High Incidence and Endemic Spread of NDM-1-Positive Enterobacteriaceae in Henan Province, China

Abstract

The emergence and spread of New Delhi metallo-␤-lactamase 1 (NDM-1)-producing carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to human health. In China, the bla NDM-1 gene has been reported mostly in Acinetobacter spp. but is rarely found in Enterobacteriaceae. Here, we report a high incidence and endemic spread of NDM-1-producing CRE in Henan Province in China. Sixteen (33.3%) of the 48 CRE isolates obtained from patients during June 2011 to July 2012 were positive for bla NDM-1 , and the gene was found to be carried on plasmids of various sizes (ϳ55 to ϳ360 kb). These plasmids were readily transferrable to recipient Escherichia coli by conjugation, conferred resistance to multiple antibiotics, and belonged to multiple replicon types. The bla NDM-1 -positive CRE isolates were genetically diverse, and six new multilocus sequence typing (MLST) sequence types were linked to the carriage of NDM-1. Five of the isolates were classified as extensively drug-resistant (XDR) isolates, four of which also carried the fosA3 gene conferring resistance to fosfomycin, an alternative drug for treating infections by CRE. In each bla NDM-1 -positive CRE isolate, the bla NDM-1 gene was downstream of an intact ISAba125 element and upstream of the ble MBL gene. Furthermore, gene environment analysis suggested the possible transmission of bla NDM-1 -containing sequences from Acinetobacter spp. to Klebsiella pneumoniae and Klebsiella oxytoca. These findings reveal the emergence and active transmission of NDM-1-positive CRE in China and underscore the need for heightened measures to control their further spread.

Genomic Characteristics of NDM-Producing Enterobacteriaceae Isolates in Australia and Their bla NDM Genetic Contexts

“…In comparison to other geographical regions, such as the United Kingdom, China, and the Indian subcontinent (21,(36)(37)(38)(39), there are relatively few reports of NDM-producing Enterobacteriaceae from Australia. In the majority of the cases preceding 2014, patients had a history of travel to high-incidence countries (32).…”

Characterization of Plasmids in Extensively Drug-Resistant Acinetobacter Strains Isolated in India and Pakistan

“…Recent reports suggest that NDM-1-producing Enterobacteriaceae may be more common than originally demonstrated in China (21,22), and it is possible that the spread of bla NDM-1 into Enterobacteriaceae could have initiated there. However, the high prevalence in some regions of the Indian subcontinent of NDMproducing Enterobacteriaceae has been well documented, and most reports of travel-associated colonization with NDM-producing bacteria involved the subcontinent (5,8).…”

“…Similar cases have been reported in Europe, but most patients probably became colonized during travel to the Balkans or North Africa (12)(13)(14). In China, bla NDM-1 has been observed many times in several Acinetobacter spp., including A. baumannii, from clinical, environmental, and farm animal samples but is less commonly reported in Enterobacteriaceae (15)(16)(17)(18)(19)(20)(21)(22).…”

Fosfomycin

“…New subtypes, with similar structure, of the gene have been described (fosA2, fosA3, fosA4, and fosA5) (108)(109)(110). Cooccurrence in plasmids with bla CTX-M , bla NDM , bla KPC , bla OXA , bla CMY , bla AmpC , bla TEM , bla SHV , bla SFO-1 , gyrA, parC, parE, sul1, sul2, strA, strB, aac(6=)-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, rmtB, and merA genes has been reported, conferring resistance to ␤-lactams, quinolones, aminoglycosides, macrolides, sulfonamides, and tetracyclines (75,80,(111)(112)(113)(114). The genes conferring resistance to fosfomycin could be transferred together with genes conferring resistance to other antibiotics in either the same or a conjugate plasmid (114).…”