The dissemination of bla_KPC-harboring Pseudomonas aeruginosa (KPC-Pa) is considered a serious public health problem. This study provides an overview of the epidemiology of these isolates to try to elucidate novel mobilization platforms that could contribute to their worldwide spread. A systematic review in PubMed and EMBASE was performed to find articles published up to June 2022. In addition, a search algorithm using NCBI databases was developed to identify sequences that contain possible mobilization platforms. After that, the sequences were filtered and pair-aligned to describe the bla_KPC genetic environment. We found 691 KPC-Pa isolates belonging to 41 different sequence types and recovered from 14 countries. Although the bla_KPC gene is still mobilized by the transposon Tn4401, the non-Tn4401 elements (NTE_KPC) were the most frequent. Our analysis allowed us to identify 25 different NTE_KPC, mainly belonging to the NTE_KPC-I, and a new type (proposed as IVa) was also observed. This is the first systematic review that consolidates information about the behavior of the bla_KPC acquisition in P. aeruginosa and the genetic platforms implied in its successful worldwide spread. Our results show high NTE_KPC prevalence in P. aeruginosa and an accelerated dynamic of unrelated clones. All information collected in this review was used to build an interactive online map.

The multi-resistance presented by P. aeruginosa has greatly increased due to the presence of genes for carbapenemases such as bla_KPC. The dissemination of this gene has been associated with the Tn4401, the main mobile genetic element that carries bla_KPC in its structure. However, some non-Tn4401 elements (NTE_KPC) associated with bla_KPC have been found in different bacteria. Here, we characterized in silico and in vitro bla_KPC-associated elements in P. aeruginosa. To identify these elements, a search algorithm was performed using NCBI databases; sequences were filtered and pair-aligned to describe the bla_KPC genetic environment. Additionally, a PCR-based strategy was designed to target Tn4401 variants and NTE_KPC groups and assessed in 61 Colombian clinical isolates. Using an in silico approach, 51 bla_KPC-positive entries longer than 3kb (in the bla_KPC upstream region) were found; from these, 72.7% carried an NTE_KPC. On the PCR assay, Tn4401 was the most frequent element among the P. aeruginosa in Colombia. However, NTE_KPC-IIf was presented on 29.5% of the isolates, in different genetic lineages and at least in four hospitals. These results show high NTE_KPC prevalence in P. aeruginosa.