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Activity of the novel sulfactam BAL30072, alone and in combination with meropenem, against Enterobacteriaceae harbouring the NDM1 lactamase

Abstract number: P1146

Walsh T., Weeks J., Toleman M., Stubbings W., Page M., Jones M.

Objectives: BAL30072 (manufactured by Basilea Pharmaceutica International Ltd.) is a new sulfated monocyclic b-lactam not hydrolysed by metallo b-lactamases (MBLs) and with activity against a broad spectrum of Gram-negative pathogens, including multidrug resistant P. aeruginosa and A. baumannii. NDM-1 is a new MBL originating in India and recently isolated from pathogens infecting patients in Europe. We investigated the in-vitro activity of BAL30072 alone and in a 1:1 combination with meropenem (MEM) against recent clinical isolates of carbapenem-resistant Enterobacteriaceae harbouring the NDM-1MBL.

Methods: 78 Enterobacteriaceae comprising: E. coli (n = 33), K. pneumoniae (n = 43), K. oxytoca (n = 1) and P. rettgeri (n = 1) were collected from hospitalized patients in India during 2009. A sample of strains further characterised contained up to 7 b-lactamases including, TEM, OXA, SHV, DHA-1, CTX-M-15, CMY and NDM-1. MICs of BAL30072, MEM, ceftazidime (CAZ), aztreonam (ATM) and 1:1 combination of BAL30072:MEM were determined by broth microdilution according to CLSI standards. All isolates were screened using PCR for the presence of the NDM-1 gene immediately prior to MIC testing.

Results: The presence of NDM-1 was confirmed in all isolates. Susceptibility (presented as % strain inhibited per concentration) of the 78 NDM-1 harbouring isolates to the test drugs is summarised in the Figure.

Conclusion: BAL30072 alone was active against 60% of the strains at 4 mg/L, while ATM, CAZ and MEM covered <10%. Strains harbouring NDM-1 are known often to express multiple b-lactamases towards some of which BAL30072 may not be stable.

This data strongly suggests that BAL30072 is stable to hydrolysis by NDM-1, but that expression of other b-lactamases contributes to decreased susceptibility to BAL30072 alone. The addition of MEM protects BAL30072 against hydrolysis by these additional enzymes, resulting in >90% of isolates being inhibited at 4 mg/L.

BAL30072 offers a potential therapeutic benefit for infections caused by NDM-1-positive Enterobacteriaceae. In addition, the activity BAL30072 is further enhanced in combination with MEM against clinical isolates carrying NDM-1 and multiple other b-lactamases gene loci.

Session Details

Date: 07/05/2011
Time: 00:00-00:00
Session name: Abstracts of 21st ECCMID / 27th ICC
Subject:
Location: Milan, Italy, 7 - 10 May 2011
Presentation type:
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