A study on bacteriological profile and prescription pattern of antibiotics in the management of diabetic foot ulcers in a tertiary healthcare teaching hospital

Infection of diabetic foot ulcers is the most common cause of hospitalization among diabetic patients. If not treated properly in time, the infection will eventually lead to septicemia, amputation and even death. It is found that more than 40 percent of amputations can be prevented by the appropriate treatment of diabetic foot ulcers. Irrational antibiotic use leads to treatment failure adverse drug reactions, superinfections, prolongation of treatment, increased cost and development of antibiotic resistance. Study of the bacteriological profile, antimicrobial susceptibility and prescription pattern aids in evaluating the rationality of antibiotic therapy and promote rational drug use and quality of life of patients. Aims and objectives: To study the prevalence and antibiogram of causative organisms, and the prescription pattern of antibiotics used in the treatment of diabetic foot infection.


Introduction
Diabetes mellitus is considered as one of the main public health issues worldwide.It is estimated that about 150-170 million of the world's population is suffering from this condition.Macrovascular and microvascular complications arise due to long-term poor control of blood glucose level.Neuropathy, retinopathy and foot ulcers are the most common complications [1].Approximately 15% of diabetic patients are found to develop foot ulcers that can lead to osteomyelitis [2].An ulcer is a result of actions of multiple contributing factors.The pathophysiology of ulcer is complicated and it includes neuropathy, vascular and immune system components.Neuropathy is a disease that affects nerves causing impaired sensations, movement and other aspects based on the affected nerve.It is found that elevated levels of intracellular advanced glycated end products, activation of protein kinase C, increased hexosamine pathway flux and polyol pathway.Damage to motor neurons cause anatomical deformities eventually leading to skin ulcerations.Sensory neuropathy results in recurrent foot injuries causing disruption in skin integrity. [3]Infection worsens the wound conditions by interfering with the healing mechanism, which if not treated in time, eventually lead to septicemia, amputation or death.In addition to optimum glycemic control, wound care, surgical debridement, pressure offloading and maintaining adequate blood supply, evaluation of microbiological profile is essential [4] .non-ischemic clean wound.(B) indicates non-ischemic infected wounds.(C) indicates ischemic wounds and (D) represents infected ischemic wounds.Clinical and laboratory data serve as criteria for each of the stages [5] .A relationship between the types of infections and the number and types of organisms recovered from wound infections has been investigated and it was found that mild infections are monomicrobial and are caused by aerobic gram-positive cocci such as Staphylococcus aureus and Streptococcus spp.Polymicrobial infections are severe and caused by aerobic gram-positive cocci, gramnegative bacilli (e.g: Pseudomonas spp, Escherichia coli, Klebsiella spp and Proteus spp) and anaerobes [6] .Recent studies have indicated the dominance of gram-negative pathogens in monomicrobial infections [7] .Development of complex colonizing flora is found in chronic wounds & they include Enterococci, various Enterobacteriaceae, obligate anaerobes, Pseudomonas aeruginosa and sometimes, other non-fermentation gram-negative rods.Patients are predisposed to antibiotic-resistant organisms [e.g., methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococci (VRE)] due to hospitalization, surgical procedures and particularly prolonged or broad-spectrum antibiotic treatment.Community cases associated with MRSA strains are now becoming common and are associated with worse therapeutic outcomes in patients with diabetic foot infections [8] .Many studies have been conducted on the bacteriology of DFIs but the results have been varied.These could be due to geographical variations, changes in pathogens over time, type and severity of infection [9] .

Study design
Non-experimental, prospective, observational study.

Study site
The study was conducted at the surgical wards and general medicine wards of Father Muller Medical College "tertiary care teaching hospital", Kankanady, Mangalore.

Duration of the study
The study was conducted over a period of 6 months.

Sources of data
The data sources required for the study were collected from the patient's medical records (case sheets, laboratory investigations, medication charts).

Steps
 The records of patients admitted with the diagnosis of Diabetic Foot Ulcer were documented using data collection form. The treatment strategy subjected to the patient was documented and analysed. The obtained results were subjected to a suitable statistical method.

Operational modality
 Identification of the patient-Patients with Diabetic Foot Ulcer along with or without complications were identified from male medical wards, female medical wards, semi private and private wards. Collection of data-Patient demographic details, past medical history, past medication history, social history, personal history, general examination, antibiogram reports were collected and recorded in the pre-designed data entry form.

Statistical analysis
Descriptive statistical tools such as frequency, percentage, mean, standard deviation was used to assess the pertinent data.

The outcome of analysis
The outcome of the analysis was to determine the prevalence of various pathogens responsible for DFIs and their antibiotic sensitivity pattern.

Results and discussion
The study was undertaken in Father Muller Multi-Specialty Hospital, Mangalore, India and was approved by IEC.This retrospective study was conducted for a period of 6 months.Patient case records were reviewed and a total of 210 subjects were selected based on the study criteria and a total of 284 microbiological investigations were done.The age of patients ranged from 31 to 87 with an average of 58.4(±10.2).The most prevalent age group was between 51 and 60 years (36.7%).The distribution in other age groups is summarized in Table 1.

