In this article an infectious diseases pharmacist identifies six steps to learning infectious diseases in pharmacotherapy, which is an important class in pharmacy school.
Authored By: Crystal K. Howell, PharmD, BCIDP, BCPS
[Last updated 2 March 2020]
What is it like to go through the infectious diseases portion of pharmacotherapy class in pharmacy school?…
Drinking out of a fire hose. This is the description most often used when discussing infectious diseases (ID) in pharmacy school. Not only are you learning a plethora of new diseases and drugs, but you are also having to recall, re-learn, or learn for the first time a significant amount of information regarding microbiology. While the complex interactions that take place from this additional puzzle piece (i.e., the bugs) can make learning ID challenging, overwhelming, and foreign, it can also make ID exciting, fulfilling, and incredibly fun.
In order to get to the fun part of ID, it is imperative to have a solid foundation which largely comes from pharmacotherapy courses in pharmacy school. As an educator and clinician, below are the six steps to learning ID that I have found to be most helpful for students of all professions. Consider re-organizing your notes in your ID pharmacotherapy course(s) to follow this format.
STEP ONE: The bugs
When studying most fields of pharmacotherapy, there is a patient’s disease state and the best drug for that patient. With ID there is a new puzzle piece: microorganisms, also known as “bugs.” Therefore, you need a solid foundation in medical microbiology so that you know all of the puzzle pieces in play.
Unfortunately, microorganisms do not follow the typical Latin rules of medicine with a prefix, root, and suffix that give clues to their meaning. This means that for clinicians, microbiology is a lot of memorization. Luckily, there is not as much memorization as there used to be for students. Thanks to revolutions in medical microbiology technology, gram stains have become a clinician’s new best friend. When studying microorganisms, first group them by type of organism (e.g., bacteria, fungi, virus). Using a gram stain, bacteria can then be further broken down into Gram-positive and Gram-negative organisms. A simple translation of a Gram stain is whether the microorganism has a cell wall. This is important to know as it changes the antibacterial agents that will be effective in killing the bug. Some additional tests to know that might be helpful in an ID course but are not as clinically relevant as they used to be include catalase, hemolysis patterns, pyr tests, lactose fermentation, and the oxidase test. Some hospitals will still use these traditional biochemical tests, so they are often still presented in ID pharmacotherapy courses.
STEP TWO: Where and when to expect the bugs
Humans exist through a symbiotic relationship with bacteria and having a normal healthy flora is important to healthy living [1]. So how do we know when the organism is a friend or foe?
There are several sites within the body that are colonized with normal flora. As one of my students put it, pretty much any part of the body that is exposed to air, is colonized. The skin, mouth, lungs, and gastrointestinal tract all have microorganisms that normally live there but do not normally cause disease. Other body sites are largely considered to be sterile. Examples of a sterile site include the blood, bone, muscle, heart, and brain.
By knowing the potential source of infection (i.e., where the bug is), one can begin differentiating colonizers from pathogens. For example, an organism in a sterile site is almost always a pathogen and should not be considered a colonizer. There are a couple of caveats with this having to do with the technique by which the specimen was collected (beware contaminated samples), but this is still a good general rule of thumb. Where it can get more complicated is when the source is a normally colonized site. For instance, the most common cause of community acquired pneumonia is Streptococcus pneumoniae. This organism is also one of the most common organisms within a person’s normal flora in the lungs [2]. Recognizing what risk factors the patient has for an infection as well as if their signs and symptoms are consistent with an infection can help you differentiate if the bug is a colonizer or a pathogen. A common scenario that happens in practice is when a patient does not have symptoms of a urinary tract infection (UTI) but has a positive urine culture with typical organisms that colonize the urethra. Because the patient does not have symptoms, the culture does not represent an infectious disease and instead represents colonization of the urethra [3]. Correlating the patient’s clinical picture can help distinguish between colonizers, contaminants, and pathogens.
STEP THREE: Drugs and Bugs/Drugs
Now that you have reviewed medical microbiology, normal flora, and common pathogens, it is time to talk about drugs.
This is another place where students commonly feel like they are drinking out of a fire house. Since the discovery of penicillin, there have been incredible strides in the development of antimicrobials. There are several drug classes and the drugs within each drug class vary just enough to frustrate students. In addition, while it may seem that the route of elimination of a drug is easy to look up and therefore does not need to be memorized, this is not the case with ID. A good clinical example would be if you have a patient that has a UTI and the team wants to use moxifloxacin. As the pharmacist you should be able to inform the team that moxifloxacin is hepatically metabolized to an inactive form and therefore will not concentrate well in the urine as the active moiety in order to treat the infection [5].
