Abstract
Multidrug‐resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta‐analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%–59.78%). The prevalence of MDR gram‐positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%–25.91%), and the prevalence of MDR gram‐negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%–39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%–15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%–5.07%)) were the main MDR‐GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR‐GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%–8.95%), 6.01% (95% CI: 4.03%–8.33%), 3.59% (95% CI: 0.42%–9.30%), 3.50% (95% CI: 2.31%–4.91%), and 3.27% (95% CI: 1.74%–5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non‐MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non‐MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR‐GNB was greater than that of MDR‐GPB in DFUs. MDR S. aureus was the main MDR‐GPB in DFUs, and MDR E. coli was the main MDR‐GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.
Keywords: diabetic foot ulcers, MDR bacteria, prevalence, risk factors
1. INTRODUCTION
Diabetic foot ulcers (DFUs) are serious complications in patients with diabetes mellitus (DM). The global prevalence of DM is increasing. The number of people with DM aged 20–79 years is predicted to increase to 642 million (uncertainty interval: 521–829 million) by 2040. 1 An increase in the incidence of DM is accompanied by an increase in the incidence of DFUs. A global meta‐analysis reported that DFUs are prevalent in 6.3% of the population. 2 Diabetic foot infections (DFIs), which include paronychia, cellulitis, myositis, abscesses, necrotizing fasciitis, septic arthritis, tendonitis, and osteomyelitis, are defined clinically as any soft tissue or bone infection below the malleoli. 3 DFIs are common in patients with DFUs, and they are associated with considerable morbidity, a high mortality rate and an increased risk of lower extremity amputation. Almost half of all DFUs are clinically infected at the time of physician visits. 3
DFIs often contribute to multidrug‐resistant (MDR) bacteria. MDR bacterial infections are defined as acquired nonsusceptibility to at least one agent in three or more antimicrobial categories. 4 Infections caused by MDR bacteria are increasingly common and represent a serious problem for public health, which has resulted in an increase in morbidity, mortality, healthcare expenditure, and antibiotic use. 5 , 6 Additionally, MDR bacterial infections in DFUs are associated with an increase in the length of hospital stay, cost of treatment, mortality rate and risk of lower extremity amputation. 7 , 8
DFUs are characterized by a schema ulcer, empirical antibiotic treatment, osteomyelitis and previous hospitalization, which contribute to MDR bacterial infections. 9 , 10 In recent years, the prevalence of MDR bacterial infections has increased, especially in DFUs. Knowledge of the prevalence of MDR bacterial infections in DFUs will therefore be important in mitigating the spread of resistant pathogens. However, most studies evaluating the prevalence of MDR bacterial infections were carried out in specific areas within a certain period and varied considerably in study design or population demographics. Thus, a comprehensive evaluation and update of the prevalence of MDR bacterial infections in DFUs worldwide is critical.
We conducted a meta‐analysis of all available studies to calculate the current prevalence of MDR bacterial infections and to further analyse the risk factors for MDR bacterial infection in patients with DFUs, which should contribute to the development of a treatment and management strategy for DFUs, improve patient quality of life, and reduce the economic burden.
2. MATERIALS AND METHODS
This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, 11 and a PRISMA checklist was completed (see Data S1).
2.1. Search strategies
The literature search was performed through electronic databases, including the PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases. The papers published as of 28 November 2023 were extracted. Using Medical Subject Headings (MeSH) terms, the terms “Diabetic foot” and “Drug Resistance, Multiple” were searched. The keywords used for the search were as follows: “Foot, Diabetic” OR “Diabetic Feet” OR “Feet, Diabetic” OR “Foot Ulcer, Diabetic” OR “Multiple Drug Resistance” OR “Resistance, Multiple Drug” OR “Multidrug Resistance” OR “Multi‐Drug Resistance” OR “Multidrug resistant bacteria” OR “Multidrug resistant organisms” OR “Multidrug resistant organism” OR “Multidrug resistant microorganisms” OR “Multidrug resistant microorganism” OR “Drug Resistant Infection.” There were no limitations on the date or type of study.
