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Diabetes Mellitus and Infectious Diseases: Current Evidence and Clinical Implications

Article information

Diabetes Metab J. 2025;49(5):915-933
Publication date (electronic) : 2025 August 27
doi : https://doi.org/10.4093/dmj.2025.0508
Taeeun Kim1orcid_icon, Sang-Ho Choi,2orcid_icon
1Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
2Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Corresponding author: Sang-Ho Choi https://orcid.org/0000-0002-4972-4531 Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea E-mail: sangho@amc.seoul.kr
Received 2025 June 10; Accepted 2025 July 28.

Abstract

Diabetes mellitus predisposes individuals to a broad spectrum of infections. People with diabetes face a 1.5- to 4-fold increased risk of both common and severe infections, and infections remain the leading cause of morbidity and mortality. Chronic hyperglycemia impairs neutrophil chemotaxis, oxidative burst, and complement activation, while vascular insufficiency and neuropathy compromise tissue perfusion and barrier integrity. These defects, together with altered skin, mucosal, and gut microbiota, influence the marked susceptibility to urinary tract infections (especially renal abscess and emphysematous pyelonephritis), osteomyelitis, diabetic foot infections, pneumonia (including influenza), tuberculosis, skin and soft tissue infections, and lifethreatening syndromes such as emphysematous cholecystitis and rhino-orbital mucormycosis that are almost exclusive to people with diabetes. Outcomes from infections are worse in diabetes. Although the core therapeutic principles align with those for patients without diabetes, management should be individualized. Glycemic control should balance infection risk and hypoglycemia; antimicrobial dosing should account for renal function and drug interactions; and strict antimicrobial stewardship is required. If needed, prompt debridement and multidisciplinary intervention are necessary to mitigate complications and reduce mortality. Preventive care relies on comprehensive vaccination (influenza, pneumococcus, severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], hepatitis B, herpes zoster, and Tdap/Td) and regular foot surveillance with offloading to avert ulceration.

Keywords: Communicable diseases; Diabetes mellitus; Hyperglycemia; Immunity; Infections

KEY FIGURE

Highlights

• Diabetes confers a 1.5– to 4-fold higher risk of common and severe infections.

• Hyperglycemia impairs host defenses; vasculopathy and neuropathy raise vulnerability.

• Clinical spectrum spans common UTI to life-threatening rhino-orbital mucormycosis.

• Management adds tailored glycemic control, stewardship and drug-safety issues.

• Prevention needs comprehensive vaccination and foot surveillance with off-loading.

INTRODUCTION

In 2024, an estimated 588.7 million adults (aged 20 to 79 years) worldwide had diabetes mellitus, and this number is projected to increase to 852.5 million by 2050 [1]. In the Western Pacific Region, the Republic of Korea ranks fifth in the absolute number of the affected adults. Moreover, approximately 45% of people with diabetes remain undiagnosed, and suboptimal glycemic control persists in a substantial proportion of those already diagnosed [1].

As Frederick Banting famously noted in his 1923 Nobel lecture, ‘Insulin is not a cure for diabetes; it is a treatment,’ underscoring that glucose-lowering therapy alone does not eliminate long-term complications. Over the past century, the discovery of insulin has been accompanied by major advances in pharmacotherapy and diabetes-management technologies. Nevertheless, gaps remain in our understanding of the relationship between diabetes and infection, and it is not yet clear whether modern diabetes care has reduced the risk of a serious infection. For example, the effect of long-term glycemic control (as measured by glycosylated hemoglobin [HbA1c]) on susceptibility to infectious diseases and on clinical outcomes remains controversial, particularly among older adults [2].

Diabetes and infectious diseases are linked by a bidirectional relationship. Diabetes is a predisposing factor in many infections, which continue to cause substantial morbidity and mortality. Conversely, certain infections can precipitate diabetes or exacerbate glycemic dysregulation [3,4]. For example, enteroviral infections in childhood have been implicated in triggering autoimmune β-cell destruction and type 1 diabetes mellitus (T1DM) [5], while emerging evidence has suggested that adult infections, most notably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may precipitate new-onset type 2 diabetes mellitus (T2DM) [6,7]. Indeed, the coronavirus disease 2019 (COVID-19) pandemic has reignited interest in this complex relationship. Moreover, some infections and their treatments (such as human immunodeficiency virus [HIV] and antiretroviral therapy) likely increase the subsequent risk of developing diabetes [8,9].

People with diabetes experience common infectious diseases, such as urinary tract infection (UTI), skin and soft tissue infection (SSTI), osteomyelitis, liver abscess, and tuberculosis (TB), more frequently and with greater severity than the general population does. They are also uniquely predisposed to certain aggressive infections, including malignant otitis externa, rhino-orbital-cerebral mucormycosis, and emphysematous UTIs (Table 1) [2]. Therefore, awareness of these associations is essential for early recognition and appropriate management.

Infections associated with diabetes

This review describes the mechanisms by which diabetes increases the infection risk and severity, summarize the epidemiology of key infections in diabetic populations, and outline the principles of treatment and prevention, including vaccination strategies.

