Several articles in publication in 2020 are looking closely at the potential direct and indirect effects of coronavirus disease 2019 (COVID-19) infection on the ongoing problem of antimicrobial resistance. Before 2019, antimicrobial resistance was already recognized as a growing global health threat; the pandemic spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a potential escalation of both health crises, as antibiotics are widely being used to treat various symptoms of COVID-19.1
More than 2.8 million people are infected with antibiotic-resistant bacteria each year in the United States, leading to at least 35,000 deaths, according to a 2019 AR Threats Report released by the Centers for Disease Control and Prevention (CDC).2 This represents a substantial increase from the mortality rates of 23,000 from the same report issued in 2013.3 The new report includes urgent threats posed by drug-resistant Candida auris and carbapenem-resistant Acinetobacter, in addition to previously listed carbapenem-resistant Enterobacteriaceae Neisseria gonorrhoeae, and Clostridioides difficile from the 2013 report, for a new total of 18 bacteria that are considered “antibiotic-resistant.”2,3
The Scope of the Challenge
Antimicrobial resistance is the result of natural evolution of some species of bacteria to combat the antibacterial and antimicrobial agents prescribed to treat them. In 2019, the CDC reported that, “Germs continue to spread and develop new types of resistance, and progress may be undermined by some community-associated infections that are on the rise.”2 Further spread of the resistant bacteria often occurs in hospital settings and has recently been detected in larger community settings in which antibiotics are frequently used.4.
The problem of resistance is exacerbated by general prescribing patterns of broad-spectrum antibiotics for the treatment and prevention of commonly suspected infections, which further spur the emergence of both new and existing antibiotic-resistant strains of bacteria.
In dermatology, the greatest single source of antibiotic abuse is in the treatment of acne, according to Adam Friedman, MD, FAAD, professor and interim chair of dermatology at the George Washington University School of Medicine in Washington, DC. “It’s the most prominent skin condition, affecting 40 to 50 million Americans yearly,” he told us. “Historically, the first-line therapies have always been antibiotics, whether it’s a topical or oral antibiotic. These still are being used for long periods of time, even after guidelines5 came out (JAAD, 2016), documenting that these shouldn’t be used relentlessly without any end point. [Clinicians] still give it.”
Antibiotics have well-established anti-inflammatory properties, Dr Friedman pointed out, making them especially useful for the treatment of acne, but they are being prescribed for much longer than their recommended durations. “Usually antibiotics would be prescribed for a week or 2 to clear infections, but for acne, we’re using these antibiotics for months. If you keep challenging these bacteria with antibiotics, you’re going to both select for resistant organisms and enable the development of resistance strategies like the development of efflux pumps or redirection of metabolic pathways.”
Best Practices for Prevention
In dermatology, the pandemic has created a new clinical environment where patients are no longer being seen in the office, but via telemedicine for non-urgent appointments. The conditions patients are seen for are often chronic, and many of the common treatments also include commonly used antibiotics and antimicrobials.
Dr Friedman observed that with patients staying home during the pandemic, clinicians are more inclined to refill a prescription to try to do right by patients. “They may be out of sight, out of mind, and we don’t always consider antibacterial stewardship when we are so concerned about the pandemic,” he said, noting that as patients may continue using antibiotic prescriptions they have on hand or request refills that allow them to continue treatment for longer periods of time, they could be unwittingly developing resistance. He emphasized that returning to careful antibiotic/antimicrobial stewardship is even more important during the coming months and years to prevent a wider occurrence of antibiotic/antimicrobial resistance.
“Pandemic or not,” Dr Friedman stated, “there are basic things that can be done to reduce risks for resistance. The first step is to limit prescriptions. The current standard of care is that you do not prescribe systemic antibiotics for acne for longer than 3 months,” he said.
A second approach is to optimize therapeutic efficacy by combining antibiotics with antimicrobials. Bacteria develop resistance when dosing is insufficient to wipe it out. This often happens with oral medications because of the long route to the site of the infection.
“Antibiotics are predominantly static, and therefore inhibit bacterial growth by blocking some biological pathway,” Dr Friedman said, “while antimicrobials can work through cidal mechanisms to kill organisms by causing stress to the outer wall or cell membrane. You can’t develop resistance to that.” Commonly prescribed antimicrobials include benzoyl peroxide, hydrogen peroxide, and chlorhexidine (often used as a surgical scrub). “In practice, when giving a topical antibiotic or an oral antibiotic, we also have patients regularly apply benzoyl peroxide to the skin in order to prevent bacteria from getting used to just the antibiotic by hitting it with a different antimicrobial,” Dr Friedman said. “That combination has been used to limit the emergence of organisms because you’re overloading the system.” He noted that the topical form of tetracycline, minocycline, is available is doses so high that bacteria cannot possibly survive and resistance cannot develop.
Although the combination approach is often effective when treating bacteria with topical antibiotics, it has limitations, especially in combination with oral antibiotics. Dr Friedman emphasized that stewardship is the most prominent and effective strategy for prevention of resistance. “It’s about meaningful, purposeful use ꟷ that is the best approach.” He suggested 2 effective strategies: The first is to use antibacterial doses of antibiotics in only short bursts, with therapeutic holidays between dosing periods. The second method is to use low, sub-antimicrobial doses that do not have the potential to induce antimicrobial resistance. An example of this, he said, is a controlled-release formulation of doxycycline 40 mg (used for acne and rosacea), in which the doses are too low to actually kill bacteria but still reduce its inflammatory spread.
According to the CDC, antibiotics should always be used when they are needed to treat disease, but in as many as 50% of cases, they are prescribed in incorrect doses or for conditions in which they are not needed at all.3 The COVID-19 pandemic has illuminated an ongoing concern about antimicrobial resistance and requires a re-commitment from clinicians to follow guidelines that promote good stewardship by prescribing the appropriate dose of the appropriate drug for the appropriate amount of time.
1. Nieuwlaat R, Mbuagbaw L, Mertz D, et al. COVID-19 and antimicrobial resistance: parallel and interacting health emergencies. Clin Infect Dis. Published online June 16, 2020. doi:10.1093/cid/ciaa773
2. CDC Antibiotic resistance threats in the United States. Atlanta (GA), USA: CDC; 2019. Accessed 8/25/20. Available at: https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.
3. CDC Antibiotic resistance threats in the United States. Atlanta (GA), USA: CDC; 2013. Accessed 8/25/20. Available at: https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.
4. Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr. 2016;4(2):10.1128/microbiolspec.VMBF-0016-2015. doi:10.1128/microbiolspec.VMBF-0016-2015
5. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. JAAD. 2016;74:945-973.