Nephrotoxicity Induced by Piperacillin–Tazobactam in Late Elderly Japanese Patients with Nursing and Healthcare Associated Pneumonia

Abstract

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin-tazobactam (PIPC-TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC-TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC-TAZ. Creatinine clearance (mean S.D.) measured before PIPC-TAZ therapy was significantly lower in the nephrotoxicity group (32.5 4.4 mL/min) than in the non-nephrotoxicity group (46.1 16.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC-TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections

“…It would be ideal to calculate the appropriate dose of TZP to achieve the maximized probability of target attainment using stimulation techniques, which could provide individualized dosing regimens and enable an accurate inter-race comparison. In addition, previously reported toxicity of piperacillin associated with impaired renal function should be compared between ethnic groups, because categorizing dosing by the degree of crude renal function may to be too high or low for patients in the same category, according to race [ 24 25 ].…”

Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia

“…Thus, using Table 5 prepared by this study, we were able to present the optimal dosing regimen for the elderly in the late stage that takes into account not only CL cr but also the MIC. Additionally, we have already reported that renal dysfunction, especially CL cr of less than 40 mL/min, could be an influential factor for nephrotoxicity induced by PIPC/TAZ-induced nephrotoxicity in late elderly patients [34]. Therefore, although the recommended dosing regimens are shown in Table 5, from the viewpoint of safety, the administration of PIPC/TAZ should be performed more carefully in patients with CL cr values of 30 mL/min or less.…”

Comparison of Appropriate Piperacillin/Tazobactam Doses in Korean Obese Patients with Cancer Based on Different Body Size Descriptor Equations in a Tertiary Care Hospital

“…32) However, the following exclusion criteria were applied: patients younger than 18 years old, patients without records of height or weight essential for calculating the BMI, patients with BMI < 30 kg/m 2 , patients without information regarding diagnosis and TZP administration (e.g., indication, dosage, and duration of treatment), patients without lab value information, patients who underwent TZP treatment for less than 72 hours, patients who received TZP again due to the same affliction in the same year, or patients allergic to penicillins, cephalosporins, or beta-lactamase inhibitors. 3,10,25,29,32)…”

“…According to a study by Karino et al in Japan, cautious TZP administration and monitoring was necessary in elderly patients with kidney dysfunction, particularly those with CrCl less than 40 mL/min owing to serious nephrotoxicity (although TZP is effective against hospital-acquired pneumonia). 10) Functional renal mass can be measured through the glomerular filtration rate (GFR) calculated from inulin injections, but this method is clinically impractical due to the time required for IV infusion and urine collection; hence, the Cockcroft-Gault (CG) equation is typically utilized to measure renal function. 11) The pharmaceutical industry also uses the CG equation to determine renal dosage adjustments for different drugs.…”