IMPACT OF DIABETES ON THE RISKS AND OUTCOMES OF INFECTIOUS DISEASES

The causal association between diabetes mellitus and infectious diseases has been demonstrated in multiple large-scale cohort studies. In a prospective Dutch cohort of 7,000 patients with diabetes followed for 1 year, T1DM and T2DM are independently associated with increased odds of lower respiratory tract infections (T1DM: adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI], 0.96 to 2.08; and T2DM: aOR, 1.32; 95% CI, 1.13 to 1.53) and UTIs (T1DM: aOR, 1.96; 95% CI, 1.49 to 2.58; and T2DM: aOR, 1.24; 95% CI, 1.10 to 1.39) compared with those of control patients who had hypertension without diabetes [10]. Most population-based cohort studies have reported a 2- to 4-fold increased risk of infection-related hospitalization and up to a 1.5-fold increased risk of infection presenting in an outpatient setting [11-13]. A study in the United States has estimated that 10% of emergency department visits by patients with diabetes are infection-related, and these patients are twice as likely to require hospitalization for infection as non-diabetic patients [14].

By infection site, the risks are most pronounced for kidney infection (3.0- to 4.9-fold), osteomyelitis (4.4- to 15.7-fold), and foot infection (6.0- to 14.7-fold) [11,15-17]. Pneumonia, SSTI, surgical site infection, and general sepsis also occur more frequently in patients with diabetes. A recent meta-analysis of case-control and cohort studies has revealed non-autoimmune diabetes is associated with increased susceptibility to several viral pathogens, especially SARS-CoV-2 (odds ratio [OR], 10.8; 95% CI, 10.3 to 11.4), hepatitis C virus (OR, 3.6%; 95% CI, 2.7 to 4.9), human herpes virus 8 (OR, 2.7; 95% CI, 1.3 to 5.4), influenza A virus subtype H1N1 (OR, 2.1; 95% CI, 1.7 to 2.5), hepatitis B virus (OR, 1.6; 95% CI, 1.2 to 2.13), and herpes simplex virus type 1 (OR, 1.5; 95% CI, 1.1 to 2.0) [18].

Globally, diabetes now predominates in low-and middle-income countries [1], where it increases the risk of TB by 3-fold [19]; consequently, it is one of the five risk factors, along with poverty, undernutrition, smoking, and HIV infection [20]. It accounts for more than half of melioidosis cases, which is caused by the Gram-negative bacterium Burkholderia pseudomallei with a 12-fold increased risk [21]. It is also a well-established risk factor for invasive Staphylococcus aureus infection, including tropical pyomyositis [22].

In a South Korean National Health Insurance Service cohort of 66,426 individuals with diabetes and 132,852 age-sex-region matched non-diabetes controls, diabetes is associated with a greater risk of almost all the types of infections compared with non-diabetes controls [23]. For example, the adjusted incidence rate ratios (aIRR) of infection-related hospitalizations are the highest for liver abscess (aIRR, 10.17; 95% CI, 7.04 to 14.67), followed by central nervous system infections (aIRR, 8.72; 95% CI, 6.64 to 11.45) and SSTIs other than cellulitis (aIRR, 3.52; 95% CI, 3.23 to 3.88). Patients with diabetes also exhibited increased risk of intensive care unit (ICU) admission and mortality due to SSTIs (aIRR, 11.75; 95% CI, 7.32 to 18.86), central nervous system infection (aIRR, 5.25; 95% CI, 3.53 to 7.79), and bone and joint infections (aIRR, 4.78; 95% CI, 3.09 to 7.39). Another population-based cohort study has analyzed 8 years of follow-up data from 4,443,177 people who underwent health screening under the National Health Insurance to assess the risk of developing TB in participants with diabetes. Overall, the incidence of active TB is 0.6%, and individuals with diabetes exhibit an adjusted hazard ratio of 1.48 (95% CI, 1.42 to 1.53). Furthermore, the incidence increases progressively with the prolonged duration of diabetes.

A meta-epidemiological review of 97 prospective cohorts comprising 820,900 people with diabetes has reported a pooled relative risk (RR) of all-cause mortality of 1.80 (95% CI, 1.71 to 1.90) compared with that of individuals without diabetes. Infection-related mortality (excluding pneumonia: RR, 2.39; 95% CI, 1.95 to 2.93) and pneumonia-specific mortality (RR, 1.65; 95% CI, 1.45 to 1.92) increase [24]. In United Kingdom primary care data on 102,493 patients aged 40 to 89 years, the IRRs for infection-related hospitalization are 3.71 (95% CI, 3.27 to 4.21) and 1.88 (95% CI, 1.83 to 1.92) for T1DM and T2DM, respectively. The corresponding increased risks of death from infection were 7.72 (95% CI, 4.47 to 13.33) for T1DM and 1.92 (95% CI, 1.75 to 2.1) for T2DM [25]. An Australian cohort has shown a 5.8-fold increase in pneumonia death, 29.6-fold increase in osteomyelitis, and 9.9-fold increase in sepsis among patients with T1DM [26].

Despite improvements in glycemic control and reductions in macrovascular and microvascular complications, the rates of infection-related hospitalization have remained stable or fluctuated over the past two decades [2,11,15,27,28]. Although higher HbA1c levels show a tendency toward more severe infections, particularly TB and renal infection, the potential of more intensive glycemic control on infection risk remains unclear and warrants further investigation.

Keynotes

• People with diabetes experience a 2- to 4-fold higher risk of infection-related hospitalization and up to a 1.5-fold higher risk of infections managed in outpatient settings.

• The greatest site-specific relative increases occur in UTI, osteomyelitis and diabetic foot infection; susceptibility to several viral pathogens is also heightened.

• In low-and middle-income countries, where diabetes is now most prevalent, it markedly amplifies the risk of endemic infections—notably tuberculosis, melioidosis and invasive S. aureus disease.

