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Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation.
Int J Antimicrob Agents 2017; 49(6):770-773IJ

Abstract

Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI. The duration of CAZ/AVI treatment ranged from 7 days to 28 days. Five patients achieved clinical cure, however two relapsed with the same carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain within 3 weeks of completion of CAZ/AVI treatment. In addition, one patient with CR-Kp pneumonia experienced clinical failure despite having a documented CAZ/AVI-susceptible CR-Kp strain [minimum inhibitory concentration (MIC) = 2 mg/L]. Consequently, the overall rate of unsuccessful outcome in this small cohort of patients was 50%. All strains carried KPC-3, OXA-9 and different TEM and SHV β-lactamases, but none carried the intrinsically avibactam-resistant class B metallo-β-lactamases. No obvious differences in antibiotic resistance genes were observed. This study provides an early glimpse of the clinical outcomes of patients with CR-Kp infections treated with CAZ/AVI. Findings of clinical failure and relapse in patients with no prior exposure to CAZ/AVI and with documented susceptibility to CAZ/AVI highlight the urgent need for well-designed clinical studies evaluating the effectiveness of CAZ/AVI in the treatment of CRE infections.

Authors+Show Affiliations

Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA. Electronic address: fiorella.krapp@northwestern.edu.Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA.Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA.Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA.Northwestern Memorial Hospital, Department of Pharmacy, Chicago, IL, USA; Rosalind Franklin University of Medicine and Science, College of Pharmacy, Department of Pharmacy Practice, North Chicago, IL, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28389354

Citation

Krapp, Fiorella, et al. "Treating Complicated Carbapenem-resistant Enterobacteriaceae Infections With Ceftazidime/avibactam: a Retrospective Study With Molecular Strain Characterisation." International Journal of Antimicrobial Agents, vol. 49, no. 6, 2017, pp. 770-773.
Krapp F, Grant JL, Sutton SH, et al. Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation. Int J Antimicrob Agents. 2017;49(6):770-773.
Krapp, F., Grant, J. L., Sutton, S. H., Ozer, E. A., & Barr, V. O. (2017). Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation. International Journal of Antimicrobial Agents, 49(6), pp. 770-773. doi:10.1016/j.ijantimicag.2017.01.018.
Krapp F, et al. Treating Complicated Carbapenem-resistant Enterobacteriaceae Infections With Ceftazidime/avibactam: a Retrospective Study With Molecular Strain Characterisation. Int J Antimicrob Agents. 2017;49(6):770-773. PubMed PMID: 28389354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation. AU - Krapp,Fiorella, AU - Grant,Jennifer L, AU - Sutton,Sarah H, AU - Ozer,Egon A, AU - Barr,Viktorija O, Y1 - 2017/04/04/ PY - 2016/10/10/received PY - 2017/01/13/revised PY - 2017/01/22/accepted PY - 2017/4/9/pubmed PY - 2018/2/21/medline PY - 2017/4/9/entrez KW - Carbapenem-resistant Enterobacteriaceae KW - Ceftazidime/avibactam KW - Klebsiella pneumoniae KW - Multidrug resistance KW - β-Lactamase inhibitor SP - 770 EP - 773 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 49 IS - 6 N2 - Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI. The duration of CAZ/AVI treatment ranged from 7 days to 28 days. Five patients achieved clinical cure, however two relapsed with the same carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain within 3 weeks of completion of CAZ/AVI treatment. In addition, one patient with CR-Kp pneumonia experienced clinical failure despite having a documented CAZ/AVI-susceptible CR-Kp strain [minimum inhibitory concentration (MIC) = 2 mg/L]. Consequently, the overall rate of unsuccessful outcome in this small cohort of patients was 50%. All strains carried KPC-3, OXA-9 and different TEM and SHV β-lactamases, but none carried the intrinsically avibactam-resistant class B metallo-β-lactamases. No obvious differences in antibiotic resistance genes were observed. This study provides an early glimpse of the clinical outcomes of patients with CR-Kp infections treated with CAZ/AVI. Findings of clinical failure and relapse in patients with no prior exposure to CAZ/AVI and with documented susceptibility to CAZ/AVI highlight the urgent need for well-designed clinical studies evaluating the effectiveness of CAZ/AVI in the treatment of CRE infections. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/28389354/Treating_complicated_carbapenem_resistant_enterobacteriaceae_infections_with_ceftazidime/avibactam:_a_retrospective_study_with_molecular_strain_characterisation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(17)30105-X DB - PRIME DP - Unbound Medicine ER -