Methicillin Resistant Staphylococcus Aureus Biology Essay


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Staphylococcus aureus is a bacterium that is very common in the environment and is a frequent cause of infections(1). The name of the organism is derived from Latin and means "golden cluster seed." Staph. aureus is round, and usually lives in colonies the shape of grape-like clusters (12). It is frequently found in the nostrils and on the skin of normal, healthy humans, usually not causing any disease. However, it does have the potential to invade the human body and cause a variety of infections, from minor ones like acne, cellulitis (infections of the upper layers of the skin) and furuncles (infections of hair follicles), to more serious and at times life threatening ones like pneumonia, endocarditis (infection of the inner layer of the heart and heart valves), bacteremia (blood infection), osteomyelitis (infection of the bone), etc. (1,12). These bacteria area also known to produce several types of toxins, which contribute to the oragnism's pathogenicity.

Methicillin-resistant Staphylococcus aureus, or MRSA, is a subtype of this bacterium that has become resistant to a large variety of antibiotics, rendering it a more difficult to treat, and as a result often leading to more serious, potentially deadly infection. Although recently popularized by the media as the new "superbug," MRSA actually emerged and has been described in literature as early as the early 1960s, very soon after methcillin was developed, and its use in the treatment of staphylococcal infections was initiated (8). Methicillin resistance is mediated by a penicillin binding protein that permits the organism to grow and divide in the presence of methicillin and other similar antibiotics, limiting the treatment options significantly (8).

MRSA is an infection which can affect patients in health care facilities such as hospitals, nursing homes, and urgent care centers. It is an infection that has spread throughout the country and worldwide, passing disease to more and more individuals and even animals. The numbers speak for themselves - According to the Centers for Disease Control and Prevention (CDC) the incidence of MRSA infection among all staph infections reported in the US was only 2% in 1974, in 1995 was 22%, whereas in 2004 that number reached 63% (4). The word-wide incidence of MRSA among staph infections is quite variable and depends on the region in question, with 1 percent noted in Scandinavia to up to 40 percent in Japan, Israel and elsewhere in Europe (10). This is an important statistic considering the fact that morbidity and mortality for MRSA infections are very high, and the number of deaths resulting from this infection is constantly growing. Accordingly to one article, 20 thousands deaths occur in the United States that can be directly linked to MRSA infections, and another 63 thousand are related to other types of hospital acquired infections (9). Moreover, sepsis and pneumonia are two common conditions caused by HA-MRSA which in 2006 took lives of 48,000 Americans (9).

Recalling previous discussion, this infection mostly affects patients in health care institutions and agencies, and if acquired in that setting, is termed hospital-associated MRSA (HA-MRSA). "Approximately 85% of all invasive MRSA infections are associated with health care" (4), which poses a significant risk to all patients who present there for treatment. While is true that HA-MRSA can effect and cause infection to anybody in the hospital, individuals with suppressed immune system, are at the highest risk of acquiring it (6). HA-MRSA is identified as a multidrug resistant invasive disease, its unique resistance to certain antibiotics is carried on staphylococcal cassette chromosome type II (SCCmec typeII). Predominant health care-associated strains are typified as USA100, USA200, USA500, USA600, and USA800 (11).

Unfortunately, a new strain of MRSA which is called CA-MRSA, (community-associated MRSA) has emerged raising new concerns for the public. It is a community-born infection that spreads mostly in the outpatient areas, and causes infections among healthy people in places often occupied by people, for example athletic settings. "Students, trainers or anyone are at risk to get infected because of the shared clothing, sports equipment, towels, balms, razors and soaps, improper care of skin trauma, direct skin-to-skin contact with MRSA lesions, artificial turf burns" (4). CA-MRSA strains are unlike the HA-MRSA in that they "have diverse lineages as they are frequently enriched with genes encoding SCCmec IV, PVL and other exotoxins" (2). Furthermore, strains of CA-MRSA in the USA differ from those in Europe. In the USA we have ST8, ST5,and ST59, whereas in Europe leading strands are ST80,ST8 and ST30 (2).