• Population-based studies show that diabetes substantially increases infection-related hospitalization, ICU admission, and mortality—particularly for pyogenic liver abscess, skin and soft tissue infection, central nervous system infection, and bone and joint infection.

• Poor glycemic control (elevated HbA1c), longer diabetes duration, and comorbidities further amplify infection risk and severity; infection-related mortality remains elevated despite advances in diabetes care.

PATHOPHYSIOLOGICAL INTERACTIONS BETWEEN DIABETES MELLITUS AND INFECTION

Diabetes mellitus is mainly characterized by impaired insulin signaling cascades caused by insufficient insulin production (T1DM) or insulin resistance (T2DM). T2DM accounts for approximately 90% of all diabetes cases, and its development are influenced by primary risk factors, namely, obesity, sedentary lifestyles, high-caloric diets, and population aging [29-31]. Functional insulin signaling maintains essential cellular processes, including glucose uptake and metabolism, biomacromolecule synthesis, and cell proliferation. As such, the repercussions of diabetes extend beyond metabolic disturbances; consequently, numerous health complications, including vascular diseases, neuropathy, myopathy, and dysregulated immune responses, occur [32-34]. Therefore, the mechanisms contributing to the increased susceptibility to infections among patients with diabetes are complex and multifactorial (Fig. 1).

Fig. 1.

Pathophysiological interactions between diabetes mellitus and infection. Chronic hyperglycemia drives low grade inflammation and directly impairs innate and adaptive immunity—diminishing neutrophil chemotaxis, phagocytosis, natural killer (NK) cell function, complement activation, and antigen presentation. Microangiopathy restricts tissue perfusion and antibiotic delivery, while peripheral and autonomic neuropathy increase trauma, skin breakdown, and delay wound repair. Hyperglycemia is also associated with dysbiosis of the skin and gut microbiota, along with enhanced bacterial proliferation, biofilm formation and virulence. Collectively, these factors predispose individuals with diabetes to a wide range of infections, including severe and opportunistic pathogens. TNF-α, tumor necrosis factor-α; IL, interleukin; IFN-γ, interferon γ.

Hyperglycemia

Chronic hyperglycemia, the hallmark of uncontrolled diabetes, alters the local nutrient milieu at infection sites; as a result, it creates an environment that favors microbial proliferation and enhanced virulence. Increased glucose concentrations in tissues serve as an abundant carbon source for many pathogens; consequently, bacterial burden increases, and key virulence behaviors such as surface adherence and biofilm formation become triggered, and contribute to chronicity and antibiotic tolerance [12,35-37]. For example, in diabetic foot infections, polymicrobial biofilms are involved in metabolic cross-feeding and phenotypic adaptations that further hinder eradication [38].

The clinical consequences of hyperglycemia extend beyond these mechanistic insights. A large English primary care cohort demonstrated a graded rise in infection risk as glycemic control worsens; that is, the rate of infection-related hospitalization (IRR, 1.41; 95% CI, 1.36 to 1.47) of patients with ‘optimal’ control (HbA1c 6%–7%) is 41% higher than that of nondiabetic individuals; conversely, patients with poor control (HbA1c ≥11%) experience a nearly 5-fold increased risk (IRR, 4.70; 95% CI, 4.24 to 5.21). The attributable fraction of poor glycemic control (versus optimal control) is particularly high for serious infections, including bone and joint infections (46%), endocarditis (26%), TB (24%), sepsis (21%); it is also high for overall infection-related hospitalization (17%) and mortality (16%) [34].

Impaired immune function

The maintenance of host defenses against infectious agents includes barrier defenses (e.g., intact skin and mucosal surfaces), cellular and humoral immunity, cytokine and chemokine production, and reactive oxygen species production. An adequate host immune response requires the appropriate coordination of these factors, which may change in diabetes cases.

Impaired innate immune cell function

Innate host defense becomes compromised in patients with diabetes through multiple interrelated mechanisms. Because of diabetes, the ability of innate immune cells to respond to infection is compromised through migratory and chemotactic mechanisms [39-41]. Neutrophils are the first responders and primary mediators of clearing invading bacteria. Neutrophils from patients with diabetes display reduced chemotaxis compared with non-diabetic individuals [39-41]. Furthermore, chronic hyperglycemia and altered metabolic signaling disrupt the metabolic reprogramming of neutrophils, monocytes, and macrophages, which are normally required for phagocytosis. These cells exhibit a reduced glucose uptake mediated by glucose transporter 1 (GLUT1); as a result, the production of nicotinamide adenine dinucleotide phosphate (NADPH), reactive oxygen species, and nitric oxide decrease [42,43].

Similarly, complement function is compromised. Diabetes and hyperglycemia represent chronic inflammation states associated with the activation of several components of the innate immune system and the increased production of several proinflammatory cytokines [44]. Although circulating C3 and C4 levels may be increased, hyperglycemia alters the C3 structure and inhibits C3b-mediated opsonization and membrane attack complex formation; consequently, the immune control of bacterial infection is inhibited. In addition, increased baseline oxidative stress promotes spontaneous neutrophil extracellular trap formation and apoptosis; thus, it exacerbates inflammation and tissue injury without effective microbial clearance [45-47].

Barrier defenses further weaken. Hyperglycemia disrupts skin and mucosal epithelial integrity, increasing susceptibility to diabetic foot ulcers and enteric infections [48]. Natural killer (NK) cell cytotoxicity also diminishes, especially in long-standing T1DM [49], further compromising early microbial clearance.