2.2. Study selection criteria
The selection criteria were as follows: (1) the study was observational (prospective/retrospective cohort study or cross‐sectional study); (2) all patients in the study were diagnosed with DFUs; (3) specimens with swabs or biopsies from patients with DFUs were obtained for microbiological culture; (4) MDR bacteria were defined as having acquired nonsusceptibility to at least one agent in three or more antimicrobial categories or as an isolate showing resistance to antibiotics belonging to three or more classes 4 ; (5) MDR bacteria prevalence data were presented in full; and (6) the study was published in English. The exclusion criteria were as follows: (1) the study had incomplete data or no data for analysis; (2) the study was published as a nonoriginal article, such as a review, case report, letter, or comment; and (3) the authors of the study whose information was unavailable had to be contacted for detailed data. All eligible studies were fully evaluated to ensure that they met the inclusion criteria and provided sufficient data for meta‐analysis. The title, abstract, and full‐text screening were performed independently by the authors (Yang Shaoling and Meng Guangzhe), with discrepancies resolved by consensus.
2.3. Data extraction and critical appraisal
The following information was extracted from the eligible studies: study design, study time, study period, geographic location, number of patients cultured, total number of microorganisms isolated, and number of MDR bacteria in the DFUs. The following clinical data were also extracted from the eligible studies: sex, peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner grade, previous hospitalization, and previous use of antibacterial drugs. The corresponding authors of the included studies were contacted to acquire the relevant information when necessary.
2.4. Quality assessment
The quality of each study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. 12 The studies were classified as low (quality score <50%), moderate (quality score ≥50% to <70%), high (≥70% to <90%), or excellent (quality score ≥90%). (See Data S2).
2.5. Data synthesis and statistical analysis
The prevalence of MDR bacteria in patients with DFUs was analysed using Stata version 17.0. Heterogeneity across the included studies was analysed using the I 2 statistic. A random‐effects model or fixed‐effects model was used to analyse the data according to the heterogeneity between the studies. A forest plot was used to visually evaluate the prevalence estimates and corresponding 95% confidence intervals (CIs) across the studies. The probability of publication bias was measured using a funnel plot, Begg's test, and Egger's test. p < 0.05 was considered to indicate statistical significance. Categorical data are represented by the number of cases, and grade data are represented by the number of cases and percentages. The chi‐square test was used for comparisons of categorical variables between the MDR bacterial group and the non‐MDR bacterial group. SPSS 26 software was used for chi‐square test‐based statistical analysis. p < 0.05 was considered to indicate statistical significance.
3. RESULTS
3.1. Search results
A total of 1707 articles were identified from the initial search. After the removal of duplicates, 1201 articles remained. Of these, 1124 articles were excluded after reading the titles and abstracts. We scrutinized the full texts of the remaining 77 articles for eligibility, 21 of which were included. The study selection process is shown in Figure 1.
FIGURE 1.
Flow diagram of the document search and selection.
3.2. Characteristics of the included articles
The main characteristics of the selected studies are summarized in Table 1. The 21 included studies were published between 2014 and 2023, while the period of participant inclusion was from January 2010 to January 2023. According to the regional locations of the included studies, 15 were conducted in Asia, 5 were conducted in Africa, and 1 was conducted in Europe. There were no available studies from America or Oceania. The obvious differences among the eligible studies from Asia, Europe, America, and Oceania were associated with the study selection criteria of the MDR bacteria definition.
TABLE 1.
The main characteristics of the selected studies.
