Diabetic Foot Ulcer Infections – Carbapenemase Producing Multidrug Resistant Organisms

Diabetic foot ulcers (DFUs) represent one of the most severe and debilitating complications of diabetes, frequently necessitating non-traumatic lower-limb amputations. The clinical challenge of managing DFUs has been profoundly aggravated by the rising prevalence of multidrug-resistant (MDR) bacteria.

Among the most alarming of these MDR pathogens are the carbapenemase and extended-spectrum β-lactamases (ESBLs) producing Gram-negative bacteria, including Escherichia coli and Klebsiella pneumoniae and Carbapenem-resistant strains of Pseudomonas aeruginosa and Acinetobacter bau mannii. The Carbapenemase Producing Organisms (CPOs) produce enzymes that dismantle carbapenem antibiotics, drugs often considered a last line of defence for severe Gram-negative infections, making these infections exceptionally difficult to treat and leading to poor clinical outcomes, including persistent infections, prolonged hospital stays, and higher amputation rates.

This retrospective, observational study analyzed 200 clinical isolates collected from DFU patients. All included patients had ulcers classified as Wagner-Meggitt grade 2 or higher. The majority of patients were male (60%), with a mean age of 63.5 years, and a high proportion (83.2%) demonstrated poor glycemic control (HbA1c > 7%).

Microbiological analysis involved phenotypic assays, including the Modified Hodge Test (MHT) and the Carba NP test, coupled with molecular techniques such as Polymerase Chain Reaction (PCR) to specifically detect carbapenemase-encoding genes.

The study confirmed a high prevalence of carbapenemase production, with 51.7% of the analyzed isolates identified as CPOs. The main pathogens producing carbapenemases included Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Molecular analysis revealed that the most common resistance genes detected were blaKPC (27.6%) and blaNDM (24.1%). Carbapenemase-producing isolates demonstrated high resistance to β-lactam antibiotics.

MDR infections were significantly associated with several adverse clinical markers and outcomes. Patients with MDR infections were strongly linked to pyrexia (p=0.017) and a history of recent antibiotic use (p=0.003). Furthermore, MDR cases were significantly more often polymicrobial (82% vs. 50.7%, p<0.001) and presented with more severe ulcers (Wagner grade >II, p=0.002).

The most concerning finding was the strong association between MDR infections and the need for amputation. The rates for both minor amputations (76% vs. 6%) and major amputations (38% vs. 4.7%) were markedly higher in patients with MDR infections compared to those with non-MDR infections (p<0.001 for both).

These results underscore the serious and increasing burden of MDR infections, particularly CPOs, in diabetic foot ulcers. To improve clinical outcomes, there is an immediate requirement for enhanced microbiological surveillance and the implementation of robust antimicrobial stewardship programs. Given the high level of resistance to carbapenems, the authors emphasize the need to explore novel therapeutic strategies, such as combination therapies, antimicrobial peptides, and bacteriophage-based treatments, to effectively combat these superbugs.

Reference Source
Saleem, M.; Moursi, S.A.; Altamimi, T.N.A.; Alharbi, M.S.; Alaskar, A.M.; Hammam, S.A.H.; Rakha, E.; Syed Muhammad, O.I.; Almalaq, H.A.; Alshammari, M.N., et al. Prevalence and Molecular Characterization of Carbapenemase-Producing Multidrug-Resistant Bacteria in Diabetic Foot Ulcer Infections. Diagnostics 2025, 15, 141. https://doi.org/10.3390/diagnostics15020141