Dataset Information

Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children.

ABSTRACT:

Importance

?-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other ?-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.

Objective

To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal ?-lactam antibiotic throughout the first week of hospitalization.

Design, setting, and participants

This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal ?-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.).

Main outcomes and measures

The primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal ?-lactam antibiotic.

Results

A total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal ?-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal ?-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14).

Conclusions and relevance

Coadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

SUBMITTER: Downes KJ

PROVIDER: S-EPMC6583633 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Publications

Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children.

Downes Kevin J KJ Cowden Carter C Laskin Benjamin L BL Huang Yuan-Shung YS Gong Wu W Bryan Matthew M Fisher Brian T BT Goldstein Stuart L SL Zaoutis Theoklis E TE

JAMA pediatrics 20171204 12

<h4>Importance</h4>β-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other β-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.<h4>Objective</h4>To assess the risk of AKI in chil ...[more]

PMID: 28973124

Similar Datasets

Project description:Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria.Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P ⟨ 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74-2.39; aOR, 2.31; 95% CI, 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.In this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy. Journal of Hospital Medicine 2017;12:77-82.

Project description:ObjectivesPiperacillin/tazobactam combined with vancomycin has been associated with a decline in renal function when compared with monotherapy. Teicoplanin is a glycopeptide similar to vancomycin. We investigated whether piperacillin/tazobactam combined with teicoplanin is associated with a decline in renal function as well.MethodsWe conducted a single-centre retrospective cohort study with data from our electronic health records from 9 August 2013 to 15 November 2019, including all adult patients that received either piperacillin/tazobactam, teicoplanin or piperacillin/tazobactam + teicoplanin. The incidence of acute kidney injury (AKI) at 48-72 h served as the primary outcome, whereas change in serum creatinine served as a secondary outcome.ResultsOf the 4202 included patients, 3188 (75.9%) received piperacillin/tazobactam, 791 (18.8%) received teicoplanin and 223 (5.3%) received piperacillin/tazobactam + teicoplanin. The incidence of AKI at 48-72 h after commencement of antibiotic therapy was 5.4% for piperacillin/tazobactam, 3.4% for teicoplanin and 11.7% for piperacillin/tazobactam + teicoplanin (P < 0.001). However, mean serum creatinine at 48-72 h was slightly higher in the piperacillin/tazobactam + teicoplanin group therapy compared with baseline [+1.61% (95% CI -2.25 to 5.70)], indicating a slight decrease in renal function, and decreased for piperacillin/tazobactam [-1.98% (95% CI -2.73 to -1.22)] and teicoplanin [-8.01% (95% CI -9.54 to -6.45)]. After correcting for significant confounders in a multivariate linear regression analysis, these patterns remained.ConclusionsOur study suggests that piperacillin/tazobactam + teicoplanin is associated with a higher prevalence of AKI compared with monotherapy. However, as the overall decline in renal function with piperacillin/tazobactam + teicoplanin is very small, its clinical relevance is likely limited. Therefore, piperacillin/tazobactam + teicoplanin can probably be safely combined.

Project description:Background and objectivesHigh-quality epidemiologic data on AKI in children are particularly lacking in developing countries. This study aimed to assess the epidemiology and clinical correlates of AKI among hospitalized children in China.Design, setting, participants, & measurementsWe performed a multicenter study, in a cohort of hospitalized children aged 1 month to 18 years, from 25 general and children's hospitals in China during 2013-2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all children who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. We identified AKI events according to the creatinine criteria of Kidney Disease Improving Global Outcomes. The in-hospital outcomes of AKI, including mortality, kidney recovery, and length of stay, were assessed. We estimated the corresponding hazard ratios using a Cox proportional hazard model, with adjustment for age, sex, comorbidities, and clinical procedures.ResultsA total of 19,908 (20%) patients with AKI were identified among 101,836 pediatric inpatients, of which 7220 (7%) were community acquired and 12,688 (13%) were hospital acquired. Up to 96% of these AKI events were not diagnosed on the discharge records. The cumulative incidence of AKI in infants (28%) was twice that in adolescents (12%). The profiles of risk factors differed between community-acquired and hospital-acquired AKI and varied with age. Diarrhea and sepsis were the top risk factors for community-acquired AKI, each contributing 6% of the risk. Congenital heart disease/cardiac surgery was the major risk factor for hospital-acquired AKI, contributing to 19% of cases. Exposure to nephrotoxic drugs, mostly nonsteroidal anti-inflammatory drugs and proton pump inhibitors, was common in hospitalized children and was associated with a higher risk of AKI. Death occurred in 842 out of 19,908 patients (4%) with AKI versus 450 out of 81,478 children (0.5%) without AKI. The risk of in-hospital death was higher among children with severe AKI, shock, and respiratory failure. Pediatric AKI was associated with longer hospital stay and higher daily cost, even after adjustment for covariates.ConclusionsPediatric AKI is common and is substantially underdiagnosed in China.

Project description:ImportanceCefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.ObjectiveTo determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.Design, setting, and participantsThe Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.InterventionsPatients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.Main outcomes and measuresThe primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.ResultsThere were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).Conclusions and relevanceAmong hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.Trial registrationClinicalTrials.gov Identifier: NCT05094154.

Dataset Information

Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children.

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children.

Similar Datasets

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