1. C1-132
48th Interscience Conference on Antimicrobial Agents and Chemotherapy
October 25-28, 2008.
Washington, DC
Examining Temocillin Activity in Combination with Five Antimicrobials Against Organisms Expressing Extended Spectrum (ESBL) and Metallo-β-lactamases (MBL) M. Wootton1 T. R. Walsh2 and R. A. Howe1 1NPHS Microbiology, University Hospital Wales, Cardiff, UK. 2 Cardiff University, Cardiff, UK.
Introduction
Materials and Methods
Results
Table 2: Susceptibility testing: MIC ranges for antimicrobials used
Temocillin (TEM) is a 6-α-methoxy derivative of ticarcillin, with potent activity against Enterobacteriaceae including those with extended spectrum β-lactamases (ESBL) and ampC type enzymes. TEM is poorly hydrolysed by the metallo β-lactamase IMP, ESBLs, and AMPCs, and therefore in addition to intrinsic activity may have useful activity as an enzyme inhibitor in combination with other beta-lactams. This study examines whether synergy can be demonstrated between TEM and ceftazidime (CAZ), piperacillin/tazobactam, or carbapenems (CARB).
(8:1 ratio), meropenem and cefepime in the range 0.03 to 256mg/L. Fractional Indices were calculated and synergy and antagonism determined using the criteria <0.25 and >4 respectively. Beta-lactam hydrolysis was performed on 10 isolates, each representing known resistance mechanisms. Whole cell lysates were produced using sonication and hydrolysis was measured with TEM, CAZ and imipenem at the most appropriate wavelength.
Susceptibility results (mg/L) are shown in Table 1. TEM showed similar activity against all strains compared to the other antimicrobials. No synergy or antagonism was detected in any combination tested.
Hydrolysis was similar for TEM, CAZ and imipenem. Prior incubation with TEM (1μM) demonstrated inhibitory activity of between 38-65% with strains containing IMP, VIM, GIM and SPM enzymes. .
Conclusions
Table 1: TEM susceptibility alone and in combination with other antimicrobials
TEM is inhibitory to metallo-beta-lactamases (MBLs) in hydrolysis assays.
However this does not translate into synergy in checkerboard experiments.
This may be due to additional resistance mechanisms in the strains tested.
Materials and Methods
Agar dilution checkerboards were used to test 99 strains; 33 E. coli (EC), 7 Enterobacter cloacae. (E), 1 Morganella morganii. (M), 10 Klebsiella pneumoniae. (K), 13 Serratia spp. (S), 20 Pseudomonas aeruginosa. (PS) and 15 Acinetobacter baumannii. (AC) species. TEM was tested alone and in combination with aztreonam, ceftazidime, pipercillin/tazobactam
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