First clinical cases of NDM-1-producing Klebsiella pneumoniae from two hospitals in Bulgaria

Todorova, Bozhana; Sabtcheva, Stefana; Ivanov, Ivan N.; Lesseva, Magdalena; Chalashkanov, Tzano; Ioneva, Magda; Bachvarova, Assya; Dobreva, Elina; Kantardjiev, Todor

doi:10.1016/j.jiac.2016.03.014

Cited by 16 publications

(12 citation statements)

References 11 publications

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“…Multidrug resistant, conjugative IncA/C plasmids were recovered from two K. pneumoniae ST11 isolates obtained from a hospital in Bulgaria in 2014. The larger (176-kb) plasmid possessed bla NDM-1 with bla CMY-4 , bla CTX-M-15 , bla TEM-1b , and qnrB while the smaller (86-kb) plasmid had bla NDM-1 with bla TEM-1 , and aac(6′)-Ib [Todorova 2016]. bla OXA-48 has additionally been identified on an IncA/C plasmid in Taiwan (2015) and Tunisia (2011) [Ktari 2011].…”

Section: Inca/cmentioning

confidence: 99%

The rapid spread of carbapenem-resistant Enterobacteriaceae

Potter

D’Souza

Dantas

2016

Drug Resistance Updates

320

211

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Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments.

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Section: Inca/cmentioning

confidence: 99%

The rapid spread of carbapenem-resistant Enterobacteriaceae

Potter

D’Souza

Dantas

2016

Drug Resistance Updates

320

211

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“…The Simpson’s index may vary depending on the sample heterogeneity. There are 158 identical strains MLVA 7 (ST11), a clonal group that is widespread in Bulgaria [ 30 , 31 , 32 , 33 ]. In addition, 103/464 strains are MLVA 3 and 4 (ST258), which is the second most spread clonal group in the country [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Improvement and Validation of a Multi-Locus Variable Number of Tandem Repeats Analysis (MLVA8+) for Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae

et al. 2023

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The genotyping of the multidrug-resistant Klebsiella pneumoniae species complex is essential to identify outbreaks and to track their source and spread. The aim of this study was to improve and extend the typeability, availability, cost and time efficiency of an existing multi-locus VNTR analysis (MLVA). A modified scheme (MLVA8+) was adopted and validated for strain-level differentiation of the three Klebsiella species involved in human pathology. A diverse set of 465 K. pneumoniae clinical isolates from 22 hospitals and 3 outpatient laboratories in Bulgaria were studied, where 315 were carbapenem-resistant. The MLVA8+ typeability was significantly improved and the typing data were validated against 158 isolates which were previously typed by WGS. The MLVA8+ results were highly concordant with the classic 7-locus MLST and the novel K. variicola MLST, but had greater congruency coefficients (adjusted Wallace). A major advantage was the differentiation of the hybrid cluster ST258 into its corresponding clades. Furthermore, the applicability of MLVA8+ was demonstrated by conducting a retrospective investigation of the intra-hospital spread of blaKPC-, blaNDM- and blaOXA-48-like producers. The MLVA8+ has improved utility and extended typing scope to K. variicola and K. quasipneumoniae, while its cost and time-to-result were reduced.

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“…The MIC strips were placed at 90º at the point of intersection using an applicator system (MTS-SAS, Liofilchem) and incubated at 35°C for 18 h. Afterward, the individual MICs of antibiotics were applied in calculating fractional inhibitory concentrations (FICs), according to the following formula displayed in Figure 1 [20], [21]. The obtained interaction effect was defined following the accepted criteria: Synergy (FIC ≤0.5); additive (FIC >0.5 to ≤1.0); indifference (FIC >1 to ≤4.0); and antagonism (FIC > 4) [28], [29], [30], [31] as seen on the tested strains as shown in Figure 2.…”

Section: Methodsmentioning

confidence: 99%

“…Finally, genomic DNA was isolated with PureLink™ Genomic DNA Mini Kit (Invitrogen, Thermo Fisher Scientific, USA). Multiplex polymerase chain reaction was performed to detect carbapenemase genes (bla KPC, bla VIM, bla IMP, bla SIM , bla GIM, bla SPM, bla NDM-1, bla GES, and bla OXA-48 ) using previously described protocol [31]. Multi-locus sequence typing (MLST) was performed according to Protocol 2 described in the K. pneumoniae MLST database of Pasteur Institute [32].…”

Section: Methodsmentioning

confidence: 99%

In vitro Investigation of Antibiotic Combinations against Multi- and Extensively Drug-Resistant Klebsiella pneumoniae

Dobreva

Ivanov

Donchev

et al. 2022

Open Access Maced J Med Sci

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Objectives: Community and hospital acquired K. pneumoniae infections have become a ubiquitous medical issue due to the limited treatment options and high mortality rate therefore the aims of this study are in vitro investigation of double antimicrobial combinations against multidrug resistant (MDR) and extensively drug resistant (XDR) isolates. Materials and Methods: Antimicrobial susceptibility of twelve isolates from eight Bulgarian hospitals was determined to study the interaction effect of selected double combinations in accordance to fractional inhibitory concentration (FIC) method. Furthermore, the isolates were subjected to genotyping by Multilocus sequence typing (MLST) and detection of carbapenemase genes by multiplex PCR. The results were assessed by groups of strains with either NDM or KPC carbapenemase. Results: Nine antimicrobial combinations: meropenem-colistin, meropenem-fosfomycin, meropenem-gentamicin, meropenem-rifampicin, meropenem-tigecycline, colistin-fosfomycin, colistin-gentamicin, colistin-rifampicin and colistin-tigecycline were tested for synergism on twelve K. pneumoniae, producing either KPC-2 (KPC-KP, 41.7%, 5/12) or NDM-1 (NDM-KP, 58.3%, 7/12). The isolates were distributed in three sequence types: ST11 (58.3%, 7/12), ST15 (25%, 3/12) and ST258 (16.7%, 2/12). All KPC-KP (ST258 and ST15) originated from three hospitals. The rest were NDM-1 carriers isolated from six hospitals and belonged to ST11. The highest synergistic effect was determined for MER-GEN (83.3%, 10/12) and COL-RIF (83.3%, 10/12). The MER-FOS combination was most efficient against NDM-KP, opposite to the KPC strains. Antagonism was not observed for any combinations. Conclusions: The evaluated joint synergistic effect of the MER-GEN and COL-RIF may facilitate the treatment options for patients infected with NDM- and KPC-KP, whereas MER-FOS is highly synergetic against NDM-KP.

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First clinical cases of NDM-1-producing Klebsiella pneumoniae from two hospitals in Bulgaria

Cited by 16 publications

References 11 publications

The rapid spread of carbapenem-resistant Enterobacteriaceae

The rapid spread of carbapenem-resistant Enterobacteriaceae

Improvement and Validation of a Multi-Locus Variable Number of Tandem Repeats Analysis (MLVA8+) for Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae

In vitro Investigation of Antibiotic Combinations against Multi- and Extensively Drug-Resistant Klebsiella pneumoniae

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