Efficacy of ceftazidime-avibactam in various combinations for the treatment of experimental osteomyelitis due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae
Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved..
BACKGROUND: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis.
METHODS: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×108 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log10 CFU.
RESULTS: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination.
CONCLUSIONS: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
|---|---|
| Enthalten in: |
International journal of antimicrobial agents - 61(2023), 1 vom: 07. Jan., Seite 106702 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Davido, Benjamin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 22.02.2023 Date Revised 22.02.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ijantimicag.2022.106702 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM349893683 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM349893683 | ||
| 003 | DE-627 | ||
| 005 | 20231226043718.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ijantimicag.2022.106702 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1166.xml |
| 035 | |a (DE-627)NLM349893683 | ||
| 035 | |a (NLM)36476965 | ||
| 035 | |a (PII)S0924-8579(22)00227-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Davido, Benjamin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy of ceftazidime-avibactam in various combinations for the treatment of experimental osteomyelitis due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae |
| 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 22.02.2023 | ||
| 500 | |a Date Revised 22.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. | ||
| 520 | |a BACKGROUND: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis | ||
| 520 | |a METHODS: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×108 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log10 CFU | ||
| 520 | |a RESULTS: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination | ||
| 520 | |a CONCLUSIONS: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Ceftazidime-avibactam | |
| 650 | 4 | |a KPC | |
| 650 | 4 | |a Klebsiella pneumoniae | |
| 650 | 4 | |a Osteomyelitis | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a avibactam, ceftazidime drug combination |2 NLM | |
| 650 | 7 | |a Azabicyclo Compounds |2 NLM | |
| 650 | 7 | |a beta-Lactamase Inhibitors |2 NLM | |
| 650 | 7 | |a beta-Lactamases |2 NLM | |
| 650 | 7 | |a EC 3.5.2.6 |2 NLM | |
| 650 | 7 | |a carbapenemase |2 NLM | |
| 650 | 7 | |a EC 3.5.2.6 |2 NLM | |
| 650 | 7 | |a Ceftazidime |2 NLM | |
| 650 | 7 | |a 9M416Z9QNR |2 NLM | |
| 650 | 7 | |a Colistin |2 NLM | |
| 650 | 7 | |a Z67X93HJG1 |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a Fosfomycin |2 NLM | |
| 650 | 7 | |a 2N81MY12TE |2 NLM | |
| 650 | 7 | |a Gentamicins |2 NLM | |
| 700 | 1 | |a Crémieux, Anne-Claude |e verfasserin |4 aut | |
| 700 | 1 | |a Vaugier, Isabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Gatin, Laure |e verfasserin |4 aut | |
| 700 | 1 | |a Noussair, Latifa |e verfasserin |4 aut | |
| 700 | 1 | |a Massias, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Laurent, Frederic |e verfasserin |4 aut | |
| 700 | 1 | |a Saleh-Mghir, Azzam |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of antimicrobial agents |d 1991 |g 61(2023), 1 vom: 07. Jan., Seite 106702 |w (DE-627)NLM090678974 |x 1872-7913 |7 nnns |
| 773 | 1 | 8 | |g volume:61 |g year:2023 |g number:1 |g day:07 |g month:01 |g pages:106702 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ijantimicag.2022.106702 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 61 |j 2023 |e 1 |b 07 |c 01 |h 106702 | ||