Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model

Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and en...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Vaughn D. Craddock [verfasserIn] Evan L. Steere [verfasserIn] Hannah Harman [verfasserIn] Nicholas S. Britt [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	delafloxacin multidrug-resistance carbapenem-resistance carbapenem-resistant cystic fibrosis

Übergeordnetes Werk:	In: Antibiotics - MDPI AG, 2013, 12(2023), 6, p 1078
Übergeordnetes Werk:	volume:12 ; year:2023 ; number:6, p 1078

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/antibiotics12061078

Katalog-ID:	DOAJ094221049

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allfields	10.3390/antibiotics12061078 doi (DE-627)DOAJ094221049 (DE-599)DOAJa87061bf6fe14efc8df3fa549ab29003 DE-627 ger DE-627 rakwb eng RM1-950 Vaughn D. Craddock verfasserin aut Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis Therapeutics. Pharmacology Evan L. Steere verfasserin aut Hannah Harman verfasserin aut Nicholas S. Britt verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 6, p 1078 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:6, p 1078 https://doi.org/10.3390/antibiotics12061078 kostenfrei https://doaj.org/article/a87061bf6fe14efc8df3fa549ab29003 kostenfrei https://www.mdpi.com/2079-6382/12/6/1078 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 6, p 1078
spelling	10.3390/antibiotics12061078 doi (DE-627)DOAJ094221049 (DE-599)DOAJa87061bf6fe14efc8df3fa549ab29003 DE-627 ger DE-627 rakwb eng RM1-950 Vaughn D. Craddock verfasserin aut Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis Therapeutics. Pharmacology Evan L. Steere verfasserin aut Hannah Harman verfasserin aut Nicholas S. Britt verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 6, p 1078 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:6, p 1078 https://doi.org/10.3390/antibiotics12061078 kostenfrei https://doaj.org/article/a87061bf6fe14efc8df3fa549ab29003 kostenfrei https://www.mdpi.com/2079-6382/12/6/1078 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 6, p 1078
allfields_unstemmed	10.3390/antibiotics12061078 doi (DE-627)DOAJ094221049 (DE-599)DOAJa87061bf6fe14efc8df3fa549ab29003 DE-627 ger DE-627 rakwb eng RM1-950 Vaughn D. Craddock verfasserin aut Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis Therapeutics. Pharmacology Evan L. Steere verfasserin aut Hannah Harman verfasserin aut Nicholas S. Britt verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 6, p 1078 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:6, p 1078 https://doi.org/10.3390/antibiotics12061078 kostenfrei https://doaj.org/article/a87061bf6fe14efc8df3fa549ab29003 kostenfrei https://www.mdpi.com/2079-6382/12/6/1078 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 6, p 1078
allfieldsGer	10.3390/antibiotics12061078 doi (DE-627)DOAJ094221049 (DE-599)DOAJa87061bf6fe14efc8df3fa549ab29003 DE-627 ger DE-627 rakwb eng RM1-950 Vaughn D. Craddock verfasserin aut Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis Therapeutics. Pharmacology Evan L. Steere verfasserin aut Hannah Harman verfasserin aut Nicholas S. Britt verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 6, p 1078 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:6, p 1078 https://doi.org/10.3390/antibiotics12061078 kostenfrei https://doaj.org/article/a87061bf6fe14efc8df3fa549ab29003 kostenfrei https://www.mdpi.com/2079-6382/12/6/1078 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 6, p 1078
allfieldsSound	10.3390/antibiotics12061078 doi (DE-627)DOAJ094221049 (DE-599)DOAJa87061bf6fe14efc8df3fa549ab29003 DE-627 ger DE-627 rakwb eng RM1-950 Vaughn D. Craddock verfasserin aut Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis Therapeutics. Pharmacology Evan L. Steere verfasserin aut Hannah Harman verfasserin aut Nicholas S. Britt verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 6, p 1078 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:6, p 1078 https://doi.org/10.3390/antibiotics12061078 kostenfrei https://doaj.org/article/a87061bf6fe14efc8df3fa549ab29003 kostenfrei https://www.mdpi.com/2079-6382/12/6/1078 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 6, p 1078
language	English
source	In Antibiotics 12(2023), 6, p 1078 volume:12 year:2023 number:6, p 1078
sourceStr	In Antibiotics 12(2023), 6, p 1078 volume:12 year:2023 number:6, p 1078
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topic_facet	delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis Therapeutics. Pharmacology
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container_title	Antibiotics
authorswithroles_txt_mv	Vaughn D. Craddock @@aut@@ Evan L. Steere @@aut@@ Hannah Harman @@aut@@ Nicholas S. Britt @@aut@@
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callnumber-first	R - Medicine
author	Vaughn D. Craddock
spellingShingle	Vaughn D. Craddock misc RM1-950 misc delafloxacin misc <i<Pseudomonas aeruginosa</i< misc multidrug-resistance misc carbapenem-resistance misc carbapenem-resistant <i<Pseudomonas aeruginosa</i< misc cystic fibrosis misc Therapeutics. Pharmacology Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model
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topic_title	RM1-950 Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model delafloxacin <i<Pseudomonas aeruginosa</i< multidrug-resistance carbapenem-resistance carbapenem-resistant <i<Pseudomonas aeruginosa</i< cystic fibrosis
topic	misc RM1-950 misc delafloxacin misc <i<Pseudomonas aeruginosa</i< misc multidrug-resistance misc carbapenem-resistance misc carbapenem-resistant <i<Pseudomonas aeruginosa</i< misc cystic fibrosis misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc delafloxacin misc <i<Pseudomonas aeruginosa</i< misc multidrug-resistance misc carbapenem-resistance misc carbapenem-resistant <i<Pseudomonas aeruginosa</i< misc cystic fibrosis misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc delafloxacin misc <i<Pseudomonas aeruginosa</i< misc multidrug-resistance misc carbapenem-resistance misc carbapenem-resistant <i<Pseudomonas aeruginosa</i< misc cystic fibrosis misc Therapeutics. Pharmacology
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title	Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model
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title_full	Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model
author_sort	Vaughn D. Craddock
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author_browse	Vaughn D. Craddock Evan L. Steere Hannah Harman Nicholas S. Britt
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title_sort	activity of delafloxacin and comparator fluoroquinolones against multidrug-resistant <i<pseudomonas aeruginosa</i< in an in vitro cystic fibrosis sputum model
callnumber	RM1-950
title_auth	Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model
abstract	Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF.
abstractGer	Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF.
abstract_unstemmed	Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant <i<Pseudomonas aeruginosa</i< (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (<i<p</i< = 0.033) and Cmin (<i<p</i< = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (<i<p</i< = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF.
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container_issue	6, p 1078
title_short	Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model
url	https://doi.org/10.3390/antibiotics12061078 https://doaj.org/article/a87061bf6fe14efc8df3fa549ab29003 https://www.mdpi.com/2079-6382/12/6/1078 https://doaj.org/toc/2079-6382
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up_date	2024-07-03T21:57:15.955Z
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Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant <i<Pseudomonas aeruginosa</i< in an In Vitro Cystic Fibrosis Sputum Model

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