What is antimicrobial resistance?
Impact of AMR on cancer management
Impact of AMR on cancer immunotherapy
Impact of AMR on cancer care outcomes
References
Further reading
Cancer patients are at higher risk of developing infections due to a weakened immune system. Antimicrobial resistance (AMR) can negatively affect cancer patients by reducing anticancer treatment efficacy, inducing chronic infection, and increasing mortality risk.
What is antimicrobial resistance?
Antimicrobial resistance (AMR) occurs when microorganisms, such as bacteria, viruses, fungi, and parasites, acquire genetic mutations over time and subsequently develop resistance against therapeutic interventions to eliminate them. This makes it hard to treat microbial infections and inhibits the chain of microbial transmission.
The World Health Organization (WHO) declared AMR one of the top ten global public health threats. Inappropriate use or overuse of antimicrobial medicines is primarily responsible for AMR development. The emergence of drug-resistant microbes makes existing antimicrobial treatments ineffective, which in turn increases the risk of life-threatening infections during various medical procedures, such as surgery, organ transplantation, and cancer chemotherapy.
Impact of AMR on cancer management
AMR can negatively impact cancer treatment outcomes and increase cancer-related mortality. A reduction in the number and functionality of white blood cells is the hallmark of cancer, which generates an immunocompromised state in cancer patients. Various cancer therapies, including surgery, bone marrow transplantation, radiotherapy, and chemotherapy, further suppress the immune system of cancer patients. All these factors collectively increase their susceptibility to infections.
Infection is the primary cause of hospitalization for one in five cancer patients undergoing treatment. The most common infections in hospitalized cancer patients are bacterial pneumonia and sepsis. According to the current estimation, the mortality rate due to severe sepsis is 8.5% in cancer patients.
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Antibiotics are considered the first line of choice for treating bacterial infections in cancer patients. In this scenario, the rapid emergence of drug-resistant bacteria burdens cancer management, leading to poor prognosis and increased mortality.
Impact of AMR on cancer immunotherapy
Antibodies targeting immune checkpoints, such as cytotoxic T-lymphocyte antigen 4 and programmed death receptor 1, have recently gained immense attention because of their high potency in treating different types of cancers.
Immunotherapies involving these check-point inhibitors are associated with a range of immune-related adverse effects, including skin rash, colitis, pancreatitis, hepatitis, and pneumonitis. These adversities are caused by drug-induced upregulation of the immune system.
The treatment of refractory or severe adversities is primarily done by immunosuppressants, such as steroids and tumor necrosis factor (TNF) inhibitors. These drugs increase the susceptibility of cancer patients to infections. Moreover, immune check-point inhibitors can increase the risk of certain infections in cancer patients, including tuberculosis and listeriosis.
There is evidence showing that cytotoxic T-lymphocyte antigen 4 inhibitor (ipilimumab) therapy increases the susceptibility of melanoma patients to opportunistic infections, including invasive aspergillosis, cytomegalovirus-induced hepatitis, and pneumocystis pneumonia.
Studies have shown that the risk of acquiring infection is significantly higher in cancer patients who receive immunosuppressive drugs, including corticosteroids and infliximab. Regarding immune check-point inhibitors, existing evidence shows that the risk of severe infection is higher in patients who receive combination therapy with nivolumab and ipilimumab than those who receive pembrolizumab. This variation is likely due to the differences in the severity of drug-induced adversities.
Cancer patients with microbial infections primarily undergo prolonged antibiotic treatment. However, long-term use of broad-spectrum antibiotics can significantly increase the risk of the emergence of AMR. This further complicates the management of cancer-related morbidity and mortality.
Why AMR is a major issue for cancer treatment and care
Moreover, cancer patients exhibit higher susceptibility to hospital-acquired infection, which is another major source of AMR. Hospital-acquired infection is also the major reason of intensive care unit (ICU) admission for cancer patients.
Impact of AMR on cancer care outcomes
AMR exerts a significant negative effect on cancer management because of the high reliance of cancer patients on antibiotics to prevent and treat infections. Although advancement in medical care facilities has considerably increased the survival of cancer patients, current therapeutics continuously increase the risk of infection and development of AMR.
According to available literature, about 26% of infections that arise in cancer patients after chemotherapy develop resistance to standard prophylactic antibiotics. It has been predicted that a reduction in antibiotic efficacy of 30 – 70% in hematological cancer patients would lead to 4,000 – 10,000 additional infections and 500 – 1,000 additional deaths annually in the United States.
The most common reasons for antibiotic-resistant infections include pre-existing health conditions, previous antibiotic therapies, urinary catheters, or other sources associated with urinary infections. For cancer patients, having antibiotic-resistant infections increases the risk of persistent bacteremia, metastatic infection, ICU admission, and mortality. These unfavorable outcomes are observed in both adult and pediatric patients with hematological cancers or solid tumors.
In patients with solid tumors, chemotherapy- or radiation therapy-related neutropenia, anatomic barrier disruption by medical devices or surgical procedures, and obstruction due to primary or metastatic tumors are the major causes of infection.
AMR has been found to have a higher impact on cancer patients of certain ethnicities, including African American, Latinx, and indigenous communities. This could be due to higher usage of unprescribed antibiotics, inaccessibility to healthcare facilities, higher rates of travel to countries with high AMR burden, and higher employment in food animal production.
AMR-mediated reduction in antibiotic effectiveness significantly increases healthcare costs globally. In the United States, AMR is estimated to cost nearly 20 billion USD in healthcare and 35 billion USD a year in lost productivity. It has been observed that cancer patients with methicillin-resistant S. aureus infection have a 3-times higher risk of prolonged hospital stay than those without this infection, which further increases healthcare costs.
References
Further Reading
Hormonal steroids found to boost drug resistance in gonorrhea bacteria