In this episode I’ll:
1. Discuss an article about the combination of vancomycin and piperacillin-tazobactam and the development of acute kidney injury.
2. Answer the drug information question “When using steroids for the treatment of septic shock, should they be abruptly stopped or tapered?”
3. Share a resource for remembering antibiotic sensitivity.
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Article
Lead author: Christopher Giuliano
Published in manuscript form online in Pharmacotherapy November 2016
Background
The combination of piperacillin-tazobactam and vancomycin is often used to treat health care–associated infections. Multiple studies, with conflicting results, have attempted to answer the question of whether there is an association of acute kidney injury (AKI) with the combination of piperacillin-tazobactam and vancomycin. The authors of this meta-analysis systematically examined the association between the combination of vancomycin and piperacillin-tazobactam with AKI.
Methods
This meta-analysis included 15 observational cohort studies totaling 3258 adult patients. Only studies that evaluated the association of AKI with the combined use of piperacillin-tazobactam and vancomycin were included. The primary outcome was to evaluate the association of development of AKI with the combined use of piperacillin-tazobactam and vancomycin. A subgroup analysis examined the outcome by comparison groups (vancomycin alone or vancomycin + beta-lactam).
Results
The study found a significant association with the occurrence of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin ± beta-lactam (odds ratio 3.641). This association remained significant even after standard meta-analysis techniques such as removing studies or removing low-quality studies were applied.
During the subgroup analysis, the association for the development of AKI remained significant only with the vancomycin + piperacillin-tazobactam compared with vancomycin alone group. The association was not significant for the vancomycin + beta-lactam group.
Conclusion
The authors concluded:
Vancomycin + piperacillin-tazobactam was associated with increased risk of AKI compared to vancomycin ± beta-lactam. Practitioners need to be vigilant about this association when prescribing this combination of antibiotics.
Discussion
In episode 77, I reviewed a retrospective cohort study that reached the same conclusion as this meta-analysis. That study was included in this meta-analysis. It was the only study out of the 15 included that reported APACHE scores and included critically ill patients.
If we are to avoid the combination of vancomycin and piperacillin-tazobactam, which drug do we replace? Linezolid is an easy choice in patients with pneumonia, but not in bacteremia. Cefepime leaves out anaerobic coverage. Meropenem or daptomycin seem like excessively broad and expensive replacements. The use of ceftaroline plus piperacillin-tazobactam doesn’t seem logical to me.
I can’t come up with a reasonable solution other than to consider whether alternatives to the combination are feasible. Let me know your thoughts in the comment section below.
Drug information question
Q: “When using steroids for the treatment of septic shock, should they be abruptly stopped or tapered?”
A: Either option is OK, but if hemodynamic instability returns after steroids are abruptly stopped, they should be resumed and tapered.
Shout out to “Intensivist Zoi” for asking this drug information question!
The 2012 sepsis guidelines recommend tapering steroids if they are used for septic shock. This recommendation was based on a 40 patient study from 2003 that found hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects.
In 2015, SCCM published a “Clinical Controversies” article that concluded:
Low-dose hydrocortisone can be continued for five to seven days and at least for 24 hours after cessation of vasopressors, with tapering doses if the patient exhibits any decompensation after steroid withdrawal.
Resource
Dr. Michael Shamoon of the blog Coreem.net published an excellent Antibiotic Sensitivity Overview. The overview provides a visual representation of antibiotic coverage.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
One of my hospitals target a lower vancomycin trough (10-15) whenever zosyn and Vanco are given together. That goes for all infections.
I can’t find any articles on this, although I am sure it’s out there. Can you link me to this recommendation?
We have for the most part converted to Vanco – cefepime unless there is a need to cover anaerobes
I am hoping anaerobes are discussed in the latest CAP guidelines. It seems like anaerobic coverage is provided more often than it is needed.