Sequential Emergence of Resistance to Multiple Antimicrobial Agents in KPC-Producing-Klebsiella pneumoniae

Klebsiella pneumoniae is one of the most important gramnegative bacteria causing hospitalacquired infections. In this report is presented a patient with an abdominal infection caused by carbapenemase producingKlebsiella pneumonia (K. pneumonia). In spite of administrating the combination therapy, successive resistance to lastresort antimicrobial agents (colistin and tigecycline) was observed. The use of combination therapy, in four successive isolates recovered from this patient, was analyzed by killing curves. The genetic relatedness among the isolates was assessed. All four isolates were Klebsiella pneumoniae carbapenemase (KPC) positive and showed resistance to all βlactams including carbapenems and to other antimicrobial agents like aminoglycosides, fluoroquinolones, minocycline and trimetoprimsulfametoxazol (TMS). Isolates 1 and 2 showed susceptibility to colistin, whereas isolate 3 was colistinresistant and isolate 4 became tigecyclineresistant as well. Synergy was only observed with colistin plus rificin and with the triple combination of colistin, rificin and fosfomycin. The four isolates were indistinguishable genotypically. We described the sequential emergence of resistance to colistin and tigecycline in KPCproducingK. pneumonia (KPCKp) isolates that occurred under treatment with these antimicrobial agents despite the use of combination therapy.