| Study | Study design | Study date | Country | Cases | MDR‐GPB | MDR S.aureus | MDR Enterococcus spp | MDR‐ GNB | MDR E. coli | MDR P. aeruginosa | MDR K. pneumoniae | MDR Enterobacter spp | MDR P. mirabilis | MDR bacteria | Total bacteria |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ji et al. 2014 13 | ① | 2011.01–2012.01 | China | 118 | 41 | 13 | 7 | 37 | 4 | 12 | ― | 13 | 6 | 78 | 146 |
| Shahi et al. 2016 14 | ① | 2010.01–2011.10 | India | 116 | ― | ― | ― | ― | ― | ― | ― | ― | ― | 38 | 142 |
| Miyan et al. 2017 15 | ① | 2013.01–2014.03 | Pakistan | 342 | 42 | 38 | ― | 188 | 51 | ― | 35 | 2 | 15 | 230 | 687 |
| Saltoglu et al. 2018 16 | ① | 2011.05–2015.12 | Turkey | 791 | 33 | 33 | ― | 53 | 27 | 21 | 5 | ― | ― | 86 | 469 |
| Wu et al. 2018 17 | ① | 2014.01–2017.06 | China | 428 | ― | ― | ― | ― | ― | ― | ― | ― | ― | 182 | 488 |
| Pessoa et al. 2020 18 | ① | 2018.01–2018.12 | Portugal | 96 | ― | ― | ― | ― | 3 | 4 | 4 | ― | ― | 25 | 112 |
| Sannathimmappa et al. 2021 19 | ① | 2013.01–2018.12 | Oman | 74 | 26 | ― | ― | 62 | ― | ― | ― | ― | ― | 88 | 233 |
| Ma et al. 2021 20 | ① | 2015.07–2018.12 | China | 199 | 66 | 30 | ― | 49 | 9 | ― | 10 | ― | ― | 115 | 212 |
| Mashaly et al. 2021 21 | ① | 2016.05–2017.04 | Egypt | 104 | 36 | ― | ― | 42 | ― | ― | ― | ― | ― | 78 | 82 |
| Adeyemo et al. 2021 8 | ① | 2016.07–2017.04 | Nigeria | 90 | 33 | 18 | 11 | 88 | 16 | 10 | ― | 9 | 6 | 121 | 188 |
| Ismail et al. 2021 22 | ② | 2019.12–2020.05 | Egypt | 120 | 12 | ― | ― | 54 | 4 | ― | ― | 8 | ― | 66 | 124 |
| Li et al. 2022 23 | ③ | 2013.10–2020.12 | China | 101 | 11 | ― | ― | 24 | ― | ― | ― | ― | ― | 35 | 118 |
| Ma et al. 2022 24 | ② | 2018.01–2020.01 | China | 242 | 64 | 30 | 2 | 88 | ― | ― | ― | ― | ― | 152 | 251 |
| Yan et al. 2022 25 | ③ | 2018.06–2019.12 | China | 180 | 38 | 32 | 6 | 66 | 28 | 26 | ― | ― | ― | 104 | 182 |
| Liu et al. 2022 26 | ② | 2020.05–2021.11 | China | 348 | 88 | 21 | 18 | 152 | 20 | 12 | 16 | ― | ― | 240 | 475 |
| Atlaw et al. 2022 27 | ① | 2020.11–2021.05 | Ethiopia | 130 | 35 | 28 | 4 | 83 | 21 | ― | 10 | ― | 4 | 118 | 127 |
| Shi et al. 2023 28 | ③ | 2018.01–2021.03 | China | 89 | ― | ― | ― | ― | ― | ― | ― | ― | ― | 79 | 148 |
| Guo et al. 2023 29 | ② | 2018.01–2021.09 | China | 147 | 35 | 33 | ― | 36 | 16 | 13 | 5 | ― | ― | 71 | 154 |
| Liu et al. 2023 30 | ③ | 2018.01–2021.12 | China | 581 | ― | ― | ― | ― | ― | ― | ― | ― | ― | 271 | 635 |
| Dawaiwala et al. 2023 31 | ② | 2019.10–2020.09 | Indian | 84 | 25 | 21 | ― | 27 | 9 | 8 | 4 | ― | 1 | 52 | 110 |
| Chen et al. 2023 32 | ③ | 2020.02–2023.01 | China | 505 | 172 | 75 | ― | 232 | 41 | 25 | 13 | ― | 33 | 404 | 509 |
Abbreviations: ―, No data; ①, Cross sectional study; ②, Prospective observational study; ③, Retrospectively observational study; E. coli, Escherichia coli; GNB, gram‐negative bacteria; GPB, gram‐positive bacteria; K. pneumoniae, Klebsiella pneumoniae; MDR, multidrug‐resistant; P. aeruginosa, Pseudomonas aeruginosa; P. mirabilis, Proteus mirabilis; S. aureus, Staphylococcus aureus.
The definition of MDR bacteria in our study was based on an international expert proposal for interim standard definitions for MDR bacteria in 2012. 4 The total bacteria in our study were referred to as aerobic bacteria, excluding fungi and anaerobic bacteria.
