Fellow: Ashley Jenkins, MD, Medicine-Pediatric Hospital Medicine Fellow, Cincinnati Children’s Hospital Medical Center and University of Cincinnati Medical Center
Article: Downes KJ, Cowden C, Laskin BL, et al. Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children. JAMA Pediatrics. October 2017:e173219.
Summary: The authors conducted a multicenter retrospective cohort study using a large administrative database (PHIS+) to evaluate the association of Vancomycin plus Piperacillin/Tazobactam (Pip/Tazo) with acute kidney injury (AKI) in children 6 months to 18 years of age admitted to pediatric hospitals. Even when adjusted for variables such as severity of illness, Vancomycin and Pip/Tazo combination therapy was associated with a higher odds of AKI (adjusted OR 3.4) and longer length of stay (LOS, 13 day vs. 10 days) when compared to either Vancomycin or Vancomycin plus another antipseudomonal b-lactam antibiotic combination. In all patients who sustained antibiotic-associated AKI, they also had increase in-hospital mortality (4.5% vs. 1.3%).
Describe how this article should impact our practice:
Clinicians should strongly consider avoiding concomitant use of Vancomycin and Pip/Tazo, especially if the patient has or is going to receive IV contrast material or other nephrotoxic agents.
What are the key strengths of the article?
By using PHIS+, the authors were able to access “real-word” healthcare data in an unselected cohort of patients. They then appropriately described and justified their inclusion/exclusion criteria as well as methods for reducing bias in the database.
To identify patients with AKI the authors used KDIGO AKI serum creatinine change criteria, which allowed more accurate capture of antibiotic associated-AKI. They also controlled for severity of illness in a variety of ways, including comparing Pip/Tazo with other antipseudomonal b-lactam antibiotic co-administration. Finally, their analysis adjusted for administration of other nephrotoxic medications and IV contrast.
Are there any limitations or flaws in the article?
There are inherent limitations when conducting research with large administrative databases that include population and outcome identification, as well as lack of clinical data such as vital signs and fluid status. It may be difficult to generalize this study’s findings as the cohort was limited to children admitted through the emergency room, administered these antibiotics on hospital days 1 and 2, and those who developed AKI in the first 7 days of hospitalization.
What is the major takeaway message?
While multiple studies exist documenting the increased risk of AKI in adult patient co-administered Vancomycin and Pip/Tazo, this is the first that demonstrates a similar association in a large pediatric cohort. Vancomycin remains a mainstay for coverage of serious gram-positive infection, but there are other antimicrobial agents with similar coverage to Pip/Tazo. Clinicians must be aware the combined use of Vancomycin and Pip/Tazo confers additional risk that includes AKI, longer LOS, and mortality, taking that into consideration with empiric antibiotic decisions.
Article: Downes KJ, Cowden C, Laskin BL, et al. Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children. JAMA Pediatrics. October 2017:e173219.
Summary: The authors conducted a multicenter retrospective cohort study using a large administrative database (PHIS+) to evaluate the association of Vancomycin plus Piperacillin/Tazobactam (Pip/Tazo) with acute kidney injury (AKI) in children 6 months to 18 years of age admitted to pediatric hospitals. Even when adjusted for variables such as severity of illness, Vancomycin and Pip/Tazo combination therapy was associated with a higher odds of AKI (adjusted OR 3.4) and longer length of stay (LOS, 13 day vs. 10 days) when compared to either Vancomycin or Vancomycin plus another antipseudomonal b-lactam antibiotic combination. In all patients who sustained antibiotic-associated AKI, they also had increase in-hospital mortality (4.5% vs. 1.3%).
Describe how this article should impact our practice:
Clinicians should strongly consider avoiding concomitant use of Vancomycin and Pip/Tazo, especially if the patient has or is going to receive IV contrast material or other nephrotoxic agents.
What are the key strengths of the article?
By using PHIS+, the authors were able to access “real-word” healthcare data in an unselected cohort of patients. They then appropriately described and justified their inclusion/exclusion criteria as well as methods for reducing bias in the database.
To identify patients with AKI the authors used KDIGO AKI serum creatinine change criteria, which allowed more accurate capture of antibiotic associated-AKI. They also controlled for severity of illness in a variety of ways, including comparing Pip/Tazo with other antipseudomonal b-lactam antibiotic co-administration. Finally, their analysis adjusted for administration of other nephrotoxic medications and IV contrast.
Are there any limitations or flaws in the article?
There are inherent limitations when conducting research with large administrative databases that include population and outcome identification, as well as lack of clinical data such as vital signs and fluid status. It may be difficult to generalize this study’s findings as the cohort was limited to children admitted through the emergency room, administered these antibiotics on hospital days 1 and 2, and those who developed AKI in the first 7 days of hospitalization.
What is the major takeaway message?
While multiple studies exist documenting the increased risk of AKI in adult patient co-administered Vancomycin and Pip/Tazo, this is the first that demonstrates a similar association in a large pediatric cohort. Vancomycin remains a mainstay for coverage of serious gram-positive infection, but there are other antimicrobial agents with similar coverage to Pip/Tazo. Clinicians must be aware the combined use of Vancomycin and Pip/Tazo confers additional risk that includes AKI, longer LOS, and mortality, taking that into consideration with empiric antibiotic decisions.