According to Laxminarayan (9), the numbers of people who are infected with a CA-MRSA have been escalating for the past few years. This would suggest that we are dealing with an epidemic, mainly in the outpatient units of the hospital. Considering the fact that doctors, nurses and other hospital staff move a lot between outpatient and inpatient units, this rise of CA-MRSA poses a great threat to everybody, particularly to hospitalized patients. After completing his study, Laxminarayan was able to conclude that CA-MRSA is responsible for more than 50 percent of all "staph" infections (9). Therefore, the overall increase of MRSA infections in the hospitals was in part due to an outbreak of this new strain. Even though CA-MRSA is consider less virulent and responds better to antibiotics, it can still produce a great harm to the patients. Even though CA-MRSA generally infects children, adults are also at risk to get infected, and the numbers infected in that patient population have been on the rise (2).

Thus, the question must be raised "How this everything started, and how genetic mechanisms are responsible for methicilin resistance?" In 1959, shortly after methicillin was introduced the three pandemic MRSA clones were found in Denmark and England (8). After some investigating, it was found that in order for bacteria to acquire methicillin resistance it has to have the mec gene (8). Without this gene the bacteria are vulnerable to penicillin and other similar antibiotics, i.e. they are methcillin-susceptible Staphylococcus aureus (8).

The mec gene is one part of the mec operon, part which is a functioning part of the staphylococcoal cassette chromosome mec (SCCmec) (8). One modality of confering resistance is via the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins and carbapenems) than the normal protein present is methicillin sensitive strains (8). The mec gene also consists of two regulatory components that control expression of the gene. One of them is mecR1-mecI, which is a negative regulator of mecA transcription (8). Due to negative regulation, which is not tightly controlled, the expression of resistance following exposure to beta-latams is comparatively rapid. The other regulatory components are the beta-lactamase genes blaI, blaRI, and blaZ (8). They have similar sequence to the mecR1-mecI genes, so they can also down regulate mecA gene transcription, but in addition to that, beta-lactamase protein encoded by these genes hydrolyzes the beta-lactam ring, rendering it ineffective (8). Another significant defense mechanism is the penicillin binding protein located in the membrane of the bacterium, responsible for catalyzing the traspeptidation reaction of peptidoglycan during cell wall synthesis (8).

As mentioned earlier, the mec gene is located on staphylococcal cassette chromosome (SCCmec), and in MRSA strains at least six SCCmec types(I-VI) have been observed, each having a unique genetic makeup and size (8). SCCmec types I, II, and III are multidrug resistant and associated with the majority of healthcare-associated MRSA clones, whereas community-associated MRSA clones are linked with SCCmec type IV, and sometimes V(8).

Long and carful studies allowed Franklin D Lowy, MD to be able to further describe the pathogenesis of MRSA. In many CA-MRSA strains with SCCmec type IV and V consist genes lukS-PV and lukF-PV, known together as a lukSF-PV(8). These genes encode Panton-Valentine leukocidin (PVL) ,which is a cytotoxin that causes leukocyte destruction and tissue necrosis, and it is asociated with soft tissue infection and necrotizing pneumonia (8). Actually it is proved that there is a strong epidemiologic association between skin, soft tissue infections and PVL production by the MRSA strain USA300 (8). "Among 320 patients with soft tissue infections presenting to emergency departments in 11 US cities in 2004, MRSA was the predominant pathogen (78 percent of isolates), and 98 percent of these were USA300" (8).

MRSA is not only a pathogen of humans, but also a pathogen of animals.Researchers compared MRSA and MSSA (methicillin-susceptible Staphylococcus aureus) and concluded that they did not find identifiable differences between MRSA and MSSA infections in dogs with regard to signalment, types of infections, and clinical outcome (13). However, they established that risk factors related to acquisition of these infections are similar to those for humans (13). One such risk factor was a receipt of antimicrobial drugs such as B-lactams and fluoroquinolones prior to the start of the study, which are antimicrobial agents used to treat infections of the skin and ears respectively (13).

Prolonged antimicrobial drug treatment could have contributed to development of antimicrobial dug resistance, especially considering the fact that fluoroquinolones are often used for small animal because it is a drug active against a wide range of bacteria and comes in an oral formulation, rendering it very convenient (13). "Specifically, use of fluoroquinoloneshas [has] been positively correlated with the incidence of hospital-associated MRSA infections" (13). Another risk factor, which is also linked with increased rates of MRSA infections in humans, was intravenous catherization (13). Although, this study is too small to refer its results to the general dog population, it is a important one because "this finding strengthens the need for veterinarians to consider prudent antimicrobial drug- use guidelines and to restrict the use of fluoroquinolones as empirical or first-line therapy" (13).

