Abstract

BackgroundThe purpose of this study was to investigate the bactericidal effects of levofloxacin and ceftazidime as both monotherapy and combination therapy, and to determine their effects on resistance suppression in patients with normal and abnormal (Ccr:16–20 mL/min) renal function. Common clinical administration regimens to provide reference values were further evaluated.MethodsThe 7-d hollow-fiber infection model was used to inject the Pseudomonas aeruginosa standard strain (ATCC27853), which simulated common clinical administration regimens for patients with different renal function. Ten regimens were stratified into 2 categories based on renal function, and each category contained 3 monotherapy regimens and 2 combination therapy regimens. Total and resistant populations were quantified. Drug concentrations were determined by high-performance liquid chromatography (HPLC).ResultsMonotherapy regimens resulted in about 0.5-log-CFU/mL bacterial kill in the total population at 6 or 8 h, whilst combination regimens resulted in 2- to 3-log-CFU/mL within 2 days. For levofloxacin monotherapy regimens in patients with normal renal function, resistance emergence was seen after 6 h, and was seen at 0 h in the ceftazidime monotherapy regimen, as well as in all regimens of patients with abnormal renal function. Although resistant subpopulation in combination regimens with abnormal renal function began to increase at 0 h, there was a definite downward trend after 8 h, while resistant population in the normal renal function group increased after 16 h.ConclusionsCombination therapy had greater bactericidal efficacy and resistance inhibition compared with monotherapy. Studying combination regimens in randomized clinical trials is warranted.

Highlights

  • The purpose of this study was to investigate the bactericidal effects of levofloxacin and ceftazidime as both monotherapy and combination therapy, and to determine their effects on resistance suppression in patients with normal and abnormal (Ccr:16–20 mL/min) renal function

  • The fractional inhibitory concentration (FIC) value of levofloxacin combined with ceftazidime was measured to be 1.0

  • The assay of levofloxacin was linear over a range of 1.5625–50 μg/mL (y = 59.97x-24.055, r2 = 0.9998) and the assay of ceftazidime was linear over a range of 10–320 μg/mL (y = 0.4659x + 2.9403, r2 = 0.9999)

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Summary

Introduction

The purpose of this study was to investigate the bactericidal effects of levofloxacin and ceftazidime as both monotherapy and combination therapy, and to determine their effects on resistance suppression in patients with normal and abnormal (Ccr: mL/min) renal function. Abnormal renal function is common in ICUs patients. Doses of antibacterial therapy need to be adjusted for ICUs patients. This is explained by the kidney is the main organ for drug elimination, so without dose adjustment, the accumulation of drugs and their metabolites in plasma would increase the possibility of toxicity [2]. The resistance to P. aeruginosa is increasing [3]. The main cause of bacterial resistance is the unreasonable use or even abuse of antibacterial drugs. In the process of exploring how to reasonably use antibiotics and reduce bacterial resistance, the establishment of the in vitro hollow-fiber infection model (HFIM) has become an important research method

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