In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates
Objectives: Combination therapy has been recommended when using ceftazidimeâavibactam (CAZâAVI) 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 cip...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-12-01
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| Series: | International Journal of Infectious Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971217302412 |
| _version_ | 1818280135763165184 |
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| author | Paolo Gaibani Russell E. Lewis Silvia L. Volpe Maddalena Giannella Caterina Campoli Maria Paola Landini PierLuigi Viale Maria Carla Re Simone Ambretti |
| author_facet | Paolo Gaibani Russell E. Lewis Silvia L. Volpe Maddalena Giannella Caterina Campoli Maria Paola Landini PierLuigi Viale Maria Carla Re Simone Ambretti |
| author_sort | Paolo Gaibani |
| collection | DOAJ |
| description | Objectives: Combination therapy has been recommended when using ceftazidimeâavibactam (CAZâAVI) 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 cephalosporinâβ-lactamase inhibitor combination CAZâAVI in this study. Methods: Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZâAVI-susceptible (n = 11) and resistant (n = 2) clinical isolates. In vitro interactions of CAZâAVI 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 CAZâAVI 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, CAZâAVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZâAVI in combination with imipenem achieved higher SBPI values than other CAZâAVI-based combinations. Conclusions: These data suggest that combinations of CAZâAVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections. Keywords: KPC-producing Klebsiella pneumoniae, Ceftazidimeâavibactam, Synergy, Carbapenem, Imipenem |
| first_indexed | 2024-12-12T23:44:25Z |
| format | Article |
| id | doaj.art-fbae3b803e8d426c8a62106b8a3a132d |
| institution | Directory Open Access Journal |
| issn | 1201-9712 |
| language | English |
| last_indexed | 2024-12-12T23:44:25Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj.art-fbae3b803e8d426c8a62106b8a3a132d2022-12-22T00:06:58ZengElsevierInternational Journal of Infectious Diseases1201-97122017-12-016513In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolatesPaolo Gaibani0Russell E. Lewis1Silvia L. Volpe2Maddalena Giannella3Caterina Campoli4Maria Paola Landini5PierLuigi Viale6Maria Carla Re7Simone Ambretti8Operative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy; Corresponding author at: Operative Unit of Microbiology, S. Orsola-Malpighi University Hospital, Regional Reference Centre for Microbiological Emergencies (CRREM), 9 via G. Massarenti, 40138 Bologna, Italy.Operative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, ItalyOperative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, ItalyOperative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, ItalyOperative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, ItalyRizzoli Orthopaedic Institute, ItalyOperative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, ItalyOperative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, ItalyOperative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, ItalyObjectives: Combination therapy has been recommended when using ceftazidimeâavibactam (CAZâAVI) 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 cephalosporinâβ-lactamase inhibitor combination CAZâAVI in this study. Methods: Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZâAVI-susceptible (n = 11) and resistant (n = 2) clinical isolates. In vitro interactions of CAZâAVI 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 CAZâAVI 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, CAZâAVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZâAVI in combination with imipenem achieved higher SBPI values than other CAZâAVI-based combinations. Conclusions: These data suggest that combinations of CAZâAVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections. Keywords: KPC-producing Klebsiella pneumoniae, Ceftazidimeâavibactam, Synergy, Carbapenem, Imipenemhttp://www.sciencedirect.com/science/article/pii/S1201971217302412 |
| spellingShingle | Paolo Gaibani Russell E. Lewis Silvia L. Volpe Maddalena Giannella Caterina Campoli Maria Paola Landini PierLuigi Viale Maria Carla Re Simone Ambretti In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates International Journal of Infectious Diseases |
| title | In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates |
| title_full | In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates |
| title_fullStr | In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates |
| title_full_unstemmed | In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates |
| title_short | In vitro interaction of ceftazidimeâavibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates |
| title_sort | in vitro interaction of ceftazidimeaavibactam in combination with different antimicrobials against kpc producing klebsiella pneumoniae clinical isolates |
| url | http://www.sciencedirect.com/science/article/pii/S1201971217302412 |
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