Defining optimal dosing of ciprofloxacin in patients with septic shock
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Defining optimal dosing of ciprofloxacin in patients with septic shock. / Roberts, Jason A.; Alobaid, Abdulaziz S.; Wallis, Steven C.; Perner, Anders; Lipman, Jeffrey; Sjövall, Fredrik.
In: Journal of Antimicrobial Chemotherapy, Vol. 74, No. 6, dkz069, 2019, p. 1662-1669.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Defining optimal dosing of ciprofloxacin in patients with septic shock
AU - Roberts, Jason A.
AU - Alobaid, Abdulaziz S.
AU - Wallis, Steven C.
AU - Perner, Anders
AU - Lipman, Jeffrey
AU - Sjövall, Fredrik
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1093/jac/dkz069
DO - 10.1093/jac/dkz069
M3 - Journal article
C2 - 30809648
AN - SCOPUS:85066874696
VL - 74
SP - 1662
EP - 1669
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 6
M1 - dkz069
ER -
ID: 241366696