Staphylococcus (page 5)
© Kenneth Todar, PhD
Pathogenic Staphylococcus epidermidis
In contrast to S. aureus, little is known about mechanisms of
pathogenesis of S. epidermidis infections. Adherence is obviously a crucial
step in the initiation of foreign body infections. Bacteria-plastic
interactions are probably important in colonization of catheters, and a
polysaccharide adhesion (PS/A) has been identified. In addition, when host proteins
deposit on the implanted device S. epidermidis will bind to
fibronectin.
A characteristic of many pathogenic strains of
S. epidermidis is the production of a slime resulting in biofilm formation.
The slime is predominantly a secreted teichoic acid, normally found in the cell
wall of the staphylococci. This ability to form a biofilm on the surface of
a prosthetic device is probably a significant determinant of virulence
for these bacteria.
Resistance of Staphylococci to Antimicrobial Drugs
Hospital strains of S. aureus are usually resistant to a
variety of different antibiotics. A few strains are resistant to all clinically
useful antibiotics except vancomycin, and vancomycin-resistant strains
are increasingly-reported. The term MRSA refers to Methicillin
resistant Staphylococcus aureus. Methicillin resistance is
widespread and most methicillin-resistant strains are also multiply drug-resistant. A
plasmid associated with vancomycin resistance has been detected in Enterococcus
faecalis which can be transferred to S. aureus in the laboratory, and it
is speculated that this transfer may occur naturally (e.g. in the gastrointestinal
tract). In addition, S. aureus exhibits resistance to antiseptics
and disinfectants, such as quaternary ammonium compounds, which may aid its survival
in the hospital environment.
Staphylococcal disease has been a perennial problem in the hospital
environment since the beginning of the antibiotic era. During the 1950's
and early 1960's, staphylococcal infection was synonymous with
nosocomial infection. Gram-negative bacilli (e.g. E. coli and Pseudomonas
aeruginosa) have replaced staph as the most frequent
causes of nosocomial infections, although the staphylococci have remained a
problem, especially in surgical wounds. S aureus responded to the introduction
of antibiotics by the usual bacterial means to develop drug resistance:
(1) mutation in chromosomal genes followed by selection of resistant
strains and (2) acquisition of resistance genes as extrachromosomal plasmids,
transducing particles, transposons, or other types of DNA inserts. S. aureus
expresses its resistance to drugs and antibiotics through a variety of
mechanisms.
Beginning with the use of the penicillin in the 1940's, drug
resistance has developed in the staphylococci within a very short time after
introduction of an antibiotic into clinical use. Some strains are now resistant to
most conventional antibiotics, and there is concern that new antibiotics
have not been forthcoming. New strategies in the pharmaceutical industry to
find antimicrobial drugs involve identifying potential molecular
targets in cells (such as the active sites of enzymes involved in cell division),
then developing inhibitors of the specific target molecule. Hopefully,
this approach will turn up new antimicrobial agents for the battle
against staph infections. Indeed, since 2003, alternatives
to vancomycin have been approved for treatment of MRSA.
MRSA
MRSA are strains of the Staphylococcus aureus that are resistant to the action
of methicillin and related beta-lactam antibiotics (e.g. penicillin,
oxacillin, amoxacillin). MRSA have evolved resistance not only to
beta-lactam antibiotics, but to several classes of antibiotics. Some
MRSA are resistant to all but one or two antibiotics, including
vancomycin. Reports of VRSA (Vancomycin-Resistant Staph aureus) or VRSA
are troublesome in the ongoing battle against staph infections.
Methicillin-Resistant Staphylococcus aureus
MRSA are often sub-categorized as Hospital-Associated MRSA (HA-MRSA) or
Community-Associated MRSA (CA-MRSA), depending upon the circumstances
of acquiring disease. Based on current data, these are distinct strains
of the bacterial species.
HA-MRSA occurs most frequently among patients who undergo invasive
medical procedures or who have weakened immune systems and are being
treated in hospitals and healthcare facilities such as nursing homes
and dialysis centers. MRSA in healthcare settings commonly causes
serious and potentially life threatening infections, such as
bloodstream infections, surgical site infections or pneumonia.
In the case of HA-MRSA, patients who already have an MRSA infection or
who carry the bacteria on their bodies but do not have symptoms (are
colonized) are the most common sources of transmission. The main mode
of transmission to other patients is through human hands, especially
healthcare workers' hands. Hands may become contaminated with MRSA
bacteria by contact with infected or colonized patients. If appropriate
hand hygiene such as washing with soap and water or using an
alcohol-based hand sanitizer is not performed, the bacteria can be
spread when the healthcare worker touches other patients.
