Diabetic Foot Infection: A Study in a Tertiary Care Hospital

As per projections half a billion people would suffer maturity onset diabetes by 2030, world over, with concentration in middle income nations [1]. Diabetes and its complication involve complex etiology including increased susceptibility to infections. Diabetic foot ulcer is common major complication [2]. Around 15% of patients with type 2 diabetes have foot problem increasing instances of hospitalization. [3]. Neuropathy, peripheral vascular insufficiency, repeated trauma is traditionally believed to contribute to the complications. Besides the neurovascular alterations, age, gender, body mass index, duration of diabetes, glycosylated hemoglobin profiles etc are found influential in various studies [4]. Evidence on predictive value of simple indicators for risk of diabetic foot is crucially required in addressing the problem. Clinical history, examination, diagnostic investigation data must undergo continuous evaluation with such intent [5]. Infection management in diabetic foot is challenging task wherein microbial diagnosis is critical. Infective organisms and their sensitivity patterns are studied regularly with changing time, demography and region. The present study has analyzed the reports of the cases of diabetic foot infections from middle and upper middle income group of North Indian patient treated at a tertiary care hospital.


Introduction
As per projections half a billion people would suffer maturity onset diabetes by 2030, world over, with concentration in middle income nations [1]. Diabetes and its complication involve complex etiology including increased susceptibility to infections. Diabetic foot ulcer is common major complication [2]. Around 15% of patients with type 2 diabetes have foot problem increasing instances of hospitalization. [3]. Neuropathy, peripheral vascular insufficiency, repeated trauma is traditionally believed to contribute to the complications. Besides the neurovascular alterations, age, gender, body mass index, duration of diabetes, glycosylated hemoglobin profiles etc are found influential in various studies [4]. Evidence on predictive value of simple indicators for risk of diabetic foot is crucially required in addressing the problem. Clinical history, examination, diagnostic investigation data must undergo continuous evaluation with such intent [5]. Infection management in diabetic foot is challenging task wherein microbial diagnosis is critical. Infective organisms and their sensitivity patterns are studied regularly with changing time, demography and region. The present study has analyzed the reports of the cases of diabetic foot infections from middle and upper middle income group of North Indian patient treated at a tertiary care hospital.

Material and Methods
50 patients admitted at Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala between January 2013 and June 2015, for management with diagnosis of infected diabetic foot were studied. The precise diagnosis including severity of foot involvement, age, gender, habits were noted. Details of clinical findings, requisitioned laboratory investigation data, identified microbes with sensitivity pattern and employed chemotherapy were recorded. Presence of hypertension, retinopathy, peripheral neuropathy, peripheral vascular defect and albuminuria were particularly scrutinized and noted. The data was analyzed using descriptive statistics

Results
Among the 50 cases studied, 23 were males and 26 females. Age of the patients ranged from 36 to 83 years. 26 of total 50 cases (52%) were in the age-group of 51 to 60 years ( Figure 1). Poor control of the glycaemic status was the most common risk factor found to be associated (92% of the cases) ( Table 1). The clinical manifestation was mostly in the form of ulcers (42%) while gangrene developed in 10% of the patients ( Table 2). Regarding the management, the most common approach was the debridement of the wound which was performed in 40% of cases while in 5% of cases; amputation was performed ( Figure  2). Gram-negative aerobes like Pseudomonas aeruginosa and Klebsiella species and gram-positive aerobes like staphylococcus were the commonest to be found ( Table 3). Majority of the cases (62%) exhibited mixed infection with more than one causative microorganism (gram-negative) involved ( Figure 3). Combinations of Vancomycin and Linezolid for gram-positive and Gentamycin or Amikacin for gram-negative organisms have been found to be most effective as antimicrobial therapies in the patients (Tables 4 & 5).

Risk Factors Number of Cases
Poor diabetes control 46 Peripheral neuropathy 38 Hypertension 37 Albuminuria 29 Retinopathy 28 Hyperlipidaemia 25 Past history of Angina/MI 17

Smoking 9
Alcohol 5 Past history of TIA (transient ischaemic attacks) 4 Most common risk factor seems to be the lack of proper control of diabetes.

