Seasonal Genomic Dynamics of Multidrug-Resistant Pathogens in ICU Environments and Perspectives on Phage-Based
Yan Zhang1, Xiaoyu Li2, Fengli Wang3
1Medical Intensive Care Unit (MICU), Central Hospital Affiliated to Dalian University of Technology (Dalian Municipal Central Hospital), Dalian, 116033, People's Republic of China.
Background:
The emergence of multidrug-resistant (MDR) pathogens in intensive care units (ICUs) has become a pressing global health issue, contributing to mortality rates exceeding 40%. Among these, carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii are especially problematic. Seasonal fluctuations in resistance patterns have been observed, yet the genomic mechanisms underlying these trends remain insufficiently characterized.
Objective:
This study investigated the seasonal variation in resistance gene prevalence among ICU-derived bacterial isolates and elucidates the genomic features contributing to antimicrobial resistance.
Methods:
Environmental and clinical samples were collected from ICU settings over multiple seasons using a systematic, stratified approach. Whole-genome sequencing was conducted on isolates via Illumina and Nanopore platforms. Resistance genes were annotated using CARD, VFDB, and BiocideResistance databases. Statistical associations were assessed using logistic regression and generalized linear mixed models, while phylogenetic trees evaluated clonal relationships.
Results:
The blaCTX-M-3 gene was detected in 100% of autumn isolates (n=52), showing a statistically significant association with increased bed turnover and prolonged disinfection intervals (p=0.003). During winter, 75% of isolates (n=50) tested positive for qacEΔ1, correlating with elevated multidrug resistance indices (p=0.01) and patterns consistent with clonal expansion based on whole-genome SNP profiling. These winter strains also exhibited enhanced biofilm formation capacity (OD595=0.67 ± 0.11) and upregulation of efflux pump transcripts (2.3-fold increase vs summer; p=0.02), supporting environmental adaptation under low-temperature stress. Notably, aac(6')-Ib7, an aminoglycoside-modifying enzyme gene, was the most frequently detected resistance determinant, present in 68% of isolates, highlighting substantial antibiotic selection pressure.
Conclusion:
This study reveals distinct seasonal genomic patterns in ICU drug-resistant pathogens and emphasizes the necessity for adaptive infection control strategies. Targeted disinfection, antibiotic stewardship, and consideration of phage therapy as a complementary strategy particularly during winter may help mitigate the spread of high-risk resistant clones, though further in vitro and in vivo validation is required.
Insights
Multidrug-resistant pathogens in intensive care units show seasonal genomic variations. Understanding these patterns is key to developing adaptive infection control strategies against antibiotic resistance.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Intensive care units (ICUs) face a growing threat from multidrug-resistant (MDR) pathogens, leading to high mortality rates.
- Carbapenem-resistant *Klebsiella pneumoniae* and *Acinetobacter baumannii* are particularly concerning MDR pathogens.
- Observed seasonal fluctuations in antimicrobial resistance patterns lack comprehensive genomic explanations.
Purpose of the Study:
- To investigate seasonal variations in resistance gene prevalence among bacterial isolates from ICUs.
- To elucidate the genomic features contributing to observed antimicrobial resistance patterns throughout the year.
Main Methods:
- Systematic collection of environmental and clinical samples from ICUs across different seasons.
- Whole-genome sequencing of bacterial isolates using Illumina and Nanopore platforms.
- Annotation of resistance genes using CARD, VFDB, and BiocideResistance databases; statistical analysis and phylogenetic evaluation.
Main Results:
- The *bla*CTX-M-3 gene was prevalent in autumn isolates, linked to increased bed turnover and disinfection intervals (p=0.003).
- Winter isolates showed high prevalence of *qacEΔ1* (75%), associated with multidrug resistance and clonal expansion, enhanced biofilm formation, and upregulated efflux pumps (p=0.02).
- *aac(6')-Ib7* was the most frequent resistance gene (68%), indicating significant antibiotic selection pressure.
Conclusions:
- Distinct seasonal genomic patterns in ICU drug-resistant pathogens necessitate adaptive infection control strategies.
- Targeted disinfection, antibiotic stewardship, and phage therapy (especially in winter) may combat resistant clone spread.
- Further in vitro and in vivo validation is required to confirm the efficacy of proposed strategies.
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