Can someone help me please?

Question

A 45 year-old woman complaining of breast pain was diagnosed with having HER2-positive breast cancer. The patient underwent lumpectomy followed by a period of chemotherapy including adjuvant treatment. Over the course of their treatment, the patient developed a urinary tract infection that required antimicrobial therapy, which initially consisted of a trimethoprim/sulfametoxazole combination drug. However, the patient during the course of her therapy suffered multiple recurrent infections and was, consequently, enrolled in a clinical trial to test the efficacy of a new mannoside anti-infective agent.

Question: Discuss the roles of the three components of the patient’s treatment for her relapsing UPEC infection. Your discussion should include the pertinent virulence factors that contribute to the establishment of the infection and the initial treatment failure.

Answer 1

This patient has HER2-positive breast cancer. HER is a Human Epidermal growth factor Receptor 2 which is an intrinsic tyrosine kinase receptor. When this receptor is mutated it often becomes over-activated. This over-activation often leads to worsening prognosis as HER comes from the family of the epidermal growth factor receptor and further stimulate growth of cancer cells. Trastuzumab (Herceptin) is a monoclonal antibody that will bind to Human Epidermal Receptor-2 and help destroy the receptor using the bodies immune system. Patient who are (-) for HER-2 breast cancer cannot use Herceptin for treatment. Patients with breast cancer are often screened for other receptors like Estrogen & Progesterone Receptor and BRAC 1/2 as this will affect treatment. Patients who about to start Trastuzumab (Herceptin) should undergo echocardiography as this medication can be cardiotoxic and lead to cardiomyopathy with decreased left ventricle ejection fraction which will result in heart failure.

She has been undergoing chemotherapy. Chemotherapy often makes patients immunocompromised. This could explain her recurrent UTI infection. In addition, her continued use of Bactrim (trimethoprim/sulfamethoxazole) and her recurrent UTI's could indicate possible resistance. UPEC often contains several virulence factors that allows it to survive. One of particular note is the FimH which allows E. Coli to bind and adhere to the lining of the urinary tract. This prevents the bacteria from being eliminated during normal urination. In addition, woman are often more likely to get UTI's due to short length of the female urethra. Her enrolled in a clinical trial to test the efficacy of a new mannoside anti-infective agent could provide her with relief but she may also need further escalation for her antibiotics regimen, urinary analysis, and culture to determine a susceptible antibiotic.

I hope this help you. Good Luck!!

Answer 2

Great question! There are a lot of things to consider with this one. The cancer and the treatment are the key here. THink about the cancer treatment. Does it kill cells or help them survive? Is it specific for cancer cells, or does it kill other cell types too? What parts of the body are important for urinary tract infections? Then think about how she was treated for the infection, but it kept coming back.

After thinking about those questions, you'll remember that chemotherapy kills cells, typically cells dividing quickly. Your immune system is completely made up of cells that divide quickly. Chemotherapy will kill most of them. Your body fights off infection with its immune system - but you've just killed it, so you'll need some help.

Trimethoprim/sulfamethoxazole (brand name is bactrim) is a wonderful combination antibiotic. But this patient keeps getting infections - meaning the bacteria just isnt responding to it - and this is where your question really gets going.

What things impact the bacteria's ability to infect the urinary tract and the initial treatment failure?

Well we've already talked about how not having an immune system makes it hard to control an infection.

Now consider the patients gender. Males tend not to get urinary tract infections very often. This is because the urinary tracts of males and females are different. The longer urethra in men makes it a lot harder for bacteria to get far enough inside to cause an infection. The next thing is to look at how quickly resistance occurs to the antibiotic. Next look at mannose and how that is important for UPEC to survive and infect a host. How might a mannosidase (enzyme that breaks mannose) attack that bug?