Dissemination of a Multidrug-Resistant VIM-1- and CMY-99-ProducingProteus mirabilisClone in Bulgaria

Abstract

The aim of this study was to analyze the beta-lactamases and the molecular epidemiology of 19 clinically significant isolates of Proteus mirabilis with decreased susceptibility to imipenem, which have been collected from seven hospitals, located in different Bulgarian towns (Sofia, Varna, and Pleven). The isolates were obtained from blood, urine, tracheal and wound specimens. One additional isolate from hospital environment was included. Susceptibility testing, conjugation experiments, and plasmid replicon typing were carried out. Beta-lactamases were characterized by isoelectric focusing, PCR, and sequencing. Clonal relatedness was investigated by RAPD and PFGE. Integron mapping was performed by PCR and sequencing. All isolates showed a multidrug-resistance profile, but remained susceptible to piperacillin/tazobactam, cefepime, meropenem, and fosfomycin. They produced identical beta-lactamases, namely: TEM-1, VIM-1, and CMY-99. PCR mapping revealed that the bla gene was part of a class 1 integron that additionally included the aac(6')-I, dhfrA1, and ant(3″)-Ia genes. In addition, 17 of the isolates carried the armA gene. Conjugation experiments and plasmid replicon typing were unsuccessful. The isolates were clonally related according to RAPD and PFGE typing. This study reveals the nationwide distribution of a multidrug-resistant P. mirabilis clone producing VIM-1 and CMY-99 along with the presence of different aminoglycoside resistance mechanisms.

Increasing Trends of Association of 16S rRNA Methylases and Carbapenemases in Enterobacterales Clinical Isolates from Switzerland, 2017–2020

“…Such a frequent association between carbapenemase-producing and RMTase-producing Enterobacterales was already reported in different parts of the world [5][6][7][8][9][10][11][12][13]21,[27][28][29][30][31][32][33][34][35][36][37]. The origin of those isolates being identified in Switzerland could be autochthonous theoretically; nevertheless, clinical information (only partially obtained and therefore not presented in that study) showed that many of them corresponded to imported cases, and particularly from Eastern European countries, from Italy, and from the Indian subcontinent.…”

Genetics of Acquired Antibiotic Resistance Genes in Proteus spp.

“…The bla VIM−1 gene is located on class 1 integrons, inserted into the chromosome with genes aacA7, dhfr, and aadA (Vourli et al, 2006) or in conjugative plasmids carrying also bla VEB−1 , bla OXA−10 , bla TEM−1 genes (Papagiannitsis et al, 2012). In addition, an outbreak of 13 P. mirabilis isolates producing VIM-1 and CMY-99 was recently reported in Bulgaria (Markovska et al, 2017). In this clone, the bla VIM−1 gene was located into a class 1 integron that also contained the aminoglycoside (aac(6 )-Ib, ant(3 )-Ia) and trimethoprim (dhfrA1) resistance determinants (Markovska et al, 2017) Two other isolates of P. mirabilis co-producing VIM-1 and CMY-16 have also been described in the Netherlands (van Dijk et al, 2014).…”

“…In addition, an outbreak of 13 P. mirabilis isolates producing VIM-1 and CMY-99 was recently reported in Bulgaria (Markovska et al, 2017). In this clone, the bla VIM−1 gene was located into a class 1 integron that also contained the aminoglycoside (aac(6 )-Ib, ant(3 )-Ia) and trimethoprim (dhfrA1) resistance determinants (Markovska et al, 2017) Two other isolates of P. mirabilis co-producing VIM-1 and CMY-16 have also been described in the Netherlands (van Dijk et al, 2014).…”

“…KPC-2 carbapenemase in P. mirabilis was first reported in the United States in 2008 (Tibbetts et al, 2008), and then in a few studies from China 2010 (Sheng et al, 2010) and Brazil 2015 (Cabral et al, 2015). The acquisition of metallo-b-lactamase genes such as bla VIM−like genes emerged in Greece in 2006 (Vourli et al, 2006) in Italy in 2008 and more recently in Bulgaria (Markovska et al, 2017). IMP-producing P. mirabilis have been identified in only two studies from the United States (Dixon et al, 2016).…”

A single Proteus mirabilis lineage from human and animal sources: a hidden reservoir of OXA-23 or OXA-58 carbapenemases in Enterobacterales

“…Some of the most prevalent carbapenemases in Enterobacterales were sporadically described in P. mirabilis isolates including KPC-2, VIM-1, IMP-like, NDM-1 and OXA-48 [7][8][9] .…”