3.3. Prevalence of MDR bacteria in DFUs
Since there was heterogeneity among the 21 included studies (I 2 = 97.78%; p = 0.00), a random‐effects model analysis was conducted to combine the studies and the joint prevalence estimation. The forest plot showed that the total prevalence of MDR bacteria in DFUs was 50.86% (95% CI: 41.92%–59.78%) (Figure 2). We investigated the potential for publication bias using funnel plots, Egger's test, and Begg's test. The funnel plot was symmetrical (Figure 3), and most studies were within the 95% confidence interval. Begg's test (p = 0.786) and Egger's test (p = 0.269) revealed no publication bias (Table 2).
FIGURE 2.
Forest plot of the prevalence of MDR bacteria in DFUs.
FIGURE 3.
Funnel plot of the prevalence of MDR bacteria in DFUs.
TABLE 2.
Statistical analysis of the selected studies.
| Type of MDR bacteria | Number of Studies | Heterogeneity test | Effects model | Meta results | Publication bias | |||
|---|---|---|---|---|---|---|---|---|
| I 2 (%) | p‐Value | Detection rate (%) | 95% CI | Begg's test (p‐Value) | Egger's test (p‐Value) | |||
| MDR bacteria | 21 | 97.78 | 0.00 | Random | 50.86 | 41.92–59.78 | 0.786 | 0.269 |
| MDR‐GPB | 16 | 95.24 | 0.00 | Random | 19.81 | 14.35–25.91 | 0.392 | 0.180 |
| MDR S. aureus | 12 | 89.99 | 0.00 | Random | 12.13 | 8.79–15.91 | 0.064 | 0.011 |
| MDR Enterococcus spp. | 6 | 57.90 | 0.04 | Random | 3.33 | 1.92–5.07 | 0.807 | 0.851 |
| MDR‐GNB | 16 | 94.97 | 0.00 | Random | 32.84 | 26.40–39.62 | 0.444 | 0.352 |
| MDR E. coli | 13 | 77.28 | 0.00 | Random | 6.93 | 5.15–8.95 | 1.000 | 0.586 |
| MDR P. aeruginosa | 9 | 76.90 | 0.00 | Random | 6.01 | 4.03–8.33 | 0.348 | 0.132 |
| MDR Enterobacter spp. | 4 | 93.01 | 0.00 | Random | 3.59 | 0.42–9.30 | 0.089 | 0.044 |
| MDR K. pneumoniae | 9 | 67.25 | 0.00 | Random | 3.50 | 2.31–4.91 | 0.466 | 0.548 |
| MDR P. mirabilis | 6 | 70.21 | 0.00 | Random | 3.27 | 1.74–5.21 | 1.000 | 0.736 |
Abbreviations: E. coli, Escherichia coli; GNB, gram‐negative bacteria; GPB, gram‐positive bacteria; K. pneumoniae, Klebsiella pneumoniae; MDR, multidrug‐resistant; P. aeruginosa, Pseudomonas aeruginosa; P. mirabilis, Proteus mirabilis; S. aureus, Staphylococcus aureus.
3.4. Prevalence of MDR gram‐positive bacteria (GPB) in DFUs
Among all included studies, 16 reported the prevalence of MDR‐GPB and MDR gram‐negative bacteria (GNB) in DFUs. Considering the heterogeneity (I 2 = 95.24%; p = 0.00), a random‐effects model analysis was used to explore the joint prevalence estimation of MDR‐GPB. The forest plot showed that the total prevalence of MDR‐GPB in DFUs was 19.81% (95% CI: 14.35%–25.91%) (Figure 4). The funnel plot was symmetrical (Figure 5), and Begg's test (p = 0.392) and Egger's test (p = 0.180) did not show publication bias in the included studies (Table 2).
FIGURE 4.
Forest plot of the prevalence of MDR‐GPB in DFUs.
FIGURE 5.
Funnel plot of the prevalence of MDR‐GPB in DFUs.
3.4.1. Prevalence of MDR Staphylococcus aureus (S. aureus) in DFUs
Among all included studies, 12 reported the prevalence of MDR S. aureus in DFUs. A random‐effects model analysis was used to explore the joint prevalence of MDR S. aureus because there was heterogeneity (I 2 = 89.99%; p = 0.00). The total prevalence of MDR S. aureus in DFUs was 12.13% (95% CI: 8.79%–15.91%). The Begg's test (p = 0.064) and Egger's test (p = 0.011) showed publication bias in the included studies (Table 2), which may have been due to the inclusion of different articles with different study designs, study populations, study periods, and study areas.
