Skin Infections: New Knowledge, Unmet Needs, and the Evolving Landscape

Rates of skin infections have risen dramatically in recent decades and continue to exacerbate burdens already experienced by many resource-constrained health care systems. Relatively recent initiatives have led to a greater understanding of skin infections as well as how to manage certain infections not amenable to standard approaches. Although the treatment landscape continues to evolve, certain challenges in treating skin infections persist. In addition, the COVID-19 pandemic has further challenged many clinicians’ understanding of skin infection incidence and management, underscoring a need for greater research and insight into the effects of virus-driven health crises in dermatologic care.

In this article, we explore unmet needs and changes in the treatment landscape for skin infections as well as the effect of the COVID-19 pandemic on the understanding and management of skin infections.

Current Challenges, Unmet Needs

Often, the most significant challenge in treating skin infections is determining the cause of the infection as well as identifying the most optimal treatment, according to dermatologist Angela J. Lamb, MD, an associate professor in the department of dermatology at Mount Sinai in New York City. “There can be many bacteria and sometimes fungi that cause skin rashes and infections, and many times the best way forward is to get a sample,” she told us. “The challenge can be waiting for these results to come back, but often you have to start treatment before you know exactly what is causing the problem,” she said, suggesting there may be a risk of prescribing inappropriate or insufficient treatment in some cases.

Dr Lamb added that perhaps the largest limitation in the management of skin infections is related to the high prevalence of “superbugs” which “are able to evade the antibiotics and antivirals available to treat” the treatment-resistant strains. Specifically, a superbug comprises microbial strains with increased and/or multiple mutations that confer antibiotic resistance. The multidrug-resistant pathogen Mycobacterium tuberculosis is an example of a highly dangerous superbug that infects nearly one-third of the population.1


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Overuse and overreliance on certain classes of antibiotics have contributed considerably to the worldwide increase in antibiotic resistance.1 Emerging treatment options for multidrug-resistant gram-positive cocci and Gram-negative bacilli include ceftaroline, ceftobiprole, dalbavancin, fosfomycin, tedizolid, as well as regimens including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, minocycline, fosfomycin, eravacycline, plazomicin, and cefiderocol.2

Changes in the Treatment Landscape

In 2018, the estimated global treatment market for acute bacterial skin and skin structure infections was $7.27 billion, with no indication this value will remain stagnant.3 In fact, Fortune Business Insights estimates that the global treatment market for skin infections will rise to $14.97 billion by 2026, more than doubling over an 8-year period.3 The leading segment in the skin infection treatment market is expected to be related to community-acquired acute bacterial skin and skin structure infections, driven predominantly by accelerated research and development in the field as well as the unmet treatment needs for patients with these infections.3

More recent changes in the treatment landscape for skin infections have been predominantly attributed to the development of better targeted antibiotics, Dr Lamb explained. “There are more specific antibiotics to treat certain infections, and we have more information about what causes certain fungal infections and what we can do to treat them.”

Since 2005, the US Food and Drug Administration (FDA) granted fast-track approval for several new antibiotics for the treatment of skin and soft tissue infections, including omadacycline, ceftaroline, dalbavancin, tedizolid, and telavancin.4 Within the past 5 years, the FDA approved delafloxacin, a fourth-generation fluoroquinolone, for the treatment of adults with acute bacterial skin and skin structure infections “caused by designated susceptible bacteria,” according to the drug’s approved prescribing label.5

In March 2021, the FDA approved oritavancin, a long-acting lipoglycopeptide antibiotic, for the treatment of adults with acute bacterial skin and skin structure infections resulting from susceptible isolates of designated gram-positive microorganisms. Given that nearly 14 million people in the United States are affected by these skin infections each year, this approval may potentially have significant implications for patients and the health care system at large.6

The Effect of COVID-19

The COVID-19 pandemic has had devastating effects across the globe, and many of these effects on different dimensions of health and everyday life may not yet be apparent. The massive uptake in personal hygiene during the health crisis, however, may have had positive effects, particularly in the area of skin infections.