While it is important to understand the pharmacokinetics of the drugs, it is also important to recognize that the body has several protected sites with innate barriers limiting what drugs can get to the site. A common example of this is an infection in the brain. The brain is protected by the blood brain barrier prohibiting large molecules from being able to reach the brain. The pharmacist can help the patient care team by providing information on if the drug in question will be able to overcome the barrier and get to the site of the infection.
The other important phenomena to remember is that the drug acts on both the body and the bug through pharmacodynamics. With the bug, this represents the most effective way the drug kills the bug and usually falls into the categories of concentrations dependent, time dependent, and area under the curve dependent. In a person, antimicrobial agents act on the body largely through side effects. Though antimicrobials have been able to do amazing things and save lives, they are not benign. Even when used appropriately, antimicrobials can cause harm [6].
Therefore, it becomes even more imperative that the right drug is used. In order to determine the right drug, one must consider the drug’s spectrum of activity. Based on a combination of the drug’s mechanism of action, the drug’s pharmacodynamics, and the patient’s pharmacokinetics, each drug has a unique spectrum of activity (meaning each drug only works on certain bugs). For instance, vancomycin works by binding to the precursors needed for cell wall synthesis. Since only Gram-positive organisms have a true cell wall, vancomycin’s spectrum of activity is limited to Gram-positive microorganisms [7]. If you already know which microorganisms those are by reviewing medical microbiology from above, then this step should be easier than simple memorization. As with all things in ID, it is not always that simple. However, trends and concepts such as mechanisms of action can certainly help as you are initially learning spectrums of activities and can prevent mass amounts of rote memorization.
Additional resources including practice tests, quick fire tests, and rapid fire tests can be found under the training section of this site here if you are interested.
STEP FOUR: Differential and standard therapy
The next step is to match up the patient’s signs and symptoms with an illness script that is consistent with the presentation. If an infection is high on the list of possibilities (known as a differential) then the next step is to consider the potential source of infection.
Based on the anticipated source of an infection, you can determine what bugs to expect for both colonizers and pathogens. From there, match up the anticipated microorganisms with the drugs that have a spectrum of activity that would cover those organisms. This should line up well with standard therapies available in the guidelines. If there are any discrepancies, see if it is a drug issue. For example, daptomycin will kill methicillin-resistant Staphylococcus aureus (MRSA) which is a Gram-positive cocci. However, daptomycin is not recommended for MRSA pneumonia because it is inactivated by lung surfactant and therefore is not as effective as other therapies [8].
When reviewing the guidelines or best available literature, make sure to ascertain the drug, dose, route, frequency, anticipated duration, monitoring, and any important counseling points. By preparing this information you can more easily move on to step 5 and 6.
STEP FIVE: Ask why not?
While a toddler, and similarly most of your future preceptors, will continuously ask “why?” to the point of exhaustion, this is your chance to reply with: “why not?” You have gone through the necessary steps to determine what the standard therapy is and why it is considered standard. Now it is important to recognize if there are any patient or organism factors that would make the standard therapy an inappropriate choice for your current patient. This is most often tested through a patient case or interactive activity in a didactic setting. Examples of patient-centered reasons to consider when evaluating if the standard recommended therapy is the BEST therapy include but are not limited to: patient allergies, contraindications, drug-drug interactions, drug-disease interactions, drug-food/ lab interactions, tissue penetration, patient specific pharmacokinetics, and lack of access to the drug.
Examples of organism-related reasons that the standard therapy might not be appropriate in a patient case include but are not limited to risk factors for resistance, identifiable resistance patterns, and tropisms for particular areas within the body such as neural tissue. Organisms have an evolutionary rate that is exponentially faster than that of humans. Therefore, they are faster to adapt to an environment of antimicrobials than we are to organisms that are resistant to our drugs. Given recent legislation including the GAIN act, we have been fortunate to have several new antimicrobials come to the market recently [9]; however, they are designed for specific resistant organisms.
Technology is still developing the best way to differentiate genotypic capability of resistance (i.e., what we get when testing for the presence of resistance genes) from phenotypic expression of resistance (i.e., what results we get from susceptibility testing that is presented in antibiograms). Established risk factors for resistance and specific patterns within microbiologic sensitivity results can help the clinician and their team determine if a broader antimicrobial agent is necessary. In general, the narrowest agent possible is preferred because a narrow and targeted spectrum of activity will help protect the patient’s normal flora, decrease the patient’s risk for a resistant organism in the future, and will hopefully decrease local rates of resistance in the future allowing our current antimicrobials to be effective for longer. Therefore, clinicians must consider a careful balance between using broad spectrum agents to protect an acutely ill patient with risk factors for a resistant organism and using the narrowest agent possible so that they can save future acutely ill patients.
