Distribution of genes encoding tetracycline resistance and aminoglycoside modifying enzymes in Staphylococcus aureus strains isolated from a burn center M. Emaneini,1, R. Bigverdi,1 D. Kalantar,1 S. Soroush,1 F. Jabalameli,1 B. Noorazar Khoshgnab,1 P. Asadollahi,2 and M. Taherikalani2 PMID: 24133400

[cite source="doi"]10.1093/jac/dkaa485[/cite]

[cite source="doi"]10.1093/jac/45.6.763[/cite]

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. 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. The World Health Organization (WHO) has adopted a Global Action Plan and the White House has included strategic actions to improve the health and well-being of Americans by changing the course of antibiotic resistance in their 2020 National Action Plan.

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. In addition, healthcare-associated UTIs acquired in a hospital or healthcare setting are 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. Furthermore, indwelling urinary catheterization for hospitalized patients is a significant risk of 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.

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. 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.

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 the appropriate utilization of antibiotics are called antimicrobial stewardship programs. These programs are currently endorsed by the CDC and WHO and are required in many settings by the 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, an 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%.

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, the 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. 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 UTIs are just as effective as longer durations. 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, and 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 cure the infection adequately.

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 a significant impact on 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 optimal and effective antimicrobial stewardship.