Multifaceted Antibiotic Resistance in Diabetic Foot Infections: A Systematic Review
Abstract
1. Introduction
2. Methods
2.1. Study Design
2.2. Search Strategy
2.3. Inclusion and Exclusion Criteria
- Studies published between January 2014 and June 2024.
- Studies that provided data on the microbiological profile of diabetic foot infections and reported antibiotic resistance patterns.
- Research conducted on human subjects diagnosed with DFIs, either in hospital or outpatient settings.
- Full-text studies that analyzed bacterial isolates from DFIs, particularly focusing on resistance to antibiotics such as amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, ciprofloxacin, and other commonly used antibiotics.
- Review or meta-analysis papers.
- Case reports, commentaries, and opinion pieces.
- Studies without available full-text or studies not reporting data relevant to antibiotic resistance in DFIs.
- Articles that did not provide conclusive data on DFI-related microbial resistance or clinical outcomes.
2.4. Data Extraction and Analysis
- Study characteristics: author(s), year of publication, country, study design, and sample size.
- Patient characteristics: age, sex, type of diabetes (Type 1 or Type 2), duration of diabetes, and comorbidities such as peripheral neuropathy, peripheral arterial disease, and renal impairment.
- Clinical factors: type of infection (e.g., diabetic foot ulcer, osteomyelitis), severity of the infection (e.g., depth, size of ulcer), and history of previous infections or treatments.
- Microbiological data: prevalence and type of bacterial isolates, including Staphylococcus aureus (MRSA and MSSA), Pseudomonas spp., Proteus spp., Escherichia coli, Enterobacter spp., and others.
- Antibiotic resistance data: rates of resistance to specific antibiotics such as amoxicillin/clavulanate, ciprofloxacin, vancomycin, carbapenems, cephalosporins, and aminoglycosides.
2.5. Quality Assessment and Risk of Bias Analysis
- The clarity of research questions and objectives.
- The appropriateness of study designs and sample sizes.
- The robustness of microbiological testing methods for identifying bacterial isolates and antibiotic resistance.
- The reporting of relevant clinical outcomes, including treatment success and recurrence rates.
- The risk of bias in individual studies was assessed using a modified version of the Cochrane risk of bias tool for non-randomized studies. This included 20 components which were specifically developed for this study under the subheadings: research question, selection criteria, participant characteristics, sample size, outcome, methods, and analysis of which is more relevant for DFIs and antibiotic resistance research conducted as observational prospective studies. The questions were first trialed on the excluded articles to assess the tool validity. Two investigators (P.B. and J.C.) conducted the quality assessment and any discrepancies were resolved by discussion. All 20 questions were equally weighted, and individual scores were calculated based on the proportion of “yes” answers. Studies that scored <50%, 50–75%, and >75% were deemed of high, moderate, and low risk of bias, respectively, based on a collective decision taken by the investigators in line with the ROBINS-E tool guidelines [11,12].
2.6. Statistical Analysis
2.7. Outcomes of Interest
- The impact of comorbidities (e.g., vascular disease, renal impairment) on antibiotic resistance patterns. Correlation analysis was performed using R.
- The relationship between prior antibiotic use, hospitalization, and the development of resistant infections.
- The identification of risk factors for multidrug-resistant organisms (MDROs) in DFIs.
3. Results
3.1. Analysis of Study Populations
3.2. Epidemiological Analysis of Pathogens Related to Comorbidity
3.3. Epidemiological Analysis of Pathogens Related to Antibiotic Resistance
3.4. Correlation Between Types of Comorbidities Found in DFI and Types of Antibiotic Resistance
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Search Source | Yield | Articles Included | References |
---|---|---|---|
ScienceDirect | 37 | 7 | [1,2,3,4,5,6,7] |
Pubmed | 20 | 9 | [8,13,14,15,16,17,18,19,20,21] |
EbscoHost | 63 | 7 | [22,23,24,25,26,27,28] |
Google Scholar | 1900 | 5 | [29,30,31,32,33] |
Microbe | High in Monoresistance | High in MDR | Key Observations & Clinical Implications |
---|---|---|---|
Staphylococcus aureus | Very high (~75) | High (~190) | Rapid transition from monoresistance to MDR. Empirical treatment options like β-lactams may fail unless susceptibility is confirmed. |
MRSA | Moderate (~15) | Low | Shows low MDR count here, possibly underreported or isolated to β-lactam resistance. Still clinically concerning due to treatment limitations. |
MSSA | Moderate (~15) | Low | Growing evidence that even methicillin-sensitive strains are developing additional resistances. |
