Bacteria, also known as microorganisms or as microbes, play a substantial role in our lives, acting beneficially but also causing harm. Some bacterial species help in making vitamins in our gastrointestinal tract, assist in breaking down foodstuffs, and stimulate our immune systems in a healthy manner. However, disease-causing bacteria called pathogens, can make us ill and, if not treated and controlled, can kill us.

Front Matter

The American Academy of Microbiology (Academy) is the honorific branch of the American Society for Microbiology (ASM), a non-profit scientific society with nearly 40,000 members. Fellows of the Academy have been elected by their peers in recognition of their outstanding contributions to the field of microbiology. Through its colloquium program, the Academy draws on the expertise of these fellows to address critical issues in microbiology.

FAQ reports are based on the deliberations of 15-20 expert scientists who gather for a day to develop science-based answers to questions the public might have about topics in microbiology. Every effort is made to ensure that the information is accurate and complete. The contents reflect the views of the participants and are not intended to reflect official positions of the Academy or ASM. The Academy thanks Lothar Wieler, Ph.D. for his efforts in helping to plan the colloquium. Additionally the Academy thanks Leah Gibbons and Shannon Greene, Ph.D., for their contributions to earlier drafts of the report. The Academy also recognizes Chelsie Geyer, Ph.D., for her significant contribution to the final version.

Contents of the report may be distributed further so long as the authorship of the Academy is acknowledged and this disclaimer is included.

What is Staphylococcus aureus and what types of infections does it cause?

Bacteria, also known as microorganisms or as microbes, play a substantial role in our lives, acting beneficially but also causing harm. Some bacterial species help in making vitamins in our gastrointestinal tract, assist in breaking down foodstuffs, and stimulate our immune systems in a healthy manner. However, disease-causing bacteria called pathogens, can make us ill and, if not treated and controlled, can kill us.

One such bacterial pathogen is Staphylococcus aureus (SA). Although these bacteria sometimes live harmlessly on the human body, enjoying a status known as commensal, they can gain access into the body through a cut, abrasion, or wound, resulting typically in minor skin and tissue infections in healthy individuals. If the infection goes unchecked, however, SA can invade more deeply, leading to more serious disease, including complicated soft tissue infections as well as infections of the bone, blood, and heart-valves. These infections can progress, leading to organ failure and death. The extent of these complications is dependent upon both the properties of the infecting SA bacteria and the immune responses of the infected individual. In that sense, SA can be considered an opportunistic pathogen, one that awaits the right opportunities to shed its commensal status, invading our bodies and causing frank disease.

Figure

National Estimated Incidence Rates of Invasive MRSA Infections, Stratified by Epidemiologic Category^a Data are given for methicillin-resistant Staphylococcus aureus (MSRA) infections reported to the Emerging Infections Program-Active Bacterial Core surveillance (more...)

The principal habitat of SA as a commensal of humans is the nose, but this organism is found at other anatomical sites, including the skin and throat of healthy people. According to the Centers for Disease Control and Prevention (CDC), one in three people is colonized with SA in the nose (1). Although individuals who are carriers of SA have these bacteria on and in the body, they do not show signs of infection. Individuals who are SA carriers can serve as reservoirs from which this microorganism is disseminated to other people. Moreover, some people may become colonized with SA for a few hours or days, while others are colonized for months to years.

Being colonized with SA generally precedes becoming infected with this microorganism. However, all humans, irrespective of their carrier status, are capable of being infected with SA. SA infections in healthy persons typically are superficial skin and soft tissue infections such as skin sores, pimples, boils, and mild ulcers, although severe types of infections can arise from those originating in the skin, including complicated deep soft tissue infections and also bone, blood, and heart-valve infections.

SA is capable of causing such infections because it encodes virulence factors in its DNA, including toxins such as α-hemolysin, α-type phenol soluble modulins, and Panton Valentine Leukocidin (PVL). SA also produces adhesion molecules that enable these bacteria to attach to human cells (See Figure 1 and Text box 1). These virulence factors act in several different ways to damage our cells including the induction of damaging pro-inflammatory responses by the human immune system, and the prevention of our immune systems from recognizing these bacteria and mounting an attack against them (2).

