Abstract
Diabetic foot infections (DFIs) are serious complications of diabetes mellitus, yet little is known about the bacterial profile and antibiotic resistance patterns among patients with diabetic foot ulcers in this region. This study aimed to assess the prevalence and antimicrobial resistance of DFIs in the main referral governmental hospitals in the northern West Bank, Palestine. This descriptive, retrospective cross-sectional study was conducted in the Vascular Surgery Department at Rafidia Surgical Hospital in Nablus, Palestine. The medical records of patients with DFIs in 2022 were reviewed, and the data were analysed via IBM SPSS for Windows v.21.0. Among the 118 patients, 58.5% were male, and 98.3% had type II diabetes mellitus. Gram-negative bacteria were more prevalent, accounting for 58.8% of the cases, whereas gram-positive bacteria accounted for 41.2%. Staphylococcus aureus (25.4%), Escherichia coli (14.0%), and Pseudomonas aeruginosa (11.4%) were the most frequently isolated pathogens. Extended-spectrum β-lactamase (ESBL)-producing strains were detected among E. coli and Klebsiella pneumoniae isolates, and carbapenemase-producing Enterobacterales (CPEs) were also identified. Among gram-positive bacteria, Staphylococcus aureus is methicillin-resistant, and Enterococcus species are vancomycin-resistant. Multidrug-resistant (MDR) isolates, as Acinetobacter baumannii, are present in both gram-positive and gram-negative groups. A longer infection duration and longer hospital stay were significantly associated with increased amputation risk (p = 0.044 and p < 0.001, respectively), highlighting the need of early intervention and targeted antibiotic therapy. This study revealed a high prevalence of multidrug-resistant pathogens among diabetic foot infections in northern Palestine, with Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa as the leading causative organisms. The notable presence of methicillin-resistant S. aureus and extended-spectrum β-lactamase-producing Enterobacterales underscores the urgent need for robust antimicrobial stewardship and regular local surveillance to guide empirical therapy. Early diagnosis, appropriate antibiotic selection, and timely intervention are crucial to improving clinical outcomes and reducing amputation risk in this vulnerable population.
Keywords: Diabetic foot infections, Antimicrobial resistance, Gram-negative bacteria, Methicillin-resistant Staphylococcus aureus, Extended-spectrum beta-lactamase, Multidrug resistance
Subject terms: Health care, Comorbidities, Infectious diseases
Introduction
Diabetes mellitus is a widespread noncommunicable disease affecting approximately 9.3% of the global population and more than 463 million individuals worldwide1. It is associated with numerous complications, including retinopathy, nephropathy, cardiovascular diseases, and foot injuries, which significantly affect patients’ quality of life2,3. Among these complications, diabetic foot ulcers (DFUs) pose a significant burden, leading to high morbidity and mortality rates4. The global prevalence of DFUs is approximately 6.3%, which is influenced by sociodemographic and self-care factors5,6. In Palestine, DFUs have been linked to sensory loss, smoking, neuropathy, and inadequate self-care, highlighting the need for better prevention and management7.
Diabetic foot infections (DFIs) are a leading cause of hospitalization and amputation in diabetic patients8. They are often polymicrobial, commonly involving Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus spp., along with anaerobes9. Diabetic foot osteomyelitis, a severe form of infection affecting up to 68% of hospitalized DFI patients, further complicates management and increases healthcare costs10,11. Risk factors include chronic ulcers, neuropathy, renal disease, and peripheral arterial disease12,13. Management requires microbiological assessment, targeted antibiotics, wound care, and sometimes surgery8,14. The rise of multidrug-resistant (MDR) organisms underscores the importance of antimicrobial stewardship15.
Globally, DFIs affect 18.6 million individuals annually, with ulceration preceding nearly 80% of amputations16. MDR pathogens such as Pseudomonas aeruginosa and ESBL-producing bacteria complicate therapy17. Regional studies, including those from Palestine, Egypt, Lebanon, and India, have shown variation in microbial profiles and resistance patterns18–21. Mortality risk factors include peripheral artery disease, polymicrobial infections, and high thrombocyte levels22–24.
With a five-year mortality rate exceeding 50%, primarily due to cardiovascular disease and infections, early intervention integrating infection control, ischemia management, and comorbidity treatment is crucial for reducing adverse outcomes25.
In low- and middle-income countries such as Palestine, the burden of diabetes mellitus and its complications is increasing, but data on DFI microbiology and resistance are limited. Understanding the local microbial landscape is essential for guiding empirical therapy and improving outcomes. This study aimed to assess the prevalence and antimicrobial resistance patterns of DFIs in patients admitted to referral hospitals in the northern West Bank, Palestine. The findings provide evidence to guide management strategies and inform antimicrobial stewardship in this resource-limited setting.
Methods
Study design and population
The study was conducted in a retrospective cross-sectional design at Rafidia Surgical Hospital, which is one of the main referral governmental hospitals north of the West Bank, Palestine. This study included diabetic patients admitted to Rafidia Surgical Hospital with foot infections. The medical records of patients admitted between January 2022 and December 2022 were reviewed.