In 2021, data from across the globe pointed to a troubling association between COVID-19 and cutaneous manifestations, including vesicular eruptions, petechial/purpuric rashes, acral lesions, livedoid lesions, urticarial rash, and maculopapular-erythematous rash. These reports weren’t necessarily surprising, given the skin frequently presents lesions caused by other viral infections.7 Certain medications used in the treatment of COVID-19, such as the anti-interleukin 6 receptor humanized monoclonal antibody tocilizumab, may be associated with an increased risk of skin infection, along with other cutaneous side effects.8

Despite these findings, Dr Lamb noted that is currently no hard data on whether COVID-19 has contributed significantly to any specific skin infection. “COVID-19 is a viral infection that does result in some skin manifestations in some patients,” she said. “Yet we do not have data that COVID-19 caused specific skin infections nor that during the pandemic people had more skin infections related to the novel coronavirus.” Further research is likely necessary to understand the role the pandemic has played in skin infections, she indicated.

In contrast, certain skin disease may have actually decreased during the COVID-19 pandemic, according to recent research. In a retrospective study which assessed medical records of patients who visited hospitals between 2018 and 2020, researchers evaluated the rates of contagious skin diseases such as scabies, varicella, impetigo, and molluscum contagiosum.10 The investigators found a decreasing trend from 2018 to 2020 in the numbers of patients diagnosed with these skin diseases.

According to the researchers, the reduced rates of impetigo, molluscum contagiosum, and scabies may have been likely related to improvements in hand hygiene during the pandemic. Still, it is unknown whether the rates of skin infection diagnoses were truly abated due to improved personal hygiene or if the pandemic delayed diagnoses of these diseases due to social distancing recommendations.

Take Home

Given the high health and cost burdens of skin infections in the population, particularly skin infections that have become refractory or resistant to standard treatment, there is a need for more optimal management of these disorders. Further research into skin infections caused by Staphylococcus aureus, common bacteria resistant to several antibiotics, is especially needed to facilitate discovery of safer and more effective management strategies. Emerging agents are on the horizon, however, as evidenced by the expedient growth of the skin infection treatment market. Dermatologists and other clinicians who care for patients with skin infections should remain up to date on the growing research for novel and targeted agents to ensure treatment goals are ultimately met in their patients with these conditions.

References

  1. Koch N, Islam NF, Sonowal S, Prasad R, Sarma H. Environmental antibiotics and resistance genes as emerging contaminants: Methods of detection and bioremediation. Curr Res Microb Sci. 2021;2:100027.
  2. Giurazza R, Mazza MC, Andini R, Sansone P, Pace MC, Durante-Mangoni E. Emerging treatment options for multi-drug-resistant bacterial infections. Life (Basel). 2021;11(6):519.
  3. Fortune Business Insights. The global acute bacterial skin and skin structure infections (AbSSSI) treatment market size was valued at USD 7,270.9 million in 2018 and is projected to reach USD 14,972.6 million by 2026, exhibiting a CAGR of 9.5% between 2019 and 2026. Published July 2019. Accessed February 22, 2022. Available from: https://www.fortunebusinessinsights.com/industry-reports/acute-bacterial-skin-and-skin-structure-infections-absssi-treatment-market-100971#:~:text=The%20global%20acute%20bacterial%20skin,9.5%25%20between%202019%20and%202026
  4. Hindy JR, Haddad SF, Kanj SS. New drugs for methicillin-resistant Staphylococcus aureus skin and soft tissue infections. Curr Opin Infect Dis. Published online published online November 22, 2021. doi:10.1097/QCO.0000000000000800
  5. US Food and Drug Administration. Prescribing information. Delafloxacin. Accessed February 22, 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf
  6. Businesswire. Melinta Therapeutics announces FDA approval of KIMYRSA™ (oritavancin) for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI). Published March 15, 2021. Accessed February 22, 2022. Available from: https://www.businesswire.com/news/home/20210315005224/en/Melinta-Therapeutics-Announces-FDA-Approval-of-KIMYRSA™-oritavancin-for-the-Treatment-of-Adult-Patients-with-Acute-Bacterial-Skin-and-Skin-Structure-Infections-ABSSSI
  7. Fernández-Lázaro D, Garrosa M. Identification, mechanism, and treatment of skin lesions in COVID-19: A review. Viruses. 2021;13(10):1916. doi:10.3390/v13101916
  8. Türsen Ü, Türsen B, Lotti T. Cutaneous sıde-effects of the potential COVID-19 drugs. Dermatol Ther. 2020;33(4):e13476. doi:10.1111/dth.13476
  9. Chun EJ, Kim JK, Yang SY, Kim SS, Kim CW. Changes in the incidence of contagious infectious skin diseases after the COVID-19 outbreak. J Eur Acad Dermatol Venereol. 2022;36(1):e3-e4. doi:10.1111/jdv.17640

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