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Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?
BACKGROUND: Acinetobacter baumannii has been recognized as a cause of nosocomial infection. To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A. baumannii (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032916/ https://www.ncbi.nlm.nih.gov/pubmed/34409786 http://dx.doi.org/10.3947/ic.2021.0007 |
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author | Saelim, Weerayuth Changpradub, Dhitiwat Thunyaharn, Sudaluck Juntanawiwat, Piraporn Nulsopapon, Parnrada Santimaleeworagun, Wichai |
author_facet | Saelim, Weerayuth Changpradub, Dhitiwat Thunyaharn, Sudaluck Juntanawiwat, Piraporn Nulsopapon, Parnrada Santimaleeworagun, Wichai |
author_sort | Saelim, Weerayuth |
collection | PubMed |
description | BACKGROUND: Acinetobacter baumannii has been recognized as a cause of nosocomial infection. To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A. baumannii (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health. This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity. MATERIALS AND METHODS: Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015. The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method. Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥3.3 µg/mL. RESULTS: A total of 50 CRAB isolates were included. The MIC(50) and MIC(90) were 64 and 128 µg/mL, respectively, for sulbactam, 256 and 2,048 µg/mL, respectively, for fosfomycin, and 1 and 4 µg/mL, respectively, for colistin. In patients with creatinine clearance of 91 – 130 m/min, the dosing regimens of 180 mg every 12 h and 150 mg every 8 h achieved ≥ 90% of target of the area under the free drug plasma concentration–time curve from 0 to 24 hr (fAUC24)/MIC ≥25 against isolates MICs of ≤0.25 and ≤0.5 µg/mL, respectively, and their rates of colistin trough concentration more than ≥3.3 µg/mL were 35 and 54%, respectively. Colistin combined with sulbactam or fosfomycin decreased the colistin MIC of CRAB isolates from 1 – 16 µg/mL to 0.0625 – 1 and 0.0625 – 2 µg/mL, respectively. Based on CFR ≥ 90%, no colistin monotherapy regimens in patients with creatinine clearance of 91 – 130 mL/min were effective against all of the studied CRAB isolates. For improving efficacy and reducing the risk of nephrotoxicity, colistin 150 mg given every 12 h together with sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) was effective in patients with creatinine clearance of 91 – 130 mL/min. Additionally, both colistin combination regimens were effective against five colistin-resistant A. baumannii isolates. CONCLUSION: Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates. Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment. |
format | Online Article Text |
id | pubmed-8032916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS |
record_format | MEDLINE/PubMed |
spelling | pubmed-80329162021-04-15 Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? Saelim, Weerayuth Changpradub, Dhitiwat Thunyaharn, Sudaluck Juntanawiwat, Piraporn Nulsopapon, Parnrada Santimaleeworagun, Wichai Infect Chemother Original Article BACKGROUND: Acinetobacter baumannii has been recognized as a cause of nosocomial infection. To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A. baumannii (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health. This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity. MATERIALS AND METHODS: Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015. The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method. Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥3.3 µg/mL. RESULTS: A total of 50 CRAB isolates were included. The MIC(50) and MIC(90) were 64 and 128 µg/mL, respectively, for sulbactam, 256 and 2,048 µg/mL, respectively, for fosfomycin, and 1 and 4 µg/mL, respectively, for colistin. In patients with creatinine clearance of 91 – 130 m/min, the dosing regimens of 180 mg every 12 h and 150 mg every 8 h achieved ≥ 90% of target of the area under the free drug plasma concentration–time curve from 0 to 24 hr (fAUC24)/MIC ≥25 against isolates MICs of ≤0.25 and ≤0.5 µg/mL, respectively, and their rates of colistin trough concentration more than ≥3.3 µg/mL were 35 and 54%, respectively. Colistin combined with sulbactam or fosfomycin decreased the colistin MIC of CRAB isolates from 1 – 16 µg/mL to 0.0625 – 1 and 0.0625 – 2 µg/mL, respectively. Based on CFR ≥ 90%, no colistin monotherapy regimens in patients with creatinine clearance of 91 – 130 mL/min were effective against all of the studied CRAB isolates. For improving efficacy and reducing the risk of nephrotoxicity, colistin 150 mg given every 12 h together with sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) was effective in patients with creatinine clearance of 91 – 130 mL/min. Additionally, both colistin combination regimens were effective against five colistin-resistant A. baumannii isolates. CONCLUSION: Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates. Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment. The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS 2021-03 2021-03-22 /pmc/articles/PMC8032916/ /pubmed/34409786 http://dx.doi.org/10.3947/ic.2021.0007 Text en Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Saelim, Weerayuth Changpradub, Dhitiwat Thunyaharn, Sudaluck Juntanawiwat, Piraporn Nulsopapon, Parnrada Santimaleeworagun, Wichai Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? |
title | Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? |
title_full | Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? |
title_fullStr | Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? |
title_full_unstemmed | Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? |
title_short | Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? |
title_sort | colistin plus sulbactam or fosfomycin against carbapenem-resistant acinetobacter baumannii: improved efficacy or decreased risk of nephrotoxicity? |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032916/ https://www.ncbi.nlm.nih.gov/pubmed/34409786 http://dx.doi.org/10.3947/ic.2021.0007 |
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