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Defining optimal do...
Defining optimal dosing of ciprofloxacin in patients with septic shock
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- Roberts, Jason A. (författare)
- Royal Brisbane and Women's Hospital,University of Queensland
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- Alobaid, Abdulaziz S. (författare)
- University of Queensland
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- Wallis, Steven C. (författare)
- University of Queensland
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- Perner, Anders (författare)
- University of Copenhagen,Copenhagen University Hospital
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- Lipman, Jeffrey (författare)
- Royal Brisbane and Women's Hospital,Queensland University of Technology
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- Sjövall, Fredrik (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,Copenhagen University Hospital,Skåne University Hospital
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(creator_code:org_t)
- 2019-02-26
- 2019
- Engelska 8 s.
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Ingår i: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 74:6, s. 1662-1669
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
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