The Journal of the Association of Physicians of India · 2026
Integrated Genomic Phenotypic and Host-response Analysis of Multidrug-resistant Diabetic Foot Infections: A Tertiary Center Study from Kerala India.
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K Mohammed Jaseem Ibrahim
Аннотация
BACKGROUND: Diabetic foot infections (DFIs) are a primary driver of amputation, worsened by multidrug-resistant (MDR) organisms. The link between pathogen genomics, virulence (e.g., biofilm), and host immunity is poorly quantified. This study aimed to integrate these multi-omic data streams to identify predictors of treatment failure.
MATERIALS AND METHODS: This prospective, single-center cohort study enrolled 150 DFI patients. Deep-tissue and autologous healthy-skin biopsies were collected. Pathogens were identified (culture/16S rRNA), with susceptibility and biofilm capacity tested. MDR isolates (n = 76) underwent whole-genome sequencing (WGS). Host response was quantified using an eight-gene quantitative reverse transcription polymerase chain reaction (qRT-PCR) panel, normalized to autologous controls. The primary outcome was "healing failure" (amputation or persistent ulcer) at 12 weeks. A least absolute shrinkage and selection operator (LASSO)-penalized regression model was developed and cross-validated.
RESULTS: The final analytical cohort included 112 culture-positive patients; 68/112 (60.7%) had an MDR infection. WGS identified high-risk clones (Escherichia coli ST131, Klebsiella pneumoniae ST258). Healing failure occurred in 34/112 (30.4%) patients. Strong biofilm production (adjusted OR 3.81, 95% CI 1.92-7.55) and a high host IL-10:TNF-α expression ratio (AOR 2.98, 95% CI 1.41-6.30) were independent predictors of healing failure. The LASSO model achieved an optimism-corrected area under the curve (AUC) of 0.79 (95% CI 0.71-0.87) with acceptable calibration (Brier score: 0.18; slope: 0.95).
CONCLUSION: In this DFI cohort, pathogen biofilm capacity and a modulated host immune signature were independently associated with treatment failure, highlighting potential new diagnostic and therapeutic targets.
MATERIALS AND METHODS: This prospective, single-center cohort study enrolled 150 DFI patients. Deep-tissue and autologous healthy-skin biopsies were collected. Pathogens were identified (culture/16S rRNA), with susceptibility and biofilm capacity tested. MDR isolates (n = 76) underwent whole-genome sequencing (WGS). Host response was quantified using an eight-gene quantitative reverse transcription polymerase chain reaction (qRT-PCR) panel, normalized to autologous controls. The primary outcome was "healing failure" (amputation or persistent ulcer) at 12 weeks. A least absolute shrinkage and selection operator (LASSO)-penalized regression model was developed and cross-validated.
RESULTS: The final analytical cohort included 112 culture-positive patients; 68/112 (60.7%) had an MDR infection. WGS identified high-risk clones (Escherichia coli ST131, Klebsiella pneumoniae ST258). Healing failure occurred in 34/112 (30.4%) patients. Strong biofilm production (adjusted OR 3.81, 95% CI 1.92-7.55) and a high host IL-10:TNF-α expression ratio (AOR 2.98, 95% CI 1.41-6.30) were independent predictors of healing failure. The LASSO model achieved an optimism-corrected area under the curve (AUC) of 0.79 (95% CI 0.71-0.87) with acceptable calibration (Brier score: 0.18; slope: 0.95).
CONCLUSION: In this DFI cohort, pathogen biofilm capacity and a modulated host immune signature were independently associated with treatment failure, highlighting potential new diagnostic and therapeutic targets.