MRSA infections that occur in otherwise healthy people who have not
been recently (within the past year) hospitalized or had a medical
procedure (such as dialysis, surgery, catheters) are categorized as
community-associated (CA-MRSA) infections. These infections are usually
skin infections, such as abscesses, boils, and other pus-filled lesions.
About 75 percent of CA-MRSA infections are localized to skin and
soft tissue and usually can be treated effectively. However, CA-MRSA
strains display enhanced virulence, spread more rapidly and cause more
severe illness than traditional HA-MRSA infections, and can
affect vital organs leading to widespread infection (sepsis), toxic
shock syndrome and pneumonia. It is not known why some healthy people
develop CA-MRSA skin infections that are treatable whereas others
infected with the same strain develop severe, fatal infections.
Studies have shown that rates of CA-MRSA infection are growing fast. In
1999, four children in Minnesota and North Dakota were reported to have
died from fulminant CA-MRSA infections One study of children in south
Texas found that cases of CA-MRSA increased 14-fold between
1999 and 2001. By 2007, CA-MRSA was the most frequent cause of skin and
soft-tissue infections seen in emergency departments in the United
States.
Although most MRSA cases are skin and soft-tissue infections, some are
more serious with septicemia and pneumonia. It was reported in
2005 that previously healthy adolescents without any predisposing risk
factors presented more frequently with severe Staph infections (mostly
the USA 300 strain) since 2002.
CA-MRSA skin infections have been identified among certain populations
that share close quarters or experience more skin-to-skin contact.
Examples are team athletes, military recruits, and prisoners. However,
more and more, CA-MRSA infections are being seen in the general
community as well, especially in certain geographic regions.
Also, CA-MRSA are infecting much younger people. In a study of
Minnesotans published in The Journal of the American Medical
Association, the average age of people with MRSA in a hospital or
healthcare facility was 68. But the average age of a person with
CA-MRSA was only 23.
In the United States it is estimated that 31.8 out of 100,000 people are being infected by MRSA each year, more infections than meningitis, bacterial pneumonia and flesh-eating strep put together. More people in the U.S. now die from MRSA infection than from AIDS. Methicillin-resistant Staphylococcus aureus was responsible for an estimated 94,000 life-threatening infections and 18,650 deaths in 2005, as reported by CDC in the Oct. 17, 2007 issue of The Journal of the American Medical Association. The national estimate is more than double the invasive MRSA prevalence reported five years earlier. That same year, roughly 16,000 people in the U.S. died from AIDS, according to CDC.
While most invasive MRSA infections could be traced to a hospital stay or some other health care exposure, about 15% of invasive infections occurred in people with no known health care risk. Two-thirds of the 85% of MRSA infections that could be traced to hospital stays or other health care exposures occurred among people who were no longer hospitalized. People over age 65 were four times more likely than the general population to get an MRSA infection. Incidence rates among blacks were twice that of the general population, and rates were lowest among children over the age of 4 and teens.
MRSA Statistics
In 2010, encouraging results from a CDC study published in the Journal of the American Medical Association showed that invasive (life-threatening) MRSA infections in healthcare settings are declining. Invasive MRSA infections that began in hospitals declined 28% from 2005 through 2008. Decreases in infection rates were even bigger for patients with bloodstream infections. In addition, the study showed a 17% drop in invasive MRSA infections that were diagnosed before hospital admissions (community onset) in people with recent exposures to healthcare settings.
A parallel study from the National Healthcare Safety Network (NHSN) found that rates of MRSA bloodstream infections occurring in hospitalized patients fell nearly 50% from 1997 to 2007. Furthermore, a March 2011, CDC Vital Signs article reported that bloodstream infections from staph in ICU patients with central lines were reduced by 73%, more than from any other cause.
Taken altogether these reports provide evidence that rates of invasive MRSA infections in the United States are falling. While MRSA remains an important public health problem and more remains to be done to further decrease risks of developing these infections, this decrease in healthcare-associated MRSA infections is encouraging.
On the other hand, rates of CA-MRSA infections have increased rapidly during the past decade and there is little evidence that the risk of developing infection is following the same downward trend as HA-MRSA.
chapter continued
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