Looking for help with making antibiotic renal dose adjustments? This article is here to help. Here are important considerations as well as some resources for making antibiotic renal dose adjustments.
Authored By: Timothy P. Gauthier, Pharm.D., BCPS-AQ ID
Once a physicians makes a diagnosis on a patient, it is fairly common to consult with a pharmacist for assistance selecting the right drug and the right dose. When selecting the right antibiotic for an infection is the task at hand, consideration for kidney function is a common piece of the conversation.
There is a story from back when antibiotics were first used in the 1940s. This was a time when penicillin production was far from efficient and any way to preserve or re-use product warranted consideration. It is said that because penicillin achieves high concentrations in the urine, patients given the drug had their urine collected so the penicillin could be extracted and then re-used in another patient. Kind of gross, right? Well, perhaps this somewhat shocking story can help us to remember that penicillin (like many other antibiotics) is excreted via the kidney and therefore we need to beware the need for antibiotic renal dose adjustments.
In fact, so many antibiotics are excreted by the kidney that it is often recommend to students that they study a list of antibiotics that do not require renal dose adjustments rather than a list of the ones that do. There are always some exceptions in the world of infectious diseases, but some antibiotics to put on that “not common to require renal dose adjustment” list includes: oxacillin, nafcillin, moxifloxacin, ceftriaxone, clindamycin, linezolid and tigecycline.
So what is the big deal if an antibiotic is not dose adjusted for a patient’s kidney function? Well, if a patient with kidney dysfunction is given a usual dose (and therefore too much drug), they could end up with toxicity (e.g., a seizure from too much imipenem-cilastatin). On the other hand, if a patient gets too small of a dose as related to their kidney function, the drug concentrations may not be high enough to treat their infection.
Picking the right dose of an antibiotic that requires renal dose adjustment is not as simple as determining the patient’s creatinine clearance and choosing a dose. There are many factors to consider. Many times there is a dosing range. So which to select, a dose on the lower or higher end of the spectrum?
When someone asks you for help dosing an antibiotic you should ask a few questions. The following is not all inclusive of everything requiring consideration prior to selecting a dose, but it does cover most of what needs to be discussed. Resources and suggested readings are additionally provided.
Ask 1st: What is the site of infection?
This is always the first question to ask any time prescribing an antibiotic is being discussed. If there is no current infection or no need to provide prophylaxis, then an antibiotic is not needed and your job is done. It is very common for a positive microbiology culture to trigger a conversation on which antibiotic to give, when the conversation that should have been triggered is on whether or not the patient has an infection. It is always prudent to ensure a patient needs an antibiotic before recommending a dose for an antibiotic.
Once it is confirmed the patient has an infection, the site of infection matters. This helps answer the subsequent questions presented below, but also can help identify non-drug interventions that are necessary. If the patient has a necrotizing infection, it is likely debridement will be necessary (note, systemic antibiotics do not penetrate into dead tissue). If a patient has an abscess, it is likely incision and drainage will be necessary. If a patient has an infection related to hardware, removal of the hardware is likely necessary.
Non-drug considerations are very important to the plan of care and can have an impact on both what drug you choose as well as what dose. For example, some antibiotic doses require substantial infusions time commitments. If a patient has other needs that interfere with being tied to the antibiotic for prolonged periods, perhaps it is not picking a right dose for their kidneys that is the issue, but rather trying to find an alternate antibiotic.
Beyond identifying the non-drug factors, the infection site will help to identify if it is a “difficult to penetrate” site. Areas of the body such as the prostate, eye, cerebral spinal fluid, lungs and bone are generally difficult to penetrate sites. On the other hand, the soft tissues and kidneys are generally easy to penetrate sites.
Ability to penetrate the site of infection should be considered along with renal function when picking a dose for an antibiotic. Many times a lower dose can be used if the antibiotic being considered achieves high concentrations at the site of infection. In general, lower doses means less exposure to the antibiotic and therefore, reduced chances for toxicity.
Ask 2nd: What organism(s) are likely to cause the infection(s)?
Depending on the infection site and patient presentation, the likely organism(s) causing infection should be able to be identified.
Some organisms are notorious for being easy to treat even with relatively low concentration of antibiotic. Then there are organisms such as Pseudomonas aeruginosa. P. aeruginosa is notorious for having a high minimum inhibitory concentration and therefore can require higher doses for treatment, especially when the site of infection is difficult to penetrate with your antibiotic.
While considering what organisms to target, also remember to check the patient’s medical chart for previous microbiology results and previous resistance patterns in any positive cultures.
Ask 3rd: What antibiotics are potential options for this infection and what makes them different from one another?
Daptomycin is a poor antibiotic choice for a pneumonia, because it is inactivated by surfactant in the lung. Ertapenem is a poor antibiotic choice for Acinetobacter baumannii infection, because it does not have activity versus this organism. From answering the two above questions, many antibiotics will already be off the table, because of their antibacterial or infection-related limitations.
For the antibiotics under consideration, they can be differentiated based upon potential for toxicity, spectrum of antimicrobial activity, whether they are available in an oral formulation, and more. For renal dosing purposes, pharmacokinetics is probably the most important factor. Pharmacokinetics refers to “how the body effects the drug” and is usually categorized into four areas: absorption, distribution, metabolism, and excretion.
If an antibiotic’s primary method of excretion is via the kidney, it likely will require dose adjustment for renal function. The extent of adjustment will vary by drug. For example, some antibiotics require adjustment at a creatinine clearance below 50 mL/min while others do not require adjustment until they are below 30 mL/min.
Interestingly enough, when it comes to antibiotic dosing, renal dysfunction can actually make life easier. Less excretion can mean less frequent dosing and that can also mean better compliance to the prescribed regimen.
In picking an antibiotic and choosing the right dose based upon kidney function, being able to differentiate your antibiotic options is essential.
Ask 4th: What makes this patient different than the “average” patient?
Every patient is unique. Even in the same patient, their clinical status in the morning may be completely different by the afternoon. Acknowledging this is essential towards finding the right plan for an individual case.
Weight, age, allergies and sex are among some basics worth considering. For example if you are talking about vancomycin (which has a large volume of distribution), larger doses are likely necessary. Yet if you are talking about a person that is in their 90’s, it is likely their advanced age means their kidney function will be reduced and therefore the dosing interval should likely be extended.
For assessing kidney function directly, it is important to review urine output, serum creatinine, blood urea nitrogen and dialysis status. Note if the clinical status and lab values are trending worse or trending better, to help predict what dose will be appropriate in the coming hours, days or weeks. Also, be sure to differentiate the types of dialysis, as hemodialysis lends to a creatinine clearance of 0 mL/min, while continuous renal replacement therapy or continuous veno-venous hemofiltration typically lends to a creatinine clearance between 20 and 40 mL/min.
Antimicrobial Stewardship Program Resources On Renal Dosing
- Jackson Health System – Antimicrobial Dosing In Renal Impairment
- University of Miami – Renal Dosing Antibiotics For Pharmacists
- Nebraska Medicine – Antimicrobial Guidebook
- Johns Hopkins – Antibiotic Management Guidelines
- Maine Medical Center – Antimicrobial Formulary Guide
- Columbia University – Antimicrobial Renal Dysfunction Dosing Guidelines
- Stanford Hospital & Clinics – Antimicrobial Dosing Reference Guide
- Cleveland Clinic – Guidelines For Antimicrobial Usage
- UCLA Health – Adult Anti-Infective Dosing Guidelines
- UCLA Health – Guideline For Dosing Antimicrobials In Children
- USCF – Antimicrobial Dosing, Non-Dialysis
- UCSF – Antimicrobial Dosing, iHD and CRRT
- UCSF – Pediatric Antimicrobial Dosing
- UCSF – Neonatal Antimicrobial Dosing
- Holtz Children’s Hospital – Pediatric Antimicrobial Renal Dosing Guidelines
- University Of Wisconsin – Renal Function-Based Dose Adjustments
- Wake Forest – Antimicrobial Dosing Guideline
- Nottingham University Hospitals – Antimicrobial Doses For Adults In Renal Impairment
- Gloucestershire Hospitals – Antibiotic Doses In Renal Impairment
Suggested Readings
- Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men
- Pharmacokinetics-Pharmacodynamics of Antimicrobial Therapy: It’s Not Just for Mice Anymore
- Antimicrobial stewardship and the role of pharmacokinetics-pharmacodynamics in the modern antibiotic era
- Determination of antibiotic dosage adjustments in patients with renal impairment: elements for success
- Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy
- Antibiotic dosing in critically ill patients with acute kidney injury
Have a resource or reading to add? – Email it to: IDstewardship@gmail.com
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