to be transferred
between cells by transduction or phage-mediated transformation (37). There is some evidence
that transfer of type IV SCCmecfrom CA-MRSA to MSSA can occur (38).
Given that many infections caused by CA-MRSA are treated in hospitals and other health
care facilities, there must be some concern that this pathogen may become another type of
MRSA in hospitals. In addition to infections, it is likely that patients admitted to hospitals for a
variety of indications will be colonized with CA-MRSA.
In addition to adding to the burden of MRSA in the hospital, CA-MRSA appear to be more
virulent than HA-MRSA. The MW2 strain of CA-MRSA, a common strain in the United States,
has 18 toxins that were not found in five comparativeS. aureusgenomes (39). The majority of CA-
MRSA contain the genetic element for the Panton–Valentine leukocidin. This toxin has been
associated with necrotizing pneumonia in healthy children (6). The MW2 strain of CA-MRSA
contains genes for 11 exotoxins and four enterotoxins. All of these toxins are super-antigens (39).
CA-MRSA may also contain genes for exfoliative toxins and for hemolysins (40).
CA-MRSA most commonly cause skin and soft tissue infections in persons with no risk
factors for HA-MRSA. However, they may cause severe disease, and hospital patients may be
at particularly high risk for serious disease. It is very important that infection control programs
be on guard for ingress of CA-MRSA into hospitals, and this is particularly true for ICUs.
MRSA/VRE Colonization and Infection in the Critical Care Unit 103