Figure 1.

Crude schematic of a Staphylococcus aureus bacterial cell illustrating its mechanisms for attachment to human host cells and virulence.

Text box 1.

Characteristics of SA that contribute to its success as a pathogen.

Figure 2.

Coagulase test commonly used in the clinical laboratory to differentiate S. aureus from other less pathogenic species of Staphylococcus. S. aureus is a coagulase-positive organism (indicated by the top image, cloudy appearance; A) whereas all the other (more...)

The scientific name “staphylococcus” derives from the Greek, “stafle,” meaning wine grape because, under a light microscope, these bacteria look like grape clusters after they are subjected to a procedure known as the Gram stain (Figure 3A). The “aureus” component of its name means golden, reflecting its appearance when it is cultured in the laboratory. Clinical laboratories use a gel-like growth medium for culturing organisms, on which SA appears as round golden spots, called colonies (Figure 3B).

Figure 3.

Microscopic and phenotypic representations of Staphylococcus aureus. A) Grape-like (circular) clusters B) Gold colonies displayed on enriched culture media.

What is the difference between “ordinary” SA and MRSA? How does SA become MRSA?

MRSA, an acronym for methicillin-resistant Staphylococcus aureus, is shorthand for a type of SA that is resistant to the beta β-lactam class of antibiotics. According to the Centers for Disease Control and Prevention (CDC), MRSA is among the highest of all threats to humans of antibiotic resistant pathogens (3). Although MRSA causes serious infectious disease, many antibiotics remain available for treating it effectively. As the numbers of severe invasive MRSA infections acquired in healthcare settings continue to decline, the numbers of such infections among the general public continue to rise (3) (See chart p 1).

Historically, SA rapidly developed resistance to antibiotics as they were brought successively into clinical use, and doctors came to recognize resistance to each such new drug within months to years of its introduction. Thus, for example, penicillin was first used for treating SA infections in 1940. The first penicillin resistant SA pathogens emerged by 1942, and SA remains resistant to that original type of penicillin and to other members of this class of antibiotics (4).

Less than one year after methicillin was developed and put into clinical use, resistance among SA bacteria was being widely detected. SA becomes MRSA after acquiring genes that encode resistance to the broader class of b-lactam antibiotics. The specific gene taken up by SA to make it resistant to methicillin is called mecA. This gene is carried together with a larger set of genes, known as SCCmec (staphylococcal cassette chromosome), that is mobile and capable of inserting into the DNA of other SA bacteria. MRSA strains can also carry resistance to antibiotics other than members of the b-lactam class. This multidrug resistance makes the infections caused by these SA strains very difficult to treat (See Figure 5, showing the evolution of resistance within SA and MRSA strains).

Figure 4.

SA and MRSA colonization hotspots. These are areas that are typically warm and moist.

Figure 5.

Timeline of the emergence of antibiotic resistant Staphylococcus aureus and MRSA. The year of each event is marked on the timeline and the duration of the event is indicated by the length of the arrow. PRSA-penicillin resistant SA; VRSA-vancomycin resistant (more...)

In addition to producing toxins and virulence factors, MRSA bacteria can generate biofilms, sticky layers and clumps of cells that enable bacteria within them to adhere to medical devices such as catheters and implants. A biofilm protects the bacteria within it from the actions of antibiotics and of the human immune system (4). The protective strategies used by MRSA strains to evade the host immune system in combination with multidrug resistance all contribute to the virulence of MRSA. Patients with these infections can have high morbidity and mortality rates, and caring for them contributes to high healthcare costs for these patients (due to treatment difficulties and longer hospital stays) (4).

