Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
Beka L, Fullmer MS, Colston SM, Nelson MC, Talagrand-Reboul E, Walker P, Ford B, Whitaker IS, Lamy B, Gogarten JP, Graf J (2018) · mBio · n=37
Study Profile
- Design
- mechanistic microbiology and comparative genomics study of 37 Aeromonas isolates from leeches and patients combined with deep-sequencing of archived leech gut microbiota samples (University of Connecticut Department of Molecular and Cell Biology, USA; multi-institutional collaboration with French and Welsh partners)
- Sample size (n)
- 37
- Intervention
- Comparative-genomics analysis of 37 Aeromonas strains including environmental leech-derived and clinical patient-infection isolates; competition experiments and deep-sequencing of historical leech gut samples to trace emergence of ciprofloxacin-resistant strains
- Comparator
- Not applicable - comparative microbiology and genomics study without clinical patient outcomes as comparator
- Primary endpoint
- Identification of resistance mechanisms (gyrA/parC mutations, plasmid-borne resistance genes), competitive fitness advantage at sub-therapeutic ciprofloxacin concentrations (0.01-0.04 μg/mL), and temporal correlation between leech microbiota resistance and clinical Aeromonas infection isolates
- Primary result
- Sub-therapeutic ciprofloxacin levels (0.01-0.04 μg/mL, <1/100 of clinical breakpoint) provided a strong competitive advantage to resistant Aeromonas strains in leech gut microbiota; mutation profiles in resistant clinical isolates traced to leech-derived populations; increased frequency of ciprofloxacin-resistance-conferring mutations in 2011 coincided temporally with initial reports of ciprofloxacin-resistant infections in patients receiving leech therapy
- Follow-up duration
- multi-year archived sample analysis (longitudinal microbiology)
- PMID
- 30042201
Key Findings
- Demonstrated that even sub-therapeutic ciprofloxacin concentrations (<1/100 of clinical breakpoint) select for resistant Aeromonas in leech microbiota
- Comparative genomics of 37 strains traced clinical Aeromonas resistance to leech-derived populations
- Deep-sequencing of archived leech gut samples documented a 2011 increase in resistance-conferring mutations coinciding with the first patient resistance reports
- Established a One Health rationale for restricting veterinary fluoroquinolone use in leech-rearing facilities
- Provides the mechanistic explanation for ciprofloxacin-resistant Aeromonas infections in patients receiving leech therapy
Limitations
- Mechanistic/genomics study - does not provide patient-level clinical outcome data
- Sample-size limited to 37 strains; broader global leech microbiota surveillance not yet performed
- Resistance evolution dynamics extrapolated from limited longitudinal archived samples
- No direct patient-level RCT data on alternative prophylactic regimens
- Findings may be specific to particular leech-farming environments and antibiotic-exposure patterns
Clinical Implications
Beka 2018 is a landmark microbiology study that provides the mechanistic rationale for current concerns about ciprofloxacin prophylaxis in medical leech therapy. The work supports careful antimicrobial stewardship in leech-rearing facilities, recommends culture-tailored prophylaxis rather than universal ciprofloxacin, and bolsters the case for alternative regimens such as SXT (per Wilmer 2013) or culture-driven empiric choices. For US clinicians, the trial is essential context for understanding why the standard ciprofloxacin protocol may fail in some centers and why local Aeromonas susceptibility surveillance is increasingly recommended in K040187-cleared microsurgical-flap protocols.
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