Gender-wise distribution of the patients
Gender wise distributions of the patients were analyzed and a majority of patients were males (77.6%) with a male to female ratio of 3.46:1.The details are summarized in Table 2.

The duration of diabetes mellitus
The duration of diabetes mellitus ranged from 1 month to 40 years.A detailed summary of results is given in Table 3.

Duration of diabetic foot ulcer
The duration of diabetic foot ulcers ranged from 1 day to one year.The details are summarized in Table 4.

Duration of hospital stay
Out of 210 patients, it was found that most of the patients were hospitalized for 2-10 days (46%), followed by 11-20 days (30.9%).A detailed summary of results is given in Table 5.

Fungal species:
Candida species 2 0.70% A total of 566 antibiotics were prescribed and with respect to the class of antibiotics, Cephalosporins (34.6%) were majorly prescribed, followed by Penicillins(20.6%).356 empirical antibiotics were prescribed in 210 patients.

Prescription pattern of antibiotics
Clindamycin (45.2%),Amoxicillin-Clavulanic acid (35.2%),Cefuroxime-Sulbactam (15.2%) and Piperacillin-Tazobactam (14.8%) were the most commonly prescribed empirical antibiotics.The detailed summary is given in Table 9.The empirical antibiotics were prescribed as dual therapy in 122 patients (58%) followed by monotherapy in 76 patients (36%) and triple therapy in 12 patients (5%).45(22%) out of 200 specimens with positive bacterial culture indicated resistance to the prescribed empirical antibiotics.210 definitive antibiotics were prescribed and Linezolid constituted for 16% of the prescribed definitive antibiotics.44 bacterial isolates had no antibiotic resistance, out of which 20 were Gram-positive and 24 were Gram-negative.Cefazolin, Cefotaxime, Azithromycin and Clindamycin were found to be highly resistant in Gram-positive bacteria.Vancomycin, Teicoplanin, Linezolid and Tigecycline were the antibiotics to which gram-positive bacteria had maximum susceptibility.Table .10and Table .12present the antibiotic resistance pattern and sensitivity pattern of Gram-positive bacteria respectively.Gram-negative bacteria had high resistance to antibiotics like Amoxicillin-Clavulanic acid, Ampicillin, Cefazolin, Cefuroxime and Cefotaxime.They were highly sensitive to Piperacillin-Tazobactam, Gentamicin, Amikacin, Ciprofloxacin, Levofloxacin, Imipenem, Meropenem, Tigecycline, Aztreonam and Polymyxin B. Table .11and table.13illustrate the antibiotic resistance and sensitivity pattern of gram-negative bacteria respectively.

Conclusion
In our study, the most prevalent age group was between 51 and 60 years and majority of patients were males.Hypertension was the most common comorbidity.Gram-negative bacteria were the most commonly isolated pathogens.The majority of diabetic foot infections were monomicrobial in nature.Staphylococcus aureus is the most frequently isolated bacteria.Cephalosporins were a majorly prescribed class of antibiotics followed by Penicillins.Clindamycin was the most commonly prescribed empirical antibiotic.The empirical antibiotics were prescribed as dual therapy in most of the patients.Gram-positive bacteria were highly susceptible to Vancomycin, Teicoplanin, Linezolid and Tigecycline.Most of the Gram-negative bacteria were highly sensitive to Piperacillin-Tazobactam, Cefoperazone-Sulbactam, Imipenem, Meropenem and Tigecycline.Except for Tigecycline, no other antibiotic has 100% sensitivity in both Grampositive and Gram-negative bacteria.Hence a combination of antibiotics is preferred for empirical therapy which can then be modified based on culture-sensitivity results and patient's response.It can be concluded that our study may help in the rational prescription of antibiotics in the treatment of diabetic foot infections.

Table 1
Age wise distribution of the patients N=210

Table 3
The duration of diabetes mellitus N=210

Table 4
Duration of diabetic foot ulcer N=210

Table 5
Duration of Hospital stay N=210 4%) patients out of 210 had no comorbidity and a total of 203 comorbidities were identified from 123 patients.86patientshad hypertension (41%) which makes it the most common comorbidity identified during the study.39patientshad Ischemic Heart Disease (18.6%), followed by 24 patients with Chronic Kidney Disease (11.4%) and 17 patients with Peripheral Arterial Occlusive Disease (8%).The details are summarized in Table6(Chart 1).

Table 6
Co-morbidities of the patients N=210

Table 7
Type of infection N=210

Table 8
Microorganisms isolated from the diabetic foot wound culture N=210

Table 9
Most commonly used empirical antibiotics N=210

Table 11
Antibiotic resistance in Gram negative bacteria N=210

Table 12
Antibiotic sensitivity in Gram positive bacteria N=210

Table 13
Antibiotic sensitivity in Gram negative bacteria N=210