An additional challenging feature of MRSA bacteria is their hardiness. They can survive for prolonged periods on surfaces and objects such as sinks, toilets, door handles, floors, medical devices, bed linens, cleaning equipment, and clothing. Therefore, extensive contact control and disinfection procedures are needed to limit the spread of MRSA in healthcare and other settings.

Figure

The growth of MRSA on an enriched agar plate.

Text box 2.

Methods for classifying MRSA strains.

Are all MRSA strains alike, and how is MRSA acquired and transmitted?

MRSA strains vary in terms of their virulence, colonization capabilities, transmissibility, and degree of resistance to antibiotics beyond those belonging to the b-lactam class of antimicrobial drugs. The composition of SCCmec, the set of genes containing the methicillin resistance gene, also differs among the many kinds of MRSA strains that circulate in different environments.

MRSA strains can be categorized by using one or more of several widely available analytical methods (See Text box 2). One of these methods is called pulsed-field gel electrophoresis (PFGE). It separates bacterial DNA fragments into specific patterns that are distinctive and thus useful for identifying the bacteria from which they came, much like fingerprints are used to identify specific individuals. MRSA banding patterns typically fall into one of eight categories, designated USA100 – USA800, according to the national PFGE database for SA, established by the CDC (5). Most infections caused by healthcare-associated MRSA (See below) fall under the USA100 category, while those caused by community-associated MRSA (See p 8) fall within the USA300 banding pattern.

The spread of MRSA requires skin-to-skin contact with an individual who either had close contact with MRSA (by touching wounds, dressings, or other objects that came into contact with MRSA-infected patients) or is colonized with this organism. MRSA can be divided into groups, called “epi-vars,” based on the population that the organism tends to infect, its origin, and route of transmission. Here, we describe three major “epi-vars” (See also Table 1):

1. Healthcare-associated (HA)-MRSA infections are transmitted commonly in healthcare institutions dealing with acutely ill patients (2). In many countries, MRSA infections are acquired primarily in healthcare settings, including hospitals, long-term care facilities, dialysis centers, and other health-related centers. The proportion of MRSA infections occurring outside healthcare settings has changed since the late 1990s in many countries, especially in North America, where MRSA infections in the community have become increasingly common (6, 7, 8). The primary mechanism for transferring MRSA among patients, caretakers, and others in these settings is through poor hand hygiene and lack of consistent disinfection procedures. In healthcare facilities, items such as catheters, intubation tubes, and other implanted devices provide MRSA a means to invade patients. Surgical and other procedures that disrupt the skin and other body surfaces are additional important avenues for MRSA to access otherwise protected body sites.
   

   Image retrieved from: p 7) Phalinn Ooi-CC: BY-NC-SA

2. Community-associated (CA)-MRSA infections are transmitted from sources within a community that are not healthcare-related. The dominant CA-MRSA bacterial strain that continues to circulate in the US is referred to as USA300. As in healthcare settings, MRSA is transmitted within the community through skin contact or the sharing of items with extensive skin contact such as lotions, soaps, cosmetics, towels, razors, hairbrushes, and nail files. Some MRSA strains are shared among household members or among members of athletic clubs or people within other community settings where individuals come into close contact, including dormitories, daycare centers, barracks, jails, locker rooms, gyms, and other facilities used by sport teams. Those that participate in high impact and collision sports such as football, soccer, rugby, ice hockey, wrestling, and basketball tend to have a higher than average likelihood of contracting CA-MRSA. Other risk factors for a CA-MRSA infection in the US include lifestyle (intravenous drug users are highly susceptible), low socioeconomic status that may prevent proper hygiene, and having other health conditions (HIV, cancer, dialysis). Infection risk for both CA- and HA-MRSA is increased for individuals who carry MRSA or who have had a previous MRSA infection.
   CA-MRSA strains can vary from HA-MRSA strains in terms of their virulence factor profiles (9). For example, CA-MRSA strains tend to produce more a-type phenol soluble modulins and a-hemolysin compared to HA-MRSA strains (10). The PVL toxin is more commonly seen with MRSA strains circulating within communities but not within hospital or other healthcare settings (4).
   