3.4.2. Prevalence of MDR Enterococcus spp. in DFUs
A total of six studies reported the prevalence of MDR Enterococcus spp. in DFUs among all included studies. A random‐effects model analysis was used to explore the joint prevalence of MDR Enterococcus spp. due to heterogeneity (I 2 = 57.90%; p = 0.04). As a result, the total prevalence of MDR Enterococcus spp. in DFUs was 3.33% (95% CI: 1.92%–5.07%). There was no publication bias based on Begg's test (p = 0.851) or Egger's test (p = 0.807) (Table 2).
3.5. Prevalence of gram‐negative bacteria (GNB) in DFUs
Among all included studies, 16 reported the prevalence of MDR‐GNB in DFUs. Regarding heterogeneity (I 2 = 94.97%; p = 0.00), the total prevalence of MDR‐GNB in DFUs was 32.84% (95% CI: 26.40%–39.62%) (Figure 6). The funnel plot was symmetrical (Figure 7), and Begg's test (p = 0.444) and Egger's test (p = 0.352) showed no publication bias in the included studies (Table 2).
FIGURE 6.
Forest plot of the prevalence of MDR‐GNB in DFUs.
FIGURE 7.
Funnel plot of the prevalence of MDR‐GNB in DFUs.
3.5.1. Prevalence of MDR Escherichia coli (E. coli) in DFUs
Among all included studies, 13 reported the prevalence of MDR E. coli in DFUs. Given the heterogeneity (I 2 = 77.28%; p = 0.00), a random‐effects model was used to investigate the prevalence of MDR E. coli in DFUs. The overall prevalence of MDR E. coli in DFUs was 6.93% (95% CI: 5.15%–8.95%) based on the random‐effects model. The results of Begg's test (p = 1.000) and Egger's test (p = 0.586) showed that there was no significant difference (Table 2). Thus, there was no indication of publication bias.
3.5.2. Prevalence of MDR Pseudomonas aeruginosa (P. aeruginosa) in DFUs
Nine studies reported the prevalence of MDR P. aeruginosa in DFUs among all included studies. Based on the heterogeneity of the studies (I 2 = 76.90%; p = 0.00), a random‐effects model was used to evaluate the prevalence of MDR P. aeruginosa in DFUs. The total prevalence of MDR P. aeruginosa in DFUs was 6.01% (95% CI: 4.03%–8.33%). Begg's test (p = 0.348) and Egger's test (p = 0.132) showed no publication bias (Table 2).
3.5.3. Prevalence of MDR Enterobacter spp. in DFUs
Among all included studies, four reported the prevalence of MDR Enterobacter spp. in DFUs. Significant heterogeneity among studies was observed (I 2 = 93.201%; p = 0.00). The overall prevalence of MDR Enterobacter spp. in DFUs was 3.59% (95% CI: 0.42%–9.30%) according to the random‐effects model. Publication bias was assessed by Begg's test (p = 0.089) and Egger's test (p = 0.044), which revealed publication bias (Table 2).
3.5.4. Prevalence of MDR Klebsiella pneumoniae (K. pneumoniae) in DFUs
Among all included studies, a total of nine reported the prevalence of MDR K. pneumoniae in DFUs. The heterogeneity test of the seven included studies revealed heterogeneity (I 2 = 67.25%; p = 0.00). The overall prevalence of MDR K. pneumoniae in DFUs was 3.50% (95% CI: 2.31%–4.91%) based on the random‐effects model. The publication bias in these studies was evaluated by Begg's test (p = 0.466) and Egger's test (p = 0.548), which revealed no publication bias (Table 2).
3.5.5. Prevalence of MDR Proteus mirabilis (P. mirabilis) mirabilis in DFUs
Among all included studies, six reported the prevalence of MDR P. mirabilis in DFUs. The heterogeneity test of the seven included studies revealed heterogeneity (I 2 = 70.21%; p = 0.00). The overall prevalence of MDR P. mirabilis in DFUs was 3.27% (95% CI: 1.74%–5.21%) after applying the random‐effects model. Publication bias was assessed by Begg's test (p = 1.000) and Egger's test (p = 0.736), which showed no publication bias (Table 2).
