Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Defining optimal dosing of ciprofloxacin in patients with septic shock

Roberts, Jason A. ; Alobaid, Abdulaziz S. ; Wallis, Steven C. ; Perner, Anders ; Lipman, Jeffrey and Sjövall, Fredrik LU orcid (2019) In The Journal of antimicrobial chemotherapy 74(6). p.1662-1669
Abstract

BACKGROUND: Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. OBJECTIVES: To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. METHODS: Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. RESULTS:... (More)

BACKGROUND: Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. OBJECTIVES: To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. METHODS: Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. RESULTS: We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios. CONCLUSIONS: In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of antimicrobial chemotherapy
volume
74
issue
6
pages
8 pages
publisher
Oxford University Press
external identifiers
  • scopus:85066874696
  • pmid:30809648
ISSN
1460-2091
DOI
10.1093/jac/dkz069
language
English
LU publication?
yes
id
f8eb5a4d-af33-4d2a-a726-ffdc1fcaba66
date added to LUP
2019-07-05 12:30:05
date last changed
2024-05-29 23:06:42
@article{f8eb5a4d-af33-4d2a-a726-ffdc1fcaba66,
  abstract     = {{<p>BACKGROUND: Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. OBJECTIVES: To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. METHODS: Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio &gt;125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. RESULTS: We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, &gt;95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios. CONCLUSIONS: In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.</p>}},
  author       = {{Roberts, Jason A. and Alobaid, Abdulaziz S. and Wallis, Steven C. and Perner, Anders and Lipman, Jeffrey and Sjövall, Fredrik}},
  issn         = {{1460-2091}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1662--1669}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of antimicrobial chemotherapy}},
  title        = {{Defining optimal dosing of ciprofloxacin in patients with septic shock}},
  url          = {{http://dx.doi.org/10.1093/jac/dkz069}},
  doi          = {{10.1093/jac/dkz069}},
  volume       = {{74}},
  year         = {{2019}},
}