In this article a current pharmacy student discusses how she is preparing during pharmacy school to handle antibiotic orders as a future clinical pharmacist.
Authored By: Deidra Lee, MHA, Pharm.D. Candidate 2021
Posted 18 October 2020
During our final year of pharmacy school, we typically apply the didactic training received and learn to be competent practicing clinicians. This time period, though challenging, proves to be a time of significant growth. It is imperative to prepare during this time to be able to function independently in the role of a clinical pharmacist upon culmination of our schooling.
Although clinical pharmacists practice in a variety of healthcare settings, there are tasks that are common to all settings. Handling antibiotic orders is a usual task that spans practice sites.
As a pharmacy student on an Infectious disease (ID) APPE elective rotation, there were recurring themes pertaining to each antibiotic order. Here are five clinical scenarios to anticipate when dealing with antibiotic orders…
1. Antibiotic allergy assessment
One of the most important things you can do as a pharmacist is to keep your oath to do no harm. Patients frequently report adverse drug reactions as an allergy. Therefore, it is important that we assess whether the patient has a true allergy (e.g., an anaphylactic reaction). Allergies range from a mild reaction, such as a rash, to a more severe reaction, such as urticaria and anaphylaxis.
There are 4 types of allergies1:
- Type I – IgE mediated
- Type II – IgG, IgM or cytotoxic-mediated
- Type III – IgG and IgM or immune-complex mediated
- Type IV – T cell-mediated
Penicillin allergies are a commonly reported and have consequences when it comes to antibiotic decision making. One of the easiest things that we can do is check the patient’s medication history to see if they have used another beta-lactam in the past. If the patient reports an allergy to amoxicillin, but recently safely completed a course of amoxicillin-clavulanic acid, then they certainly do not have an amoxicillin allergy!
Another potential option to clarify a patient’s penicillin allergy is penicillin skin testing or direct to oral challenge. Even if the patient has an allergy to one beta-lactam, it does not necessarily mean they will have an allergy to all beta-lactams. In fact, a lot of “cross reactivity” actually depends on the chemical structure of the drugs and their associated side chains. Challenging an antibiotic allergy should be done with caution and only after a thorough reliable medication allergy history is obtained.
Finally, there are instances where patients may undergo desensitization to receive a drug to which they are allergic. This is a major undertaking commonly done in an ICU setting, but it is sometimes warranted for conditions such as neurosyphilis when penicillin is the most effective option. Unlike an amoxicillin oral challenge or penicillin skin test which can inform the provider if an allergy is present, penicillin desensitization allows for administration of penicillin despite the presence of a type-1 IgE-mediated anaphylaxis allergy to penicillin.
Potentially helpful readings:
- Penicillin Allergy Review (NEJM, 2019)
- Evaluation and Management of Penicillin Allergy (JAMA, 2019)
- Antibiotic Allergy Review (Lancet, 2019)
- The 3 Cs of Antibiotic Allergy-Classification, Cross-Reactivity, and Collaboration (JACIP, 2017)
2. Therapeutic drug monitoring
Another critical component of antibiotic orders is therapeutic drug monitoring (TDM). This is the practice of measuring serum drug concentrations of drugs at specified intervals to attain a target level and optimize individual dosage regimens. Dose optimization and interpretation of the drug concentration requires consideration of the sampling time, the dosage history, the patient’s response, and the desired clinical targets.2
Common antibiotics that require TDM are vancomycin and aminoglycosides. Be mindful of less used anti-infectives, such as antifungals (e.g. itraconazole, voriconazole, posaconazole, and fluctyosine) may also require TDM. Attainment of target levels serve to minimize subtherapeutic dosing, as well as prevent toxicities associated with supratherapeutic levels. Vancomycin and aminoglycosides trough levels can be measured to prevent associated nephrotoxicity. Timing for measurement of troughs may vary based on institution, patient, and convenience. Protocols for pharmacokinetic dosing calculations may also vary by institution. It is important to never assume, instead ask for the institutional protocol and get the data you need before trying to make decisions about dosing and monitoring.
Potentially helpful readings:
- ASHP Vancomycin Guideline (AJHP, 2020)
- Nebraska Medicine Pharmacokinetics Training Packet
- Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology (JAC, 2014)
- Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients (EODMT, 2091)
3. Renal dose adjustments
Appropriate dosing based on renal function is an integral aspect of appropriate antibiotic therapy. Renal dysfunction can lead to reduced clearance of renal-eliminated drugs, which can lead to increased drug effects and toxicity. Many antibiotics are eliminated renally, thus requiring dose adjustments. Discerning which agents require renal dose adjustments can facilitate an informed decision when choosing an agent.
It is imperative to assess the degree of renal decline and the patient weight, as those factors also influence the dosing. The pharmacokinetic changes in certain populations, such as geriatrics, or pediatrics must also be considered. One oversight beware is that we seldom focus on increased renal function, which is directly related to renal clearance and consequently, drug effect.
Another useful insight is that the estimated renal function for patients on dialysis is a reflection of the dialysis machine and not a true indicator of the patient’s own renal function. Also, some antibiotics may alter parameters of renal function, such as creatinine, therefore the entire patient situation must be carefully assessed rather than making decisions based on a dynamic lab value. Ultimately, the characteristics of both the patient, drug, infection type, and offending organism(s) need to be considered when determining an optimal dosing regimen.
