Antibiotic Drug Utilization Review of Diabetic Foot Infection in Surgery Ward Inpatients in a Tertiary Care Hospital: A Gyssens Criteria Based Assessment

Diabetes mellitus (DM) is a growing global public health problem, with its prevalence increasing sharply over the past two decades (1). It affects multiple vital organs and contributes substantially to morbidity and mortality. Worldwide, an estimated 382 million people were living with diabetes in recent years, and this number is projected to rise to 592 million by 2035 (2). Poorly controlled diabetes predisposes patients to long-term complications, among which diabetic foot ulcer (DFU) is one of the most common and serious outcomes. Neuropathy, peripheral arterial disease, and impaired wound healing significantly increase the risk of ulceration and subsequent infection (2,3). It is estimated that nearly one million diabetic patients undergo lower-limb amputation annually, with DFU contributing to more than 85% of these cases (4).

Diabetic foot infection (DFI) typically develops following a break in the skin, most often a neuropathic ulcer. Infection is identified when inflammatory signs or purulent discharge are present, and its severity may be categorized as mild, moderate, or severe (3). DFIs are commonly polymicrobial, involving pathogens such as Staphylococcus aureus, Streptococcus pyogenes, E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp., and Enterococcus spp. (4,5). The increasing prevalence of multidrug-resistant organisms, including MRSA, further complicates management and highlights the importance of judicious antibiotic use (4).

Rational antibiotic therapy plays a central role in DFI management. Empirical and definitive antibiotic choices should be guided by local microbial patterns, severity of infection, and established treatment guidelines (1,2). Inappropriately prescribed antibiotics—whether incorrect in dose, duration, spectrum, or frequency—contribute to antimicrobial resistance, toxicity, delayed healing, prolonged hospitalization, and increased healthcare costs (2). The Gyssens method provides a structured approach to evaluating the appropriateness of antibiotic prescribing and identifying opportunities for improvement (3).

Given the clinical complexity of DFI and the rising burden of antibiotic resistance, assessing antibiotic utilization patterns is essential. This study aims to evaluate antibiotic use among inpatients with diabetic foot infection using the Gyssens criteria and compare prescribing practices with standard recommendations to support antimicrobial stewardship efforts.

AIMS AND OBJECTIVES:

• To evaluate antibiotic usage in DFI.
• To classify the antibiotics usage according to Gyssens' criteria.
• To assess the possibility of drug-drug interaction and adverse drug reactions.

MATERIAL AND METHODS:

This study was a descriptive, cross-sectional analysis conducted using secondary data obtained from the medical records of diabetic foot infection (DFI) inpatients admitted to the Surgery Ward of Government Medical College and Hospital, Nagapattinam. Patients aged above 30 years, diagnosed with DFI, and receiving antibiotics during their hospital stay were included. Relevant clinical information such as patient demographics, comorbidities, type of infection, microbiological culture findings, and antibiotic details—including name, strength, dose, dosage form, route, frequency, and duration—were collected. All empirical antibiotic prescriptions were evaluated for appropriateness using the Gyssens criteria to assess selection, dose, route, timing, and duration. The overall outcome and rationality of therapy were determined by comparing clinical features and after antibiotic administration.

The rationality of antibiotic use in patients with diabetic foot infections was evaluated using the Gyssens criteria. The Gyssens method is a widely accepted qualitative tool for assessing the appropriateness of antibiotic therapy. In this method, each antibiotic prescription is categorised based on specific standards. Category 0 indicates that the antibiotic use is fully appropriate in terms of drug selection, dose, route, timing, and duration. Categories I–VI indicate inappropriate use: incorrect timing (Category I), incorrect dosage (Category IIa), inappropriate dosing interval (Category IIb), inappropriate route of administration (Category IIc), excessively prolonged duration (Category IIIa), insufficient duration (Category IIIb), availability of a more effective (Category IVa), less toxic (Category IVb), more cost-effective (Category IVc), or narrower-spectrum alternative (Category IVd), no valid indication for antibiotic therapy (Category V), and insufficient information for assessment (Category VI). This evaluation allowed systematic identification of prescribing errors and helped determine the overall rationality of empirical antibiotic therapy in DFI patients. Ethical approval was received from the Ethical Committee of Nagapattinam Government Medical College and Hospital, Orathur, number GMCN/IEC/2025/1/49.