   Image retrieved from: p 8) USAG- Humphreys-CC: BYNC-SA; p 10 top) Johan Pabon-CC: BY-NC-SA

3. Livestock-associated (LA)-MRSA colonization is prevalent in some livestock species from which they can spread to humans and cause disease. Infections transmitted from animals to humans are called zoonoses. During the past 10 years, livestock has become a significant source for human MRSA infections, especially affecting people working with colonized animals and to a lesser extent, members of their households (Figure 6) (12). Livestock-associated bacteria can be a reservoir for antibiotic resistance genes in general. Antibiotics are frequently used to prevent infections in these animals through a practice that is known as metaphylactic therapy. Furthermore, in several countries including the US, antibiotics are incorporated into some animal feeds to promote growth (11).
   While MRSA strains tend to circulate among the species to which they are most closely adapted, they can jump species barriers. For example, cats and dogs can become infected with HA-MRSA or CA-MRSA via contact with a colonized or infected owner through a process known as anthroponosis. Although humans are more likely to transmit MRSA to their pets rather than to become infected from them, infected or colonized animals can serve as a source of infection for their human contacts.

Image retrieved from: p 10 bottom) Wikimedia Commons “MRSA on Brilliance MRSA Chromogenic Agar”-CC: BY-NC-SA

Infections transmitted from animals to humans are called zoonoses.

FIGURE 6.

Transmission of MRSA infections. Distinguishing MRSA strains that have originated in hospitals versus communities versus livestock is getting complicated.

Figure

Meticillin/Methicillin resistant Staphylococcus aureus on Oxoid Brilliance/Spectra M.R.S.A. selective chromogenic agar.

Table 1.

Risk factors for acquisition of MRSA.

How can MRSA infections be detected, treated, and prevented at the personal and public health levels?

The CDC estimates that two in 100 people are colonized with MRSA in the nose (2). MRSA colonization, however, does not equate to a MRSA infection. An individual with an MRSA infection has signs and symptoms that are dependent upon the area of the body that is infected. For example, skin infections display redness, inflammation, heat, and could become swollen when pus or another liquid accumulates. Because of the appearance of these MRSA skin infections, they may be mistaken for insect and spider bites (Figure 7). Signs of a more serious, internal MRSA infection include fever, chills, confusion, dizziness, muscle aches, swelling of the affected body part, and wounds that will not heal.

Figure 7.

Appearance of a CA-MRSA skin infection resembling a spider bite.

MRSA colonization, however, does not equate to a MRSA infection.

When an MRSA infection is present, clinicians will need to assess the antimicrobial susceptibility of the bacterial strain that is causing the infection to determine the appropriate antibiotic therapy to administer to the patient. Determining the antibiotic susceptibility of MRSA requires taking specimens from a particular anatomic site or bodily fluid, culturing bacteria that are present in those specimens, and then testing the ability of those bacteria to grow in the presence of a variety of antibiotic agents. Results from culturing techniques usually take about 24 to 72 hours to obtain (Figure 8) (13). Rapid tests taking only about six hours are recommended for settings such as emergency rooms. In areas of the US where MRSA makes up more than 10% of the local SA infection burden, the Infectious Diseases Society of America (IDSA) recommends using non-b-lactam antibiotics such as tetracycline or sulfa drugs for initial treatment. However, severe MRSA infections involving the heart, bone tissues, or blood may require prolonged treatment with intravenous antibiotics (See 2011 IDSA MRSA treatment guidelines) (14). Ultimately, physicians will need to determine the most suitable treatment for individual patients in their care.

Figure 8.

Antibiotic susceptibility testing of a MRSA strain. Various paper disks that are infused with a specific antibiotic (indicated by the arrows) are placed on a nutrient rich agar plate. A clear zone around a disk shows that the antibiotic was able to prevent (more...)

