Diabetic Foot Infection and Lower Extremity Amputations: Recent trends, outcomes and prognostic factors

Diabetes and its complications in the lower extremity are an increasing burden that causes individual suffering for the patient and challenges and increased costs to the healthcare system in the form of high morbidity and mortality. Diabetes causes changes in lower extremity tissues, leading to the formation of diabetic foot. Diabetic foot is prone to recurrent ulceration and infections that further predispose to lower extremity amputation (LEA). LEA is a pivotal moment in the patient’s life and often leads to physical and psychosocial impairment and premature death. This dissertation aimed primarily to evaluate the rates of LEA nationally in the general population and regionally in patients with diabetes. Secondly, the dissertation aimed to investigate the outcomes of patients after diabetic foot infection (DFI) and LEA and to identify the causative pathogens of DFI.

The rate of amputations was evaluated in three cohorts. First, Study I compared cohorts of patients hospitalised due to DFI before (years 2006-7, n=124) and after (years 2013-14, n=148) the initiation of a dedicated wound centre (in 2012) at Tampere University Hospital (TAUH). A significant decrease in the rate of below knee amputations (BKA) from 25.8% (n=32) in 2006-7 to 9.5% (n=14) in 2013-14 was observed. Second, patients with diabetes undergoing LEA (n=1081) between 2008-19 were evaluated in Study V. The number of BKA as index amputation (first amputation) decreased by 40% from 20 in 2008 to 12 in 2019, while a 73% increase was identified in both below ankle (BAA, from 41 to 71) and above knee (AKA, from 11 to 19) amputations. Third, data on all LEAs performed in Finland between 1997 and 2018 were obtained from the National Hospital Discharge Register in Study IV. The incidence of BKA decreased by 46.2% (from 13 to 7 per 100 000 person-years), while BAA increased by 104.3% (from 23 to 47 per 100 000 person-years) and AKA remained unchanged (16 per 100 000 person years). Crude and index minor- major ratios increased from 1.33 (95%CI 1.23-1.44) and 1.13 (95%CI 1.03-1.24) in 2008 to 1.93 (95%CI 1.79-2.08) and 1.49 (95%CI 1.36-1.62) in 2018, respectively.

During the years 1997-2018, endovascular revascularisations increased exponentially (14-21 fold), which may have contributed to the increase in minor- major ratios (Study IV). In addition, the percentage of patients undergoing LEA without prior revascularisation decreased between 2009 and 2018. However, no significant difference was observed in frequencies of vascular surgeon consultations or revascularisations between the two cohorts of DFI in Study I. This indicates that other factors, such as the dedicated wound centre, have contributed to the observed outcomes.

Study I evaluated the outcomes for patients hospitalised due to DFI. Overall survival (OS) after DFI during one and five years was 81.2% (95%CI 77.5-84.9%) and 49.7% (95%CI 44.8-54.6%), respectively. Major amputation was the most significant risk factor (HR 6.673, 95%CI 2.836-15.700) for OS. After major amputation, OS was 41.7% (95%CI 13.9-69.5%) after one and 8.3% (95%CI 0.0- 24.0%) after five years. Other factors reducing OS included higher age, wound ischaemia and lower glomerular filtration rate (GFR). Major amputation-free survival (MAFS) was reduced by age, wound ischaemia and higher CRP. In addition, antihypertensive medication was associated with improved MAFS. Revascularisation improved MAFS in patients with ischaemic DFI (p<0.05). (Study III)

After initiation of a dedicated wound centre, the median time interval from admission to first surgical intervention reduced from 5 to 2 (p<0.05). In addition, there was indication of decreased length of hospitalisation (median 7 vs. 6, p=0.120). No significant change was observed in time interval from admission to vascular surgeon consultations.

Outcome was also evaluated for patients with diabetes who underwent LEA in Study V. OS after LEA during one and five years was 75.8% (95%CI 73.3- 78.3) and 38.3% (95%CI 34.7-41.7), respectively. Higher index amputation level decreased OS, while multiple amputations associated with improved OS. Higher age, peripheral artery disease and lower GFR reduced both OS and MAFS. In addition, dyslipidaemia and hypertension were associated with improved OS.

In Study II, bacterial culture data on patients hospitalised due to DFI at TAUH were analysed. In tissue cultures, Staphylococcus aureus (SA) was the most frequent gram positive cocci (34.8%, n=72), followed by streptococcus betahaemolyticus (BHS, 18.4%, n=38). The percentage of gram negative bacilli (GNB) was 23.2% (n=48). SA and BHS were the most common causative pathogens of bacteraemia (each 32.1%, n=9). GNB was significantly more frequent in ischaemic infection than in nonischaemic infection (40.3% vs. 21.3%, p<0.05). Superficial swab culture had 91.8-92.9 specificity and 66.7-87.5% sensitivity compared to tissue culture.

In conclusion, the overall incidence of LEA is increasing due to the rising numbers of BAA. In contrast, the incidence of BKA seems to be decreasing. The outcome after DFI and especially major amputation is poor. BAA is associated with improved prognosis (compared to BKA and AKA) and should be preferred when feasible. In addition, chronic limb threating ischaemia is a serious comorbidity and should be swiftly diagnosed and treated in DFI. The causative pathogens in patients treated at TAUH are congruent with most of the European data that advocate selecting the antibiotic treatment of DFI according to international guidelines.