Sample size and calculation
The inclusion criteria were adult patients (18 years or older) with a confirmed diagnosis of type 1 or type 2 diabetes mellitus and a clinically diagnosed foot infection. The exclusion criteria included patients with osteomyelitis, severe peripheral arterial disease, systemic infections unrelated to diabetic foot infections, or incomplete medical records. Patients who sought care at Rafidia Surgical Hospital and met the inclusion criteria were included. A total of 118 participants were recruited and included via a convenience sampling method.
Study tools and data collection
Data were collected from the medical records of the patients as well as microbiology laboratory reports. A data collection form was developed specifically for this study.
The collected data included the sociodemographic and clinical characteristics of the patients, including age, sex, marital status, education, occupation, place of residence, smoking status, weight, height, and monthly income. According to the Palestinian Central Bureau of Statistics, a monthly income of less than 3500 NIS was categorized as low, whereas an income of 3500 NIS or more was considered high26.
Clinical data, including the type of diabetes mellitus, antidiabetic medications, duration of diabetes mellitus, ulcer history (defined as the time elapsed between the onset of symptoms and hospital admission), previous hospitalizations, and prior use of antimicrobial agents, were also recorded. Data on prior antibiotic use within 90 days were collected; however, prior microbiological culture results were not consistently available in the medical records and were therefore not analysed. Comorbidities such as hypertension, coronary heart disease, stroke, peripheral arterial disease, chronic kidney disease, and hemodialysis were documented.
Finally, patient outcomes, including whether the ulcer healed or remained unhealed, whether amputation was performed, whether the patient survived or died, and the occurrence of diabetic complications such as nephropathy, retinopathy, peripheral arterial disease, and autonomic neuropathy, were recorded.
Microbiological identification, susceptibility testing, and resistance classification
The VITEK® 2 Compact automated microbiology system (bioMérieux, Marcy-I’Étoile, France) was employed for microorganism identification and antibiotic susceptibility testing. It has also been utilized for detecting extended-spectrum beta-lactamase (ESBL) producers and carbapenemase-producing Enterobacterales (CPEs). Methicillin resistance was assessed via the use of cefoxitin. Resistance rates were determined following the guidelines of the Clinical and Laboratory Standards Institute (CLSI). MDR was defined as acquired nonsusceptibility to at least one agent in three or more antimicrobial categories27.
Statistical analysis
Data were analyzed using IBM SPSS version 21.0 (IBM Corp., Armonk, NY, USA). The data were tested for normality of distribution via the Kolmogorov‒Smirnov or Shapiro‒Wilk test. Because the data were not normally distributed, as confirmed by the Kolmogorov–Smirnov and Shapiro–Wilk tests, nonparametric statistical analyses were applied. Continuous variables were summarized using medians and interquartile ranges (IQRs), and categorical variables were presented as frequencies and percentages. Comparisons between two independent groups (e.g., patients with and without major amputation) were performed using the Mann–Whitney U test for continuous variables and the Chi-square test or Fisher’s exact test for categorical variables, as appropriate. A p value of < 0.05 was considered statistically significant.
Ethical considerations
The study protocol was approved by the Institutional Review Board (IRB) of An-Najah National University [IRB Reference #: Mas. Feb,2023/19], and the necessary approval was obtained from the Ministry of Health and Rafidia Surgical Hospital. The research adhered to the principles of the Declaration of Helsinki. The participants were informed about the purpose of the study, and oral consent was obtained before their participation. Confidentiality and privacy were maintained throughout the study, with access to patient data restricted to the research team.
Results
Sociodemographic and clinical characteristics of the patients
Among the 118 patients, the study sample consisted primarily of male participants (58.5%), and the majority were married (73.7%). Over half of the participants were smokers (63.6%), and most had completed only school-level education (77.1%). The majority of the participants had a low income, earning less than 3500 NISs (82.2%). With respect to place of residence, half of the participants lived in villages (50.0%), whereas a smaller portion resided in cities (33.1%). A notable proportion of the participants were classified as obese (61.0%), and nearly 98.3% of them had type II diabetes mellitus. The most commonly used antidiabetic medication was insulin (62.7%), followed by sitagliptin (17.8%) and metformin (14.4%). Other details can be found in Table 1.
Table 1.
Sociodemographic and clinical characteristics of the patients.
