Dissemination of 16S rRNA Methylase ArmA-Producing Acinetobacter baumannii and Emergence of OXA-72 Carbapenemase Coproducers in Japan

Abstract

b Forty-nine clinical isolates of multidrug-resistant Acinetobacter baumannii were obtained from 12 hospitals in 7 prefectures throughout Japan. Molecular phylogenetic analysis revealed the clonal spread of A. baumannii sequence type 208 (ST208) and ST455 isolates harboring the armA gene and ST512 harboring the armA and bla OXA-72 genes. These findings show that A. baumannii isolates harboring armA are disseminated throughout Japan, and this is the first report to show that A. baumannii strains harboring bla OXA-72 and armA are emerging in hospitals in Japan. Multidrug-resistant Acinetobacter baumannii has become a threatening nosocomial pathogen worldwide (1). Most strains of this species develop resistance to carbapenems by mechanisms associated with carbapenem-hydrolyzing class D OXA-type ␤-lactamases (CHDLs) (2). The overproduction of intrinsic chromosomal OXA-51-like enzymes and the production of acquired OXA-23-, OXA-24/40-, OXA-58-, OXA-143-, and OXA-235-like enzymes have been associated with carbapenem-resistant A. baumannii isolates (3-5). The gene bla , one of the bla OXA-40-like genes, was first identified in an A. baumannii strain isolated in 2004 in Thailand (GenBank accession no. AY739646). Since then, Acinetobacter spp. harboring bla have been reported in Brazil (6), China (7), Colombia (8), Croatia (9), France (10), Italy (11), Lithuania (12), South Korea (13), Spain (14), Taiwan (15), and the United States (16).The armA gene, encoding a 16S rRNA methylase that confers aminoglycoside resistance, was initially identified in Citrobacter freundii in 2002 in Poland (17), and it was later detected in several including A. baumannii, in Africa, Asia, Europe, and North America (18).From July to December 2012, the BML Biomedical Laboratories R&D Center (Kawagoe, Saitama, Japan) acquired 16,343 isolates of Acinetobacter spp. from 3,015 medical settings located in 47 prefectures throughout Japan. These included 49 isolates of multidrug-resistant A. baumannii obtained from 49 patients in 12 hospitals located in 7 prefectures in Japan (see Fig. S1 in the supplemental material). Of these 49 isolates, 41 were from respiratory tract, 7 from urinary tract, and 1 from blood samples. The multidrug-resistant A. baumannii strains were defined as having MICs of Ն16 g/ml to imipenem/meropenem, Ն32 g/ml to amikacin, and Ն8 g/ml to levofloxacin/gatifloxacin or Ն4 g/ml to ciprofloxacin, according to the criteria of the Japanese Nosocomial Infection Surveillance System (JANIS) of the Japanese Ministry of Health, Labor and Welfare (MHLW). The species were determined by the Vitek system (bioMérieux SA, Marcy l'Etoile, France) and by the sequences of the 16S rRNA, gyrB, and bla OXA-51-like genes.The MICs were determined using the microdilution method, as described in the guidelines of the Clinical and Laboratory Standards Institute (19).Whole genomes of the 49 multidrug-resistant isolates were extracted by DNeasy blood and tissue kits (Qiagen, Tokyo, Japan) and sequenced by MiSeq (Illumina, San Diego, CA).More-than-10-fol...

Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii Isolates in the Gulf Cooperation Council States: Dominance of OXA-23-Type Producers

“…We also found that several large clusters of indistinguishable isolates that produce dominant OXA-23-type enzymes are not only circulating within hospitals of the GCC states but also across borders. This includes the internationally disseminated ST208 and ST195, which belong to clonal complex 92 (33)(34)(35)(36). This finding suggests that certain strains of CRAB have been prevalent in some Gulf region hospitals for an extended period.…”

Evolution of Carbapenem-Resistant Acinetobacter baumannii Revealed through Whole-Genome Sequencing and Comparative Genomic Analysis

“…Except for the type 6 AbaR island, the other types shared high homology. The type 10 AbaR island was the predominant type and was identified in 12 strains (12/32, 37.5%); it was 19.123 kb in length and contained the highest number of resistance genes, including tniB, usp, sul, tetA, tetR, arsR, and aph, similar to those noted in a strain from Japan with one different nucleotide (24). The type 5 AbaR island in 1999BJAB11 contained the largest number of genes, and the conjugal transfer gene traA was identified only in this isolate.…”

Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China

“…For example, Doi et al (19) first discovered that two of five A. baumannii isolates coproduced OXA-23 β-lactamase and ArmA in North America in 2007. In addition, further cases were reported in Korea (20,23), India (24), France (25), Bulgaria (26), Italy (27), Latvia (28), East Africa (29), Yemen (30), Japan (31), Brunei (32), Egypt (33) and China (21,34,35). The authors of the present study previously determined that extended-spectrum β-lactamase and 16S rRNA methylase are coproduced in A. baumannii (36).…”