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. 2017 Aug 1;72(8):2278-2289.
doi: 10.1093/jac/dkx136.

Activity of ceftolozane/tazobactam against surveillance and 'problem' Enterobacteriaceae, Pseudomonas aeruginosa and non-fermenters from the British Isles

David M Livermore  1   2 , Shazad Mushtaq  1 , Daniele Meunier  1 , Katie L Hopkins  1 , Robert Hill  1 , Rachael Adkin  1 , Aiysha Chaudhry  1 , Rachel Pike  1 , Peter Staves  1 , Neil Woodford  1 ; BSAC Resistance Surveillance Standing Committee
Affiliations

Activity of ceftolozane/tazobactam against surveillance and 'problem' Enterobacteriaceae, Pseudomonas aeruginosa and non-fermenters from the British Isles

David M Livermore et al. J Antimicrob Chemother. .

Abstract

Background: We assessed the activity of ceftolozane/tazobactam against consecutive isolates collected in the BSAC Bacteraemia Surveillance from 2011 to 2015 and against 'problem' isolates sent to the UK national reference laboratory from July 2015, when routine testing began.

Methods: Susceptibility testing was by BSAC agar dilution with resistance mechanisms identified by PCR and interpretive reading.

Results: Data were reviewed for 6080 BSAC surveillance isolates and 5473 referred organisms. Ceftolozane/tazobactam had good activity against unselected ESBL producers in the BSAC series, but activity was reduced against ertapenem-resistant ESBL producers, which were numerous among reference submissions. AmpC-derepressed Enterobacter spp. were widely resistant, but Escherichia coli with raised chromosomal AmpC frequently remained susceptible, as did Klebsiella pneumoniae with acquired DHA-1-type AmpC. Carbapenemase-producing Enterobacteriaceae were mostly resistant, except for ceftazidime-susceptible isolates with OXA-48-like enzymes. Ceftolozane/tazobactam was active against 99.8% of the BSAC Pseudomonas aeruginosa isolates; against referred P. aeruginosa it was active against 99.7% with moderately raised efflux, 94.7% with strongly raised efflux and 96.6% with derepressed AmpC. Resistance in P. aeruginosa was largely confined to isolates with metallo-β-lactamases (MBLs) or ESBLs. MICs for referred Burkholderia spp. and Stenotrophomonas maltophilia were 2-4-fold lower than those of ceftazidime.

Conclusions: Ceftolozane/tazobactam is active against ESBL-producing Enterobacteriaceae; gains against other problem Enterobacteriaceae groups were limited. Against P. aeruginosa it overcame the two most prevalent mechanisms (up-regulated efflux and derepressed AmpC) and was active against 51.9% of isolates non-susceptible to all other β-lactams, rising to 80.9% if ESBL and MBL producers were excluded.

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Figures

Figure 1
Figure 1
Susceptibility to ceftolozane/tazobactam among Enterobacteriaceae with ESBLs (grey bars, n = 674) or raised AmpC (white bars, n = 920) in relation to ertapenem MICs. Hard- and soft-matched isolates are included. None of the isolates included had a carbapenemase. Numbers on the bars indicate the numbers of isolates in the groups.
Figure 2
Figure 2
MICs of ceftolozane/tazobactam in relation to those of ceftazidime for S. maltophilia and Burkholderia spp., pooled. Grey squares indicate the line of equivalence, numbers below this line indicate that ceftolozane/tazobactam is more active than ceftazidime.
See this image and copyright information in PMC

References

    1. Sucher AJ, Chahine EB, Cogan P. et al. Ceftolozane/tazobactam: a new cephalosporin and β-lactamase inhibitor combination. Ann Pharmacother 2015; 49: 1046–56. - PubMed
    1. Livermore DM, Mushtaq S, Ge Y. et al. Activity of cephalosporin CXA-101 (FR264205) against Pseudomonas aeruginosa and Burkholderia cepacia group strains and isolates. Int J Antimicrob Agents 2009; 34: 402–6. - PubMed
    1. Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis 2002; 34: 634–40. - PubMed
    1. Reynolds R, Hope R, Williams L; BSAC Working Parties on Resistance Surveillance. Survey, laboratory and statistical methods for the BSAC Resistance Surveillance Programmes. J Antimicrob Chemother 2008; 62 Suppl 2: ii15–28. - PubMed
    1. A guide to sensitivity testing. Report of the Working Party on Antibiotic Sensitivity Testing of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 1991; 27 Suppl D: 1–50. - PubMed

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