The Journey of Research


Guest post by Kim Hugel

When I was approached to blog about the residency project that we were doing with one of the Calgary area residents, I admit, I was reluctant.  Research is a daunting task as it is and, for me, blogging about it ranked right up there in terms of intimidation.  However, I personally think that growth occurs from doing the very things that scare you most and some people may find it useful to see the steps taken during our project.  And so the blog begins...

Step One

The first step was to create a research question and project. The project had to be simple and practical enough to be completed within the time period a resident has, have data points that were readily available for collection and that would contribute something meaningful to clinical practice. Our research question needed to be concise and specific.  As is the case with most research projects, ours was created from an issue identified in practice. 

Osteosarcoma is the most commonly diagnosed solid bone tumour in children.  However, event free survival (EFS) has not improved significantly over the past 20 years, remaining in the 70% range overall and less than 25% for patients presenting with metastatic disease. These dismal stats make dose intensification and avoidance of treatment delays important in this patient population.

The standard of care for pediatric osteosarcoma, according to the Children's Oncology Group, is currently intense cycles of chemotherapy that include doxorubicin, cisplatin and methotrexate.  Like all oncology patients receiving intense chemotherapy, there is a risk of febrile neutropenia that can potentially delay therapy or put patients at risk of infectious complications. 

Piperacillin/tazocin is frequently used as first line therapy for episodes of febrile neutropenia, but use of beta-lactam antibiotics had been avoided in recent months at our center due to the documented interaction with methotrexate (MTX).   According to Lexi-comp, the use of beta- lactams with MTX potentially delays clearance of MTX which could lead to increased adverse effects, such as mucositis and renal dysfunction, and delay of treatment until MTX is cleared.

This led us to using more intense, broad spectrum antibiotics when patients presented with fevers close to MTX administration.  However, we had only started to avoid the use of pip/tazo in recent months, so:

  • How clinically significant was this interaction
  • How strong was the evidence supporting this interaction? 
  • Was there a way of determining which antibiotics this interaction actually pertained to?

We routinely measure MTX levels following administration based on the protocol the child is being treated based on.  In addition to MTX levels, physician orders and other lab values are readily available through an electronic medical order entry system.  We were able to retrospectively look back at patients who had received identified antibiotics during MTX cycles and determine if clearance was affected as well as look at other lab values that would indicate toxicity (such as serum creatinine, required hydration). 

Breaking It Down

As stated above, we started using more “big gun” antibiotics due to the potential interaction between beta-lactams and MTX but had previously not adjusted antibiotic choice. 

This project would help us determine if we were using broader spectrum antibiotics unnecessarily and hopefully help to guide clinical decisions.  As well, since the data was readily available through electronic records, it was reasonable to think that a resident would be able to complete the project during their allotted time. Our research question needed to be clear and specific:

In oncology patients (age 1-40) who have received MTX at doses ≥ 500 mg/m2, does administering a concurrent antibiotic (pip-tazo, meropenem, amoxicillin, cefepime, ceftriaxone or penicillin) have an effect on the clearance of MTX?”



Stayed tuned to next entry for Step Two:

Looking at the current literature and starting the proposal.