2010. Clonal Pan or Extensively Drug-Resistant KPC-2-Producing ST437 Klebsiella pneumoniae Causing Untreatable Infections Evidenced by In Vitro Synergy Testing
Session: Poster Abstract Session: Antimicrobial Resistance Mechanisms
Saturday, October 29, 2016
Room: Poster Hall
  • AB PosterIDWEEK.pdf (668.0 kB)
  • Background: Pan (PDR) or extensively drug-resistant (XDR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) has become a growing threat.

    Methods: We retrospectively investigated phenotypicprofile of 353 Kp isolates from 258 patients hospitalized from December 2014 to August 2015. Chart review was performed on cases with PDR- or XDR-Kp possible untreatable infection (UI). Proved UI was defined as any systemic infection caused by PDR/XDR strain in which the susceptible drugs are not recommended for the site of infection (including biofilm) or available in local market, the infection cannot be surgically removed and antagonism or non-synergistic action was evidenced by any combination therapy synergy testing.

    Results: Among 196 Kp detected from clinical samples, 16% (32/196) was PDR (n=4) /XDR (n=28)-Kp strains, corresponding to 38% (32/84) of MDR Kp isolates. High MICs ≥16µg/ml were found in 97% (29/30) of meropenem-resistant Kp. 15% (17/113) was polymyxin B (E-test)/colistin (Vitek 2) resistant. The incidence densities of clinical MDR, XDR and PDR Kp per 1,000 patient days were 1.0, 0.4 and 0.05, respectively (Fig. 1). We diagnosed two cases with proved UI caused by PDR KPC-2 Kp strains with none enough synergistic activity achieved at 4, 6, 8 and 24 h at target concentrations of meropenem 0.5×MIC plus colistin 1×MIC (Fig. 2 and 3). Three strains recovered from proved untreatable cases (CCBH 17440 and CCBH 17428) and a patient with XDR Kp infection, who had close contact during hospitalization, pertained to same PFGE clone (Fig. 1) and MLST 437. Through whole genome sequencing we detected resistance genes corroborating the resistance phenotype of CCBH 17440. Virulence genes and other features demonstrated several potential abilities to invade tissues and be maintained within hospital environment.

    Conclusion: ST437 is one of the most disseminated in Brazil among KPC-Kp and belongs to the worldwide spread clonal complex 11. Our findings emphasize the urgent need for global actions in the fight against PDR/XDR KPC-2 Kp and new treatment options. The association of important resistance and virulence factors makes this pathogen successful at infections and to expansion and evolution, leading to PDR phenotype and UI in Brazilian hospitals.

    Macintosh HD:Users:juwonyim:Desktop:CCHB17740.TIF

    Macintosh HD:Users:juwonyim:Desktop:CCHB17428.TIF

    Marisa Zenaide Ribeiro Gomes, MD, MSc, MBA, PhD1,2, Elisangela Martins De Lima, MD2, Polyana Silva Pereira, BMSc, MSc, PhD1, Caio Augusto Martins Aires, BMSc, MSc, PhD1, Maria José De Souza Menicalli, MD, PharmB2, Claudio Marcos Rocha De Souza, BSBio, MSc, PhD1, Rodolpho Mattos Albano, BSBio, MSc, PhD3, Juwon Yim, PharmD4, Ana Paula D'alincourt Carvalho Assef, BSBio, MSc, PhD1, Michael J. Rybak, PharmD, MPH4 and Marise Dutra Asensi, BSBio, MSc, PhD1, (1)Laboratório De Pesquisa Em Infecção Hospitalar, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil, (2)Infection Control Committee, Hospital Federal Servidores do Estado, Ministry of Health, Rio de Janeiro, Brazil, (3)Laboratório De Genoma, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, Rio de Janeiro, Brazil, (4)Anti-Infective Research Laboratory, Department of Pharmacy Practice, Wayne State University, Eugene Applebaum College of Pharmacy & Health Sciences, Detroit, MI


    M. Z. R. Gomes, None

    E. M. D. Lima, None

    P. S. Pereira, None

    C. A. M. Aires, None

    M. J. De Souza Menicalli, None

    C. M. R. D. Souza, None

    R. M. Albano, None

    J. Yim, None

    A. P. D. C. Assef, None

    M. J. Rybak, None

    M. D. Asensi, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.