In hospitals, measures such as hand hygiene (hand-washing with soap and water or with an alcohol hand-rub), environmental cleaning and disinfection, use of personal protective equipment such as gowns and gloves (contact precaution), and avoiding use of inappropriate antimicrobial agents should be scrupulously instituted. These measures can be effective against a variety of microbial pathogens in addition to and including MRSA.

MRSA-specific interventions depend upon screening individuals who are carrying this microorganism as the first step. In the future, MRSA carriers should be identified by adopting tailored and risk-based screening programs. Implementing such infection prevention measures can help greatly to avoid spreading MRSA to other patients. Such patients can be decolonized–their MRSA removed from them before they are admitted to the hospital or healthcare facility, or before surgery or other procedures are performed. The decision to decolonize individual patients will depend on doctor recommendations, the health condition of each patient, and practices being followed in a particular region or country (14). These measures include treating individuals with an antibacterial body wash and shampoo (chlorhexidine bath) or, in other cases, applying an antimicrobial cream such as mupirocin to the interior of the nose. If decolonization is not possible or not indicated, knowledge of the MRSA colonization helps when initiating the correct antibiotic therapy which is imperative for a successful clinical outcome in severe disease. Similar to HA-MRSA prevention techniques, transmission of CA-MRSA can be impeded by proper hand-washing and not touching or sharing personal items (Figure 9).

Figure 9.

Proper hand-washing (warm soapy water or an alcohol-based rub) in all settings is essential to prevent the spread of SA and MRSA. Additionally, disinfection of patient related surfaces in the hospital environment is a significant practice that needs to (more...)

Similar to HA-MRSA prevention techniques, transmission of CA-MRSA can be impeded by proper hand-washing …

As a component of the Emerging Infections Program-Active Bacterial Core surveillance system (EIP-ABCs) at the CDC, invasive (bloodstream, lung, and other serious infections) MRSA infections have been tracked in nine different metropolitan regions of the United States since 2005 (15). All participating medical labs report information about such infections to the CDC, which uses the data to estimate population-based incidence of invasive MRSA infections across the entire country. Simple skin infections caused by MRSA are not systematically tracked in the US, even if they require hospitalization. If the CDC detects a higher than expected rate of infections or colonizations within a particular population group, the CDC may investigate, although this is not a routine practice. When there is a change in the usual pattern of any type of infection in US hospitals, local hospital infection control practitioners typically investigate.

Key terms used throughout text.

Anthroponosis

– a disease that can be transmitted from a human to an animal

Gene

– a unit of heredity that, when passed from a bacterial species to its clones (offspring), imparts a specific characteristic or function

Beta β-lactam antibiotics

– antibiotics with a characteristic 4-membered, ring structure that block synthesis of bacterial cell walls

Genome

– the total genetic material of an organism

Clone

– genetically identical bacteria that arose from a single common bacterial ancestor

Infection

– the classical signs of clinical illness such as redness, inflammation, localized pain, and fever following invasion of bacteria into the body

Colonization

– the presence of bacteria on or within the body but without signs of illness or disease (asymptomatic). Common SA colonization sites include anywhere on the surface of the skin but with preference for warm, moist regions such as the nose, armpits, and groin. No treatment is necessary for colonization (Figure 4).

Opportunistic pathogen

– an organism that exists harmlessly on or in its host but may cause disease when it moves to other anatomic sites or when the host immune system becomes compromised

Pathogen

– a specific causative agent of infectious disease such as a bacterium, virus, fungus, or parasite

Commensal

– a microorganism that lives on another species such as an animal or a person without causing it harm

Strain

– a genetic variant or subtype of a microorganism; there are many strains of SA bacteria that vary in terms of virulence, pathogenicity, transmissibility, and resistance to antibiotics. Bacterial “typing” includes methods that distinguish among and thus identify different strains from one another (See Text box 2).

