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

Abstract

Introduction: Klebsiella pneumoniae is one of the most important gram-negative bacteria causing hospital-acquired infections. Case Presentation: In this report is presented a patient with an abdominal infection caused by carbapenemase producing-Klebsiella pneumonia (K. pneumonia). In spite of administrating the combination therapy, successive resistance to last-resort 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. Conclusions: All four isolates were Klebsiella pneumoniae carbapenemase (KPC) positive and showed resistance to all β-lactams including carbapenems and to other antimicrobial agents like aminoglycosides, fluoroquinolones, minocycline and trimetoprim-sulfametoxazol (TMS). Isolates 1 and 2 showed susceptibility to colistin, whereas isolate 3 was colistin-resistant and isolate 4 became tigecycline-resistant as well. Synergy was only observed with colistin plus rifampicin and with the triple combination of colistin, rifampicin and fosfomycin. The four isolates were indistinguishable genotypically. We described the sequential emergence of resistance to colistin and tigecycline in KPC-producing-K. pneumonia (KPC-Kp) isolates that occurred under treatment with these antimicrobial agents despite the use of combination therapy.