Clinical relevance, mechanisms, and evolution of polymyxin B heteroresistance carbapenem-resistant Klebsiella pneumoniae: A genomic, retrospective cohort study.
Clin Microbiol Infect
; 30(4): 507-514, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38295990
ABSTRACT
OBJECTIVES:
To study the clinical relevance, mechanisms, and evolution of polymyxin B (POLB) heteroresistance (PHR) in carbapenem-resistant Klebsiella pneumoniae (CRKP), potentially leading to a significant rise in POLB full resistant (FR) CRKP.METHODS:
Total of 544 CRKP isolates from 154 patients treated with POLB were categorized into PHR and POLB non-heteroresistance (NHR) groups. We performed statistical analysis to compare clinical implications and treatment responses. We employed whole-genome sequencing, bioinformatics, and PCR to study the molecular epidemiology, mechanisms behind PHR, and its evolution into FR.RESULTS:
We observed a considerable proportion (118 of 154, 76.62%) of clinically undetected PHR strains before POLB exposure, with a significant subset of them (33 of 118, 27.97%) evolving into FR after POLB treatment. We investigated the clinical implications, epidemiological characteristics, mechanisms, and evolutionary patterns of PHR strains in the context of POLB treatment. About 92.86% (39 of 42) of patients had PHR isolates before FR, highlighting the clinical importance of PHR. the ST15 exhibited a notably lower PHR rate (1 of 8, 12.5% vs. 117 of 144, 81.25%; p < 0.01). The ST11 PHR strains showing significantly higher rate of mgrB mutations by endogenous insertion sequences in their resistant subpopulation (RS) compared with other STs (78 of 106, 73.58% vs. 4 of 12, 33.33%; p < 0.01). The mgrB insertional inactivation rate was lower in FR isolates than in the RS of PHR isolates (15 of 42, 35.71% vs. 84 of 112, 75%; p < 0.01), whereas the pmrAB mutation rate was higher in FR isolates than in the RS of PHR isolates (8 of 42, 19.05% vs. 2 of 112, 1.79%; p < 0.01). The evolution from PHR to FR was influenced by subpopulation dynamics and genetic adaptability because of hypermutability.DISCUSSION:
We highlight significant genetic changes as the primary driver of PHR to FR in CRKP, underscoring polymyxin complexity.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Klebsiella Infections
/
Carbapenem-Resistant Enterobacteriaceae
Type of study:
Etiology_studies
/
Observational_studies
Limits:
Humans
Language:
En
Journal:
Clin Microbiol Infect
Journal subject:
DOENCAS TRANSMISSIVEIS
/
MICROBIOLOGIA
Year:
2024
Document type:
Article
Affiliation country: