Efficacy of delafloxacin against the biothreat pathogen Bacillus anthracis
Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy 2023..
OBJECTIVES: To evaluate the in vitro activity and in vivo efficacy of delafloxacin against Bacillus anthracis, the causative agent of anthrax.
METHODS: MICs were obtained according to CLSI guidelines for 30 virulent isolates and 14 attenuated antibiotic-resistant strains. For the in vivo efficacy study, mice were administered delafloxacin (30-62.5 mg/kg) subcutaneously, or ciprofloxacin (30 mg/kg) intraperitoneally beginning at either 24 or 48 ± 1 h post-challenge (post-exposure prophylaxis) and continued every 12 h for 14 days with study termination on day 30. The mean inhaled dose in the study was approximately 103 × LD50 equivalents, and the range was 87-120 × LD50.
RESULTS: Delafloxacin (MIC90 = 0.004 mg/L) was 16-fold more potent than ciprofloxacin (MIC90 = 0.06 mg/L) against a 30-strain set of virulent B. anthracis. Against a panel of attenuated antibiotic-resistant strains, delafloxacin demonstrated potency ≥128-fold over that observed with ciprofloxacin. When evaluated in vivo, mice treated with all delafloxacin doses tested at 24 h post-challenge demonstrated equivalent survival compared with mice treated with the positive control ciprofloxacin. Because of the high challenge dose of spores, mice treated at 48 h showed rapid and high mortality in all groups including the positive control. Surviving animals in all delafloxacin- and ciprofloxacin-treated groups (24 and 48 h) showed complete splenic clearance of infection and <2.2 × 103 cfu/g lung tissue.
CONCLUSIONS: Given the high bar set by the 100 × LD50 challenge dose in this study, the results from delafloxacin treatment are promising for the treatment of inhaled anthrax.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
|---|---|
| Enthalten in: |
The Journal of antimicrobial chemotherapy - 78(2023), 3 vom: 02. März, Seite 810-816 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
McCurdy, Sandra [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
5E8K9I0O4U |
|---|
| Anmerkungen: |
Date Completed 03.03.2023 Date Revised 30.03.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/jac/dkad015 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM352482702 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM352482702 | ||
| 003 | DE-627 | ||
| 005 | 20231226053827.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/jac/dkad015 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1174.xml |
| 035 | |a (DE-627)NLM352482702 | ||
| 035 | |a (NLM)36738250 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a McCurdy, Sandra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy of delafloxacin against the biothreat pathogen Bacillus anthracis |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.03.2023 | ||
| 500 | |a Date Revised 30.03.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy 2023. | ||
| 520 | |a OBJECTIVES: To evaluate the in vitro activity and in vivo efficacy of delafloxacin against Bacillus anthracis, the causative agent of anthrax | ||
| 520 | |a METHODS: MICs were obtained according to CLSI guidelines for 30 virulent isolates and 14 attenuated antibiotic-resistant strains. For the in vivo efficacy study, mice were administered delafloxacin (30-62.5 mg/kg) subcutaneously, or ciprofloxacin (30 mg/kg) intraperitoneally beginning at either 24 or 48 ± 1 h post-challenge (post-exposure prophylaxis) and continued every 12 h for 14 days with study termination on day 30. The mean inhaled dose in the study was approximately 103 × LD50 equivalents, and the range was 87-120 × LD50 | ||
| 520 | |a RESULTS: Delafloxacin (MIC90 = 0.004 mg/L) was 16-fold more potent than ciprofloxacin (MIC90 = 0.06 mg/L) against a 30-strain set of virulent B. anthracis. Against a panel of attenuated antibiotic-resistant strains, delafloxacin demonstrated potency ≥128-fold over that observed with ciprofloxacin. When evaluated in vivo, mice treated with all delafloxacin doses tested at 24 h post-challenge demonstrated equivalent survival compared with mice treated with the positive control ciprofloxacin. Because of the high challenge dose of spores, mice treated at 48 h showed rapid and high mortality in all groups including the positive control. Surviving animals in all delafloxacin- and ciprofloxacin-treated groups (24 and 48 h) showed complete splenic clearance of infection and <2.2 × 103 cfu/g lung tissue | ||
| 520 | |a CONCLUSIONS: Given the high bar set by the 100 × LD50 challenge dose in this study, the results from delafloxacin treatment are promising for the treatment of inhaled anthrax | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a delafloxacin |2 NLM | |
| 650 | 7 | |a 6315412YVF |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Ciprofloxacin |2 NLM | |
| 650 | 7 | |a 5E8K9I0O4U |2 NLM | |
| 700 | 1 | |a Halasohoris, Stephanie A |e verfasserin |4 aut | |
| 700 | 1 | |a Babyak, Ashley L |e verfasserin |4 aut | |
| 700 | 1 | |a Lembirik, Sanae |e verfasserin |4 aut | |
| 700 | 1 | |a Hoover, Randall |e verfasserin |4 aut | |
| 700 | 1 | |a Hickman, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Scarff, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Klimko, Christopher P |e verfasserin |4 aut | |
| 700 | 1 | |a Cote, Christopher K |e verfasserin |4 aut | |
| 700 | 1 | |a Meinig, J Matthew |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of antimicrobial chemotherapy |d 1981 |g 78(2023), 3 vom: 02. März, Seite 810-816 |w (DE-627)NLM000017701 |x 1460-2091 |7 nnns |
| 773 | 1 | 8 | |g volume:78 |g year:2023 |g number:3 |g day:02 |g month:03 |g pages:810-816 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/jac/dkad015 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 78 |j 2023 |e 3 |b 02 |c 03 |h 810-816 | ||