In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates.

Paolo Gaibani, Russell E. Lewis, S L Volpe, Maddalena Giannella, C Campoli, M. P. Landini, P. Viale, Maria Carla Re, S Ambretti

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study.

METHODS:
Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates. In vitro interactions of CAZ-AVI with different antimicrobials were tested using the gradient synergy test. Changes in the minimum inhibitory concentration (MIC) value were interpreted using the fractional inhibitory concentration (FIC) index and susceptible breakpoint index (SBPI).

RESULTS:
The combination of CAZ-AVI with gentamicin or ciprofloxacin displayed no synergism against any of the KPC-Kp isolates, whereas synergistic activity was observed with imipenem and meropenem against all KPC-Kp isolates. Notably, CAZ-AVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZ-AVI in combination with imipenem achieved higher SBPI values than other CAZ-AVI-based combinations.

CONCLUSIONS:
These data suggest that combinations of CAZ-AVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections.
Original languageEnglish
Pages (from-to)1-3
Number of pages3
JournalInternational Journal of Infectious Diseases
Volume65
DOIs
Publication statusPublished - 2017
Externally publishedYes

Fingerprint

Klebsiella pneumoniae
meropenem
Imipenem
Ciprofloxacin
Gentamicins
Klebsiella Infections
In Vitro Techniques
ceftazidime drug combination avibactam
Microbial Sensitivity Tests
Cephalosporins
Anti-Infective Agents
Therapeutics

Keywords

  • Carbapenem
  • Ceftazidime–avibactam
  • Imipenem
  • KPC-producing Klebsiella pneumoniae
  • Synergy

Cite this

In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. / Gaibani, Paolo; Lewis, Russell E.; Volpe, S L ; Giannella, Maddalena; Campoli, C; Landini, M. P.; Viale, P.; Carla Re, Maria; Ambretti, S.

In: International Journal of Infectious Diseases, Vol. 65, 2017, p. 1-3.

Research output: Contribution to journalArticle

Gaibani, Paolo ; Lewis, Russell E. ; Volpe, S L ; Giannella, Maddalena ; Campoli, C ; Landini, M. P. ; Viale, P. ; Carla Re, Maria ; Ambretti, S. / In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. In: International Journal of Infectious Diseases. 2017 ; Vol. 65. pp. 1-3.
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title = "In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates.",
abstract = "Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study.METHODS:Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates. In vitro interactions of CAZ-AVI with different antimicrobials were tested using the gradient synergy test. Changes in the minimum inhibitory concentration (MIC) value were interpreted using the fractional inhibitory concentration (FIC) index and susceptible breakpoint index (SBPI).RESULTS:The combination of CAZ-AVI with gentamicin or ciprofloxacin displayed no synergism against any of the KPC-Kp isolates, whereas synergistic activity was observed with imipenem and meropenem against all KPC-Kp isolates. Notably, CAZ-AVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZ-AVI in combination with imipenem achieved higher SBPI values than other CAZ-AVI-based combinations.CONCLUSIONS:These data suggest that combinations of CAZ-AVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections.",
keywords = "Carbapenem, Ceftazidime–avibactam, Imipenem, KPC-producing Klebsiella pneumoniae, Synergy",
author = "Paolo Gaibani and Lewis, {Russell E.} and Volpe, {S L} and Maddalena Giannella and C Campoli and Landini, {M. P.} and P. Viale and {Carla Re}, Maria and S Ambretti",
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T1 - In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates.

AU - Gaibani, Paolo

AU - Lewis, Russell E.

AU - Volpe, S L

AU - Giannella, Maddalena

AU - Campoli, C

AU - Landini, M. P.

AU - Viale, P.

AU - Carla Re, Maria

AU - Ambretti, S

PY - 2017

Y1 - 2017

N2 - Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study.METHODS:Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates. In vitro interactions of CAZ-AVI with different antimicrobials were tested using the gradient synergy test. Changes in the minimum inhibitory concentration (MIC) value were interpreted using the fractional inhibitory concentration (FIC) index and susceptible breakpoint index (SBPI).RESULTS:The combination of CAZ-AVI with gentamicin or ciprofloxacin displayed no synergism against any of the KPC-Kp isolates, whereas synergistic activity was observed with imipenem and meropenem against all KPC-Kp isolates. Notably, CAZ-AVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZ-AVI in combination with imipenem achieved higher SBPI values than other CAZ-AVI-based combinations.CONCLUSIONS:These data suggest that combinations of CAZ-AVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections.

AB - Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study.METHODS:Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates. In vitro interactions of CAZ-AVI with different antimicrobials were tested using the gradient synergy test. Changes in the minimum inhibitory concentration (MIC) value were interpreted using the fractional inhibitory concentration (FIC) index and susceptible breakpoint index (SBPI).RESULTS:The combination of CAZ-AVI with gentamicin or ciprofloxacin displayed no synergism against any of the KPC-Kp isolates, whereas synergistic activity was observed with imipenem and meropenem against all KPC-Kp isolates. Notably, CAZ-AVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZ-AVI in combination with imipenem achieved higher SBPI values than other CAZ-AVI-based combinations.CONCLUSIONS:These data suggest that combinations of CAZ-AVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections.

KW - Carbapenem

KW - Ceftazidime–avibactam

KW - Imipenem

KW - KPC-producing Klebsiella pneumoniae

KW - Synergy

U2 - 10.1016/j.ijid.2017.09.017

DO - 10.1016/j.ijid.2017.09.017

M3 - Article

VL - 65

SP - 1

EP - 3

JO - International Journal of Infectious Diseases

JF - International Journal of Infectious Diseases

SN - 1201-9712

ER -