3.6. Analysis of the risk factors for MDR bacterial infection in patients with DFUs
Furthermore, we analysed several risk factors for MDR bacterial infection in patients with DFUs (Table 3). The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non‐MDR bacteria in eight included studies 8 , 13 , 18 , 19 , 20 , 25 , 26 , 29 were integrated and analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non‐MDR bacterial group (p < 0.05).
TABLE 3.
Comparison of clinical variables of diabetic foot ulcer patients infected with MDR bacteria and Non‐MDR bacteria.
| Variables | MDR bacteria group | Non‐MDR bacteria group | χ2 | p‐Value |
|---|---|---|---|---|
| Gender (n = 1048) | 0.009 | 0.924 | ||
| Male | 388 | 299 | ||
| Female | 205 | 156 | ||
| Peripheral vascular disease (n = 616) | 21.424 | 0.000 | ||
| Yes | 229 | 161 | ||
| No | 89 | 137 | ||
| Peripheral neuropathy (n = 504) | 7.833 | 0.005 | ||
| Yes | 197 | 116 | ||
| No | 96 | 95 | ||
| Nephropathy (n = 1072) | 6.446 | 0.011 | ||
| Yes | 252 | 200 | ||
| No | 297 | 323 | ||
| Osteomyelitis (n = 833) | 27.232 | 0.000 | ||
| Yes | 260 | 138 | ||
| No | 206 | 229 | ||
| Wagner's grade (3 + 4 + 5) (n = 504) | 9.11 | 0.003 | ||
| Yes | 201 | 117 | ||
| No | 92 | 94 | ||
| Previous hospitalization (n = 668) | 38.526 | 0.000 | ||
| Yes | 199 | 95 | ||
| No | 163 | 211 | ||
| Previous use of antibacterial drugs (n = 1042) | 51.039 | 0.000 | ||
| Yes | 449 | 298 | ||
| No | 105 | 190 |
Abbreviation: MDR, multidrug‐resistant.
4. DISCUSSION
DFIs are common in patients with DFUs and are the most common cause of nontraumatic amputation, hospitalization, and a reduction in quality of life among patients with DFUs. MDR bacterial infections have increased in recent years due to the increased prevalence of DFUs. At present, most studies evaluating the prevalence of MDR bacterial infections in DFUs have been carried out in specific areas within a certain period and have varied considerably in study design or population demographics. The purpose of this meta‐analysis was to explore the prevalence of MDR bacterial infections in DFUs. The information provided in this meta‐analysis may contribute to improving public health interventions and therefore contribute to the treatment and management of MDR bacterial infections in DFUs.
Twenty‐one studies that included a total of 4885 participants were included in this study. This meta‐analysis summarized the available evidence on the global prevalence of MDR bacterial infections in DFUs. There were several key findings. (1) The prevalence of MDR bacteria in DFUs was 50.86% (95% CI: 41.92%–59.78%). (2) The prevalence of MDR‐GPB in DFUs was 19.81% (95% CI: 14.35%–25.91%), and the prevalence of MDR‐GNB in DFUs was 32.84% (95% CI: 26.40%–39.62%). The prevalence of MDR‐GNB was greater than that of MDR‐GPB in DFUs. (3) MDR S. aureus and MDR Enterococcus spp. were the main MDR‐GPB strains in DFUs. The pooled prevalence of MDR S. aureus in DFUs was 12.13% (95% CI: 8.79%–15.91%). The prevalence of MDR Enterococcus spp. in DFUs was 3.33% (95% CI: 1.92%–5.07%). MDR S. aureus was the main MDR‐GPB in DFUs. (4) MDR E. coli, MDR P. aeruginosa, MDR Enterobacter spp., MDR K. pneumoniae and MDR P. mirabilis were the main MDR‐GNBs in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%–8.95%), 6.01% (95% CI: 4.03%–8.33%), 3.59% (95% CI: 0.42%–9.30%), 3.50% (95% CI: 2.31%–4.91%) and 3.27% (95% CI: 1.74%–5.21%), respectively. MDR E. coli was the main MDR‐GNB in DFUs.
