Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)

Hernández-García, Marta; García‐Fernández, Sergio; García-Castillo, María; Melo‐Cristino, José; Pinto, Margarida; Gonçalves, Elsa; Alves, Valquíria; Costa, Eliana; Ramalheira, Elmano; Sancho, Luísa; Diogo, José; Ferreira, Rui M.; Silva, Tânia; Chaves, Catarina; Pássaro, Leonor; Paixão, Laura; Romano, João

doi:10.1016/j.ijantimicag.2020.106259

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…Ceftolozane-tazobactam is a new cephalosporin-β-lactamase inhibitor combination with a wide antimicrobial spectrum and high activity against MDR Gram-negative bacteria, with the exception of carbapenemase producers [23]. However, ceftolozane-tazobactam resistance has been recently described in ESBL-producing Enterobacterales populations, including those recovered during the STEP and SUPERIOR surveillance studies [24,25]. The selection pressure in the intestinal microbiota caused by the extensive use of antibiotics during decades has led to the emergence of MDR/XDR pathogens carrying multiple antibiotic resistance determinants, including mechanisms involved in quinolone resistance but also β-lactamases genes such as ESBL and carbapenemases.…”

Section: Discussionmentioning

confidence: 99%

Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain

et al. 2021

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CrpP enzymes have been recently described as a novel ciprofloxacin-resistance mechanism. We investigated by whole genome sequencing the presence of crpP-genes and other mechanisms involved in quinolone resistance in MDR/XDR-Pseudomonas aeruginosa isolates (n = 55) with both ceftolozane-tazobactam susceptible or resistant profiles recovered from intensive care unit patients during the STEP (Portugal) and SUPERIOR (Spain) surveillance studies. Ciprofloxacin resistance was associated with mutations in the gyrA and parC genes. Additionally, plasmid-mediated genes (qnrS2 and aac(6′)-Ib-cr) were eventually detected. Ten chromosomal crpP-like genes contained in related pathogenicity genomic islands and 6 different CrpP (CrpP1-CrpP6) proteins were found in 65% (36/55) of the isolates. Dissemination of CrpP variants was observed among non-related clones of both countries, including the CC175 (Spain) high-risk clone and CC348 (Portugal) clone. Interestingly, 5 of 6 variants (CrpP1-CrpP5) carried missense mutations in an amino acid position (Gly7) previously defined as essential conferring ciprofloxacin resistance, and decreased ciprofloxacin susceptibility was only associated with the novel CrpP6 protein. In our collection, ciprofloxacin resistance was mainly due to chromosomal mutations in the gyrA and parC genes. However, crpP genes carrying mutations essential for protein function (G7, I26) and associated with a restored ciprofloxacin susceptibility were predominant. Despite the presence of crpP genes is not always associated with ciprofloxacin resistance, the risk of emergence of novel CrpP variants with a higher ability to affect quinolones is increasing. Furthermore, the spread of crpP genes in highly mobilizable genomic islands among related and non-related P. aeruginosa clones alert the dispersion of MDR pathogens in hospital settings.

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Section: Discussionmentioning

confidence: 99%

Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain

et al. 2021

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“…Although the K. variicola isolates were susceptible, in our study both species carried bla KPC-2 , highlighting the importance of Klebsiella complex in the dissemination of resistance mediated by KPC 65 . K. variicola harboring bla KPC has been reported in countries with high frequency of KPC-producing isolates, such as Colombia, China, United States and Portugal, the last one associated with Tn 4401b 66 – 70 .…”

Section: Discussionmentioning

confidence: 99%

Within patient genetic diversity of blaKPC harboring Klebsiella pneumoniae in a Colombian hospital and identification of a new NTEKPC platform