| Characteristics | Categories |
N
N = 118 |
% |
|---|---|---|---|
| Sex | Male | 69 | 58.5 |
| Female | 49 | 41.5 | |
| Marital status | Single | 5 | 4.2 |
| Married | 87 | 73.7 | |
| Widowed | 26 | 22.0 | |
| Smoking status | No | 43 | 36.4 |
| Yes | 75 | 63.6 | |
| Educational level | School | 91 | 77.1 |
| University | 27 | 22.9 | |
| Income | < 3500 NIS | 97 | 82.2 |
| ≥ 3500 NIS | 21 | 17.8 | |
| Place of residence | Village | 59 | 50.0 |
| City | 39 | 33.1 | |
| Refugee camp | 20 | 16.9 | |
| Body mass index (BMI) | Normal weight (< 24.9 kg/m2) | 14 | 11.9 |
| Overweight (25–29.9 kg/m2) | 32 | 27.1 | |
| Obese (≥ 30 kg/m2) | 72 | 61.0 | |
| Diabetes type | Type I | 2 | 1.7 |
| Type II | 116 | 98.3 | |
| Antidiabetic medications | Insulin | 74 | 62.7 |
| Metformin | 17 | 14.4 | |
| Vildagliptin/Metformin | 5 | 4.2 | |
| Sitagliptin | 21 | 17.8 | |
| Glimepiride | 1 | 0.8 |
Clinical characteristics and laboratory test results of the participants
The most common reasons for hospitalization among the participants were heel pressure ulcers (44.9%) and infected toes (39.0%). Half of the patients had diabetic nephropathy (50.0%), 29.7% had retinopathy, and 11.0% had neuropathy. The most prevalent comorbidities were hypertension (65.3%) and hyperlipidemia (55.1%), with a significant number also having heart failure (22.9%) and respiratory disease (33.1%). Approximately half of the patients had been hospitalized in the last 90 days (47.5%), and a large majority had used antibiotics during this period (88.1%). Regarding lipid profiles, 43.2% had abnormal total cholesterol levels, and 47.5% had elevated triglycerides. Additionally, 89.8% of patients had an HbA1c level of 7% or higher, indicating poor glycemic control. These details are shown in Table 2.
Table 2.
Clinical characteristics and laboratory test results of the participants.
| Characteristics | Categories | n | % |
|---|---|---|---|
| Reason for hospitalization | Heel pressure ulcers | 53 | 44.9 |
| Infected toe | 46 | 39.0 | |
| Plantar abscess | 14 | 11.9 | |
| Amputated stump infection | 5 | 4.2 | |
| Diabetes complications | Nephropathy | 59 | 50.0 |
| Retinopathy | 35 | 29.7 | |
| Neuropathy | 13 | 11.0 | |
| Comorbidities and history of hospitalization | End-stage renal disease | 14 | 11.9 |
| Heart failure | 27 | 22.9 | |
| Hypertension | 77 | 65.3 | |
| Hyperlipidemia | 65 | 55.1 | |
| Chronic kidney disease | 12 | 10.2 | |
| Chronic liver disease | 5 | 4.2 | |
| Neurological disease | 19 | 16.1 | |
| Respiratory disease | 39 | 33.1 | |
| Malignancy | 22 | 18.6 | |
| History of hospitalization and use of antibiotics | Previous hospitalization in the last 90 days | 56 | 47.5 |
| Previous ICU admission in the last 90 days | 1 | 0.8 | |
| Use of antibiotics in the last 90 days | 104 | 88.1 | |
| Total cholesterol | Normal (< 200 mg/dL) | 67 | 56.8 |
| Abnormal (≥ 200 mg/dL) | 51 | 43.2 | |
| Triglyceride | Normal (< 150 mg/dL) | 62 | 52.5 |
| Abnormal (≥ 150 mg/dL) | 56 | 47.5 | |
| Low density lipoprotein cholesterol (LDL-C) | Normal (< 130 mg/dL) | 106 | 89.8 |
| Abnormal (≥ 130 mg/dL) | 12 | 10.2 | |
| High density lipoprotein cholesterol (HDL-C) | Normal (≥ 40 mg/dL) | 55 | 46.6 |
| Abnormal (< 40 mg/dL) | 63 | 53.4 | |
| HbA1c | Normal (< 7%) | 12 | 10.2 |
| Abnormal (≥ 7%) | 106 | 89.8 |
ICU: intensive care unit.
Frequency of isolated microorganisms
Table 3 shows the distribution of the isolated bacteria, where gram-negative bacteria were more predominant, accounting for 58.8% of the total isolates, and gram-positive bacteria accounted for 41.2% of the isolates. Among the gram-negative isolates, Escherichia coli was the most prevalent (14.0%), followed by Pseudomonas aeruginosa (11.4%) and Proteus mirabilis (8.8%). Among the gram-positive isolates, Staphylococcus aureus accounted for 25.4%, whereas coagulase-negative staphylococci and Enterococcus spp. accounted for 6.1% and 5.3%, respectively. Notably, 4.4% of the cultures showed no growth.
Table 3.
Frequencies of isolated microorganisms.
