Academic Journal
727. Potency of the β-Lactamase Inhibitor QPX7728 Is Minimally Affected by KPC Mutations that Reduce Potency of Ceftazidime–Avibactam
| العنوان: | 727. Potency of the β-Lactamase Inhibitor QPX7728 Is Minimally Affected by KPC Mutations that Reduce Potency of Ceftazidime–Avibactam |
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| المؤلفون: | Lomovskaya, Olga, Nelson, Kirk J, Rubio-Aparicio, Debora |
| المصدر: | Open Forum Infectious Diseases ; volume 6, issue Supplement_2, page S326-S326 ; ISSN 2328-8957 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Infectious Diseases, Oncology |
| الوصف: | Background In the United States, carbapenem-resistant Enterobacteriaceae (CRE) are mainly represented by KPC-producing strains and ceftazidime–avibactam (C/A) is increasingly used to treat infections caused by KPC-producers. C/A resistant (C/A-R) mutants with mutations in blaKPC can be isolated in vitro and were reported in patients treated with C/A. QPX7728 (QPX) is a new ultra-broad-spectrum β-lactamase inhibitor based on a cyclic boronic acid pharmacophore with a potent activity against serine and metallo-β-lactamases. QPX in combination with meropenem (MER), M/Q, or cefepime (FEP), F/Q, has potent activity against all types of CRE (KPC, MBLs and OXA-48). The objective of these studies was to evaluate the activity of QPX in combination with various antibiotics against KPC-producing strains with C/A-R due to mutations in blaKPC. Methods Ten strains of KPC-producing Klebsiella pneumoniae with C/A MIC varied from 0.5 µg/mL to 8 µg/mL were used in resistance studies using C/A at 2x–8x the MIC (with avibactam [AVI] fixed at 4 µg/mL). Mutations in blaKPC were identified by sequence analysis. Ceftazidime (CAZ), MER and FEP MIC alone and with AVI and QPX (both BLIs at 4 µg/mL) were determined using the reference broth microdilution method. Five C/A-R clinical isolates with mutations in blaKPC were also included in the panel. Results Mutations in blaKPC that result in C/A resistance were selected in all strains. Mutants had 4- to 64-fold (16-fold average) increase in C/A MIC that varied from 16 to 128 μg/mL. In contrast, there was a 2-fold increase for CAZ-QPX MICs (MICs between ≤0.125 to 2 μg/mL. Similarly, there was no more than 2-fold increase in MER/QPX and FEP/QPX MICs, and the majority of mutants did not have an increase in MER/QPX or FEP/QPX MICs (MICs varied from ≤0.125 to 1 µg/mL). For five clinical C/A-R isolates, C/A, M/Q and F/Q MIC varied from 16 to ≥128 μg/mL, ≤0.125 to 4 μg/mL, and ≤0.125 to 2 μg/mL, respectively. Conclusion These data indicate that KPC mutations that affect the potency of C/A ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/ofid/ofz360.795 |
| الاتاحة: | http://dx.doi.org/10.1093/ofid/ofz360.795 http://academic.oup.com/ofid/article-pdf/6/Supplement_2/S326/30274293/ofz360.795.pdf |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.C012CB9D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ofid/ofz360.795 |
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