Coagulase-negative Staphylococci | Present | High (~160) | Often dismissed as contaminants, but high MDR burden signals emerging pathogenic roles, especially in device-related infections. |
Streptococcus spp. | Present | High (~160) | High resistance burdens in both categories signal reduced efficacy of penicillin-class drugs in wound and soft tissue infections. |
Enterococcus spp. | Low | High (~160) | Not prominent in monoresistance but highly represented in MDR—concerning for vancomycin resistance and nosocomial infections. |
Corynebacterium spp. | Low | Very high (~280) | A striking MDR surge despite low monoresistance. Often under-recognized, but data suggest it may be a significant reservoir of resistance genes. |
Acinetobacter spp. | Moderate (~25) | Highest (~280) | Dominates MDR list despite modest monoresistance. Known for rapid resistance development and survival in healthcare settings. |
Pseudomonas spp. | Moderate (~35) | Moderate (~80) | Common culprit in chronic and biofilm-associated infections. Resistance mechanisms include efflux pumps and porin mutations. |
Morganella morganii | Low | Moderate (~90) | Rarely spotlighted, but its MDR profile is growing, suggesting need for surveillance in polymicrobial infections. |
Escherichia coli | Low | Moderate (~110) | Resistance likely due to ESBL or AmpC production. Empirical fluoroquinolone or cephalosporin use may be ineffective. |
Proteus, Klebsiella, Enterobacter spp. | Low to moderate | Low to moderate | These organisms can serve as reservoirs of plasmid-mediated resistance, with potential to evolve into extended-spectrum or carbapenem-resistant forms. |
Comorbidity | Antibiotic | Pearson’s r | p Value | Significance |
---|---|---|---|---|
Nephropathy | Penicillin | 0.956 | 0.0051 | Significant correlation |
Erythromycin | 0.952 | 0.0047 | Significant correlation | |
Clindamycin | 0.93 | 0.0032 | Significant correlation | |
Hypertension | Penicillin | 0.90 | 0.0010 | Significant correlation |
Erythromycin | 0.90 | 0.0037 | Significant correlation | |
Clindamycin | 0.88 | 0.0045 | Significant correlation | |
Dyslipidemia | Penicillin | 0.95 | 0.0136 | Significant correlation |
Erythromycin | 0.97 | 0.0051 | Significant correlation | |
Clindamycin | 0.99 | 0.0002 | Significant correlation |
Pathogen | Comorbidity | Associated Antibiotic Resistance | Strength of Correlation |
---|---|---|---|
S. aureus | Dyslipidemia | Clindamycin, Gentamicin, Vancomycin, Erythromycin, Penicillin | Very Strong |
Hypertension | Erythromycin | Strong | |
Pseudomonas spp. | Neuropathy | Cephalosporins, Tetracycline, Gentamicin, Quinolones, Carbapenems | Very Strong |
Smoking | Erythromycin, Piperacillin-tazobactam, Imipenem | Strong | |
PAD | Carbapenems, Gentamicin, Piperacillin-tazobactam | Moderate | |
Nephropathy | Carbapenems, Gentamicin, Piperacillin-tazobactam | Moderate | |
Hypertension | Carbapenems, Gentamicin, Erythromycin | Moderate | |
Enterococcus spp. | Smoking | Vancomycin, Tetracycline, Gentamicin | Strong |
Hypertension | Vancomycin, Tetracycline, Gentamicin | Strong | |
Nephropathy | Vancomycin, Tetracycline, Gentamicin | Moderate | |
PAD | Vancomycin, Tetracycline, Gentamicin | Moderate | |
E. coli | Smoking | Piperacillin-tazobactam, Imipenem, Cephalosporins, Quinolones, Penicillin, Gentamicin | Strong |
Nephropathy | Aminoglycosides, Carbapenems, Tetracycline, Gentamicin | Moderate | |
Amputation | Aminoglycosides, Carbapenems, Tetracycline, Gentamicin | Moderate | |
Hypertension | Penicillin, Tetracycline, Gentamicin | Moderate | |
Proteus spp. | Current Smoking | Erythromycin, Amoxicillin/clavulanate, Piperacillin-tazobactam, Imipenem, Cephalosporins, Quinolones, Penicillin, Gentamicin | Very Strong |
Previous Amputation | Gentamicin, Penicillin, Erythromycin, multiple others | Very Strong | |
Nephropathy | Aminoglycosides | Strong | |
Former Smoker | Tetracycline | Strong |
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Li, W.; Sadeh, O.; Chakraborty, J.; Yang, E.; Basu, P.; Kumar, P. Multifaceted Antibiotic Resistance in Diabetic Foot Infections: A Systematic Review. Microorganisms 2025, 13, 2311. https://doi.org/10.3390/microorganisms13102311
Li W, Sadeh O, Chakraborty J, Yang E, Basu P, Kumar P. Multifaceted Antibiotic Resistance in Diabetic Foot Infections: A Systematic Review. Microorganisms. 2025; 13(10):2311. https://doi.org/10.3390/microorganisms13102311
Chicago/Turabian StyleLi, Weiqi, Oren Sadeh, Jina Chakraborty, Emily Yang, Paramita Basu, and Priyank Kumar. 2025. "Multifaceted Antibiotic Resistance in Diabetic Foot Infections: A Systematic Review" Microorganisms 13, no. 10: 2311. https://doi.org/10.3390/microorganisms13102311
APA StyleLi, W., Sadeh, O., Chakraborty, J., Yang, E., Basu, P., & Kumar, P. (2025). Multifaceted Antibiotic Resistance in Diabetic Foot Infections: A Systematic Review. Microorganisms, 13(10), 2311. https://doi.org/10.3390/microorganisms13102311