| Culture result | n | % |
|---|---|---|
| No growth | 4 | |
| Gram-positive bacteria | 47 | 41.2 |
| Staphylococcus aureus | 29 | 25.4 |
| Coagulase-negative staphylococci | 7 | 6.1 |
| Enterococcus spp. | 6 | 5.3 |
| Streptococcus agalactiae | 3 | 2.6 |
| Viridans streptococci | 1 | 0.9 |
| Bacillus spp. | 1 | 0.9 |
| Gram-negative bacteria | 67 | 58.8 |
| Escherichia coli | 16 | 14.0 |
| Pseudomonas aeruginosa | 13 | 11.4 |
| Proteus mirabilis | 10 | 8.8 |
| Klebsiella pneumoniae | 8 | 7.0 |
| Morganella morganii | 5 | 4.4 |
| Acinetobacter baumannii | 4 | 3.5 |
| Citrobacter spp. | 2 | 1.8 |
| Enterobacter cloacae | 2 | 1.8 |
| Klebsiella oxytoca | 2 | 1.8 |
| Serratia marcescens | 2 | 1.8 |
| Proteus vulgaris | 1 | 0.9 |
| Providencia stuartii | 1 | 0.9 |
| Acinetobacter spp. | 1 | 0.9 |
Antibiotic susceptibility of the most frequent gram-positive bacteria
Our study showed that Staphylococcus aureus was highly susceptible to vancomycin (93.1%), gentamicin (89.7%), tetracycline (72.4%), and trimethoprim/sulfamethoxazole (75.9%), susceptible to clindamycin (48.3%) and ciprofloxacin (41.4%), and had low susceptibility to ampicillin (6.9%) and cefotaxime (24.1%). Coagulase-negative staphylococci were completely susceptible to vancomycin and susceptible to both tetracycline and doxycycline (both 85.7%) but were moderately susceptible to both gentamicin (57.1%) and trimethoprim/sulfamethoxazole (42.9%) and were less susceptible to erythromycin (14.3%) and cefotaxime (14.3%). Enterococcus spp. were susceptible to vancomycin (83.3%), ampicillin (83.3%), and gentamicin (66.7%) and were moderately susceptible to ciprofloxacin (50%) and piperacillin/tazobactam (33.3%) (Table 4).
Table 4.
The antibiotic susceptibility of the most frequent organisms.
| Antibiotic | Gram-positive | Gram-negative | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Staphylococcus aureus (n = 29) | Coagulase-negative staphylococci (n = 7) | Enterococcus spp. (n = 6) | Escherichia coli (n = 16) | Pseudomonas aeruginosa (n = 13) | Proteus mirabilis (n = 10) | Klebsiella pneumoniae (n = 8) | ||||||||
| n | % | n | % | n | % | n | % | n | % | n | % | n | % | |
| Ampicillin | 2 | 6.9 | 0 | 0.0 | 5 | 83.3 | 1 | 6.3 | - | - | 3 | 30.0 | 0 | 0.0 |
| Amoxicillin/clavulanic acid | 6 | 20.7 | ND | ND | 1 | 16.7 | 10 | 62.5 | - | - | 8 | 80.0 | 6 | 75.0 |
| Piperacillin/tazobactam | 1 | 3.4 | ND | ND | 2 | 33.3 | 13 | 81.3 | 10 | 76.9 | 10 | 100.0 | 6 | 75.0 |
| Ceftazidime | ND | ND | ND | ND | 0 | 0.0 | 3 | 18.8 | 11 | 84.6 | 9 | 90.0 | 1 | 12.5 |
| Cefotaxime | 7 | 24.1 | 1 | 14.3 | 0 | 0.0 | 4 | 25.0 | 1 | 7.7 | 9 | 90.0 | 1 | 12.5 |
| Ceftriaxone | 1 | 3.4 | ND | ND | 0 | 0.0 | 4 | 25.0 | 1 | 7.7 | 8 | 80.0 | 1 | 12.5 |
| Cefepime | 0 | 0.0 | ND | ND | 0 | 0.0 | 4 | 25.0 | 9 | 69.2 | 7 | 70.0 | 3 | 37.5 |
| Meropenem | ND | ND | ND | ND | ND | ND | 16 | 100.0 | 10 | 76.9 | 10 | 100.0 | 7 | 87.5 |
| Imipenem | ND | ND | ND | ND | ND | ND | 11 | 68.8 | 9 | 69.2 | 3 | 30.0 | 3 | 37.5 |
| Vancomycin | 27 | 93.1 | 7 | 100.0 | 5 | 83.3 | 1 | 6.3 | ND | ND | ND | ND | 0 | 0.0 |
| Erythromycin | 9 | 31.0 | 1 | 14.3 | 1 | 16.7 | ND | ND | ND | ND | ND | ND | ND | ND |
| Clindamycin | 14 | 48.3 | 2 | 28.6 | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Tetracycline | 21 | 72.4 | 6 | 85.7 | 0 | 0.0 | 0 | 0.0 | ND | ND | ND | ND | ND | ND |
| Doxycycline | 16 | 55.2 | 6 | 85.7 | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Gentamicin | 26 | 89.7 | 4 | 57.1 | 4 | 66.7 | 8 | 50.0 | 9 | 69.2 | 7 | 70.0 | 6 | 75.0 |
| Amikacin | 4 | 13.8 | ND | ND | 1 | 16.7 | 15 | 93.8 | 9 | 69.2 | 9 | 90.0 | 7 | 87.5 |
| Ciprofloxacin | 12 | 41.4 | 2 | 28.6 | 3 | 50.0 | 4 | 25.0 | 5 | 38.5 | 5 | 50.0 | 3 | 37.5 |
| Levofloxacin | 0 | 0.0 | ND | ND | 0 | 0.0 | 1 | 6.3 | 4 | 30.8 | 1 | 10.0 | ND | ND |
| Trimethoprim/sulfamethoxazole | 22 | 75.9 | 3 | 42.9 | 0 | 0.0 | 4 | 25.0 | 1 | 7.7 | 4 | 40.0 | 4 | 50.0 |
ND: Not determined.
