Reply to “Clonal Complex 258, the Most Frequently Found Multilocus Sequence Type Complex in KPC-2-Producing Klebsiella pneumoniae Isolated in Brazilian Hospitals”

We acknowledge the letter by Nicoletti et al. (6) in response to the study in which different genetic platforms carrying the blaKPC-2 gene among several species of Enterobacteriaceae from Brazil were identified (2). Nicoletti et al. (6) confirm the circulation of diverse KPC-2-producing Klebsiella pneumoniae clones (2, 3, 7) from six Brazilian states and from the city of Brasilia in the Federal District of Brazil and further document the predominance of ST437, followed by ST11, and the description of a new sequence type, ST617. While some CC258 clones, such as ST258 or ST11, are globally spread, others, such as ST437, have been documented to occur in only a few locations. It would be of interest to analyze the continental spread of such clones during nonoutbreak situations and to evaluate whether such clonal expansion is independent of the emergence of blaKPC. We also observed the presence of blaCTX-M-2, a gene that encodes resistance to extended-spectrum cephalosporins and is widespread in Brazil and other South American countries, such as Argentina, where K. pneumoniae ST437-producing KPC-2 has been detected (3) among different Klebsiella backgrounds (2). It could be hypothesized that blaCTX-M-2 acquisition by ST437 would have facilitated the spread of ST437, with a resulting increased connectivity with other bacterial (donor) populations, in a way that facilitates the acquisition of different plasmids or genetic elements in some areas. Obviously, ST437 might have increased its connectivity for other reasons, and the capture of either blaCTX-M-2 or blaKPC-2 could be a coincidental consequence of the clonal spread. In addition to K. pneumoniae ST437 and ST11, we identified amplification of different lineages of KPC producers, at a local level, which have not been identified in other Brazilian studies. These producers included the globally spread K. pneumoniae ST258 clone, which was associated with a nosocomial outbreak in a single hospital from Ribeirão Preto (representing the first and only description of ST258 isolated in Brazil to date), Enterobacter cloacae from Rio Grande do Sul, and Serratia marcescens and Citrobacter freundii from Rio de Janeiro. A diversity of genetic contexts for blaKPC (Tn4401a, Tn4401b, and Tn4401c located on IncFII, IncN, IncL/M, IncFI, or small untypeable plasmids) among Enterobacteriaceae and Pseudomonas may also be inferred from available studies (1, 2, 4). Similarly to the clonal distribution, some elements were amplified in different areas, such as a 130-kb IncFII plasmid carrying Tn4401a among ST258, ST11, and ST48 isolates from Ribeirão Preto and a 50to 60-kb IncL/M plasmid carrying Tn4401b to Serratia and Citrobacter species from Rio de Janeiro. Others, such as a 40-kb IncN plasmid with a replicon similar to that of the widespread plasmid pNL194 (5), were disseminated in different states linked to K. pneumoniae ST437 and ST327 and Enterobacter cloacae. All these studies show that the blaKPC-2 gene is “moving through” among different backgrounds. This complex epidemiological scenario highlights the relevance of comprehensive local studies and the need to perform them to understand the evolvability of clones and bacterial populations under different ecological conditions. The diversity of highly transmissible clonal and also plasmid backgrounds carrying blaKPC-2 found in Brazil is of great concern, as these backgrounds can drive a rapid spread of blaKPC and other adaptive traits in South America, a continent highly connected with North America and South Europe for different social and economical links. Besides detection of both clones and plasmids, it would be necessary to differentiate between endemic and imported high-risk clonal complexes and plasmids involved in the spread of blaKPC-2.