Cefepime/sulbactam combination as a treatment alternative for extended spectrum beta-lacatmase producing Enterobacterales: A multicentric study from India

Background: Piperacillin/tazobactam has limited activity against Enterobacterales, which concurrently express ESBL/ampC/OXA-1 beta-lactamases, which are widely prevalent in India. Thus, there is a severe dearth for carbapenem sparing options that aggravate more dependent carbapenem therapy. In the I...

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Main Authors: Yamuna Devi Bakthavatchalam (Author), Dhanalakshmi Solaimalai (Author), Anand Ashok (Author), Harthi Ragothaman (Author), Soniya Krishnamoorthy (Author), Nivedhana Subburaju (Author), Sanjay bhattacharya (Author), Rudresh Sm (Author), Shripad Murlidhar Taklikar (Author), Barney Isaac (Author), Kamini Walia (Author), Balaji Veeraraghavan (Author)
Format: Book
Published: Elsevier, 2024-07-01T00:00:00Z.
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Summary:Background: Piperacillin/tazobactam has limited activity against Enterobacterales, which concurrently express ESBL/ampC/OXA-1 beta-lactamases, which are widely prevalent in India. Thus, there is a severe dearth for carbapenem sparing options that aggravate more dependent carbapenem therapy. In the Indian market, various cefepime/BLI combinations in diiferent fixed ratios were introduced to clinical practice. We investigated the activity of cefepime with increased sulbactam ratios against contemporary isolates of ESBL/OXA-1 expressing Enterobacterales. Methods: Non-duplicate contemporary ESBL and/or OXA-1 expressing E. coli (n = 117) and K. pneumoniae (n = 71) isolates were included in this study. The MIC of cefepime/sulbactam and its comparators were determined using a broth microdilution method. The presence of ESBL and OXA-1 genes were identified using multiplex PCR. Results: Against ESBL and OXA-1 co-producing E. coli, cefepime combined with sulbactam at 8 mg/L, inhibited 82% of the isolates. Cefoperazone susceptibility against ESBL-E. coli increased from 52% at 4 mg/L to 77% at 8 mg/L with sulbactam. When tested against K. pneumoniae co-expressing ESBL and OXA-1, cefepime susceptibility was 77% at 4 mg/L sulbactam and 88% at 8 mg/L sulbactam. PTZ consistently showed limited activity against ESBL co-harbouring OXA-1 (E. coli, 43% and K. pneumoniae, 61%). Conclusion: The present study demonstrates that adding an increased sulbactam concentration enhances cefepime's activity against contemporary ESBL/OXA-1 expressing Enterobacterales. A reformulated cefepime/sulbactam (2 g/2 g) combination may be the best carbapenem sparing option until cefepime/tazobactam and cefepime/enmetazobactam become available in the future.
Item Description:2213-3984
10.1016/j.cegh.2024.101510