Taking into account the dangers associated with these bacteria and the prevalence of these infections, another question ought to be raised - How we can prevent the further spread of this dangerous "bug?" According to researchers who conducted the study for CA-MRSA, there are a few options: one of them is a regional surveillance system and the other, infection control (9).

The regional surveillance system can monitor the incidence of all healthcare associated infections, including both strains of MRSA (9). This will allow hospitals and health care professionals better control and management of both endemic and epidemic incidents of this threatening infection (9). Development of rapid testing could also help separate the strain of MRSA, and therefore help hospitals to treat their patients more effectively with the appropriate antibiotics (9). There are some strains of MRSA, for example, CA-MRSA that can respond in much better and quicker way to a cheaper kinds of antibiotics (9). This means that rapid testing would be able to protect a national stock of widely use antibiotics, and at the same time save a huge amount of money (9).

Effective and rapid detection of methicillin-resistant Staphylococcus aureus carriers is crucial, so that the MRSA transmission in health care facilities can be effectively controlled. This was a motive of the study of researches who tried to verify the performance of the IDI-MRSA real-time PCR assay through direct MRSA detection in diverse mucocutaneous swabs from hospitalized patients(1). This study was triggered by the fact that one of the main causes of MRSA transmission is from MRSA- colonized or infected patients to another one through indirect contact via the transiently colonized hands of healthcare workers (1). They researchers attempted to find the method that could rapidly identify who is a MRSA carrier and efficiently start to prevent dissemination but implementing proper hygiene techniques (1). Investigators tried to determine if the current methods of culturing bacteria from nares and other skin and mucosal sites with enrichment broth and selective media is good enough, or if the PCR methods should substitute the conventional screening methods, for which results are not available before 48 hours (1).

The study was set up in a 858-bed teaching hospital (Erasme Hospital) in fourth month period of the time (1). Investigators collected swabs from 466 patients, who were hospitalized in various areas of the hospital including: the intensive care unit, cardiology, orthopedic surgery, geriatrics, neurology, revalidation, vascular surgery, cardiac surgery, endocrinology, gastroenterology, dermatology, and thoracic surgery departments (1). There were a total of 1,000 collected swabs that included 522 swabs from nares, 212 swabs from throat, 206 from perineum and 60 samples from skin wounds (1). From any one patient anywhere between 1 and 18 samples were collected. (1)

A number of steps were followed in order to prevent contamination and after a careful review the study protocol was approved by the ethical committee of the institution (1). First, samples were taken on the dry swabs were immediately inoculated in Stuart transport medium brought to the bedside, thus immediately available (1). The next step involved plating of the swabs onto selective MRSA agar (MRSA-ID medium) (1). Then the swabs were suspended in the sample buffer for PCR assay. The final step involved inoculating enrichment broth with the swabs, which were made of brain hear infusion supplemented with 7 per cent NaCl (1). Following an approximately twenty four hour incubation period where the media was maintained at 35C (1). The samples were then subcultured broths onto selective MRSA-ID agar, and reincubated these for another 48 hours at 35C, with daily monitoring(1). After the incubation period was completed, the suspected MRSA green-pigmented colonies were identified using the coagulase test and the oxacillin resistance test by the cefoxitin disk diffusion method (1). For the IDI-MRSA assay researches followed the manufacture's recommendation and they vortexed the sample buffer at high speed and after that they transferred the cell suspension into a lysis tube, where the sample in each tube was centrifuged at the room temperature(1). After that they inserted each reaction tube into Smart-Cycler II instrument for PCR amplification, yielding results within one hour (1).

Once the practical part of the research was completed, date had to be analyzed. The researchers compared all the results by dividing their data by specimen and by patient(1). When they got discrepant results they obtained a new sample from the same site of the body of the same patient, and repeated the procedure(1). Additionally, patient history was reviewed in great detail when they got a negative culture but a positive PCR results (1). Lastly, they collate all their results and set the table that compares IDI-MRSA diagnostic performance to enrichment culture for MRSA detection in hospitalized patients(1).