Dysregulated adaptive immunity

Adaptive immunity is attenuated in patients with diabetes through impaired antigen-presenting cell recruitment and function; as a result, the expansion of T helper subsets (Th1, Th2, and Th17 lymphocytes) is reduced, the pathogen-specific cytokine production is decreased. This defect undermines the lymphocyte-mediated clearance of intracellular pathogens and diminishes vaccine responsiveness; thus, it contributes to the increased incidence and severity of infections such as TB in individuals with poor glycemic control [50].

Microangiopathy, neuropathy, and impaired wound healing

Diabetes induces endothelial dysfunction through oxidative stress, dyslipidemia, and impaired angiogenesis and vasodilation, resulting in microvascular damage and tissue hypoxia [51]. This ischemia diminishes oxygen-dependent bacterial killing by leukocytes; thus, it creates a favorable niche for microaerophilic and anaerobic organisms. Concurrent microangiopathy also impairs the delivery of immune cells and antimicrobial agents to infected tissues, further compromising infection control [52]. In addition, delayed wound healing in patients with diabetes predisposes them to SSTIs, particularly diabetic foot ulcers [53].

Peripheral sensory neuropathy increases the risk of unnoticed trauma and ulcer formation by impairing protective sensation and cutaneous blood flow. Similarly, autonomic neuropathy disrupts gastrointestinal motility, which may cause malnutrition and secondary immune dysfunction.

Enhanced colonization of S. aureus

Preferentially glucose‐utilizing bacterial pathogens, such as S. aureus, streptococci, and enterococci, exploit the hyperglycemic milieu in patients with diabetes [12,34-36,54]. Anterior nares and compromised skin sites (e.g., diabetic foot ulcers) exhibit markedly higher S. aureus colonization rates in people with diabetes than in healthy individuals. Mechanistically, chronic hyperglycemia promotes the nonenzymatic glycation of extracellular matrix proteins, thereby enhancing bacterial adhesion; concomitant microangiopathy and neuropathy further impair innate clearance, collectively facilitating persistent carriage. Notably, the prevalence of methicillin‐resistant S. aureus colonization is also increased in this population [55,56].

Other contributory factors

Antibiotic exposure is substantially greater in patients with diabetes than in healthy individuals; in 1995 to 2003, the prescription rates for lower respiratory tract infections and UTIs increased by 60% and 15%, respectively [57]. With this increased antibiotic use, multidrug-resistant bacterial infections, including those complicating diabetic foot ulcers, have increased [58,59]. The diabetic infection microenvironment characterized by high glucose, impaired immune clearance, and recurrent antimicrobial exposure favors the selection of tolerant and resistant strains. Moreover, this problem may be exacerbated by diabetes-associated immune suppression because of resistant organisms that establish and propagate more readily.

People with diabetes are hospitalized more frequently than non-diabetic individuals for a various comorbid conditions, thereby increasing their exposure to the nosocomial environment. Invasive procedures, such as central venous catheterization and urinary catheterization, further increase the risk of healthcare-associated infections. The progression of diabetic nephropathy to chronic kidney disease induces additional immunosuppression, and dialysis initiation further heightens susceptibility to infection.

CHARACTERISTICS OF INFECTIOUS DISEASES IN PATIENTS WITH DIABETES MELLITUS

UTI

People with diabetes have an increased risk of UTI at all levels of severity, from asymptomatic bacteriuria through cystitis and acute pyelonephritis to renal and perinephric abscess and lifethreatening emphysematous cystitis and pyelonephritis [60]. Glycosuria creates an abundant nutrient milieu for uropathogens such as Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and group B Streptococcus, promoting their growth and persistence in the urinary tract [61,62]. Uropathogenic E. coli exploits hyperglycemia‐induced accumulation of advanced glycation end products on urothelial surfaces as alternative receptors for type 1 pili; consequently, bacterial adhesion, bladder epithelial cells invasion, and intracellular bacterial community formation are enhanced [63-66]. These risks are complicated by autonomic neuropathy by impairing detrusor reflexes and bladder sensation; as a result, urinary stasis, increased residual volume, and vesicoureteric reflux occur [67]. Fungal infections, most notably candiduria, and UTIs caused by non‐E. coli organisms are more frequent in diabetes [60]. Although sodium-glucose cotransporter 2 (SGLT‐2) inhibitor use is related to an increased risk of genital infections, it does not appear to considerably affect UTI incidence [68].

Asymptomatic bacteriuria

Asymptomatic bacteriuria is approximately 3- to 4-fold more prevalent in women with diabetes than in non‐diabetic women; conversely, no increase has been demonstrated in males with diabetes [69]. However, the clinical significance of this finding is uncertain because antimicrobial treatment neither reduces progression to symptomatic UTI or pyelonephritis nor decreases hospital admissions, and may expose patients to antibiotic-related adverse events [60,69]. Accordingly, the routine screening for and antimicrobial therapy of asymptomatic bacteriuria are not recommended for individuals with diabetes [70].

Cystitis and acute pyelonephritis

The clinical presentation of cystitis and acute pyelonephritis in patients with diabetes is similar to that in non-diabetic individuals. However, patients with diabetes more frequently develop bilateral renal involvement in acute pyelonephritis [71], and the risk of bacteremia is approximately four times higher [72]. They are also at an increased risk for complications such as renal or perinephric abscesses and emphysematous pyelonephritis [72]. Fever persisting beyond 72 hours should prompt investigations into such complications, and renal ultrasound or preferably computed tomography (CT) should be performed for definitive evaluation [73].