MDR bacteria were defined as those that were resistant to more than one antimicrobial agent. One of the methods used by various authors and authorities to characterize organisms as MDR is based on in vitro antimicrobial susceptibility test results when they test ‘resistant to multiple antimicrobial agents, classes or subclasses of antimicrobial agents.’ 4 , 33 Another method defines bacteria as MDR when they are ‘resistant to one key antimicrobial agent’. 34 Many different definitions for MDR bacteria used in the medical literature result in unreliable comparisons of surveillance data for MDR bacterial infections and unreliable assessments of their global, regional and local epidemiological and public health characteristics. Therefore, the MDR bacteria identified in our study that adopted standardized international terminology were defined as having acquired nonsusceptibility to at least one agent in three or more antimicrobial categories or as having acquired resistance to antibiotics belonging to three or more classes.
MDR bacterial infections have become important in recent years and have increased in prevalence in DFUs. However, the prevalence of MDR bacterial infections varies by area, study design and population demographics. Gadepalli et al. reported that 72% of patients were positive for multidrug‐resistant organisms. 35 Noor et al. reported that 57% of patients were positive for MDR organisms. 36 Zubair et al. reported that 45% of patients were positive for MDR organisms. 37 The highest prevalence of MDR bacterial infections has been observed in DFUs. However, the prevalence of MDR bacterial infections in these studies was expressed in terms of the infection rate of positive patients, which does not show the detection rate of MDR bacteria or the distribution of MDR strains among the total detected strains. Our study was a meta‐analysis of all available studies to calculate the current prevalence of MDR bacterial infections in DFUs by the detection rate of MDR bacteria, which better assesses their global epidemiology. Our results showed that the pooled prevalence of MDR bacteria in DFUs was 50.86% (95% CI: 41.92%–59.78%).
DFIs are considered polymicrobial, especially infections that are chronic or have been previously treated with antimicrobials, including those with GPB and GNB. 3 , 38 Recent studies have shown that GNB are more common in DFUs. Rastogi et al. reported that the majority of isolated bacterial species were gram‐negative organisms (79.9% of specimens) among 317 causative organisms. 39 Li et al. reported that 551 species were isolated from all specimens, including 57.5% GNP and 39.6% GPB, by a multicentre surveillance programme conducted in eight hospitals in Beijing from 2010 to 2014. 40 Goh et al. carried out a prospective analysis from 2016 to 2018, and the results showed that a greater percentage of gram‐negative pathogens (54%) were identified than gram‐positive pathogens (33%). 41 Jouhar et al. conducted a retrospective observational study among patients with DFIs admitted to the American University of Beirut Medical Centre from January 2008 to June 2017, and the results showed that aerobic gram‐negative rods were present in 55% and that gram‐positive cocci were present in 39% of infections. 42 Recently, Du et al. have conducted a meta‐analysis and showed that the prevalence of GPB (43.4%) was lower than that of GNB (52.4%). 43 Therefore, GNB has a high prevalence and plays an important role in DFUs. Our study revealed that the prevalence of MDR‐GPB in DFUs was 19.81% (95% CI: 14.35%–25.91%), and the prevalence of MDR‐GNB in DFUs was 32.84% (95% CI: 26.40%–39.62%). The prevalence of MDR‐GNB was greater than that of MDR‐GPB in DFUs.
Among GPB, S. aureus, Enterococcus, and Streptococcus are the most common bacteria in DFUs. Bouharkat et al. reported that among gram‐positive bacteria, the most commonly isolated species were S. aureus (25.97%), followed by coagulase‐negative Staphylococci (5.20%), Streptococcus sp. (3.89%), and Enterococcus faecalis (2.16%), among a total of 231 isolates. 44 Dörr et al. reported that the most common gram‐positive species were S. aureus (20.6%), Enterococci (9.4%), coagulase‐negative Staphylococci (8.4%), Streptococci (6.9%), and Corynebacteria (6.9%) among 888 isolates. 45 Shahrokh conducted a meta‐analysis and showed that the prevalence of S. aureus was 24.29%, followed by coagulase‐negative Staphylococci (14.80%), Enterococcus spp. (13.58%), and Streptococcus spp. (4.04%). 46 Our study also showed that S. aureus was the most common MDR‐GPB and the most commonly isolated MDR bacteria among the total isolates. The pooled prevalence of MDR S. aureus in DFUs was 12.13% (95% CI: 8.79%–15.91%), followed by that of Enterococcus spp. at 3.33% (95% CI: 1.92%–5.07%). Among all included studies, a total of three studies reported the prevalence of MDR Staphylococcus epidermidis and Streptococcus spp. Due to the inclusion of fewer studies, our study did not analyse these factors.