Culture specimen

– a sample of a bodily fluid such as blood, urine, or sputum, or a swab of an anatomic site or wound that is sent to the laboratory for testing to determine what microorganisms may be present

Zoonosis

– an infectious disease that can be transmitted from an animal to a human (e.g., SA, rabies, anthrax, ringworm)

References

1.

Methicillin-resistant Staphylococcus aureus (MRSA) infections. 2013. http://www​.cdc.gov/mrsa/community/index​.html. Accessed 21 August 2014.

2.

Lowy FD. 1998. Staphylococcus aureus infections. N Engl J Med 339:520-32. [PubMed: 9709046]

3.

Antibiotic Resistance Threats in the United States, 2013. http://www​.cdc.gov/drugresistance​/threat-report-2013​/pdf/ar-threats-2013-508.pdf. Accessed 18 August 2014.

4.

Otto M. 2012. MRSA virulence and spread. Cell Microbiol 14:1513-21. [PMC free article: PMC3443268] [PubMed: 22747834]

5.

DeLeo FR, Chambers HF. 2009. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest. 119:2464-74. doi: 10​.1172/JCI38226. [PMC free article: PMC2735934] [PubMed: 19729844]

6.

David MZ, Cadilla A, Boyle-Vavra S, Daum RS. 2014. Replacement of HA-MRSA by CAMRSA infections at an academic medical center in the midwestern United States, 2004-5 to 2008. PLoS One 9:e92760. [PMC free article: PMC3995643] [PubMed: 24755631]

7.

David MZ, Mennella C, Mansour M, Boyle-Vavra S, Daum RS. 2008. Predominance of methicillin-resistant Staphylococcus aureus among pathogens causing skin and soft tissue infections in a large urban jail: risk factors and recurrence rates. J Clin Microbiol 46:3222-7. [PMC free article: PMC2566069] [PubMed: 18685002]

8.

Diekema DJ, Richter SS, Heilmann KP, Dohrn CL, Riahi F, Tendolkar S, McDanel JS, Doern GV. 2014. Continued emergence of USA300 methicillin-resistant Staphylococcus aureus in the United States: results from a nationwide surveillance study. Infect Control Hosp Epidemiol 35:285-92. [PubMed: 24521595]

9.

David MZ, Daum RS. 2010. Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23:616-87. [PMC free article: PMC2901661] [PubMed: 20610826]

10.

Peschel A, Otto M. 2013. Phenol-soluble modulins and staphylococcal infection. Nat Rev Microbiol 11:667-73. [PMC free article: PMC4780437] [PubMed: 24018382]

11.

Institute of Medicine. What You Need to Know About Infectious Disease. Washington, DC: The National Academies Press, 2010. [PubMed: 24983051]

12.

Mole B. 2013. MRSA: Farming up trouble. Nature 499:398-400. [PubMed: 23887415]

13.

Zimmermann JL, Shimizu T, Schmidt H-U, Li Y-F, Morfill GE, Isbary G. 2012. Test for bacterial resistance build-up against plasma treatment. New J Phys 14 073037.

14.

Liu C., Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray B, Rybak MJ, Talan DA, Chambers HF. 2011. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children. Clin Infect Dis 52:e18-25. [PubMed: 21208910]

15.

Dantes R, Mu Y, Belflower R, Aragon D, Dumyati G, Harrison LH, Lessa FC, Lynfield R, Nadle J, Petit S, Ray SM, Schaffner W, Townes J, Fridkin S. 2013. National Burden of Invasive Methicillin-Resistant Staphylococcus aureus Infections, United States, 2011. JAMA Intern Med 173:1970. doi: 10​.1001/jamainternmed.2013.10423. [PubMed: 24043270]

16.

Köck R, Schaumburg F, Hellman A, Koksal M, Juke A, Beeker K, Fredrich AW. 2013. Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) as causes of human infection and colonization in Germany. PLoS One 8:e55040. [PMC free article: PMC3572123] [PubMed: 23418434]

Cover: Staphylococcus aureus bacteria, MRSA. Image retrieved from Microbe World.