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      Acute Kidney Injury in Pediatric Treated with Vancomycin and Piperacillin-Tazobactam in Tertiary Care Hospital

      1 , 2 , 1 , 2 , 2 , 3 , 1 , 2
      International Journal of Pediatrics
      Hindawi Limited

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          Abstract

          Background. Vancomycin and piperacillin-tazobactam (PTZ) are commonly used as empirical therapy for patients with health care associated infections. Vancomycin has been recognized as a nephrotoxic agent and in a few cases in the literature PTZ has been associated with interstitial nephritis nevertheless; the combination of these agents has routinely been used for many years. However, there have been some observational studies that showed high rates of acute kidney injury (AKI) in patients receiving vancomycin and PTZ concomitant treatment compared to patients receiving vancomycin alone. The incidence of AKI in adult patients receiving vancomycin and PTZ concomitant treatment was reported in these studies to be relatively high. Similar studies in pediatric patients are lacking. Method. We conducted a single center retrospective chart review of 248 pediatric patients receiving one of the following treatments: vancomycin alone 36 patients, vancomycin/PTZ 62 patients, vancomycin/ceftazidime 99 patients, and vancomycin/ceftriaxone 51 patients. Result. Our results showed a low incidence of AKI in patients on vancomycin/PTZ concomitant treatment where overall incidence was only (4.8%) three cases and only one of them (2.0%) in a patient receiving the vancomycin/ceftriaxone concomitant treatment. No cases of AKI present in patients receiving vancomycin with ceftazidime or vancomycin alone. There were no statistically significant differences between the four treatment groups in terms of AKI incidence, vancomycin trough, and use of nephrotoxins. Conclusion. Overall, the incidence of AKI was low in our study sample with no statistically significant increased risk when PTZ was used in combination with vancomycin in a pediatric population. However, further investigation with an equal larger sample size is needed to confirm our findings.

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          Most cited references15

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          Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial.

          Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, gender, race, dose, length of therapy, use of other nephrotoxins (including contrast media), intensive care unit (ICU) residence, episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a ≥ 50% increase from the baseline for two consecutive measurements. MICs of vancomycin for the MRSA isolates were also determined. A total of 288 patients were studied between February 2008 and June 2010, with approximately one-half having initial trough concentrations of ≥ 15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough concentrations >15 mg/ml and for 13 (8.9%) with trough concentrations of ≤ 15 mg/ml. Multivariate analysis revealed vancomycin trough concentrations of >15 mg/ml and race (black) as risk factors for nephrotoxicity in this population. Vancomycin trough concentrations of >15 mg/ml appear to be associated with a 3-fold increased risk of nephrotoxicity.
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            Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam.

            To determine whether the addition of piperacillin-tazobactam leads to an increased incidence of nephrotoxicity in patients receiving vancomycin and to explore potential confounding factors that may increase the risk of vancomycin-induced nephrotoxicity. Single-center, retrospective cohort study. Large, academic, tertiary-care hospital. One hundred ninety-one adults hospitalized between July 1, 2009, and July 1, 2012, with normal baseline renal function who received a minimum of 48 hours of vancomycin for any indication were included in the analysis. Of these patients, 92 received a minimum of 48 hours of intravenous piperacillin-tazobactam concurrently with vancomycin, with piperacillin-tazobactam being initiated within 48 hours of the initiation of vancomycin (combination group); 99 received vancomycin without piperacillin-tazobactam (vancomycin group). A univariate analysis was performed to assess the effect of the following risk factors on the incidence of nephrotoxicity within the first 7 days of vancomycin treatment: concomitant nephrotoxic agents, advanced age, steady-state vancomycin trough concentration of 15 μg/ml or greater, elevated Charlson Comorbidity Index, and a total daily vancomycin dose of 4 g or greater. A multivariate model was constructed to compare the incidence of the primary end point of nephrotoxicity, defined as a minimum 1.5-fold increase in serum creatinine concentration, between groups. Nephrotoxicity developed in 8 (8.1%) of 99 patients in the vancomycin group and in 15 (16.3%) of 92 patients in the combination group (1-sided χ(2) test, p=0.041). In the univariate analysis, only vancomycin trough concentration of 15 μg/ml or greater (odds ratio 3.67) was associated with an increased risk of developing nephrotoxicity. In the multivariate analysis, patients with piperacillin-tazobactam added to vancomycin exhibited an increased incidence of nephrotoxicity, with an odds ratio of 2.48 (1-sided χ(2) test, p=0.032). We observed an increased incidence of nephrotoxicity in vancomycin-treated patients who received concomitant piperacillin-tazobactam. A steady-state vancomycin trough concentration of 15 μg/ml or greater was also associated with an increased risk of the development of nephrotoxicity. These findings should be confirmed in larger, randomized studies. © 2014 Pharmacotherapy Publications, Inc.
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              Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis.

              To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patients with Gram-positive infections. MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration (C(min)) for InI and steady-state concentration (C(ss)) for CoI; area under the curve at 24 h (AUC(24)) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I(2) test was calculated to assess heterogeneity across studies. One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P = 0.02; I(2)= 0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P = 0.9; I(2)= 0). Our meta-analysis suggests that administration of vancomycin for the treatment of Gram-positive infections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug. RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio.
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                Author and article information

                Journal
                International Journal of Pediatrics
                International Journal of Pediatrics
                Hindawi Limited
                1687-9740
                1687-9759
                December 16 2018
                December 16 2018
                : 2018
                : 1-7
                Affiliations
                [1 ]King Abdulaziz Medical City, Pharmaceutical Care Services, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
                [2 ]College of Pharmacy, King Saud Bin Abdul-Aziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
                [3 ]Prince Sultan Military Medical City, Department of Pharmacy, Riyadh, Saudi Arabia
                Article
                10.1155/2018/9256528
                5203b0a4-302a-41fa-9dac-4f055beb425d
                © 2018

                http://creativecommons.org/licenses/by/4.0/

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