By Xiaoxu Sean Lin and Health 1+1
During the COVID-19 pandemic, a life-threatening infection of a superbug spiked in hospitals, raising a big concern.
MRSA, which stands for methicillin-resistant Staphylococcus aureus, is one of the well known superbugs, which are bacterias that are resistant to most antibiotics.
Since 2010, laboratory-identified cases of MRSA infection have been significantly decreasing. However, as the COVID-19 pandemic swept through the United States, hospitals have experienced an increase in the number of MRSA infections. The hospital overload has resulted in higher health-care associated infections. During the fourth quarter of 2020, the national MRSA bacteremia standardized infection ratio was 34 percent higher than that of 2019. Several states reported even greater increases in 2020, such as Arizona with a 80 percent increase and New Jersey with a 99 percent increase.
The situation is also becoming increasingly common in nursing homes. From September to October 2021, 48.7 percent of residents in nursing homes were found to harbor MRSA at any body site.
Therefore, when the hygiene conditions deteriorated during COVID peak time, when the hospitals were overcrowded and staff overworked, patients hospitalized or visitors to hospitals also had a higher chance of cross contamination with other infections. This further created additional challenge to treat COVID patients, as opportunistic infections would worsen the diseases progress for the patients.
80 Percent Mortality, Antibiotics, and the Comeback
The story begins with Staphylococcus (“Staph”) aureus. It is a grape-like, golden bacteria. It’s often colonized on the skin and in the nose of healthy people. Approximately 20-30 percent of the population carries the bacteria persistently, while another 20-60 percent of people are intermittent carriers. It usually doesn’t cause any harm to people with healthy skin. However, when it is allowed to enter the bloodstream or internal tissues, it may cause a variety of potentially serious infections, such as pneumonia and blood infections; and it may even lead to sepsis or death.
In the pre-antibiotic era, the mortality of patients with S. aureus exceeded 80 percent. The introduction of penicillin in the early 1940s dramatically reduced the number of deaths. However, in less than two years, penicillin-resistant Staphylococcus aureus emerged. Afterwards, another antibiotic of the penicillin class, methicillin, was invented. However, another two years passed, and S. aureus fought back once again. The dangerous bacteria MRSA appeared this time.
S. aureus has a cell wall, which is essential for maintaining its life. Methicillin inhibits its cell wall synthesis, which leads to its destruction. However, MRSA has developed a gene called mecA, which prevents this from happening. As its cell wall cannot be harmed by methicillin with this gene, the bacteria can survive.
What’s worse is that the mecA gene can be spread to other bacteria, so other S. aureus can gain the drug-resistant feature as well.
MRSA also has developed other genes that lead to resistance to other antibiotics, immune evasion, tissue disruption, and pathogenic islands that cause more severe diseases. Therefore, the antibiotic-resistant superbug has been becoming stronger and stronger.
Hospital-Associated MRSA is More Deadly
MRSA is one of the very few bacteria that is “very good at” causing infections in healthy people and sick people in the hospital, as per the comment on the school website by Dr. John Ross, an infectious disease specialist and professor of medicine at Harvard Medical School.
MRSA was first observed among hospitalized patients in the 1960s, and since 1990, it has spread rapidly in the community.
However, healthcare-associated MRSA can be more deadly.
In hospitals, patients are commonly exposed to antibiotics and receive lots of hands-on care, making it an environment more susceptible to lethal bacteria. Community-associated MRSA is resistant to only some types of antibiotics, while hospital and other healthcare-associated MRSA is resistant to most of the antibiotics.
As a result, treatment for healthcare-associated MRSA has fewer options of antibiotics to choose, and currently vancomycin is the first choice. Sometimes a few other antibiotics can also be used, such as daptomycin and linezolid.
Vancomycin has historically been the drug of choice and sometimes the last resort for the treatment of serious MRSA infections. However, its increased use has already led to vancomycin-resistant S. aureus.
Community-associated MRSA commonly causes serious skin and soft tissue infections, particularly in young and healthy individuals. Healthcare-associated MRSA usually causes more invasive infections, including surgical site infections, bloodstream infections, and pneumonia.
Healthcare-associated MRSA infections are often difficult to treat, and have a significant mortality.
MRSA Colonization Is Less Severe Than Infection, but Still Increases Mortality
Studies have also compared the mortality rates between MRSA and MSSA (methicillin-susceptible S. aureus).
A study (pdf) published in the journal Antimicrobial Agent and Chemotherapy found that, in patients with MRSA bloodstream infection, their 30-day mortality is higher than that of the control group without S. aureus bloodstream infection, with an odds ratio between 4.4 and 4.8; and patients with MSSA have a higher mortality than the controls, with an odds ratio between 2.4 and 3.3.
One thing worth noting is that pathogenicity is not necessarily associated with drug resistance. It mainly depends on how many and what kind of pathogenic genes a bacteria carries.
Mere MRSA colonization, not yet advanced to the stage of infection, can also bring about higher mortality in elderly patients. Sometimes MRSA colonization can enhance other bacteria infection. A study of 6,000 community-dwelling adults aged 40 to 85 years found that the 11-year mortality rates were 35.9 percent for MRSA-colonized and 17.8 percent for non-colonized participants, respectively.
The Future of the Superbug
MRSA in hospitals is often associated with environmental cleaning and medical device disinfecting. To control MRSA, proper hand hygiene of doctors and nurses and thorough cleaning of equipment are needed.
Patients usually get infected during surgical procedures or due to the use of invasive medical devices. As many elderly people do hemodialysis regularly, it is very important to make sure the devices are free of pathogens, including MRSA. However, sometimes bacteria such as MRSA can form biofilms, by secreting a slimy material that forms a protective barrier around the colony and can grow on metal and other surfaces. Biofilms are very tenacious and extremely difficult to remove.
A more serious problem is the bacteria’s drug resistance.
Both bacteria and viruses can escape treatment through gene mutation, but bacteria have a unique feature, as some of their genes are transmissible. Once a type of bacteria gains a drug-resistant gene, the gene is able to “swim” from one bacterium to another, and in the end, all of the bacteria get the drug-resistant “weapon.” That’s why it’s so easy for bacteria to become drug-resistant.
Some bacteria even become dependent on certain antibiotics, and thrive better when antibiotics exist.
One problem with methicillin and other similar antibiotics is that they only target the cell walls of the bacteria, instead of destroying the entire bacteria cell. This leaves room for the bacteria to linger on their last breath and figure out ways to fight back, especially when the bacteria gene replication and expression mechanism were not disrupted. Cocktail therapy was used to resolve this issue, by mixing multiple antibiotics and intending to accelerate the bacteria removal. However, this raises another issue, as in some cases the bacteria are not eradicated, and they increase mortality and gain broader resistance to more drugs.
As viruses mutate faster than vaccine development, bacteria also upgrade faster than antibiotics development. Superbugs have already become one of the biggest crises in the world. Drugs fight and, at the same time, train the microorganism. Battles with diseases seem to be another story on the micro level.
Under antibiotics abuse, the drug-resistance and pathogenicity of MRSA will be higher and higher with no doubt. Two years of the COVID-19 pandemic have added fuel to the fire. If one day MRSA causes 80 percent mortality again, we may realize that we should find another way to resolve the fundamental problem of the war with the micro world.