Emphysematous cystitis

Emphysematous cystitis is a rare but almost exclusively diabetic complication of lower UTI [74]. E. coli is the most common pathogen although Enterobacter, Proteus, Klebsiella, and Candida species may be responsible [75]. Clinical symptoms often resemble uncomplicated cystitis, but the presence of gross hematuria or pneumaturia should raise suspicion. Radiographic demonstration of gas within the bladder wall confirms the diagnosis. Some patients report chronic lower abdominal discomfort. Unlike emphysematous pyelonephritis, emphysematous cystitis generally responds to medical therapy alone [76].

Emphysematous pyelonephritis

Emphysematous pyelonephritis is a necrotizing complication of acute pyelonephritis characterized by gas formation in the renal collecting system, renal parenchyma, and/or perirenal tissues [77]. Approximately 70% to 90% of cases occur in patients with diabetes, with a 2-fold female predominance and an association with urinary tract obstruction [77,78]. Patients typically present with high fever, chills, flank pain, nausea, and vomiting; a palpable flank mass or crepitus may be noted on examination. E. coli accounts for 50% to 75% of cases; other implicated organisms include Klebsiella spp., Enterobacter spp., Proteus spp., Streptococcus spp., and Candida spp. [79]. Despite gas production, obligatory anaerobes are not primary pathogens, and anaerobic coverage is not required. CT is the diagnostic modality of choice because ultrasound has lower sensitivity [77].

• When gas is confined to the renal pelvis (emphysematous pyelitis), obstruction relief and antibiotic therapy alone are usually sufficient.

• When the renal parenchyma is affected, percutaneous drainage should be performed in addition to antibiotics treatment; extensive perirenal gas or failure to improve may require nephrectomy.

Respiratory tract infection

Community-acquired pneumonia

Patients with T2DM have a 1.3- to 2.6-fold (approximately 1.5-fold) higher risk of community-acquired pneumonia than non-diabetic individuals, and the risk increases with poorer glycemic control [11,15,80]. Although Streptococcus pneumoniae remains the most common pathogen, patients with diabetes more frequently develop pneumonia because of S. aureus and Gram-negative organisms such as K. pneumoniae. In cases of pneumococcal pneumonia, the rates of bacteremia and mortality of patients with diabetes are higher than those of non-diabetic patients. Diabetes is the most common underlying predisposing factor for thoracic empyema, in which Klebsiella spp., streptococci, S. aureus, and anaerobes are notable pathogens [81,82].

Influenza

Influenza remains a leading cause of global mortality and accounts for approximately 500,000 deaths annually [83]. Individuals with diabetes are at a markedly increased risk of severe influenza‐related outcomes; meta‐analytic data show that the likelihood of hospitalization, secondary pneumonia, and the need for intensive care or mechanical ventilation increases, and the odds of severe disease are up to 4-fold greater in young adults (aged 15 to 50 years) with diabetes than in non-diabetic peers [84,85]. Population‐based analyses report a 3.7-fold increase in influenza-associated healthcare utilization among people with diabetes in recent seasons [86].

Mechanistically, influenza, and subsequent bacterial pneumonia exacerbates a prothrombotic and proinflammatory milieu in patients with diabetes; they consequently cause acute coronary events that may persist for weeks to months post-infection. Moreover, mortality rates from influenza are significantly higher in diabetic populations than in healthy individuals, and the diabetic status has been identified as an independent predictor of in-hospital death due to influenza or pneumonia [87,88].

Head and neck infection

Malignant otitis externa

Malignant otitis externa is a life-threatening infection of the external auditory canal and skull base, occurring predominantly in elderly patients with diabetes [89]. In a retrospective case-control data, 54.8% of malignant otitis externa cases have pre-existing diabetes versus 13.9% of matched controls (OR, 7.50; 95% CI, 6.22 to 9.03) [90]. A case series report has shown that 51% to 93% of patients with malignant otitis externa have diabetes, and most studies have focused on the elderly with poorly controlled diabetics [91]. In another retrospective series of 28 patients admitted to a tertiary care center between 2000 and 2014, 23 (82.1%) had diabetes. The results also showed that Pseudomonas aeruginosa was the most frequently isolated pathogen (13/28, 46.4%), followed by methicillin-resistant S. aureus (10/28), Enterobacter spp. (3/28), K. pneumoniae (2/28), and Aspergillus fumigatus (2/28) [92]. Predisposing factors include recent aural surgery, ear canal irrigation with water, and hearing aid use.

Clinically, patients present with severe otalgia, purulent otorrhea, conductive hearing loss, and canal wall tenderness [93]. The infection spreads via the osseocartilaginous junction, affecting the temporal-mandibular joint and skull base and leading to osteomyelitis; it may extend further to the meninges, sigmoid sinus, and cerebral parenchyma. The invasion of the stylomastoid foramen causes facial nerve palsy in approximately one-third of cases, while the involvement of additional cranial foramina manifests as other cranial nerve deficits. Magnetic resonance imaging is necessary to delineate soft tissue and bony involvement. Optimal management combines early otolaryngologic evaluation, microbiologic culture, aggressive surgical debridement of necrotic tissues, and a prolonged and targeted antimicrobial therapy [89].