Their following data concludes that in 47 patients the positive MRSA was recovered in 100 specimens (10.0%), of which 81 (81.0%) were detected by agar culture and 19 (19.0%) by enriched broth (1). For IDI-MRSA they collected 108 specimens (10.8%) from 62 patients and found that 81 swabs from 42 patients were positive for MRSA (1). When they compared the sensitivity and specify they results were 81.0 and 97.0% respectively, with noticeable higher sensitivity with nasal swabs (90.6%) and lower among other samples (76.5%) (1).

When the PCR assay results were analyzed at the patient level it was found that sensitivity equaled 89.4% and specifity was 95.2% for detecting MRSA colonization (1). "The positive and negative predictive values in the study population were 67.7 and 98.8%, respectively" (1). Moreover, researches also obtained 19 samples from 17 patients yielding MRSA by culture showed false-negative PCR results, whereas when they extracted DNA from MRSA isolates all tested positive by PCR (1). They also got a result of 26 patients who had culture-negative but PCR-positive, and what they did they decided to consider 11 patients to be probable MRSA carriers because they had a recent history of MRSA carriage and they were still receiving topical decolonization treatment at the time of sampling (1). After sampling was repeated 7 of the 11 patients tested positive by culture (1).

Despite the fact that predicted values reported in this study are biased by the sampling strategy, as only patients admitted to wards with an expectedly pretest probability of MRSA carriage of 10% were included (where the incidence of MRSA carriage in the population is closer to 5%) the study is nonetheless significant, because it established that the IDI-MRSA PCR assay should be utilized more often, since it is a rapid, highly specific and sensitive testing modality (1). Furthermore, the results of the study suggest that the recommendation of using selective enrichment broths and solid media for MRSA screening in many European countries should be little updated(1). This is due to the fact that recently a multiplex PCR was developed that permits simultaneous detection of the methicillin resistance determinant, the mecA gene, and the S. aureus species-specific gene such as femA (1). Nevertheless, like with everything else in our lives this method was not perfect, therefore the investigators suggest further evaluation of the cost-effectiveness of rapid PCR screening. for MRSA control in healthcare settings (1).

Concluding my research, I have to definitely agree that it is imperative to establish a rapid and reliable method for detection of methicillin- resistant Staphylococcus aureus in order to provide effective control of MRSA transmission in healthcare settings (1). To date, the best technique available for MRSA detection from diverse mucocutaneous swabs is IDI-MRSA polymerase chain reaction assay, making it the test of choice at this point (1). Research shows that this method yields more rapid results than using enrichment broth and chromogenic agar to select culture of MRSA (1). The IDI-MRSA PCR assay is certainly more rapid, because the median reporting time takes 19 hours, whereas for agar takes 3 days and broth 6 days. It is also quite reliable with a sensitivity of 89%, and specificity 95 (1).

Moreover, I also emphasize that I absolutely support Debbie B. Noble argument, that the single best manner to tackle prevention of the MRSA infections is to educate patients and families about best practices to prevent or minimize the spread of organism (3). Furthermore, the general population should be educated more about prevalence, locations, reservoirs, spread and risk factors of CA-MRSA and HA-MRSA, as certainly there are more people out there like me, who have no clue about this bacteria causing deadly infection.

Furthermore, I concur with professor and environmental health sciences program coordinator Timothy J. Ryan who states that school facilities should be focused on promoting good hygiene as well as conducting regular disinfection regiments in order to deter growth of MRSA bacteria (4). Moreover, the idea of healthy and bacteria-free environment should be promoted in any other public locale, and perhaps placement of message boards with information about MRSA at such locations can help to deter the spread of this deadly infection.

Lastly, it is important to note that people have contributed that MRSA's resistant to many antibiotics, because we have a tendency not to finish prescribed antibiotics. As a result bacteria are not completely killed off, but instead continue to evolve, multiply and generate more "offspring" that are progressively more resistant to the antibiotic. In other words, if one completed the entire course of antibiotics, all of the bacteria would be quickly destroyed, leaving none behind to divide and create generations of bugs no longer sensitive to a specific antibiotic (7). So next time when you bring your child to the doctor, and the medical professional will not prescribe antibiotic it is because it is not necessary, because the infection is viral and the antibiotics do not help, instead being upset, be glad that doctors reduced level of prescribing antibiotics. Otherwise one day we may wake up in a world where bacteria developed to that point of being resistant to all antibiotic and then what we going to do?

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