Antibiotic susceptibility of the most common gram-negative bacteria
Escherichia coli exhibited high susceptibility to meropenem (100%), amikacin (93.8%), and piperacillin/tazobactam (81.3%); moderate susceptibility to imipenem (68.8%) and gentamicin (50%); and low susceptibility to ampicillin (6.3%) and cefotaxime (25%). Pseudomonas aeruginosa was susceptible to ceftazidime (84.6%), meropenem (76.9%), piperacillin/tazobactam (76.9%), gentamicin (69.2%), and cefepime (69.2%). Proteus mirabilis was highly sensitive to piperacillin/tazobactam and meropenem (100% each), amikacin (90%), and cefotaxime (90%), moderately sensitive to cefepime and gentamicin (70% each), and relatively less sensitive to ciprofloxacin (50%) and levofloxacin (10%). Klebsiella pneumoniae had good sensitivity to meropenem and amikacin (87.5% each) but had low sensitivity to ceftazidime, cefotaxime, and ceftriaxone (12.5% each), with intermediate sensitivity to imipenem and ciprofloxacin (37.5% each). The most prevalent organisms and their antibiotic sensitivities are provided in Table 4.
Frequency of multidrug-resistant organisms
MDR organisms were prevalent, accounting for 32.6% of all isolates, and Staphylococcus aureus had the highest proportion of MDR at 48.3%, followed by Klebsiella pneumoniae (37.5%) and Escherichia coli (25.0%). Methicillin-resistant Staphylococcus aureus (MRSA) was also prevalent, accounting for 31.0% of the S. aureus isolates. Resistance against carbapenem strains was also observed in 15.4% of Pseudomonas aeruginosa strains and 12.5% of Klebsiella pneumoniae strains. Although vancomycin resistance was indeed low in all the strains (3.4%), it was observed in 6.9% of the S. aureus strains and 16.7% of the Enterococcus spp. as demonstrated in Table 5.
Table 5.
Frequencies of multidrug-resistant (MDR) organisms.
| Organism | Total Isolates | ESBL | CPE | Vancomycin-resistant | Methicillin-resistant | MDR |
|---|---|---|---|---|---|---|
| Gram-positive | ||||||
| Staphylococcus aureus | 29 | - | - | 2 (6.9%) | 9 (31.0%) | 14 (48.3%) |
| Coagulase-negative Staphylococci | 7 | - | - | 0 (0.0%) | - | 2 (28.6%) |
| Enterococcus spp. | 6 | - | - | 1 (16.7%) | - | 1 (16.7%) |
| Gram-negative | ||||||
| Escherichia coli | 16 | 4 (25.0%) | 0 (0.0%) | - | - | 4 (25.0%) |
| Pseudomonas aeruginosa | 13 | - | 2 (15.4%) | - | - | 2 (15.4%) |
| Proteus mirabilis | 10 | - | 0 (0.0%) | - | - | 3 (30.0%) |
| Klebsiella pneumoniae | 8 | 2 (25.0%) | 1 (12.5%) | - | - | 3 (37.5%) |
| Total | 89 | 6 (6.7%) | 4 (4.5%) | 3 (3.4%) | 9 (10.1%) | 29 (32.6%) |
ESBL: extended-spectrum β-lactamase, CPE: carbapenemase-producing Enterobacterales, MDR: multidrug resistant, MRSA: methicillin-resistant Staphylococcus aureus.
Associations between duration of infection and length of hospital stay with amputation
The patients who had major amputations had increased infection rates and hospital stay lengths, as shown in Table 6. Patients who underwent major amputation had a much greater duration of infection, with a median of 2.7 months, than patients who did not undergo major amputation, with a median of 2.0 months. In addition, the length of hospital stay was much longer among those who underwent major amputation, with a median of 22.0 days, than among those without major amputation, with a median of 11.0 days. These differences were statistically significant and indicated that there was a strong relationship between prolonged infection, longer hospital stays, and the likelihood of amputation.
Table 6.
Association between duration of infection and length of hospital stay with amputation.
| Variable | Major amputation | Q1 | Median | Q3 | p |
|---|---|---|---|---|---|
| Duration of infection (month) | No | 1.0 | 2.0 | 3.5 | 0.044 |
| Yes | 2.0 | 2.7 | 6.0 | ||
| Length of hospital stay (day) | No | 7.5 | 11.0 | 20.0 | < 0.001 |
| Yes | 20.0 | 22.0 | 34.0 |
Discussion
DFIs are a major cause of morbidity and mortality globally, resulting in compromised quality of life for infected individuals28. The present study focused on the microbiological pattern and antimicrobial resistance of DFIs in Palestine, addressing a gap in the literature. The study population included 118 patients, which is consistent with the findings of previous studies29. The median age was 62 years, and the median BMI was 31.3 kg/m², both of which are known risk factors for type II diabetes mellitus30. More than half of the patients were male, which is consistent with global trends in diabetes mellitus incidence31, and some had other risk factors, such as smoking32 and low income, which have been linked to worse outcomes in patients with diabetes mellitus33. The majority of patients also had high HbA1c levels and poor cholesterol profiles, again indicating poor control of diabetes mellitus. Some patients also have advanced disease, often requiring insulin therapy, highlighting the need for healthcare professionals to treat complications such as DFIs.