RESULTS AND DISCUSSION:

Table 1: Age Distribution

In the present study, most diabetic foot infection (DFI) patients belonged to the 51–70 years age group (54%). This finding is relevant to the study by Lipsky et al. (7) and several other epidemiological reports, which indicated that DFI commonly affects individuals above 50 years due to long-standing diabetes, peripheral neuropathy, and impaired immunity. Studies by Zubair et al.(8) and Pemayun et al.(9) have similarly reported a peak incidence in the 50–70 years range, supporting the age trend observed in our population          

Table 2: Gender Distribution

Concerning gender, table 2, the majority of patients in this study were males (56%), while females accounted for 44%. This predominance of males is relevant to previous studies, including those by Akhi et al.(10) and Boulton et al. (11), which consistently showed higher DFI prevalence among males. The gender difference is often explained by occupational exposure, increased outdoor activities, reduced foot care practices, and higher smoking rates among males, contributing to a greater risk of foot trauma and ulceration. However, the slightly narrower male–female difference observed in the present study compared to some international reports is irrelevant to studies showing extremely high male predominance, suggesting possible sociocultural or lifestyle variations in this study population.

Table 3: Duration of Diabetes

In the present study, the majority of patients (90%) had diabetes for 1–10 years, while only 10% had a disease duration of 10–20 years. This finding is relevant to the report by Pemayun et al.,(9) who highlighted that most diabetic foot infection (DFI) cases occur in patients with a disease duration of more than 5 years, owing to progressive neuropathy and vascular impairment. Similarly, Zubair et al(8). also observed that the risk of foot ulceration and subsequent infection increases with longer diabetes duration, particularly beyond five years of diagnosis. The high proportion of patients in the 1–10 year category in our study indicates that DFI may occur earlier in the disease course, suggesting poor glycemic control and inadequate foot-care practices in this region, which is irrelevant to studies showing later onset (>10 years) of foot complications in better-controlled populations.

Table 4: Comorbidities

Fig1: Comorbidities

Hypertension (60%) was the most common comorbidity among DFI patients, which is relevant to the findings of Boulton et al. (11), who emphasised that hypertension is a frequent coexisting condition in individuals with diabetic foot complications due to its contribution to peripheral arterial disease and microvascular impairment. Likewise, the presence of coronary artery disease (24%) and cerebrovascular disease (5%) in our study aligns with Boulton et al. (11), who reported that macrovascular complications commonly accompany diabetic foot pathology as part of the systemic vascular burden associated with long-standing diabetes.

The absence of chronic kidney disease (CKD) in this sample contrasts with previous literature, as CKD is commonly reported as a risk factor for severe DFI and poor wound healing; therefore, this result is less relevant to studies like those of Ndosi et al.,(12), which found high CKD prevalence in DFI cohorts. Minor comorbidities such as anaemia (3%) and pulmonary tuberculosis (3%) were identified. Anaemia, although less common in this study, has been associated with impaired tissue oxygenation and delayed ulcer healing; hence, the lower frequency observed here is less relevant to reports where anaemia is more prevalent among DFI patients.

Overall, the comorbidity profile of this population shows strong alignment with global trends, particularly regarding hypertension and cardiovascular involvement, while variations such as the absence of CKD reflect local clinical and demographic differences.

Table 5: Site of Infection

Fig. 2: Diabetic foot infection affected site

In this study, the toe was the most frequently affected site in diabetic foot infections (48%), followed by the heel (18%), dorsum (15%), and plantar region (14%). The high prevalence of toe involvement is relevant to the findings of Boulton et al. (11), who reported that the toes and forefoot are the most common ulcer locations in diabetic patients due to persistent pressure points, neuropathy, and repeated minor trauma.

Heel ulcers (18%) were less frequent but still clinically significant. This pattern is relevant to the study by Prompers et al. (13), who found heel ulcers to be less common than forefoot ulcers but associated with higher severity due to ischemia.

