Carbapenem Resistance in UPEC: Current Global Trends
Carbapenem resistance in uropathogenic E. coli (UPEC) is emerging as a critical global threat, with recent surveillance showing resistance rates ranging from approximately 10-15% in hospital settings, driven predominantly by NDM-5 and OXA-48 carbapenemase genes, particularly in high-risk clones ST405 and ST167.
Geographic Variation and Resistance Rates
The current landscape of carbapenem resistance in UPEC shows significant geographic heterogeneity:
Pakistan (2023-2024): Among 1,100 hospitalized patients, 118 carbapenem-resistant UPEC isolates were identified, with ST405 (35.6%) and ST167 (21.2%) being the predominant sequence types carrying blaCTX-M-15 and blaNDM-5 genes 1.
China (2017-2020): In Shandong Province, 17 carbapenem-resistant UPEC isolates were collected from hospitalized patients, with 88% (15/17) being blaNDM producers, and ST167 being the most common sequence type 2.
Iraq: Among outpatient phylogroup B2 UPEC isolates, carbapenemase genes were detected in 76.3% of isolates, though phenotypic carbapenem resistance rates remained relatively low, with blaOXA-48 being most frequent (57.8%) 3.
Iran (2018): All tested UPEC isolates were negative for carbapenemases by both phenotypic and molecular methods, indicating regional variation in resistance patterns 4.
Molecular Mechanisms Driving Resistance
The predominant carbapenemase genes identified in recent surveillance include:
blaNDM-5: The most clinically significant mechanism, particularly prevalent in Asian hospital settings, with high transferability via conjugative plasmids 1, 2.
blaOXA-48: Frequently detected in Middle Eastern isolates, often co-occurring with other resistance genes 3.
Co-production patterns: Multiple carbapenemase genes are increasingly found in single isolates, with blaOXA-48 and blaPER combinations being common (41.1% of carbapenemase producers) 3.
High-Risk Clones and Transmission
Specific sequence types represent globally disseminated high-risk clones:
ST405 and ST167: These clones carry extensive antimicrobial resistance genes (ARGs) conferring resistance to aminoglycosides, fluoroquinolones, tetracyclines, and sulfonamides, in addition to carbapenem resistance 1.
ST410: An emerging clone identified in Chinese surveillance with carbapenem resistance 2.
Transferability: Approximately 27% (4/15) of blaNDM-producing isolates demonstrated the ability to transfer resistance genes to recipient E. coli cells, indicating high horizontal gene transfer potential 2.
Associated Multidrug Resistance Patterns
Carbapenem-resistant UPEC universally exhibit extensive multidrug resistance:
Near-universal resistance to sulfamethoxazole-trimethoprim (96.6%) and doxycycline (96.6%) in carbapenem-resistant isolates 1.
100% MDR rates among carbapenemase-producing phylogroup B2 isolates 3.
Preserved susceptibility: Colistin and tigecycline maintain 100% susceptibility against carbapenem-resistant UPEC, with relatively low resistance to aminoglycosides and nitrofurantoin 1, 3.
Critical Clinical Pitfalls
The most concerning trend is the emergence of plasmid-mediated colistin resistance (mcr-1) in carbapenem-resistant isolates, creating pan-resistant strains with extremely limited treatment options 2.
Additional concerns include:
Biofilm formation: Carbapenem-resistant UPEC frequently produce biofilms, contributing to persistence and treatment failure 2, 4.
High virulence: Carbapenem-resistant clones carry diverse virulence factors, making infections more severe and difficult to treat 1.
Hospital amplification: The concentration of carbapenem-resistant UPEC in hospital settings creates reservoirs for further dissemination 1, 2.
Treatment Implications
Current evidence indicates carbapenem overreliance has accelerated resistance dissemination, necessitating alternative strategies including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and for metallo-β-lactamase producers, ceftazidime-avibactam combined with aztreonam 5.