Antimicrobial resistance continues to play a significant role in clinicians’ everyday practice. Healthcare providers are now faced with clinical scenarios where selecting an antibiotic to treat an infection is becoming increasingly more difficult, and in some cases impossible. Highly resistant microbes, or “superbugs”, are becoming increasingly common, and for many physicians, the everyday norm. One of the ways in which bacteria become resistant is through the acquisition of resistance genes. These resistance genes can be shared between species of bacteria, rapidly amplifying the spread and threat of these organisms. An important example is the OXA-48 resistance gene, which can cause bacteria to become resistant to last line antibiotics [1]. The Centers for Disease Control and Prevention (CDC) estimates that 2.8 million people are infected with an antibiotic resistant infection, with more than 35,000 people dying as a result [2]. The World Health Organization (WHO) has adopted a Global Action Plan and the White House has included strategic actions to improve the health wellbeing of Americans by changing the course of antibiotic resistance in their 2020 National Action Plan [3].
Urinary tract infections (UTIs) are described as the most common type of infection seen by healthcare providers in the outpatient setting. Studies demonstrate that incidence can be as high as 60% in women, with risks increasing with age, and with sexual activity in younger women [4]. In addition, healthcare associated UTIs acquired in a hospital or healthcare setting, is the most common form of healthcare acquired infection. The CDC notes that in 2015 there were 62,700 UTIs in acute care hospitals and that UTIs account for more than 9.5% of infections reported there [5]. Furthermore, indwelling urinary catheterization for hospitalized patients is a significant risk to urinary tract infection. With estimates as high as 25% of hospitalized patients receiving a short term indwelling urinary catheter, the risk for UTIs is increased. Urinary catheters are also used in many nursing home patients, representing approximately 5% of the residents, translating to about 50,000 patients at a given time [6].
Many studies have demonstrated that the overdiagnosis of UTIs is a significant cause of antibiotic prescription and overutilization. In one study, patients were prescribed antibiotics, even when urine cultures were negative [7]. Another study demonstrated that excessive workup for UTIs resulted in overtreatment with antibiotics, placing an exponential burden and cost on the healthcare system. In 2011, it was estimated that an average hospitalization with a primary diagnosis of a UTI was $2.8 billion in healthcare costs [8].
A focus on improving how healthcare providers diagnose and treat UTIs can have a profound effect on limiting risks of antimicrobial resistance, direct patient care and their subsequent outcomes, and the costs to the healthcare system. Programs put in place to improve appropriate utilization of antibiotics are called antimicrobial stewardships programs. These programs are currently endorsed by the CDC and WHO and are required in many settings by Centers for Medicare & Medicaid Services (CMS) and the Joint Commission.
An important point of focus to improve antibiotic prescription for UTIs is education on the distinction between symptomatic bacteriuria, and asymptomatic bacteriuria. Bacteriuria is defined as the presence of bacteria in a patient’s urine. However, in the absence of symptoms consistent with UTI, or asymptomatic bacteriuria, infection may not be implicated and antibiotics may not be required. With few exceptions (preoperatively for urological procedures and during pregnancy to name a few) antibiotics are typically not indicated for asymptomatic bacteriuria. Many studies demonstrate that bacteria can be detected in the absence of infection. According to the Infectious Disease Society of America’s (IDSA) most recent guidelines on asymptomatic bacteriuria, elderly men and women in long term care may have an incidence of asymptomatic bacteriuria as high as 50%. Furthermore, the IDSA notes that patients with long term urinary catheterization can have an incidence of asymptomatic bacteriuria up to 100% [9].
Another important point to consider when treating UTIs is deciding which antibiotic to use. Often, providers erroneously believe that so long as an antibiotic has activity, it doesn’t matter which antibiotic is selected for treatment. However, appropriate selection of an antibiotic is key to proper antimicrobial stewardship and can have a significant impact on both the outcome of the infection and the patient. Certain antibiotics, like fluoroquinolones (such as ciprofloxacin or levofloxacin), should be reserved when no other options are available, due to significant adverse reactions associated with its use [10]. Other antibiotics which are considered broad-spectrum (such as meropenem or ertapenem) should only be used when resistant microbes are suspected. There are many other intricate nuances that should be considered prior to selecting antibiotic therapy.
