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In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates.
Int J Infect Dis 2017; 65:1-3IJ

Abstract

OBJECTIVES

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.

Authors+Show Affiliations

Operative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy. Electronic address: paolo.gaibani@unibo.it.Operative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, Italy.Operative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy.Operative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, Italy.Operative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy.Rizzoli Orthopaedic Institute, Italy.Operative Unit of Infectious Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, Italy.Operative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy; University of Bologna, Bologna, Italy.Operative Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28951106

Citation

Gaibani, Paolo, et al. "In Vitro Interaction of Ceftazidime-avibactam in Combination With Different Antimicrobials Against KPC-producing Klebsiella Pneumoniae Clinical Isolates." International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, vol. 65, 2017, pp. 1-3.
Gaibani P, Lewis RE, Volpe SL, et al. In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. Int J Infect Dis. 2017;65:1-3.
Gaibani, P., Lewis, R. E., Volpe, S. L., Giannella, M., Campoli, C., Landini, M. P., ... Ambretti, S. (2017). In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, 65, pp. 1-3. doi:10.1016/j.ijid.2017.09.017.
Gaibani P, et al. In Vitro Interaction of Ceftazidime-avibactam in Combination With Different Antimicrobials Against KPC-producing Klebsiella Pneumoniae Clinical Isolates. Int J Infect Dis. 2017;65:1-3. PubMed PMID: 28951106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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,Silvia L, AU - Giannella,Maddalena, AU - Campoli,Caterina, AU - Landini,Maria Paola, AU - Viale,PierLuigi, AU - Re,Maria Carla, AU - Ambretti,Simone, Y1 - 2017/09/22/ PY - 2017/08/09/received PY - 2017/09/15/revised PY - 2017/09/16/accepted PY - 2017/9/28/pubmed PY - 2018/4/18/medline PY - 2017/9/28/entrez KW - Carbapenem KW - Ceftazidime–avibactam KW - Imipenem KW - KPC-producing Klebsiella pneumoniae KW - Synergy SP - 1 EP - 3 JF - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases JO - Int. J. Infect. Dis. VL - 65 N2 - OBJECTIVES: 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. SN - 1878-3511 UR - https://www.unboundmedicine.com/medline/citation/28951106/In_vitro_interaction_of_ceftazidime_avibactam_in_combination_with_different_antimicrobials_against_KPC_producing_Klebsiella_pneumoniae_clinical_isolates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1201-9712(17)30241-2 DB - PRIME DP - Unbound Medicine ER -