The participants in this study were admitted to the hospital due to infections such as heel pressure ulcers and infected toes, among other diabetes-related complications such as nephropathy and retinopathy10. The majority of these patients have comorbidities such as hypertension and hyperlipidaemia, which are major risk factors for diabetic foot infection complications34. Several patients had been recently treated with antibiotics, which could have affected the way their infections were being treated. Gram-positive and gram-negative bacteria, e.g., Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, were the most common pathogens isolated, which was in accordance with the results of a meta-analysis conducted in China35.
Importantly, the elevated sensitivity (~ 90%) of P. mirabilis to ceftazidime and cefotaxime observed in this study may reflect partial susceptibility within the local strain population. This is likely due to the heterogeneous expression of extended-spectrum β-lactamases (ESBLs) and the relatively low prevalence of AmpC β-lactamase activity. In contrast, the reduced susceptibility to cefepime (~ 70%) may be attributed to the presence of inducible or derepressed AmpC β-lactamases and other resistance mechanisms that compromise the activity of this fourth-generation cephalosporin. These findings emphasize the multifactorial nature of Proteus mirabilis β-lactam resistance and highlight the importance of local antimicrobial susceptibility testing in guiding empirical antibiotic therapy decisions36.
Most of these pathogens are multidrug resistant, as reported in other studies37–39, which implies treatment challenges. These findings underscore the need for recent antibiotic resistance findings to inform local treatment guidelines optimally4. These findings highlight the urgent need to reinforce antimicrobial stewardship policies in Palestinian healthcare settings, including guidelines for empirical antibiotic use and restrictions on over-the-counter antibiotic access.
The study also confirmed that some patients presented with severe lower limb complication, that required amputation40. The intensity of DFIs makes prevention early enough before it is difficult to treat. Ulcer size was related to other diabetes mellitus complications, comorbidities, hospitalizations, and major amputations, which is in agreement with previous findings41. These findings reaffirm that better management of diabetes mellitus and comorbid conditions can avoid DFIs and contribute to better patient outcomes. Although we observed notable antimicrobial resistance patterns, we were unable to correlate specific pathogens or resistance phenotypes with outcomes such as amputation or mortality because of the limited subgroup analysis. Future prospective studies should explore these associations.
Several limitations need to be considered when the findings of the study are interpreted. The retrospective design employs available medical records, which may be incomplete or inexact, hence potentially introducing bias. As this was a single-center study conducted at Rafidia Surgical Hospital, generalizability is uncertain in other regions or contexts of healthcare provision. A cross-sectional design does not allow for the establishment of changes in bacterial patterns or resistance trends over time. Additionally, the use of convenience sampling may have introduced selection bias, as the study population may not fully represent all DFI patients in the region. Moreover, the absence of stratified analysis by variables such as age, ulcer severity, and comorbidities may limit our ability to assess their impact on infection patterns and outcomes. Data on prior antibiotic use were collected, but prior microbiological culture results were not consistently available, which may have limited the assessment of previous infection profiles and antibiotic resistance patterns. This study also provides a limited correlation analysis of the relationships among some pathogens, resistance patterns, and clinical outcomes, such as amputation rates or mortality. Additionally, the study did not employ multivariate regression or calculate odds ratios, which could have enhanced the analysis by adjusting for confounding variables. Finally, a small number of patients with prior amputations (5, 4.2%) who were admitted with stump infections were included in the study. This may have introduced bias, as post-amputation anatomical and biomechanical changes could influence infection recurrence, bacterial colonization, and treatment outcomes.
Conclusions
This study provides significant insight into the microbiological trends and antimicrobial resistance of diabetic foot infection in the northern West Bank, Palestine. The findings are indicative of an intense presence of gram-negative organisms, such as Escherichia coli and Klebsiella pneumoniae, and the intensity of Staphylococcus aureus among the gram-positive isolates. This study highlights the disconcerting prevalence of antimicrobial resistance, such as elevated rates of ESBL production among gram-negative bacteria and MRSA production in S. aureus. The dominance of multidrug-resistant organisms, especially Acinetobacter baumannii, also makes the treatment of DFIs challenging in this region. This study highlights the urgent need for implementing hospital-based antimicrobial stewardship programs, establishing regional resistance surveillance, and promoting early multidisciplinary management to prevent severe complications such as amputation.
Acknowledgements
We would like to acknowledge the support of An-Najah National University and its faculty for providing the necessary resources and a conducive environment for research.
Abbreviations
- BMI
Body mass index
- CLSI
Clinical and Laboratory Standards Institute
- CPE
Carbapenemase-producing enterobacterales
- DFIs
Diabetic foot infections
- DFUs
Diabetic foot ulcers
- ESBL
Extended-spectrum beta-lactamase
- HDL
High-density lipoprotein
- IRB
Institutional Review Board
- MDR
Multidrug-resistant
- MRSA
Methicillin-resistant Staphylococcus aureus
- SPSS
Statistical Package for Social Sciences software
Author contributions
S.Z. and A.A.T. contributed to the idea conception. S.Z. and A.A.T. planned the study and its methodology and critically reviewed and finalized the manuscript. A.A. collected the data. A.A. and B.A. performed the data analysis, and B.A., A.A. and D.A. prepared the initial draft of the manuscript under A.A.T. supervision. All authors revised and approved the submission of the final version of the manuscript.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author upon request.
