Update on MRSA and MSSA

A STAPHYLOCOCCUS infection is one of the more common conditions a physician will treat. It can also be among the most challenging. While there are more than 30 different types of Staphylococcus bacteria identified, one species — Staphylococcus aureus — is responsible for most staph infections in humans. In fact, about 30 percent of all people have Staphylococcus aureus on their skin or in their nasal passages, where it simply lives without harming the host most of the time.¹

While most Staphylococcus aureus infections will manifest as mild skin infections easily treated with standard antibiotics, when it gets into the bloodstream, it can be life-threatening — with sepsis, endocarditis or osteomyelitis common complications. There are more than 100,000 of these cases each year in the United States alone, with about one-fifth proving fatal.² Anther potential lethal Staphylococcus aureus complication is toxic shock syndrome.³

Staphylococcus aureus can also cause food poisoning and pneumonia. Food poisoning, which is the body’s reaction to toxins produced by the Staphylococcus bacteria, is only rarely serious,⁴ while Staphylococcal pneumonia is much less common although quite dangerous even with prompt treatment.⁵

Staphylococcus aureus is easily spread through physical contact — primarily skin to skin, although the bacteria can also survive on other items, such as furniture, clothing, door knobs, etc., long enough to be passed on.⁶ Its ability to form biofilms also makes it notoriously difficult to fully remove from invasive medical devices, including endoscopes, invasive ventilators and implants.⁷ 

Then there is this: Staphylococcus aureus has developed the ability to bypass much of the human body’s intricate immune system. These bacteria secrete enzymes that attack the body’s defenses.⁸ 

If all that isn’t enough of a challenge for the medical community, it is also one of the most rapidly adaptable types of bacteria, with strains arising that can resist most drugs introduced to combat it to date. As one researcher wrote, “Staphylococcus aureus is notorious for its ability to become resistant to antibiotics.”⁹ 

Suddenly, that mild skin infection isn’t quite as easy to treat, and the more serious infections are degrees more dangerous. These resistant strains have not only proven to be the bane of healthcare facilities where they have thrived despite all efforts at controlling them, but they have now spread into the community causing physicians new challenges in trying to treat an infection that does not respond to readily available treatments.

What Is MRSA?

Staphylococcus was first described in 1880 by Scottish physician Alexander Ogston, who noticed clusters of bacteria while using his microscope to examine samples taken from surgical wounds that had become infected.¹⁰ Four years later, German doctor Friedrich Julius Rosenbach divided Staphylococcus into two variants based on the color of their colonies: Staphylococcus aureus for the yellow-colored bacteria, and Staphylococcus albus for the white (later renamed Staphylococcus epidermidis due to its common habitat in the skin).¹¹ 

The only treatment for a Staphylococcus aureus infection in the 19th century was a topical application of carbolic acid, which meant wounds had to be open to treat the infection. The development of penicillin treatments during World War II proved highly effective vs. Staphylococcus aureus — until, just two years after penicillin was first used to fight the disease, resistant strains of Staphylococcus aureus were detected.¹⁰ Other antibiotics were developed to counter this, but in 1961 the first strains that could survive the penicillin derivative methicillin were noted — a mere year after its introduction.⁹ 

Today, “MRSA” is used as shorthand to denote not only “methicillin-resistant Staphylococcus aureus” but Staphylococcus aureus that is resistant to a variety of antibiotics. And all strains of Staphylococcus aureus are now classified as either MRSA, which is resistant, or MSSA, methicillin-susceptible Staphylococcus aureus, which responds to antibiotic treatment.

Treating patients with a MRSA infection is challenging, as the specific strain may not respond to first-line antibiotics. And in a troubling development, new strains of Staphylococcus aureus have arisen that are resistant to vancomycin, an antibiotic of last resort in treating stubborn cases of MRSA. Vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) were first reported in 2002, and fortunately remain extremely rare.¹² They also are still susceptible to some even newer antiobiotics — for now.

