Vancomycin-Piperacillin-Tazobactam Combo Ups AKI Risk in Kids

Marcia Frellick

October 02, 2017

Treating hospitalized children with the widely used combination antibiotic therapy of intravenous vancomycin hydrochloride and piperacillin-tazobactam (TZP) significantly increases their risk for acute kidney injury (AKI), new data from a large, multicenter study indicate.

Previous studies had made the association in adults. Now Kevin J. Downes, MD, from the Division of Infectious Diseases at The Children's Hospital of Philadelphia in Pennsylvania, and colleagues find that when hospitalized children are given the combination therapy, their risk increases for AKI, which is linked to a higher risk for chronic kidney disease and death.

Results were published online October 2 in JAMA Pediatrics.

In hospitals, β-lactam antibiotics are often given together with intravenous vancomycin hydrochloride for children when serious infections are suspected. Vancomycin is the go-to drug when providers suspect serious gram-positive infection, and the β-lactam antibiotics provide gram-negative coverage.

Dr Downes and colleagues say pediatricians should be aware of the AKI risk in choosing antibiotics, and "must limit the duration of vancomycin plus TZP combination therapy, as is feasible, and closely monitor children for whom both of these drugs are necessary," adding that when there are good substitutes for TZP, other broad-spectrum β-lactam antibiotics should be considered.

The study looked at children aged 6 months to 18 years entering through the emergency department, who were hospitalized for 3 or more days, and who received intravenous vancomycin plus 1 other antipseudomonal β-lactam combination therapy at one of six large children's hospitals from 2007 through 2012. Its primary outcome was AKI on hospital days 3 to 7 and within 2 days of combination therapy.

After researchers adjusted for age, level of care, receipt of nephrotoxins, and hospital, they found that intravenous vancomycin plus TZP therapy was linked to higher odds of AKI each hospital day compared with vancomycin plus one other antipseudomonal β-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% confidence interval, 2.26 - 5.14).

They identified 1915 hospitalized children who received combination therapy. Of those who received intravenous vancomycin plus one other antipseudomonal β-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. Among recipients of any combination therapy on at least hospital days 1 and 2, antibiotic-associated AKI was detected most often in children who received vancomycin plus TZP (117 [11.7%]).

A limitation of this study is that it includes only children admitted through the emergency department, who started combination therapy right away. Risk factors for AKI in children starting antibiotics later in their hospital stay may be different, as they may be sicker or have more comorbidities, so results may not be generalizable to those in other settings.

Dr Downes received research support (unrelated to this study) from Merck and Pfizer. Coauthors report receiving research support (unrelated to this study) from Pfizer, Merck, Ansun Biopharma, and T2 Biosystems, and providing consultant services to T2 Biosystems and Nabriva Therapeutics. A coauthor also reports receiving support from the National Institute of Diabetes and Digestive and Kidney Diseases.

JAMA Pediatr. Published online October 2, 2017.

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