Anaerobes in diabetic foot infections: pathophysiology, epidemiology, virulence, and management

Abstract

SUMMARYDiabetic foot infections (DFI) are a public health problem worldwide. DFI are polymicrobial, biofilm-associated infections involving complex bacterial communities organized in functional equivalent pathogroups, all including anaerobes. Indeed, multiple pathophysiological factors favor the growth of anaerobes in this context. However, the prevalence, role, and contribution of anaerobes in wound evolution remain poorly characterized due to their challenging detection. Studies based on culture reviewed herein showed a weighted average of 17% of patients with anaerobes. Comparatively, the weighted average of patients with anaerobes identified by 16S rRNA gene sequencing was 83.8%. Culture largely underestimated not only the presence but also the diversity of anaerobes compared with cultivation-independent approaches but both methods showed that anaerobic Gram-negative bacilli and Gram-positive cocci were the most commonly identified in DFI. Anaerobes were more present in deeper lesions, and their detection was associated with fever, malodorous lesions, and ulcer depth and duration. More specifically, initial abundance of Peptoniphilus spp. was associated with ulcer-impaired healing, Fusobacterium spp. detection was significantly correlated with the duration of DFI, and the presence of Bacteroides spp. was significantly associated with amputation. Antimicrobial resistance of anaerobes in DFI remains slightly studied and warrants more consideration in the context of increasing resistance of the most frequently identified anaerobes in DFI. The high rate of patients with DFI-involving anaerobes, the increased knowledge on the species identified, their virulence factors, and their potential role in wound evolution support recommendations combining debridement and antibiotic therapy effective on anaerobes in moderate and severe DFI.

Keywords: anaerobes; diabetic foot infection; diversity; epidemiology; management; pathophysiology; resistance; virulence.

Fig 1

Results of the literature search on anaerobes in the context of diabetic foot infections (PubMed database, search date: February 16, 2024) and flow diagram of study selection.

Fig 2

Geographical heterogeneity in the relative prevalence of the main types of anaerobes cultivated from specimens sampled in patients with diabetic foot infections. GPAC, Gram-positive anaerobic cocci; GNAC, Gram-negative anaerobic cocci; GPAB, Gram-positive anaerobic bacilli; GNAB, Gram-negative anaerobic bacilli.

Fig 3

Main mechanisms of virulence developed by anaerobic Gram-positive cocci, notably Finegoldia magna. Four main virulence factors are involved at the different stages of infection: protein L in activation of immune system, PAB in invasion, SufA in invasion and escape from host immune system, and FAF in adhesion and colonization. Moreover, the production of short-chain fatty acids (SCFA) by anaerobic Gram-positive cocci allows them to resist the action of anti-inflammatory immune cells and inhibit the fibroblasts and fibrinogen, which participate in the wound healing process. They also produce several hydrolytic enzymes (hyaluronidase, gelatinase, collagenase, and chondroitin sulfatase) causing tissue destruction. Finally, anaerobes are organized in biofilm to persist in the wound, participate in the chronicity of the ulcers, and collaborate with other aerobes and anaerobes in FEP.

Fig 4

Origin of anaerobes in diabetic foot infection; main anaerobes following the ulcer size and depth and their impact on wound outcome.