After its discovery in 1961, MRSA was primarily a healthcare setting-acquired condition (HA-MRSA). However, beginning in the 1990s, MRSA spread beyond clinics and hospitals, and now, community-associated MRSA (CA-MRSA) is likely responsible for a majority of total MRSA infections, although Staphylococcus aureus remains the second-leading cause of healthcare-associated infections (HAIs), accounting for some 11 percent of all HAIs, according to the Centers for Disease Control and Prevention (CDC).¹³ (The government now divides HA-MRSA into two distinct types: healthcare-associated community-onset [HACO-MRSA] and hospital-onset [HO-MRSA].¹⁴)

A Minnesota Department of Health fact sheet defines CA-MRSA as those that occur in patients with a positive MRSA culture test who have not had any of the following events within the previous year:¹⁵ 

• Hospitalization or surgery
• Residence in a long-term care facility
• Permanent catheter or other percutaneous device
• Dialysis
• A positive MRSA culture within 48 hours of hospital admission

That same fact sheet points out some differences between CA-MRSA and HA-MRSA:

• CA-MRSA patients are younger on average.
• HA-MRSA infections are more resistant to treatment.
• There are genetic differences between the two strains.

How Prevalent Is MRSA?

While as noted above roughly 30 percent of all people carry Staphylococcus aureus, CDC estimates only 2 percent of the population carries MRSA on their skin or in their nasal passages, which would make it roughly 6.5 percent of all people carrying Staphylococcus aureus.¹⁶ As with nonresistant Staphylococcus aureus, most of these will never develop an active infection.

A recent study from Japan found that from 2014 to 2019, HA-MRSA decreased from 50.2 percent to 19 percent of documented MRSA cases, while CA-MRSA increased from 44.7 percent to 76.4 percent of all MRSA cases in the Kyoto and Shiga regions.¹⁷ A 2016 study from California showed a similar pattern of CA-MRSA cases becoming more common while HA-MRSA decreased, likely due to increased emphasis on fighting HAIs.¹⁸ 

The overall number of people diagnosed with MRSA was declining before the COVID-19 panic, when it shot up. CDC estimates that as of last year, MRSA caused more than 70,000 severe infections, with some 9,000 of them proving fatal.¹⁹ 

How Does Resistance Develop?

In complex organisms, species more or less die with the genome they’re born with (outside random mutations in individual cells) — meaning species only gain native resistance to disease vertically, from surviving members passing their resistant genes to their offspring.

However, Staphylococcus aureus possess the ability to engage in horizontal gene transfer where bacterial cells acquire and deploy DNA from other organisms. This allows for a gene that confers resistance to a particular drug to be spread throughout a population rather quickly. The methods of horizontal gene transfer include:²⁰ 

• Transduction: bacteriophages (viruses that infect bacteria) that carry DNA from one to another
• Transformation: free DNA molecules are absorbed through a cell’s outer membrane
• Conjugation: two bacteria temporarily connect and exchange DNA

Researchers believe that transduction is the most likely path for sharing genes between members of Staphylococcus aureus.²¹ 

So not only do resistant bacteria survive exposure to an antibiotic and share that with their descendants, but they can actually spread their resistance to their neighbors that weren’t previously resistant.

With penicillin, strains of Staphylococcus aureus that possessed the blaZ gene were able to create an enzyme that counteracted the antibiotic properties of penicillin. Later, some strains had the mecA gene that changed their cellular membrane to remove the protein that methicillin would bind to in order to destroy the bacteria.²² 

Who Is Most at Risk from MRSA?

The risk factors of contracting MRSA vary significantly between CA-MRSA and HA-MRSA.

Of course, patients with a compromised immune system are most at risk, regardless of strain or setting.

For HA-MRSA, anyone who is hospitalized is at greater risk of contracting a resistant staph infection, as are those admitted to a long-term care facility. But the elderly are at heightened risk — as is anyone with invasive medical devices, including intravenous lines, urinary catheters or mechanical ventilators. Mechanical implants, including artificial joints, also increase one’s risk.

Risk factors for CA-MRSA include injecting illegal drugs, working around farm animals, playing contact sports or having a chronic skin condition.⁶ 

MRSA Symptoms and Progression

Symptoms of a Staphylococcus aureus infection will depend on where the infection is manifesting. They range from pimples or boils on the skin, to shivering, confusion or shortness of breath for a blood infection. Infected surgical sites are not uncommon, with redness and swelling, and infections of medical implants may include internal pain in addition to fever and swelling.