Rhino-orbital-cerebral mucormycosis

Rhino-orbital-cerebral mucormycosis is the most common and most severe presentation of mucormycosis in immunocompromised hosts caused by fungi belonging to the order Mucorales (e.g., Rhizopus, Mucor, Rhizomucor, and Cunninghamella) [94,95]. It accounts for approximately 40% to 50% of all mucormycosis cases and occurs predominantly in patients with diabetes, especially those in diabetic ketoacidosis (DKA) [96,97]. The global incidence of mucormycosis ranges from 0.005 to 1.7 per million population per year, and the rates in Asia are substantially higher (up to 140 per million in India) [98]. In an Asian tertiary-care cohort of 64 patients treated between 1996 and 2012, 36 (56.3%) had rhino-orbital-cerebral disease. Of these patients, 19 had a rhinocerebral disease without orbital extension, 14 had isolated sinusitis, and three had sino-orbital involvement. Overall, 43/64 patients (67.2%) had diabetes, and among those with rhino-orbital-cerebral involvement, 27/36 (75.0%) had diabetes [99].

Rhino-orbital-cerebral mucormycosis typically begins in the nasal cavity or paranasal sinuses and then extends to the palate, sphenoid sinus, cavernous sinus, orbit, and intracranial structures [95]. Early features include fever, headache, facial pain and swelling, periorbital ache, and nasal congestion; then, they likely progress to vision loss, conjunctival edema, ophthalmoplegia, cranial nerve palsies, and stroke. Ischemic necrosis produces black eschar in the nasal mucosa or palate in up to 40% of cases.

DKA profoundly increases risk [100-102]. Acidosis impairs neutrophil chemotaxis, while reduced transferrin binding increases free iron, a critical growth factor for Mucorales. Consequently, exogenous iron supplementation and deferoxamine are contraindicated. Although deferasirox, an iron chelator, showed synergistic benefit with liposomal amphotericin B in preclinical and small salvage cohorts [103], a randomized trial has demonstrated higher mortality with its use; however, it should be further investigational [104].

Definitive diagnosis requires tissue biopsy to reveal broad, non-septate hyphae with angioinvasion, and culturing confirms species identity [105]. Imaging (CT or magnetic resonance imaging [MRI]) defines the extent of involvement. Treatment demands prompt and aggressive surgical debridement of infected tissues combined with high-dose lipid‐formulation amphotericin B (5 to 10 mg/kg/day), correction of DKA, and strict glycemic control. In refractory cases or when oral therapy is indicated, step-down to posaconazole or isavuconazole is recommended [105].

Skin and soft tissue infection

The incidence of SSTIs arising from Gram-positive cocci in individuals with diabetes is greater than that in non-diabetic individuals [106]. Diabetic SSTIs include superficial skin infections (e.g., dermatophyte infections and candidal intertrigo), bacterial cellulitis, skin abscesses, and severe necrotizing fasciitis; they most frequently manifest on the lower extremities, which are known as diabetic foot infections. SSTIs pose a substantial burden on patients with diabetes [107], causing complications such as gangrene, osteomyelitis, bacteremia, and sepsis. Cellulitis or abscess may herald systemic bacteremia, and diabetes is related to an increased sepsis‐related mortality, particularly in older patients. Predisposing factors include peripheral sensory and sudomotor neuropathy (leading to dry, fissured skin), dermatophytosis, and microangiopathy, all of which compromise the skin barrier [108]. β-Hemolytic streptococci and S. aureus, increasingly methicillin‐resistant in diabetic cohorts because of frequent healthcare exposures, are the principal pathogens for cellulitis [106].

Necrotizing fasciitis

A less common but life‐threatening infection is necrotizing fasciitis, which is characterized by rapidly progressive inflammation and necrosis of the fascia, subcutaneous fat, and muscle. Diabetes is the most important risk factor. Up to 60% of cases of Fournier’s gangrene, a form of necrotizing fasciitis affecting the perineum, have comorbid diabetes [109]. In a multicenter series (2012–2015) of 161 patients with necrotizing fasciitis, 41% had diabetes [110]. Another retrospective review of 165 cases in a tertiary center (1997–2013) revealed that 51% of patients had diabetes; they were more susceptible to polymicrobial diseases and were more likely to receive limb amputation [111]. Moreover, a nationwide cross-sectional analysis of Health Insurance Review and Assessment Service claims from 2012 to 2017 reported an average annual necrotizing fasciitis incidence of 0.86 per 100,000 population. This incidence increased with age, and it was 2.5 times higher in males than in females; two-thirds of the cases occurred in patients with diabetes and exhibited a pronounced summer peak, suggesting temperature-related seasonal variation [112].

The lower extremities are most often involved although the upper limbs, abdominal wall, and perineum may also be affected. Infections may spread hematogenously or directly extend from the skin. Early in its course, patients may report pain out of proportion to skin findings, and the subsequent signs include tenderness, swelling, and fever; when fascial vessels thrombose, overlying skin discoloration, bullae, ncerosis, and sensory loss occur. Soft tissue gas may be visible on plain radiographs in approximately 25% of cases, and crepitus may be palpable in up to one-third of cases. Polymicrobial infections, including aerobic gram-negatives (E. coli, Klebsiella spp., Proteus spp., and Enterobacter spp.) and anaerobes (e.g., Bacteroides spp., anaerobic streptococci), typically occur. Management hinges on a high index of suspicion, prompt broad-spectrum antibiotic therapy, and early aggressive surgical debridement of all necrotic tissues.