Potentially helpful readings:
- Renal Dosing of Antibiotics: Are We Jumping the Gun? (CID, 2019)
- Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update (Annals of Pharmacotherapy, 2020)
- Comprehensive Guidance for Antibiotic Dosing in Obese Adults (Pharmacotherapy, 2017)
4. Antimicrobial de-escalation or discontinuation
Antimicrobial de-escalation is one of the fundamental tenets of antimicrobial stewardship. It reduces the risk of drug resistant pathogens due to overuse of broad-spectrum antimicrobials and can simultaneously also reduce healthcare expenditures.
As a student on an infectious disease rotation, de-escalation of antibiotics was the core of my interventions. De-escalation in this sense refers to either switching to a narrower spectrum antibacterial agent or discontinuing therapy when appropriate. Appropriate knowledge of antimicrobial spectrum of activity, local antibiograms, patient history, and clinical guidelines dictate empiric therapy. However, microbiology data is what guides definitive therapy. Factors to consider include minimum inhibitory concentration (MIC) breakpoints, potential toxicity, patient preference, cost of agents, as well as convenience of dosing. One thing that I have learned as a student is to always have multiple options. With microbiology data, it is wise to be forward-thinking especially when dealing with multidrug resistant organisms and consider additional options to be tested for susceptibilities in the event that it is needed.
Another aspect of de-escalation often forgotten is discontinuation of antibiotic agents when no longer necessary. A recent example of this is the continuation of community-acquired bacterial pneumonia (CAP) treatment in COVID-19 pneumonia patients although no bacterial co-infection is apparent. The likely reasoning behind this maybe providers’ strict reliance on durations set by guidelines or preference based on experience.3 Another example is the delayed de-escalation of vancomycin despite negative MRSA nares in pneumonia patients. Ultimately, the patient’s condition, the microbiology data, and guidelines should be used conditionally when determining duration of treatment.
Potentially helpful readings:
- Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance (CMI, 2012)
- A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit (CID, 2016)
- Editorial Commentary: Antimicrobial De-escalation: What’s in a Name? (CID, 2016)
- Insights And Resources: Antibiotic Renal Dose Adjustments (IDstewardship)
5. IV to PO switch
The ideal administration of any medication is the one that achieves optimal drug concentrations with the least adverse effects. Oral administration is generally preferred over intravenous due to safety and convenience. Safety outcomes include reduced risk of catheter-related bloodstream infections, reduced hospital length of stay, and less risk of phlebitis.4 Convenience of dosing, as well as cost savings from oral options are also benefits of oral relative to intravenous medications.
However, there are some instances that warrant intravenous therapy. Nonetheless, when appropriate, step-down therapy from IV to PO should be considered. This intervention has similar outcomes to de-escalation and frequently reduces costs. Step-down to oral therapy requires the clinician to first assess the patient’s clinical status and the appropriateness of oral therapy (e.g., functional gastrointestinal tract, hemodynamic stability). Next the microbiology data should be assessed for susceptibilities. Antibiotic pharmacokinetic factors such as bioavailability, side effects, and frequency of dosing, coupled with patient factors should be considered when determining an agent.
Knowledge of IV to PO conversions and antibiotics with good oral bioavailability will be useful in facilitating easy transitions. It is important to familiarize yourself with the institution’s guidance as some institutions may have their own step-down protocols that pharmacists can follow without physician interventions.
Potentially helpful readings:
- Intravenous to Oral Therapy Conversion. Chapter 29 from the Competence Assessment Tools for Health-System Pharmacists Fourth Edition. 2008.
- Implementing a program for switching from i.v. to oral antimicrobial therapy (AJHP, 2001)
- Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines (Lancet, 2016)
- Switch over from intravenous to oral therapy: a concise review (Journal of Pharmacology and Pharmacotherapeutics, 2014)
- A Resource To Help With Changing From IV To PO Antibiotics (IDstewardship)
Clinical pharmacists practice in numerous healthcare settings such as outpatient clinics, hospitals, long-term care facilities, and physician offices. Irrespective of the various settings, most clinicians will have to process antibiotic orders. Pharmacists are uniquely positioned to promote antimicrobial stewardship, reduce healthcare costs, and optimize outcomes. Five simple interventions that clinical pharmacists can make include: (1) Allergy assessments; (2) Therapeutic drug monitoring; (3) Renal dosage adjustments; (5) De-escalation or discontinuation of antimicrobials, and (5) IV to PO conversion. I look forward to taking part in these activities as a future clinical pharmacist.
1. Bailey, R. 4 Types of Hypersensitivity Reactions. Thoughtco.com website. https://www.thoughtco.com/types-of-hypersensitivity-reactions-4172957. Published August 27, 2020. Accessed October 01,2020.
2. Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med. 2009;24(1):1-10. doi:10.3904/kjim.2009.24.1.1
3. Roope LSJ, Buchanan J, Morrell L, et al. Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey. BMC Medicine. 2020;18(1):196.
4. Cyriac JM, James E. Switch over from intravenous to oral therapy: A concise overview. J Pharmacol Pharmacother. 2014;5(2):83-87. doi:10.4103/0976-500X.130042
Article mentor: Meenakshi R. Ramanathan, Pharm.D., BCPS, BCIDP; Assistant Professor, Infectious Diseases; HSC College of Pharmacy
ABOUT THE AUTHOR
Deidra Lee is a fourth-year pharmacy student at the HSC College of Pharmacy in Fort Worth, Texas. Prior to pharmacy school Deidra taught chemistry and physics at the high school level for several years. She is an active member of the Student National Pharmacy Association (SNPhA).
After graduation, she plans to pursue PGY1 Pharmacy Residency training, followed by a PGY2 Pharmacy Residency in Ambulatory Care or Emergency Medicine. She hopes to one day go back to her roots in Academia.
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