Among GNB, E. coli, K. pneumoniae, P. aeruginosa, and Acinetobacter baumannii are the most common bacteria in DFUs. Bouharkat et al. reported that among GNB, the most commonly isolated species was E. coli (19.91%), followed by P. aeruginosa (15.59%), A. baumannii (7.36%), and Klebsiella oxytoca (6.06%). 44 Dörr et al. reported that the most common GNB were P. aeruginosa (5.6%) and Enterobacteriaceae, such as Proteus spp. (5.6%), followed by Enterobacter spp. (4.6%), E. coli (4.2%), and Klebsiella spp. (3.7%). 45 The different prevalence rates among GNB may be due to the inclusion of different articles with different study designs, study populations, study periods, and study areas. Macdonald et al. conducted a meta‐analysis and showed that the most frequently isolated aerobic GNB were E. coli (11.5%), followed by Pseudomonas spp. (11.1%), Proteus spp. (8.3%), Klebsiella spp. (6.9%), and Enterococcus spp. (5.4%). 47 Our study showed that MDR E. coli, P. aeruginosa, K. pneumoniae, and P. mirabilis were the most common MDR‐GNB among the DFUs. The most frequently isolated MDR‐GNB was MDR E. coli (6.93%, 95% CI: 5.15%–8.95%), followed by MDR P. aeruginosa (6.01%, 95% CI: 4.03%–8.33%), MDR Enterobacter spp. (3.59%, 95% CI: 0.42%–9.30%), MDR K. pneumoniae (3.50%, 95% CI: 2.31%–4.91%), and MDR P. mirabilis (3.27%, 95% CI: 1.74%–5.21%). MDR E. coli was the main MDR‐GNB in DFUs.
Studies have suggested that peripheral vascular disease, osteomyelitis, previous hospitalization, and previous use of antibacterial drugs are associated with an increased risk of MDR infection. 9 , 25 , 48 In our study, peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non‐MDR bacterial group (p < 0.05). Our study indicated that these risk factors were associated with MDR bacterial infections in patients with DFUs. Therefore, diabetic foot patients with these risk factors for MDR bacteria should be closely monitored and given more attention during treatment, thus reducing the incidence of MDR bacterial infections in patients with DFUs.
This meta‐analysis highlighted a high prevalence of MDR bacterial infections in DFUs. Our findings suggest that the prevalence of MDR‐GNB is greater than that of MDR‐GPB in DFUs. S. aureus was the most common MDR‐GPB, and MDR E. coli was the most common MDR‐GNB in DFUs. Moreover, our study revealed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were associated with MDR bacterial infections in DFUs. Our findings can contribute to the treatment and management of MDR bacterial infections in DFUs. However, our study has limitations. Given the study selection criteria regarding the definition of MDR bacteria, there were no available studies from America or Oceania. In the future, more research is needed to improve the data on MDR bacteria in DFUs.
5. CONCLUSION
We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR‐GNB was greater than that of MDR‐GPB in DFUs. Among MDR‐GPB, S. aureus and Enterococcus spp. are the common MDR bacteria in DFUs. MDR S. aureus was the main MDR‐GPB. Among MDR‐GNB, MDR E. coli, MDR P. aeruginosa, MDR Enterobacter spp., MDR K. pneumoniae, and MDR P. mirabilis are the common MDR bacteria in DFUs. MDR E. coli was the main MDR‐GNB. Our results also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.
CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest to declare.
Supporting information
Data S1. Supporting Information.
Data S2. Supporting Information.
ACKNOWLEDGEMENTS
This study was supported by the incubation project of the Bethune International Peace Hospital and Health Commission of Hebei Province (Grant No. 20240696).
Yang S, Hu L, Zhao Y, Meng G, Xu S, Han R. Prevalence of multidrug‐resistant bacterial infections in diabetic foot ulcers: A meta‐analysis. Int Wound J. 2024;21(4):e14864. doi: 10.1111/iwj.14864
DATA AVAILABILITY STATEMENT
All data are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1. Supporting Information.
Data S2. Supporting Information.
Data Availability Statement
All data are available from the corresponding author upon reasonable request.