Lastly, the duration of therapy makes a significant impact as well on the development of antimicrobial resistance and adverse drug reactions. Multiple studies demonstrate that shorter courses of antibiotics for UTI are just as effective as longer durations [11]. The longer a patient is exposed to an antibiotic, the more at risk they are for potential side effects such as Clostridioides difficile, renal failure, hepatic toxicity, amongst others. Therefore, it is imperative that the appropriate duration of treatment is selected, one with the minimal amount of exposure necessary to adequately cure the infection.
Without drastic change and intervention antimicrobial resistance will continue to worsen. UTIs are among the most common causes of infection, and therefore one of the most common reasons antibiotics are used. Therefore, intervention in regard to the management of UTIs can provide significant impact in the reduction of antibiotic use. Education on the appropriate criteria for treatment, the antibiotic of choice, as well as the appropriate duration of therapy, is vital for an optimal and effective antimicrobial stewardship.
About the Author
Ari Frenkel is a board certified infectious disease and internal medicine physician as well as a children’s book author and musician. He has served as infectious disease medical director in multiple settings and established successful antimicrobial stewardship programs in underserved areas. His experience includes medical director of infectious disease for RCCH (Regional Care Partners), a corporate hospital system that had 14,000 employees and 2,000 doctors across 16 hospitals throughout the United States. Dr. Frenkel also served as a medical director in the nursing home and rehab setting and is well versed on infectious diseases pertaining to long term care. He served as a clinical instructor and preceptor for Lincoln Memorial University-DeBusk College of Osteopathic Medicine and Alabama College of Osteopathic Medicine. Currently, Dr. Frenkel is expanding his education and obtaining his masters in public health, via Yale’s School of Public Health. He serves as the chair for infection control at North Alabama Medical Center and the chief science officer of Arkstone Medical Solutions.
Due to the rising global threat of antimicrobial resistance, Dr. Frenkel dedicated his career to solving this predicament. He co-founded Arkstone Medical Solutions, a biomedical technology company that uses artificial intelligence and machine learning to democratize infectious disease expertise across many clinical settings. Using this technology, thousands of physicians and healthcare facilities now have access to the tools they need to provide antimicrobial stewardship and better care to their patients.
References
- Mairi, A., Pantel, A., Sotto, A. et al. OXA-48-like carbapenemases producing Enterobacteriaceae in different niches. Eur J Clin Microbiol Infect Dis 37, 587–604 (2018). https://doi.org/10.1007/s10096-017-3112-7
- https://www.cdc.gov/drugresistance/index.html
- https://www.hhs.gov/sites/default/files/carb-national-action-plan-2020-2025.pdf
- Medina M, Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol. 2019;11:1756287219832172. Published 2019 May 2. doi:10.1177/1756287219832172
- https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf
- https://www.cdc.gov/infectioncontrol/guidelines/cauti/background.html
- Sebesta EM, March A, Sayegh C, Li G, Love M, Badalato GM, Ferdschneider M, Cooper KL. Reducing overprescribing of antibiotics for suspected urinary tract infections in a health sciences campus student health service. Neurourol Urodyn. 2020 Jan;39(1):220-224. doi: 10.1002/nau.24173. Epub 2019 Oct 2. PMID: 31578755.
- Simmering JE, Tang F, Cavanaugh JE, Polgreen LA, Polgreen PM. The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998-2011. Open Forum Infect Dis. 2017;4(1):ofw281. Published 2017 Feb 24. doi:10.1093/ofid/ofw281
- Lindsay E Nicolle, Kalpana Gupta, Suzanne F Bradley, Richard Colgan, Gregory P DeMuri, Dimitri Drekonja, Linda O Eckert, Suzanne E Geerlings, Béla Köves, Thomas M Hooton, Manisha Juthani-Mehta, Shandra L Knight, Sanjay Saint, Anthony J Schaeffer, Barbara Trautner, Bjorn Wullt, Reed Siemieniuk, Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America, Clinical Infectious Diseases, Volume 68, Issue 10, 15 May 2019, Pages e83–e110, https://doi.org/10.1093/cid/ciy1121
- https://www.fda.gov/news-events/fda-brief/fda-brief-fda-warns-fluoroquinolone-antibiotics-can-cause-aortic-aneurysm-certain-patients
- Lee RA, Centor RM, Humphrey LL, Jokela JA, Andrews R, Qaseem A; Scientific Medical Policy Committee of the American College of Physicians, Akl EA, Bledsoe TA, Forciea MA, Haeme R, Kansagara DL, Marcucci M, Miller MC, Obley AJ. Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians. Ann Intern Med. 2021 Jun;174(6):822-827. doi: 10.7326/M20-7355. Epub 2021 Apr 6. PMID: 33819054.