The plantar region accounted for 14% of infections in our study, which aligns with the observations of Armstrong DG et al. (14), who noted that plantar ulcers typically arise at high-pressure neuropathic sites but occur less frequently than toe ulcers.

Dorsal foot ulcers (15%) represent a moderate proportion in this study and may be associated with improper footwear and trauma. This distribution, however, is irrelevant to the findings of Reiber et al. (15), who reported that plantar and toe ulcers are overwhelmingly the dominant ulcer types, with dorsal ulcers much less common internationally.

Overall, our findings support established epidemiological trends that the toes and forefoot are the most vulnerable areas for diabetic foot infection, consistent with structural deformities and neuropathy described in the literature. These patterns emphasise the need for preventive foot care and protective footwear to reduce trauma in high-risk regions.

Table 6: Types of Bacteria infecting during the period of 6 months

In this study, gram-negative bacteria were the predominant organisms isolated from diabetic foot infections (76%), while gram-positive organisms accounted for 24% of cases. Staphylococcus aureus (14.6%) and MRSA (9.6%) were the most common gram-positive pathogens. This finding is relevant to Lipsky et al. (7), who reported S. aureus as a frequent cause of diabetic foot infections due to its ability to colonise broken skin (Lipsky et al., 2012).

Among gram-negative organisms, E. coli (31%) was the most common isolate, followed by Klebsiella pneumoniae (16.2%), Klebsiella oxytoca (12.9%), and Pseudomonas spp. (8%), Citrobacter spp. (4.8%), and Acinetobacter spp. (3.2%). The predominance of gram-negative organisms in our study is relevant to Zubair et al. (8), who also found gram-negative bacteria to be more common in diabetic foot infections in India (Zubair et al., 2010). The presence of Klebsiella and Pseudomonas species is similarly relevant to Gadepalli et al.,(16) who reported these organisms in chronic and long-standing foot ulcers (Gadepalli et al., 2006).

Overall, the microbial profile in our study matches common patterns seen in Indian and Asian DFI studies, where gram-negative bacteria frequently dominate, emphasising the importance of culture-based antibiotic selection.

Table 7: Dose of antibiotic treatment for Diabetic foot infection

The evaluation of antibiotic dosing demonstrated that several agents were prescribed appropriately in accordance with standard diabetic foot infection (DFI) guidelines. Ceftriaxone, piperacillin–tazobactam, cefotaxime, cefoperazone–sulbactam, metronidazole, linezolid, and topical clotrimazole were administered at doses consistent with recommended therapeutic ranges, which aligns with the dosing strategies outlined by Lipsky et al. (7) and the Sanford Guide (17).

In contrast, several deviations from standard dosing were observed. Ciprofloxacin IV (200 mg BD) was prescribed at half the recommended dose, which does not meet the therapeutic level described by Joseph (18). Oral amoxiclav (625 mg BD) was also underdosed relative to the TID regimen advised in the NICE guideline (19). Meropenem administered as 1 g BD was below the recommended 1 g TID, indicating inadequate coverage for severe infections described in standard DFI guidelines (1). Cephalexin (250 mg TDS) and doxycycline (100 mg OD) were similarly lower than recommended doses, differing from the therapeutic recommendations outlined in the Sanford Guide (17) and Lipsky et al. (7), respectively.

A notable concern was the prescription of amikacin 500 mg BD, which exceeds the once-daily dosing of 15–20 mg/kg recommended in aminoglycoside therapy guidelines. This pattern contradicts the pharmacological principles described in Goodman & Gilman’s (20) and the Sanford Guide (17), which advise extended-interval dosing to minimise nephrotoxicity.

Additionally, systemic azithromycin (500 mg BD) was prescribed despite the absence of its role in DFI management. This practice diverges from the WHO Model Formulary (21), which does not include systemic azithromycin for the treatment of diabetic foot infections.

Overall, although several antibiotics were dosed appropriately, a significant proportion exhibited underdosing, overdosing, or incorrect drug/route selection. These findings highlight the need for stricter adherence to standard DFI antibiotic guidelines and emphasize the importance of antimicrobial stewardship to optimize therapeutic outcomes.

Table 8:Gyssens Classification of Antibiotic Use in Diabetic Foot Infection Patients