Emergence and dissemination of colistin-resistant Klebsiella pneumoniae isolates expressing OXA-48 plus CTX-M-15 in patients not previously treated with colistin in a Spanish university hospital

Barragán-Prada, Hugo; Ruiz-Hueso, Paula; Tedim, Ana P.; Gónzález-Candelas, Fernando; Galán, Juan Carlos; Morosini, Marı́a-Isabel

doi:10.1016/j.diagmicrobio.2018.08.014

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…It has only been reported in a limited number of studies because it cannot be assessed using ordinary minimum inhibitory concentration (MIC) testing methods. There have been many studies on the heteroresistance to various antibiotics for specific bacterial species, which also encompass colistin heteroresistance in K. pneumoniae isolates [13,14,15,16,17,18]. Although little is known about the clinical significance of antibiotic heteroresistance, instances of treatment failure associated with colistin heteroresistance in K. pneumoniae have been reported [19].…”

Section: Introductionmentioning

confidence: 99%

Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations

Cheong

Kim

et al. 2019

JCM

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Heteroresistance may pose a threat to the prognosis of patients following colistin treatment. We investigated colistin heteroresistance in Klebsiella pneumoniae isolates from South Korea. Among 252 K. pneumoniae blood isolates, 231 were susceptible to polymyxins. Heteroresistance to colistin was determined using population analysis profiles, disk diffusion assays, and E-test strip tests for the susceptible isolates. As a result, we identified three colistin-heteroresistant K. pneumoniae isolates belonging to separate clones (ST11, ST461, and ST3217) by multilocus sequence typing analysis. Two colistin-resistant subpopulations were selected from each heteroresistant isolate in either disk diffusion testing or E-testing. Two resistant subpopulations from the same isolate exhibited different amino acid substitutions in the two-component regulatory systems PmrAB and PhoPQ. An in vitro time–kill assay showed that meropenem combined with colistin had a 1× minimum inhibitory concentration bactericidal effect against a multidrug-resistant, colistin-heteroresistant isolate.

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Section: Introductionmentioning

confidence: 99%

Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations

Cheong

Kim

et al. 2019

JCM

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“…Resistance to colistin is associated with LPS modifications altering the immunogenic nature of lipid A as a result of enzyme synthesis mutations (10, 15, 27, 38). It is important to note that we did not find plasmid genes, nor mutations on the pmrB, pmrA , or mgrB genes, nor other reported mechanisms, including pho P/Q mutations in CR-Kp (39); thus, the subjacent genotype for this modification remains elusive. Dogan et al .…”

Section: Discussionmentioning

confidence: 62%

“…Immune checkpoints either activate or inhibit the immune system (22, 38); their blockade is a successful treatment for lung and melanoma cancer (38, 39). Although bacterial LPS had been shown to also induce the expression of immuno-checkpoints (19, 20, 40) the effects of LPS modifications remained unexplored, particularly those related to colistin-resistance.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Colistin Resistance on the Activation of Innate Immunity by Lipopolysaccharide Modification

Avendaño-Ortíz

Ponce-Alonso

Llanos-González

et al. 2022

Preprint

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Colistin resistance is caused by different lipopolysaccharide (LPS) modifications, and we propose to evaluate the effect on the innate immune response of in vivo and in vitro colistin resistance acquisition. We used 2 pairs of isogenic strains: (1) Escherichia coli ATCC25922, susceptible to colistin and its isogenic transconjugant-carrying mcr-1 gene; and (2) OXA-48, CTX-M-15 K. pneumoniae susceptible to colistin (CS-Kp) isolated from a urinary infection and its colistin-resistant variant (CR-Kp) from the same patient after prolonged treatment with colistin. No mutation of described genes for colistin resistance (pmrA, pmrB, mgrB. phoP/Q and crrAB) were found in the CR-Kp genome; however, LPS modifications were characterized by negative-ion MALDI-TOF. The strains were co-cultured with human monocytes to determine their survival after phagocytosis and induction to apoptosis. Also, monocytes were stimulated with bacterial LPS to study cytokine and immunecheckpoint production. The addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A of CR-Kp accounted for the colistin resistance. CR-Kp survived significantly longer inside human monocytes after being phagocytosed compared with the CS-Kp strain, whereas no significant differences were observed for the E. coli isogenic strains. In addition, LPS from CR-Kp induced both higher apoptosis in monocytes and higher levels of cytokine and immune checkpoint production than LPS from CS-Kp. This effect was strictly the opposite for E. coli. Our data reveal a variable impact of colistin resistance on the innate immune system, depending on the responsible mechanism. Adding Ara4N to LPS increases bacterial survival after phagocytosis and elicits a higher inflammatory response than its colistin-susceptible counterpart.

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“…The presence of ESBL- and carbapenemase-producing E. coli in livestock has been associated with colistin resistance [1,12,13,14] and we observed in a previous study that Colistin-resistant E. coli in pigs has also been linked to colistin sales [6]. Colistin has been the treatment of first choice to control these bacteria in pig production and it has habitually used as a prophylactic approach as well [7].…”

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confidence: 99%

Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain

et al. 2019

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Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Gram-negative bacteria have become widespread in hospitals, community settings, and the environment, reducing the range of effective therapeutic alternatives. The use of colistin to treat infection caused by these multi-drug bacteria may favour the selection and persistence of carbapenem-resistant bacteria. In this study, it is described, for the first time to our knowledge, a carbapenemase-producing isolate of Elizabethkingia meningoseptica from healthy pigs in Spain. The isolate we report was recovered during a study to detect colistin-resistant bacteria from faecal samples of healthy food-production animals using a chromogenic selective medium. Unexpectedly, we found an isolate of Elizabethkingia meningoseptica with high Minimum Inhibitory Concentration (MIC) values for several antibiotics tested. Molecular analysis did not show any mcr family genes related with colistin resistance, but two carbapenemase genes, blaB-12_1 and blaGOB-17_1, were detected. This finding in healthy animals could suggest that colistin may favour the selection and persistence of carbapenem-resistant bacteria.

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Emergence and dissemination of colistin-resistant Klebsiella pneumoniae isolates expressing OXA-48 plus CTX-M-15 in patients not previously treated with colistin in a Spanish university hospital

Cited by 7 publications

References 38 publications

Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations

Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations

The Impact of Colistin Resistance on the Activation of Innate Immunity by Lipopolysaccharide Modification

Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain

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