What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline

David M. Livermore (1) , Marina Warner (1) , Shazad Mushtaq (1) , Michel Doumith (1) , Jiancheng Zhang (1) , Neil Woodford (1)

1 Health Protection Agency Microbiology Services-Colindale

Carbapenem-resistant Enterobacteriaceae present an increasing and diverse problem, including strains of multiple species with metallo-β-lactamases (IMP, NDM or VIM) and non-metallo KPC and OXA-48 enzymes as well as those combining an extended-spectrum β-lactamase (ESBL) or AmpC enzyme with porin loss. Most strains, except those with OXA-48 alone, are broadly resistant to β-lactams and have multiple aminoglycoside-modifying enzymes; those with NDM-1 carbapenemase typically also have 16S rRNA methylases, conferring complete aminoglycoside resistance. In this study, the activity of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline was evaluated against 81 carbapenem-resistant Enterobacteriaceae isolates from the UK. Testing was performed by the Clinical and Laboratory Standards Institute (CLSI) agar dilution method. Chloramphenicol, ciprofloxacin and nitrofurantoin inhibited <25% of the isolates at the breakpoint, whereas colistin was active against 75/81 isolates (92.6%), the exceptions being four and isolates along with members of inherently resistant genera. Fosfomycin was active against 49/81 isolates (60.5%), including 7/7 , 16/20 and spp., but only 25/52 spp. Tigecycline was active against 38/81 isolates (46.9%) and was intermediate against another 27 (33.3%), with resistance scattered among and spp. The activity of colistin, fosfomycin and tigecycline was unrelated to the isolates' carbapenem resistance mechanisms. Temocillin was fully active [minimum inhibitory concentration (MIC) ≤8mg/L] against only 4/81 isolates (4.9%), but inhibited a further 22 isolates (27.2%) at the British Society for Antimicrobial Chemotherapy (BSAC) urinary breakpoint (32mg/L), predominantly comprising those isolates with combinations of impermeability and an ESBL or AmpC enzyme, along with 6/11 isolates producing KPC carbapenemases. Studies with transconjugants and transformants confirmed the small effect of KPC enzymes against temocillin, whereas OXA-48 and NDM-1 conferred clear resistance.

Mots clés: NDM β-lactamase; VIM β-lactamase; KPC β-lactamase; OXA-48 β-lactamase; Carbapenemase

Domaines: Microbiologie et Parasitologie

David M. Livermore, Marina Warner, Shazad Mushtaq, Michel Doumith, Jiancheng Zhang, et al.. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. International Journal of Antimicrobial Agents, 2011, 37 (5), pp.415. ⟨10.1016/j.ijantimicag.2011.01.012⟩. ⟨hal-00685788⟩