Declarations
Competing interests
The authors declare no competing interests.
Ethical approval and consent to participate
Verbal informed consent was obtained from all participants prior to their inclusion in the study. The study protocol received ethical approval from the Institutional Review Board (IRB) of An-Najah National University (IRB Reference #: Mas.Feb,2023/19), and the necessary permissions were granted by the relevant local authorities. The interviewer obtained verbal consent from each participant who agreed to take part in the study after explaining its purpose and procedures. All collected data were used solely for research purposes and were treated with strict confidentiality. As no personal identifiers were collected and the study posed minimal risk to participants, the IRB approved the use of verbal rather than written consent. All procedures were conducted in accordance with institutional guidelines, relevant national and international regulations, and the ethical principles outlined in the Declaration of Helsinki.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Saeedi, P. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the international diabetes federation diabetes Atlas. Diabetes Res. Clin. Pract.157, 107843. 10.1016/j.diabres.2019.107843 (2019). [DOI] [PubMed] [Google Scholar]
- 2.Chawla, A., Chawla, R. & Jaggi, S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J. Endocrinol. Metab.20, 546–551. 10.4103/2230-8210.183480 (2016). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Rask-Madsen, C. & King, G. L. Vascular complications of diabetes: Mechanisms of injury and protective factors. Cell. Metab.17, 20–33. 10.1016/j.cmet.2012.11.012 (2013). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Coskun, B., Ayhan, M., Ulusoy, S. & Guner, R. Bacterial profile and antimicrobial resistance patterns of diabetic foot infections in a major research hospital of Turkey. Antibiotics13. 10.3390/antibiotics13070599 (2024). [DOI] [PMC free article] [PubMed]
- 5.Zhang, P. et al. Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis (dagger). Ann. Med.49, 106–116. 10.1080/07853890.2016.1231932 (2017). [DOI] [PubMed] [Google Scholar]
- 6.Abdissa, D., Adugna, T., Gerema, U. & Dereje, D. Prevalence of diabetic foot ulcer and associated factors among adult diabetic patients on follow‐up clinic at Jimma Medical Center, Southwest Ethiopia, 2019: An institutional‐based cross‐sectional study. J. Diabetes Res.2020, 4106383. 10.1155/2020/4106383 (2020). [DOI] [PMC free article] [PubMed]
- 7.Salameh, B. S., Abdallah, J. & Naerat, E. O. Case-control study of risk factors and self-care behaviors of foot ulceration in diabetic patients attending primary healthcare services in Palestine. J. Diabetes Res.2020, 7624267. 10.1155/2020/7624267 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Yang, L., Rong, G. C. & Wu, Q. N. Diabetic foot ulcer: challenges and future. World J. Diabetes. 13, 1014–1034. 10.4239/wjd.v13.i12.1014 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Banu, A., Noorul Hassan, M. M., Rajkumar, J. & Srinivasa, S. Spectrum of bacteria associated with diabetic foot ulcer and biofilm formation: A prospective study. Australas. Med. J.8, 280–285. 10.4066/AMJ.2015.2422 (2015). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Senneville, E. et al. IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023). Diabetes Metab. Res. Rev.40, e3687. 10.1002/dmrr.3687 (2024). [DOI] [PubMed] [Google Scholar]
- 11.Wada, F. W. et al. Bacterial profile and antimicrobial resistance patterns of infected diabetic foot ulcers in sub-Saharan Africa: A systematic review and meta-analysis. Sci. Rep.13, 14655. 10.1038/s41598-023-41882-z (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Giurato, L., Meloni, M., Izzo, V. & Uccioli, L. Osteomyelitis in diabetic foot: A comprehensive overview. World J. Diabetes. 8, 135–142. 10.4239/wjd.v8.i4.135 (2017). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Yammine, K. Conservative surgery in the management of diabetic foot complications (excluding Charcot). The role of the orthopedic surgeon. J. Clin. Orthop. Trauma.55, 102513. 10.1016/j.jcot.2024.102513 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Jones, A. W. et al. The efficacy of custom-made offloading devices for diabetic foot ulcer prevention: A systematic review. Diabetol. Metab. Syndr.16, 172. 10.1186/s13098-024-01392-y (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Tone, A. et al. Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: A multicenter open-label controlled randomized study. Diabetes Care38, 302–307. 10.2337/dc14-1514 (2015). [DOI] [PubMed] [Google Scholar]
- 16.Faramarzi, M. R. et al. Healing of diabetic foot ulcer in an amputation candidate with below-knee cellulitis using combination of negative pressure wound therapy and platelet-rich plasma injection: A case report study. Int. J. Surg. Case Rep.127, 110838. 10.1016/j.ijscr.2025.110838 (2025). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Raspovic, K. M. & Wukich, D. K. Self-reported quality of life and diabetic foot infections. J. Foot Ankle Surg.53, 716–719. 10.1053/j.jfas.2014.06.011 (2014). [DOI] [PubMed] [Google Scholar]
