Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile
PURPOSE: Clostridium difficile infection (CDI) is an increasing cause of nosocomial diarrhoea worldwide, which has been partly attributed to the emergence of hypervirulent strains including C. difficile BI/NAP1/ribotype 027 and BK/NAP7/ribotype 078. Cadazolid is a new antibiotic currently in late-stage clinical studies for the treatment of CDI. The present study evaluated the in vitro bactericidal effect of cadazolid and comparator antibiotics against four C. difficile strains. The data demonstrate the potent and bactericidal activity of cadazolid against different ribotypes of C. difficile.
METHODOLOGY: MICs for test antibiotics were determined in brain- heart infusion-supplemented broth (BHIS) containing 5 g l-1 yeast extract and 0.025 % (w/v) l-cysteine. Time-kill kinetics to investigate the rate of killing of each antibiotic at sub- and supra-MIC concentrations were performed at concentrations of 0.5, 1, 2, 4, 8 or 16× the MIC of cadazolid, vancomycin and fidaxomicin at intervals over a 48 h period.Results/key findings. Cadazolid-mediated killing of C. difficile was faster and occurred at lower concentrations than observed for vancomycin, while potency and killing was largely comparable to those observed for fidaxomicin. Notably, cadazolid also displayed a potent bactericidal effect against fluoroquinolone-resistant hypervirulent ribotype 027 and 078 strains. C. difficile spore formation was largely inhibited by all three antibiotics at concentrations >1× MIC; however, none were able to eliminate spores effectively, which were present at the start of the experiment.
CONCLUSION: The data presented here demonstrate the potent in vitro bactericidal activity of cadazolid against different ribotypes of C. difficile, although on a limited set of strains.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
|---|---|
| Enthalten in: |
Journal of medical microbiology - 67(2018), 9 vom: 27. Sept., Seite 1402-1409 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Skinner, Kirsty [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
2OEA2UN10Y |
|---|
| Anmerkungen: |
Date Completed 11.09.2018 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1099/jmm.0.000808 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM286921987 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM286921987 | ||
| 003 | DE-627 | ||
| 005 | 20231225052837.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1099/jmm.0.000808 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0956.xml |
| 035 | |a (DE-627)NLM286921987 | ||
| 035 | |a (NLM)30052178 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Skinner, Kirsty |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile |
| 264 | 1 | |c 2018 | |
| 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 11.09.2018 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Clostridium difficile infection (CDI) is an increasing cause of nosocomial diarrhoea worldwide, which has been partly attributed to the emergence of hypervirulent strains including C. difficile BI/NAP1/ribotype 027 and BK/NAP7/ribotype 078. Cadazolid is a new antibiotic currently in late-stage clinical studies for the treatment of CDI. The present study evaluated the in vitro bactericidal effect of cadazolid and comparator antibiotics against four C. difficile strains. The data demonstrate the potent and bactericidal activity of cadazolid against different ribotypes of C. difficile | ||
| 520 | |a METHODOLOGY: MICs for test antibiotics were determined in brain- heart infusion-supplemented broth (BHIS) containing 5 g l-1 yeast extract and 0.025 % (w/v) l-cysteine. Time-kill kinetics to investigate the rate of killing of each antibiotic at sub- and supra-MIC concentrations were performed at concentrations of 0.5, 1, 2, 4, 8 or 16× the MIC of cadazolid, vancomycin and fidaxomicin at intervals over a 48 h period.Results/key findings. Cadazolid-mediated killing of C. difficile was faster and occurred at lower concentrations than observed for vancomycin, while potency and killing was largely comparable to those observed for fidaxomicin. Notably, cadazolid also displayed a potent bactericidal effect against fluoroquinolone-resistant hypervirulent ribotype 027 and 078 strains. C. difficile spore formation was largely inhibited by all three antibiotics at concentrations >1× MIC; however, none were able to eliminate spores effectively, which were present at the start of the experiment | ||
| 520 | |a CONCLUSION: The data presented here demonstrate the potent in vitro bactericidal activity of cadazolid against different ribotypes of C. difficile, although on a limited set of strains | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CDI | |
| 650 | 4 | |a Clostridium difficile | |
| 650 | 4 | |a cadazolid | |
| 650 | 4 | |a time-kill kinetics | |
| 650 | 7 | |a Aminoglycosides |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Oxazolidinones |2 NLM | |
| 650 | 7 | |a cadazolid |2 NLM | |
| 650 | 7 | |a 2OEA2UN10Y |2 NLM | |
| 650 | 7 | |a Vancomycin |2 NLM | |
| 650 | 7 | |a 6Q205EH1VU |2 NLM | |
| 650 | 7 | |a Fidaxomicin |2 NLM | |
| 650 | 7 | |a Z5N076G8YQ |2 NLM | |
| 700 | 1 | |a Birchall, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Corbett, David |e verfasserin |4 aut | |
| 700 | 1 | |a Thommes, Pia |e verfasserin |4 aut | |
| 700 | 1 | |a Locher, Hans H |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of medical microbiology |d 1968 |g 67(2018), 9 vom: 27. Sept., Seite 1402-1409 |w (DE-627)NLM000052272 |x 1473-5644 |7 nnns |
| 773 | 1 | 8 | |g volume:67 |g year:2018 |g number:9 |g day:27 |g month:09 |g pages:1402-1409 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1099/jmm.0.000808 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 67 |j 2018 |e 9 |b 27 |c 09 |h 1402-1409 | ||