Discussion
Good glycaemic control is crucial to stop and even regress the complications of diabetes mellitus. Uncontrolled hyperglycemia co-exists in vast majority of studied diabetic foot infection patients. It can be the cause or effect of the complication but stands as most important target for prevention or management. The neuropathic diagnosis was derived from lost vibration sense tested with tuning fork and peripheral vascular deficiency from absent posterior tibial and/or dorsalis pedis pulsations. The two complications were present in large majority of cases. Additionally retinopathy, albuminuria and hyperlipidaemia also occurred in the subjects. Atherosclerotic basis has been suggested as dominant since diabetics have three times accelerated atherosclerosis development compared to nondiabetic individuals [6]. Observations of study underline the need of identifying and aggressively managing associated vascular risk factors eg. obesity, cigarette-smoking, dyslipidaemia, hypertension and sedentary behavior [7].
Staphylococcus aureus and beta haemolytic streptococci were the first organisms to colonize through breach of pedal skin. Chronic wound however acquires mixed infections. Inadequate episodes of infection treatment markedly increase gram-negative microbial load. Pseudomonas aeruginosa is specifically associated to instances of wet dressings [8]. Mixed infections provide mutual synergy among one another and add to global severity of state of infection [9]. The fact that majority of cases had mixed infections plus uncontrolled diabetes indicates diabetic foot ulcer in studied sample as vary severe disease state needing kind of intense management. The deeper involvement, especially bone was diagnosed by radiology and hence under-estimated. The antimicrobial therapy was based on wider consideration than usual sensitivity report [10]. The patients continued to receive antimicrobial therapy often combined throughout hospitalization that lasted 1 week to 6 weeks. Reports of continued antibiotic therapy for deeper spread of infection in diabetic foot for 3 to 6 month periods indicate that as prudent for clinical success [11]. Diabetic foot infection as such is facilitated by intrinsic immunologic deficits, specially neutrophil dysfunction [12].
Among the studied 50 cases only 13 had staphylococcal infection evident in cultures. This is too low compared to expectations. Invasive staphylococcal infections are prevalent carrying poor prognosis in diabetics [13]. Diabetes also increases invasive infections due to group B streptococci [14]. Risk of serious infection due to Klebsiella pneumoniae increases in poorly controlled diabetics [15]. Urinary tract infections due to Gram-negative organisms are much increased in diabetics as well and are recurrent [16]. Over 60% instances of Burkholderia pseudomellei (Melioidosis) gram-negative infections occur in association with diabetes [17].
While debridement was done in majority of foot ulcers, no surgical efforts for revascularization were made in conjunction. The fact that most patients had neurovascular deficits, net impact of such deficiency on the clinical outcome is most warranted through study at centers that do surgical revascularization. Antiangiogenic factors are believed to be raised in patients with diabetic foot ulcers that inhibit Wnt/β-Catenin signaling poor wound healing [18]. Agents becoming available, which activate β-Catenin signaling, deserve trials to improve healing of diabetic foot ulcer disease. Hyperglycemia-induced formation and build-up of advanced glycation end products (AGEs) are prime contributors to infection susceptibility in diabetes via multiple mechanisms [19][20][21][22]. Newly available agents causing breakdown of AGE products and agents inhibiting their formations must be part of therapeutic regimes in diabetic foot infection and be evaluated to build clinical evidence base.

Conclusion
Poor diabetic control has been the major contributing factor to foot infections in the diabetics in addition to peripheral neuropathy, retinopathy and nephropathy. Most commonly affected age-group was found to be 51-60 years. While few patients of diabetic foot infections respond to conservative line of management but the best modality of management is early debridement followed by antimicrobial coverage. Gram-positive aerobes like staphylococcus and gram-negative aerobes like Pseudomonas aeruginosa and Klebsiella species are the commonest to be found. Combination of Vancomycin and Linezolid for gram-positive and Gentamycin or Amikacin for gram-negative organisms have been found to be most effective. Evaluation of new therapeutic regimes is necessitated in the future to optimize the management and long-term outcomes in the patients.