- 18.Shaheen, M. M., Dahab, S., Abu Fada, M. & Idieis, R. Isolation and characterization of bacteria from diabetic foot ulcer: Amputation, antibiotic resistance and mortality rate. Int. J. Diabetes Dev. Ctries.42, 529–537. 10.1007/s13410-021-00997-7 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Mashaly, M., Kheir, M. A. E., Ibrahim, M. & Khafagy, W. Aerobic bacteria isolated from diabetic foot ulcers of Egyptian patients: Types, antibiotic susceptibility pattern and risk factors associated with multidrug-resistant organisms. Germs11, 570–582. 10.18683/germs.2021.1292 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Jouhar, L. et al. Microbiological profile and antimicrobial resistance among diabetic foot infections in Lebanon. Int. Wound J.17, 1764–1773. 10.1111/iwj.13465 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Kale, D. S., Karande, G. S. & Datkhile, K. D. Diabetic foot ulcer in India: Aetiological trends and bacterial diversity. Indian J. Endocrinol. Metab.27, 107–114. 10.4103/ijem.ijem_458_22 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Sen, P. & Demirdal, T. Evaluation of mortality risk factors in diabetic foot infections. Int. Wound J.17, 880–889. 10.1111/iwj.13343 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lynar, S. A., Robinson, C. H., Boutlis, C. S. & Commons, R. J. Risk factors for mortality in patients with diabetic foot infections: a prospective cohort study. Intern. Med. J.49, 867–873. 10.1111/imj.14184 (2019). [DOI] [PubMed] [Google Scholar]
- 24.Chen, L., Sun, S., Gao, Y. & Ran, X. Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies. Diabetes Obes. Metab.25, 36–45. 10.1111/dom.14840 (2023). [DOI] [PubMed] [Google Scholar]
- 25.Cortes-Penfield, N. W. et al. Evaluation and management of diabetes-related foot infections. Clin. Infect. Dis.77, e1–e13. 10.1093/cid/ciad255 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Palestinian Central Bureau of Statistics. PCBS. https://www.pcbs.gov.ps/default.aspx (2025).
- 27.Magiorakos, A. P. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect.18, 268–281. 10.1111/j.1469-0691.2011.03570.x (2012). [DOI] [PubMed] [Google Scholar]
- 28.Rubio, J. A., Jimenez, S. & Lazaro-Martinez, J. L. Mortality in patients with diabetic foot ulcers: Causes, risk Factors, and their association with evolution and severity of ulcer. J. Clin. Med.9, 3009. 10.3390/jcm9093009 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Balakrishnan, T. et al. A geographical paradox: Microbiological profile and antibiotic resistance of diabetic foot infection in North West England. Pract. Diabetes41, 35–40. 10.1002/pdi.2514 (2024). [Google Scholar]
- 30.Ouyang, W., Jia, Y. & Jin, L. Risk factors for diabetic foot ulcer in patients with type 2 diabetes: A retrospective cohort study. Am. J. Transl. Res.13, 9554–9561 (2021). [PMC free article] [PubMed] [Google Scholar]
- 31.Kautzky-Willer, A., Leutner, M. & Harreiter, J. Sex differences in type 2 diabetes. Diabetologia66, 986–1002. 10.1007/s00125-023-05891-x (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Maddatu, J., Anderson-Baucum, E. & Evans-Molina, C. Smoking and the risk of type 2 diabetes. Transl. Res.184, 101–107. 10.1016/j.trsl.2017.02.004 (2017). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Hsu, C. C. et al. Poverty increases type 2 diabetes incidence and inequality of care despite universal health coverage. Diabetes Care35, 2286–2292. 10.2337/dc11-2052 (2012). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Nanwani, B., Shankar, P., Kumar, R. & Shaukat, F. Risk factors of diabetic foot amputation in Pakistani type II diabetes individuals. Cureus11, e4795. 10.7759/cureus.4795 (2019). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Du, F. et al. Microbial infection and antibiotic susceptibility of diabetic foot ulcer in China: Literature review. Front. Endocrinol. 13, 881659. 10.3389/fendo.2022.881659 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Jacoby, G. A. AmpC beta-lactamases. Clin. Microbiol. Rev.22, 161–182. 10.1128/CMR.00036-08 (2009). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Maity, S. et al. A systematic review of diabetic foot infections: pathogenesis, diagnosis, and management strategies. Front. Clin. Diabetes Healthc.5, 1393309. 10.3389/fcdhc.2024.1393309 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Sadeghpour Heravi, F., Zakrzewski, M., Vickery, K., Armstrong, D. G. & Hu, H. Bacterial diversity of diabetic foot ulcers: Current status and future prospectives. J. Clin. Med.8, 1935 (2019). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Wheat, L. J. et al. Diabetic foot infections. Bacteriologic analysis. Arch. Intern. Med.146, 1935–1940 (1986). [PubMed] [Google Scholar]
- 40.Roberts, R. H. R., Davies-Jones, G. R., Brock, J., Satheesh, V. & Robertson, G. A. Surgical management of the diabetic foot: The current evidence. World J. Orthop.15, 404–417. 10.5312/wjo.v15.i5.404 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Abdulghani, H. M. et al. Prevalence of diabetic comorbidities and knowledge and practices of foot care among diabetic patients: A cross-sectional study. Diabetes Metab. Syndr. Obes.11, 417–425. 10.2147/DMSO.S171526 (2018). [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author upon request.