Diabetic foot infection

Diabetic foot infections are the most common skin and softtissue infections of the lower extremities in people with diabetes; thus, they account for frequent hospitalizations and represent the leading precipitant of lower-limb amputation [113-115]. The lifetime incidence of diabetic foot ulcers ranges from 19% to 35%; of these cases, 50% to 60% become infected [116]. Among those with diabetic foot infections, 15% to 20% require amputation to achieve adequate source control, which is followed by a marked reduction in life expectancy over the subsequent 2 years [116].

Predisposing factors include peripheral sensory and sudomotor neuropathy that result in the loss of protective sensation and dry, fissured skin; foot deformities that generate focal pressure points; and microangiopathic ischemia that both precipitates ulceration and impairs the delivery of immune cells and antibiotics [51,117]. Poor glycemic control and coexisting peripheral artery disease further increased the risk; ischemic ulcers are predisposed to deep infection, osteomyelitis, and systemic sepsis, often without prominent fever or chills in neuropathic patients. Up to half of the cases are attributed to polymicrobial causes. S. aureus and β-hemolytic streptococci predominate; gram-negative rods (E. coli, Klebsiella spp., Proteus spp., and Enterobacter spp.) and anaerobes are more common in chronic, deep, or previously treated wounds [118]. Hyperglycemic tissues foster increased. The growth and virulence of these pathogens increase in hyperglycemic tissues.

Diagnosis should be clinical based on at least two local signs of inflammation (erythema, warmth, swelling, pain, and purulence) and graded by the International Working Group on the Diabetic Foot (IWGDF)/Infectious Diseases Society of America (IDSA) severity scale (mild-severe) to guide management (Table 2) [119]. When clinical signs are equivocal (e.g., neuropathy or ischemia), serum biomarkers (C-reactive protein, erythrocyte sedimentation rate [ESR], or procalcitonin) may help with diagnosis. Because superficial swab or wound‐bed cultures often yield a polymicrobial mix that overrepresents contaminants and under detects anaerobic pathogens, deep tissue or bone specimens obtained aseptically are preferred for culture, and conventional microbiological techniques remains the first‐line method for pathogen identification [119].

Severity classification system and key recommendations on diagnosing and treating foot infection in a person with diabetes

Bone infection of the foot should be diagnosed because its presence greatly increases the risk of minor and major amputations. Osteomyelitis is diagnosed using a probe-to-bone test (palpation of the bone through the ulcer with a sterile probe having a sensitivity of 0.87 and a specificity 0.83) and radiographs (insensitive to acute osteomyelitis) plus inflammatory markers (ESR ≥70 mm/hr having a sensitivity of 0.81 and a specificity of 0.80); in cases of uncertainties, it is diagnosed through MRI or nuclear imaging as an alternative to MRI. MRI provides high sensitivity and specificity for osteomyelitis and uniquely allows the assessment of the extent of adjacent soft tissue involvement. Bone biopsy for culture is advised when feasible [119].

Empiric antibiotic therapy should cover likely pathogens; for instance, mild diabetic foot infections without prior antibiotics are managed with agents targeting aerobic gram-positive cocci only (β-hemolytic streptococci and S. aureus). Conversely, moderate-severe infections require broader regimens, including gram-negatives and anaerobes, including ampicillin/sulbactam, typically for 1 to 2 weeks (extend to 3–4 weeks if response is slow or if peripheral artery diseases are severe). Empiric anti‐Pseudomonas coverage is reserved for those with recent isolation or in high-risk regions. Clinically uninfected ulcers should never receive antibiotics (Table 2).

When tissue necrosis or gangrene is present, prompt marginal surgical debridement and drainage are required. When an infection fails to respond to antimicrobial therapy or is accompanied by gangrene, amputation is recommended. In a person with diabetes and a bone or joint infection, antibiotic therapy for up to 3 weeks should be considered after minor amputation for diabetes-related osteomyelitis of the foot and positive bone margin culture and 6 weeks for diabetes-related foot osteomyelitis without bone resection or amputation (Table 2) [119]. Strict glycemic control, patient education on foot care, and assessment/correction of vascular insufficiency should be implemented to prevent recurrence.

Intra-abdominal and gastrointestinal infections

Emphysematous cholecystitis

Emphysematous cholecystitis is a rare, life-threatening variant of acute cholecystitis characterized by gas formation within the gallbladder wall [120]. Approximately 30% to 50% of emphysematous cholecystitis cases occur in patients with diabetes [120,121]. Clinical presentation is similar to that of uncomplicated acute cholecystitis, but rates of gallbladder necrosis, perforation, and mortality (15% to 25%) are substantially higher. Gallstones are present in only approximately half of the patients. Physical examination often lacks peritoneal signs, and crepitus may be occasionally palpable in the adjacent abdominal wall. Mixed infections with enteric Gram-negative bacilli and anaerobes are common. Diagnosis is confirmed by plain abdominal radiography or CT demonstrating intramural gas. Management requires early broad-spectrum antibiotic therapy and prompt cholecystectomy [121].