Abril

Vergara

Palacios

et al. 2021

Sci Rep

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Resistance to carbapenems in Klebsiellapneumoniae has been mostly related with the worldwide dissemination of KPC, largely due to the pandemic clones belonging to the complex clonal (CC) 258. To unravel blaKPC post-endemic clinical impact, here we describe clinical characteristics of 68 patients from a high complexity hospital, and the molecular and genetic characteristics of their 139 blaKPC—K.pneumoniae (KPC-Kp) isolates. Of the 26 patients that presented relapses or reinfections, 16 had changes in the resistance profiles of the isolates recovered from the recurrent episodes. In respect to the genetic diversity of KPC-Kp isolates, PFGE revealed 45 different clonal complexes (CC). MLST for 12 representative clones showed ST258 was present in the most frequent CC (23.0%), however, remaining 11 representative clones belonged to non-CC258 STs (77.0%). Interestingly, 16 patients presented within-patient genetic diversity of KPC-Kp clones. In one of these, three unrelated KPC-Kp clones (ST258, ST504, and ST846) and a blaKPC—K.variicola isolate (ST182) were identified. For this patient, complete genome sequence of one representative isolate of each clone was determined. In K.pneumoniae isolates blaKPC was mobilized by two Tn3-like unrelated platforms: Tn4401b (ST258) and Tn6454 (ST504 and ST846), a new NTEKPC-IIe transposon for first time characterized also determined in the K.variicola isolate of this study. Genome analysis showed these transposons were harbored in different unrelated but previously reported plasmids and in the chromosome of a K.pneumoniae (for Tn4401b). In conclusion, in the blaKPC post-endemic dissemination in Colombia, different KPC-Kp clones (mostly non-CC258) have emerged due to integration of the single blaKPC gene in new genetic platforms. This work also shows the intra-patient resistant and genetic diversity of KPC-Kp isolates. This circulation dynamic could impact the effectiveness of long-term treatments.

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“…isolates over time, although the K. variicola isolates were susceptible in our study both species carry the blaKPC-2 gene, highlighting the importance that the Klebsiella complex may have in the dissemination of resistance mediated by KPC [65]. K. variicola harboring blaKPC has been reported in countries with a high frequency of KPC-producing isolates, blaKPC-2 in Colombia, China, and the United States, while blaKPC-3 in Portugal, this last associated with Tn4401b [66][67][68][69][70].…”

Section: Discussionmentioning

confidence: 62%

Within-patient Genetic Diversity of blaKPC Harboring K. pneumoniae Isolates in a Colombian High Complexity Hospital. Identification of a New Tn3-based NTEKPC-IIe Mobilization Platform.

Abril

Vergara

Palacios

et al. 2021

Preprint

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Resistance to carbapenems in Klebsiella pneumoniae has been mostly related with the worldwide dissemination of KPC, largely due to the pandemic clones belonging to the complex clonal (CC) 258. To unravel blaKPC post-endemic clinical impact, here we describe clinical characteristics of 68 patients from a high complexity hospital, and the molecular and genetic characteristics of their 139 blaKPC - K. pneumoniae (KPC-Kp) isolates. Of the 26 patients that presented relapses or reinfections, 16 had changes in the resistance profiles of the isolates recovered from the recurrent episodes. In respect to the genetic diversity of KPC-Kp isolates, PFGE revealed 45 different clonal complexes (CC). MLST for 12 representative clones showed ST258 was present in the most frequent CC (23.0%), however, remaining 11 representative clones belonged to non-CC258 STs (77.0%). Interestingly, 16 patients presented within-patient genetic diversity of KPC-Kp clones. In one of these, three unrelated KPC-Kp clones (ST258, ST504, and ST846) and a blaKPC - K. variicola isolate (ST182) were identified. For this patient, complete genome sequence of one representative isolate of each clone was determined. In K. pneumoniae isolates blaKPC was mobilized by two Tn3-like unrelated platforms: Tn4401b (ST258) and Tn6454 (ST504 and ST846), a new NTEKPC-IIe transposon for first time characterized also determined in the K. variicola isolate of this study. Genome analysis showed these transposons were harbored in different unrelated but previously reported plasmids and in the chromosome of a K. pneumoniae (for Tn4401b). In conclusion, in the blaKPC post-endemic dissemination in Colombia, different KPC-Kp clones (mostly non-CC258) have emerged due to integration of the single blaKPC gene in new genetic platforms. This work also shows the intra-patient resistant and genetic diversity of KPC-Kp isolates. This circulation dynamic could impact the effectiveness of long-term treatments.

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Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)

Cited by 14 publications

References 42 publications

Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain

Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain

Within patient genetic diversity of blaKPC harboring Klebsiella pneumoniae in a Colombian hospital and identification of a new NTEKPC platform

Within-patient Genetic Diversity of blaKPC Harboring K. pneumoniae Isolates in a Colombian High Complexity Hospital. Identification of a New Tn3-based NTEKPC-IIe Mobilization Platform.

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