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Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model

OBJECTIVES: Pharmacodynamic profiling of oral ciprofloxacin dosing for urinary tract infections caused by ceftriaxone-resistant Escherichia coli isolates with ciprofloxacin MIC ≥ 0.25 mg/L. BACKGROUND: Urine-specific breakpoints for ciprofloxacin do not exist. However, high urinary concentrations ma...

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Autores principales: Abbott, Iain J, van Gorp, Elke, Cottingham, Hugh, Macesic, Nenad, Wallis, Steven C, Roberts, Jason A, Meletiadis, Joseph, Peleg, Anton Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890216/
https://www.ncbi.nlm.nih.gov/pubmed/36473954
http://dx.doi.org/10.1093/jac/dkac402
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author Abbott, Iain J
van Gorp, Elke
Cottingham, Hugh
Macesic, Nenad
Wallis, Steven C
Roberts, Jason A
Meletiadis, Joseph
Peleg, Anton Y
author_facet Abbott, Iain J
van Gorp, Elke
Cottingham, Hugh
Macesic, Nenad
Wallis, Steven C
Roberts, Jason A
Meletiadis, Joseph
Peleg, Anton Y
author_sort Abbott, Iain J
collection PubMed
description OBJECTIVES: Pharmacodynamic profiling of oral ciprofloxacin dosing for urinary tract infections caused by ceftriaxone-resistant Escherichia coli isolates with ciprofloxacin MIC ≥ 0.25 mg/L. BACKGROUND: Urine-specific breakpoints for ciprofloxacin do not exist. However, high urinary concentrations may promote efficacy in isolates with low-level resistance. METHODS: Ceftriaxone-resistant E. coli urinary isolates were screened for ciprofloxacin susceptibility. Fifteen representative strains were selected and tested using a dynamic bladder infection model. Oral ciprofloxacin dosing was simulated over 3 days (250 mg daily, 500 mg daily, 250 mg 12 hourly, 500 mg 12 hourly and 750 mg 12 hourly). The model was run for 96 h. Primary endpoint was change in bacterial density at 72 h. Secondary endpoints were follow-up change in bacterial density at 96 h and area-under-bacterial-kill-curve. Bacterial response was related to exposure (AUC(0–24)/MIC; C(max)/MIC). PTA was determined using Monte-Carlo simulation. RESULTS: Ninety-three clinical isolates demonstrated a trimodal ciprofloxacin MIC distribution (modal MICs at 0.016, 0.25 and 32 mg/L). Fifteen selected clinical isolates (ciprofloxacin MIC 0.25–512 mg/L) had a broad range of quinolone-resistance genes. Following ciprofloxacin exposure, E. coli ATCC 25922 (MIC 0.008 mg/L) was killed in all dosing experiments. Six isolates (MIC ≥ 16 mg/L) regrew in all experiments. Remaining isolates (MIC 0.25–8 mg/L) regrew variably after an initial period of killing, depending on simulated ciprofloxacin dose. A >95% PTA, using AUC(0–24)/MIC targets, supported 250 mg 12 hourly for susceptible isolates (MIC ≤ 0.25 mg/L). For isolates with MIC ≤ 1 mg/L, 750 mg 12 hourly promoted 3 log(10) kill at the end of treatment (72 h), 1 log(10) kill at follow-up (96 h) and 90% maximal activity (AUBKC(0–96)). CONCLUSIONS: Bladder infection modelling supports oral ciprofloxacin activity against E. coli with low-level resistance (ciprofloxacin MIC ≤ 1 mg/L) when using high dose therapy (750 mg 12 hourly).
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spelling pubmed-98902162023-02-02 Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model Abbott, Iain J van Gorp, Elke Cottingham, Hugh Macesic, Nenad Wallis, Steven C Roberts, Jason A Meletiadis, Joseph Peleg, Anton Y J Antimicrob Chemother Original Research OBJECTIVES: Pharmacodynamic profiling of oral ciprofloxacin dosing for urinary tract infections caused by ceftriaxone-resistant Escherichia coli isolates with ciprofloxacin MIC ≥ 0.25 mg/L. BACKGROUND: Urine-specific breakpoints for ciprofloxacin do not exist. However, high urinary concentrations may promote efficacy in isolates with low-level resistance. METHODS: Ceftriaxone-resistant E. coli urinary isolates were screened for ciprofloxacin susceptibility. Fifteen representative strains were selected and tested using a dynamic bladder infection model. Oral ciprofloxacin dosing was simulated over 3 days (250 mg daily, 500 mg daily, 250 mg 12 hourly, 500 mg 12 hourly and 750 mg 12 hourly). The model was run for 96 h. Primary endpoint was change in bacterial density at 72 h. Secondary endpoints were follow-up change in bacterial density at 96 h and area-under-bacterial-kill-curve. Bacterial response was related to exposure (AUC(0–24)/MIC; C(max)/MIC). PTA was determined using Monte-Carlo simulation. RESULTS: Ninety-three clinical isolates demonstrated a trimodal ciprofloxacin MIC distribution (modal MICs at 0.016, 0.25 and 32 mg/L). Fifteen selected clinical isolates (ciprofloxacin MIC 0.25–512 mg/L) had a broad range of quinolone-resistance genes. Following ciprofloxacin exposure, E. coli ATCC 25922 (MIC 0.008 mg/L) was killed in all dosing experiments. Six isolates (MIC ≥ 16 mg/L) regrew in all experiments. Remaining isolates (MIC 0.25–8 mg/L) regrew variably after an initial period of killing, depending on simulated ciprofloxacin dose. A >95% PTA, using AUC(0–24)/MIC targets, supported 250 mg 12 hourly for susceptible isolates (MIC ≤ 0.25 mg/L). For isolates with MIC ≤ 1 mg/L, 750 mg 12 hourly promoted 3 log(10) kill at the end of treatment (72 h), 1 log(10) kill at follow-up (96 h) and 90% maximal activity (AUBKC(0–96)). CONCLUSIONS: Bladder infection modelling supports oral ciprofloxacin activity against E. coli with low-level resistance (ciprofloxacin MIC ≤ 1 mg/L) when using high dose therapy (750 mg 12 hourly). Oxford University Press 2022-12-07 /pmc/articles/PMC9890216/ /pubmed/36473954 http://dx.doi.org/10.1093/jac/dkac402 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Abbott, Iain J
van Gorp, Elke
Cottingham, Hugh
Macesic, Nenad
Wallis, Steven C
Roberts, Jason A
Meletiadis, Joseph
Peleg, Anton Y
Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model
title Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model
title_full Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model
title_fullStr Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model
title_full_unstemmed Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model
title_short Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model
title_sort oral ciprofloxacin activity against ceftriaxone-resistant escherichia coli in an in vitro bladder infection model
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890216/
https://www.ncbi.nlm.nih.gov/pubmed/36473954
http://dx.doi.org/10.1093/jac/dkac402
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