The symptoms do not vary depending on whether the infection is caused by a MRSA or MSSA variant. If untreated, or if treatment is unsuccessful, systemic staph infections can progress rapidly and quickly become life-threatening. Once in the bloodstream, the bacteria can infect organs such as the heart valves or bones, or it can lead to sepsis.

MRSA Diagnosis and Treatment

 Because treatment will vary between resistant and susceptible strains, it is crucial that culture samples be tested to confirm both Staphylococcus aureus infection, as well as whether it is resistant.²³ In cases of severe infection, a polymerase chain reaction test may be called for since results can be available in just a few hours, allowing for treatment to begin quickly.

MSSA will be treated by draining and cleaning an infected skin lesion. Mild skin infections may be treated by topical ointments containing an antibiotic, while more serious infections will typically call for oral or intravenous application. Antibiotics should be employed only if that is not successful. Antibiotics typically prescribed for MSSA are dicloxacillin, erythromycin, nafcillin and clindamycin.²⁴

If a blood culture tests positive, other symptoms may call for additional tests such as imaging to look for oseomyelitis or renal or splenal infarct. If there is risk of endocarditis, an echocardiogram may be called for.²⁵ The above antibiotics are still likely to be called for, but will most certainly be given intravenously.

MRSA treatment will follow the same path as MSSA, but with a different set of antibiotics — possibly a “cocktail” of antibiotics to overwhelm the bacteria’s defenses. The antibiotics could include vancomycin, rifampin, trimethoprim/sulfamethoxazole (TMP/SMX), ceftaroline linezolid, daptomycin, doxycycline and/or delafloxacin.

When the infection is in the bloodstream, hospitalization will generally be required, with careful observation of the patient to catch any worsening of symptoms.²⁶ 

For the new, even more resistant VISA (vancomycin-immediate Staphylococcus aureus) and VRSA (vancomycin-resistant Staphylococcus aureus) variants, there is no set recommended treatment due to the very small number of people who have contracted these infections. Instead, a physician will consider the many antibiotics that are effective in treating MRSA. Ceftaroline has shown promise, as have televancin, quinupristin/dalfopristin and other combinations of available antibiotics, which are discussed in a paper from the University of Nebraska Medical Center.²⁷ 

There is also evidence that intravenous immune globulin is an effective antibody therapy for CA-MRSA necrotizing pneumonia, particularly when used in conjunction with antibiotics.²⁸

MRSA Prevention

While there is ongoing research into a vaccine for Staphylococcus aureus, at present the best preventive measures are hygienic: washing hands after touching someone else; avoiding sharing personal items such as razors, towels or needles; keeping wounds clean and properly dressed; and showering immediately after contact sports.

Healthcare facilities can do their part by following local, state and national protocols on disinfection and sterilization, as well as following infection control measures with patients with easily communicable diseases.

Ongoing Research

On the U.S. Food and Drug Administration’s clinicaltrials.gov website, there are hundreds of recent and ongoing experiments into detecting, treating and, hopefully, preventing MSSA, MRSA and VRSA.

One manufacturer is testing a device to detect Staphylococcus aureus in the nose, which could greatly speed up diagnosis.²⁹ 

A German team is studying a new compound, HY-133, as a nasal spray to see if it can prevent Staphylococcus aureus from colonizing the nasal passage of uninfected patients in hospitals.³⁰ 

And an American study is looking at a new phage, AP-SA02, used in conjunction with existing best available therapies to treat Staphylococcus aureus in the bloodstream.³¹ 

Looking Ahead

While Staphylococcus aureus is a uniquely challenging disease-causing bacteria due to its ability to evade new treatments, as well as the body’s own defenses, researchers continue to try to outpace the pathogen’s ability to adapt. However, for the foreseeable future, resistant strains of Staphylococcus aureus will continue to challenge physicians to effectively respond to their patients’ infections — particularly those that are resistant.