Ceftolozane-tazobactam is considered to be a last resort treatment for infections caused by multidrug-resistant (MDR) Although, resistance to this antimicrobial have been described , development of resistance was rarely reported. Here, we described the evolution of resistance to ceftolozane-tazobactam of isolates recovered from the same patient during recurrent infections over 2.5 years.Antimicrobial susceptibility testing results showed that 24 of the 27 isolates recovered from blood (n=18), wound (n=2), pulmonary sample (n=1), bile (n=2) and stools (n=4) of the same patient were susceptible to ceftolozane-tazobactam and ceftazidime-avibactam but resistant to ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Three clinical isolates acquired resistance to ceftolozane-tazobactam and ceftazidime-avibactam along with a partial restoration of piperacillin-tazobactam and carbapenems susceptibilities. Whole genome sequencing analysis reveals that all isolates were clonally related (ST-111) with a median of 24.9 single nucleotide polymorphisms (SNPs) (range 8-48). The ceftolozane-tazobactam and ceftazidime-avibactam resistance was likely linked to the same G183D substitution in the chromosome-encoded cephalosporinase.Our results suggest resistance to ceftolozane-tazobactam in might occur upon treatment through amino-acid substitution in the intrinsic AmpC leading to ceftolozane-tazobactam and ceftazidime-avibactam resistance accompanied by re-sensitization to piperacillin-tazobactam and carbapenems.
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| http://dx.doi.org/10.1128/AAC.01637-19 | DOI Listing |
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