KPC-2 producing Pseudomonas putida as an unexpected pathogen of catheter-associated bloodstream infection

Infections due to multidrug resistant Gram-negative pathogens are of great concern worldwide, as they are frequently associated with high mortality and morbidity rates. The occurrence of Pseudomonas spp. producing Klebsiella pneumoniae carbapenemases (KPCs) imposes a great challenge through treatment course of bloodstream infections (BSIs). Pseudomonas putida has been recognized as an emerging pathogen of healthcare associated infections (HAIs). Therefore, we aimed to report a case of a non-fatal case of peripheral line associated BSI (PLA-BSI) in an immunocompromised host due to P. putida harboring blaKPC-2 gene in Brazil. A P. putida isolate was recovered from a blood culture of a 72-year-old man admitted at a University Hospital, identified by BD Phoenix™ 100 (Becton, Dickinson and Company), causing PLA-BSI. The species identification was confirmed by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and resistance to carbapenems were confirmed by Epsilometer test (E-test®). Additionally, the presence of important carbapenemases genes (blaKPC, blaNDM, blaOXA-48-like, blaSPM, blaIMP, blaVIM) was investigated by Polymerase Chain Reaction. The bacterial isolate was confirmed as meropenem resistant P. putida harboring blaKPC-2 gene.Thereofre, these fidings suggest that P. putida can work as a reservoir for resistance genes as this bacterium has the ability to disseminate through water-fluids inside hospital and community settings. Moreover, this paper highlights that a frequent and worldwide disseminated mechanism of resistance (blaKPC-2) is currently occurring among uncommon agents of BSI.

Characterization of the genetic environment of blaKPC in Escherichia coli isolates from hospitals in China

ABSTRACT Carbapenem resistance in Enterobacteriaceae members has become a major challenge, and the genetic environment of blaKPC, encoding Klebsiella pneumoniae carbapenemases, has not been fully clarified in China. In this study, we aimed to explore the genetic environment of blaKPC in 25 carbapenem-resistant E. coli isolates from hospitals in Hangzhou Province, China. Antimicrobial susceptibility against 22 common antimicrobial agents was tested. Polymerase chain reaction (PCR) analysis was performed for screening of the resistent genes, such as blaKPC, blaCTX-M, blaTEM, blaSHV, blaNDM, qnrA, qnrB, qnrS, aac(6’)-Ib, armA and rmtB. The genetic environment of blaKPC were determinedin one isolate. blaKPC was detected by PCR in all the clinical E. coli isolates. There were no strains carrying blaNDM, qnrA and armA. The genetic environment of blaKPC showed that blaKPC dissemination is plasmid mediated and that it is located in the Tn3–Tn4401 transposon complex. Encoding of blaKPC-2 was responsible for carbapenem resistance in the 25 E. coli isolates. The genetic environment of blaKPC was characterized by the Tn3–Tn4401 complex. Our findings may provide a theoretical basis for clinical drug-resistance monitoring, anti-infection treatment and hospital infection control.

Ceftazidime/avibactam versus standard-of-care agents against carbapenem-resistant Enterobacteriaceae harbouring blaKPC in a one-compartment pharmacokinetic/pharmacodynamic model

Background‘Last-line’ antimicrobial usage has promoted the emergence of MDR bacteria. Production of Klebsiella pneumoniae carbapenemases (KPCs) is increasingly common and leads to resistance to most antimicrobials. However, ceftazidime/avibactam demonstrates activity against KPC-producing strains. Ceftazidime/avibactam in the empirical setting remains unknown.MethodsStrains underwent genetic analysis evaluating blaKPC presence/production and MICs were determined. Four strains were assessed in an in vitro, one-compartment pharmacokinetic (PK)/pharmacodynamic (PD) model for 96 h. The following bolus dosing exposures were tested: 2.5 g of ceftazidime/avibactam every 8 h, 2 g of meropenem every 8 h, 1.25 mg/kg polymyxin B every 12 h, amikacin ‘once-daily dosing’ (peak of 70–80 mg/L), tigecycline at 200 mg ×1 dose followed by 100 mg every 12 h, and a drug-free growth control.ResultsThirty blaKPC-producing strains were evaluated; 97% of strains were ceftazidime/avibactam susceptible with MIC50/MIC90 values of 0.38/1.5 mg/L (range 0.032–16 mg/L). Two K. pneumoniae strains, one Klebsiella oxytoca strain and one Citrobacter freundii strain underwent further analysis in PK/PD models. Ceftazidime/avibactam displayed potent activity with a reduction of 4.23 ± 0.42 cfu/mL from the initial inoculum at 96 h. Against susceptible isolates, amikacin displayed similar activity compared with ceftazidime/avibactam at 96 h, although this was not demonstrated against all strains. Polymyxin B produced comparable activity to ceftazidime/avibactam against two strains. Neither meropenem nor tigecycline produced effective killing and were comparable to the drug-free growth control at 96 h.Conclusionsbla KPC-producing organisms demonstrated susceptibility to ceftazidime/avibactam and bactericidal activity was observed in the PK/PD model. Based on these data, ceftazidime/avibactam is a valuable agent for treating KPC-producing organisms and should be considered for treatment of infections caused by these pathogens.