Re-evaluating the role of piperacillin-tazobactam in the treatment of hospital-acquired infections

Abstract

The objectives were to determine the minimum inhibitory concentrations (MICs) of piperacillin-tazobactam against blood culture isolates over a two-year period, and to compare the MICs with isolates from the same site upon the South African launch of piperacillin-tazobactam. The intention was to to use the MIC data to evaluate and contextualise contemporary dosing strategies of piperacillin-tazobactam in South Africa. MICs were determined using broth microdilution antimicrobial susceptibility testing. A comparison of susceptibility between the two time periods was carried out using Fisher's exact test. The MIC data were then used to evaluate current dosing strategies based on current evidence-based pharmacodynamic parameters for piperacillin-tazobactam. A significant decrease in susceptibility was observed for Eschericha coli (p-value = 0.0009), Klebsiella spp. (p-value = 0.0001), Citrobacter spp. (p-value = 0.0001) and Acinetobacter baumannii (p-value = 0.0388) with MIC₉₀ ≥ 128. Enterobacter spp., Serratia marcescens, Morganella morganii and Proteus spp./Providencia spp. demonstrating reduced susceptibility (combined intermediate and resistant) of 44%, 11%, 20% and 0%, respectively. No significant difference in susceptibility between current extended spectrum beta-lactamase (ESBL)- and non-ESBL-producing isolates was seen with a lower MIC₉₀ for ESBL-producing Klebsiella spp. and Enterobacter spp., compared to their non-ESBL-producing counterparts. The MIC data suggest that more targeted dosing strategies that aim to optimise pharmacodynamic parameters are needed. Piperacillin-tazobactam remains a valuable antimicrobial agent whose continued longevity will depend on appropriate optimisation of pharmacodynamic parameters. This requires the application of MIC-based susceptibility data to clinical use, with local assessment of the applicability of various dosing strategies that is based on cumulative antimicrobial susceptibility data.