Andrew William, Yan Efrata Sembiring, Agung Dwi Wahyu Widodo, Hermina Novida

Analysis of Risk Factors for Antimicrobial Resistance in Bacterial Infections among Diabetic Foot Ulcer Patients

Introduction

Analysis of risk factors for antimicrobial resistance in bacterial infections among diabetic foot ulcer patients. Explore risk factors for antimicrobial resistance in diabetic foot ulcer patients. This study links Wagner grades to bacterial pathogen profiles & antibiotic susceptibility, guiding empirical antibiotic selection.

Abstract

Introduction: Diabetic foot ulcer (DFU) is a chronic and progressive complication of diabetes mellitus resulting from macroangiopathy and microangiopathy disorders. Acknowledging the relationship between the Wagner diabetic foot ulcer classification system and infection severity may offer a promising instrument for guiding empirical antibiotic selections in clinical settings. This study aimed to assess the relationship between Wagner grades and the pathogen profiles of patients with DFU, along with their susceptibility to antibiotic therapy.Methods: A cross-sectional study was conducted from January 2021 to August 2023, utilizing 33 secondary datasets obtained from electronic medical records. The data contained the patients' Wagner grades alongside the results of their complete microbiological analysis and antibiotic susceptibility test. The association between determinant factors and patients' pathogen profiles and antibiotic susceptibility patterns was examined using the Chi-square bivariate analysis (p<0.05).Results: Positive culture results were observed in 32 patients (97%), with 59% exhibiting resistance to first-line antibiotics. The most commonly isolated pathogen was Staphylococcus aureus. The antibiotic susceptibility patterns indicated that gentamicin-syn demonstrated the highest activity against Gram-positive bacteria (GPB) isolates, while erythromycin was the most effective against Gram-negative bacteria (GNB) isolates. With escalating Wagner grades, there was an increased proportion of mixed infections, GNB infections (n=8, X²=23.28, p=0.003), and antibiotic resistance (n=8, X²=39.97, p=0.000). GNB isolates showed higher resistance compared to GPB isolates (n=18, X²=42.15, p=0.001).Conclusion: Our findings suggest that DFU patients with varying Wagner grades exhibit different bacterial profiles, infection patterns, and antibiotic sensitivities. Highlights:1. This is the first study conducted in Indonesia to analyze the relationship between the Wagner diabetic foot ulcer classification system and patients' pathogen profiles and antimicrobial susceptibility.2. This study incorporated an in-depth analysis of several infection patterns and the occurrence of antimicrobial resistance, hence offering valuable information on the application of the Wagner classification system not only as a tool for grading infection severity but also for guiding clinicians in selecting the appropriate antibiotics for patients with diabetic foot ulcers.

Review

This study addresses a critically important clinical challenge in diabetic foot ulcer (DFU) management: the escalating burden of antimicrobial resistance (AMR) and the necessity for informed empirical antibiotic selection. By investigating the relationship between the Wagner classification system, pathogen profiles, and antibiotic susceptibility, the authors aim to provide valuable insights for guiding treatment decisions. The stated novelty as the first such study conducted in Indonesia is noteworthy, highlighting its potential local significance in a region where DFU and AMR represent considerable public health concerns. The premise of using Wagner grades to refine antibiotic choices offers a promising approach to optimizing patient outcomes. Utilizing a cross-sectional design and secondary data from 33 electronic medical records, the study identified positive cultures in an overwhelming 97% of patients, with a concerning 59% exhibiting resistance to first-line antibiotics. *Staphylococcus aureus* was identified as the predominant isolate. A key finding was the significant association between escalating Wagner grades and an increased proportion of mixed infections, Gram-negative bacterial (GNB) infections, and overall antibiotic resistance. Specifically, GNB isolates demonstrated greater resistance compared to Gram-positive bacteria (GPB). The study also indicated gentamicin-syn as having the highest *in vitro* activity against GPB and erythromycin against GNB within the tested panel. While the study offers initial valuable data and a foundational step for local research in Indonesia, several limitations temper the interpretation of its findings. The small sample size (N=33, with some sub-analyses on even smaller cohorts of N=8 or N=18) significantly constrains the generalizability and statistical power, warranting caution in drawing definitive conclusions from the reported p-values. The cross-sectional design precludes establishing causal relationships or observing changes in resistance patterns over time. Additionally, the finding that erythromycin was the most effective against GNB is unusual and warrants further investigation or clarification, as it is not typically a broad-spectrum agent against many common GNB pathogens implicated in DFU. Despite these limitations, the study successfully highlights the evolving bacterial profiles and increasing resistance with higher DFU severity, underscoring the urgent need for larger, prospective, and multi-center studies to validate these relationships and inform more comprehensive, evidence-based guidelines for empirical antibiotic therapy in DFU patients.

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