Activity of temocillin against carbapenem-resistant clinical Enterobacteriaceae
Abstract number: O362
Mushtaq S., Warner M., Zhang J-C., Maharjan S., Doumith M., Woodford N., Livermore D.
Objectives: Until recently, carbapenems retained near-universal activity against Enterobacteriaceae but resistance is now emerging, mediated either by combinations of ESBL or AmpC enzyme and porin loss or by carbapenemases. The prevalent emerging carbapenemases vary by country: KPC enzymes in the USA and Israel, OXA-48 in Turkey, VIM in southern Europe and NDM in Italy. The UK sees small numbers of isolates with each of these types, some imported, some representing domestic spread. Most are multiresistant. We examined their susceptibility to temocillin a 6-a-methoxy derivative of ticarcillin, notable for stability to ESBLs and AmpC.
Methods: The 81 isolates tested isolates variously had KPC (n = 10), SME-1 (1), IMP (13), VIM (5), NDM (17) or OXA-48 (19 carbapenemases or had combinations of impermeability with an AmpC enzyme or ESBL (16); they included 52 Klebsiella spp., 18 Enterobacter spp., 6 E. coli and 5 others. Transformants and transconjugants were prepared in E. coli DH5-a and J621, respectively. Carbapenemase genes were identified by PCR and sequencing; MICs were measured by CLSI agar dilution.
Results: MICs for isolates with KPC carbapenemases were from 1664 mg/L (geom. mean 40 mg/L) and introduction of a KPC+ plasmid into E. coli only raised the MIC from 8 to 16 mg/L; by contrast MICs for isolates with metallo-b-lactamases were >128 mg/L in 22/36 cases, and introduction of plasmids coding NDN carbapenemase (the commonest MBL in the UK) into E. coli DH5a raised the temocillin MIC from 4 to >64 mg/L. Temocillin MICs for isolates with OXA-48 enzyme were >128 mg/L in 18/19 cases, and the MIC shift on transformation of E. coli DH5-a was from 4 to >128 mg/L. Temocillin MICs for isolates with combinations of porin loss and AmpC or an ESBL were from 8 to 128 mg/L (geom. mean 25 mg/L).
Conclusion: If the dosage can be raised from the present 2 g bds, temocillin may be a therapeutic option in some infections due to Enterobacteriaceae with KPC carbapenemases or combination of AmpC or ESBL and porin loss, not against those with OXA-48 or metallo-carbapenemases.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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