One way to help you practice with understanding the appropriate “why not?” questions to ask is to utilize the antimicrobial selection worksheet available on the IDstewardship training site.
STEP SIX: Tailoring therapy
You now know all the pieces to the puzzle. As one of my professors put it: “You know the bugs, the drugs, and about the patient also known as Doug.”
(In this figure, the name Doug is representing a person)
- You are anticipating that the patient has an infection based on their signs and symptoms being consistent with that of an infection.
- You have done your best to use those signs and symptoms to clue you in to a possible source of infection.
- Based on the possible source, you have a list of expected pathogens and a list of potential colonizers.
- You have matched that information up to the drugs most likely to cover those potential pathogens and if the drug can reach the suspected site of infection.
- You have looked up the necessary resources to come up with viable, evidence-based solutions and evaluated those solutions for any caveats for why they may not be appropriate for a specific case.
- Now, the last step, tailor the therapy to the most optimized regimen.
In practice this will hopefully be a discussion between the physician, nurse, pharmacist, and most importantly, the patient. Often, it will also be important to bring the patient’s insurance in on the conversation. In a pharmacotherapy course, this may not always be possible.
The ability to synthesize information and apply it to a unique case is often tested through a patient case. There is usually only one correct answer, or at least one BEST answer to facilitate grading. To practice, try coming up with your own cases and design scenarios that have multiple caveats that force you down to one answer. For example, consider creating a case with a drug allergy and a drug – drug interaction. Or have a case with risk factors for resistance, and a drug – disease interaction.
Closing Comments
Pharmacy school is hard. Students take a significant amount of college credit hours each semester, are encouraged to work outside of school for real world practice, and are told to participate in the “silent curriculum” of extra-curricular activities. In a 24-hour day, that alone can be overwhelming. In courses such as ID where there is a whole new puzzle piece to consider, it can often lead to a paradigm shift in the way students think. Not every student realizes this at the same time in the course. Therefore, it is not uncommon for students to feel as if they are drinking out of a fire hose during their ID course.
I have seen many students succeed by utilizing the six steps outlined above when they study. Hopefully, this will also help you while you are in the pharmacotherapy course, because like it or not ID never goes away. It is one of the only universal and non-discriminatory disease processes out there. I recommend all students also take an ID APPE rotation so that they can get more practice with real world application of the material prior to becoming a licensed pharmacist. In order to help prepare you for an ID APPE and the NAPLEX, consider reading the articles “Five Tips to Help Prepare for a Pharmacy School Rotation in Infectious Disease” and “How to Study Antibiotics for the NAPLEX or an ID Rotation Using LearnAntibiotics.com” available on this site.
Welcome to the world of ID. We need your help in the great fight to eliminate infectious diseases.
REFERENCES
1. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy D. Role of the normal gut microbiota. World J Gastrolenterol 2015;21(29):8787-803. Doi: 10.3748/wjg.v21.i29.8787.
2. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of Adults with Community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200(7):e45-e67. Doi: 10.1164/rccm.201908-1581ST
3. Nicolle LE, Gupta K, Bradley SF, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis 2019;68(1):e83-e110. Doi: 10.1093/cid/ciy1121
4. Centers for Disease Control and Prevention. About Antibiotic Resistance. https://www.cdc.gov/drugresistance/about.html . Published: November 4, 2019 Accessed: February 24, 2020.
5. Moxifloxacin (Systemic). In: Lexi-Drugs Online. Hudson, OH : Lexi-Comp, Inc.; [Updated February 19, 2020; Accessed February 24, 2020]. http://online.lexi.com.proxy.hsc.unt.edu/lco/action/doc/retrieve/docid/patch_f/1799129?cesid=aBnLSn5Rp4R&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dmoxifloxacin%26t%3Dname%26va%3Dmoxifloxacin
6. Jones BE, Ying J, Stevens V, et al. Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia. JAMA Intern Med 2020 Epub ahead of print doi: 10.1001/jamainternmed.2019.7495
7. Vancomycin [package insert]. Baudette, MN; ANI Pharmaceuticals, Inc.; January 2017.
8. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63(5):e61-e111 doi: 10.1093/cid/ciw353
9. CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019.
10. Centers for Disease Control and Prevention. U.S. Action to Combat Antibiotic Resistance. https://www.cdc.gov/drugresistance/us-activities.html Published: November 4, 2019. Accessed February 24, 2020.
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