Pyogenic liver abscess

Diabetes mellitus independently increases the incidence and adverse outcomes of pyogenic liver abscess [122,123]. Population‐based data show a higher diabetes prevalence among the affected patients (11.2% vs. 2.6%) and a 3.6-fold adjusted risk (aRR, 3.6; 95% CI, 2.9 to 4.5) than non-diabetic controls [122]. Poor glycemic control impairs neutrophil phagocytosis, particularly against K. pneumoniae; it is associated with a dose-response increase in the incidence of abscess, and obesity further amplifies this risk independent of the diabetic status [124,125]. For diagnosis, abdominal CT is preferred (sensitivity 100% vs. 85.8% for ultrasound) and should be performed whenever feasible [126].

In diabetic hosts, imaging typically shows large (>10 cm), multifocal, bilobar, gas-forming abscesses [127]. In addition, K. pneumoniae-associated lesions more often present as solitary, unilobar, solid, multilocular cavities with portal or hepatic vein thrombosis [128]. Microbiologically, K. pneumoniae, especially hypervirulent K1/K2 strains exhibiting a hypermucoviscous phenotype, predominates in diabetic hosts [123,129]. Hypervirulent K1/K2 strains, which are driven by regulators of the mucoid phenotype A (rmpA)/rmpA2 and enhanced siderophore systems, predominate, and their hypermucoviscous capsule impedes percutaneous drainage and facilitates metastatic spread (e.g., endophthalmitis and meningitis) [123,129,130]. Although most remain pan-sensitive except to ampicillin, the potential for acquiring multidrug-resistance plasmids complicates therapy [130-132]. Diabetic pyogenic liver abscess is linked to prolonged hospitalization, increased risk of multiorgan dysfunction, and recurrence; thus, it requires prompt source control, susceptibility-guided antimicrobial regimens, and rigorous glycemic optimization to improve outcomes [123,125,129,132].

Gastrointestinal infections

Certain enteric pathogens, such as Salmonella enterica serovar Enteritidis, Campylobacter spp., and Listeria monocytogenes, have an increased incidence in patients with diabetes. This increased susceptibility is likely caused by diabetic gastroparesis and reduced intestinal motility, which impair mucosal defenses and facilitate pathogen overgrowth [133,134].

Tuberculosis

People with diabetes are approximately two to three times more likely to develop active TB than the general population; this risk increases further in settings where diabetes and TB are endemic, particularly in low- and middle-income countries in Africa and Southeast Asia [135,136]. In Hong Kong, the TB risk differential between people with and without diabetes has remained at 2- to 3-fold over a decade for middle-aged adults and reached 7-fold in younger age groups [15]. In India, diabetes contributes to 15% of pulmonary TB and 20% of smear-positive TB cases; among them, the greatest burden is recorded in urban areas [137].

This excess TB risk in diabetes is possibly attributed to the diabetes-associated impairment of cell-mediated immunity. Prolonged diabetes duration, older age, and low body mass index further amplify TB susceptibility. Moreover, patients with diabetes more frequently present with atypical pulmonary TB manifestations, such as lower-lobe or multilobar involvement and concomitant pleural effusions [138]. Although the rates of extrapulmonary TB do not appear to be increased, the relapse risk following successful treatment is approximately four times higher, and mortality during TB therapy is more than six times greater in people with diabetes [138,139].

The bidirectional interplay between TB and diabetes worsens the outcomes of both conditions. TB infection can exacerbate hyperglycemia via stress-induced mechanisms, often necessitating the intensification of glucose-lowering regimens until the infection resolves. Latent TB infection has been related to a 20% increased risk of progressing to T2DM, independent of TB treatment [140]. In light of these interactions, the World Health Organization recommends screening all patients with newly diagnosed active TB for diabetes where resources permit since early glucose control may improve TB outcomes [141]. Routine TB screening in people with diabetes is generally reserved for high-incidence settings (TB prevalence >100 per 100,000), patients presenting with TB symptoms or signs, or individuals experiencing unexplained deterioration in glycemic control.

ISSUES IN THE MANAGEMENT OF INFECTIOUS DISEASES IN PATIENTS WITH DIABETES MELLITUS

The treatment of common infections in people with diabetes generally follows the same evidence-based principles as for the general population. Clinical practice guidelines do not recommend different antimicrobial regimens or a lower threshold for the initiation of therapy in most cases although some cases have exceptions. For example, early antiviral therapy, with agents such as nirmatrelvir/ritonavir (Paxlovid, Pfizer, New York, NY, USA) for COVID-19 or neuraminidase inhibitors for influenza, should be considered at a lower threshold in people with diabetes.

Glycemic control during acute infections

Hyperglycemia on admission and during hospitalization for sepsis and other serious infections is consistently associated with extended lengths of stay and increased mortality. However, in the landmark Normoglycemia in Intensive Care Evaluation- Survival Using Glucose Algorithm Regulation (NICESUGAR) trial, targeting intensive blood glucose control (4.5 to 6.0 mmol/L) in ICU patients, of whom approximately 20% had sepsis, does not improve survival compared with that of a conventional target (≤10 mmol/L); it is also linked to a marked increase in severe hypoglycemia (6.8% vs. 0.5%) and a increase in 90-day mortality (27.5% vs. 24.9%) [142]. Accordingly, current guidelines recommend moderate glycemic targets (e.g., 7.8 to 10 mmol/L) in critically ill patients to balance the risks of hyperglycemia and hypoglycemia [143].

Because of the risk of euglycemic DKA in acute illness, SGLT-2 inhibitors should be held in critically ill or hemodynamically unstable patients. In the Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE- 19) randomized trial of dapagliflozin versus placebo in hospitalized patients with COVID-19 and cardiometabolic comorbidities, the in-hospital initiation of therapy neither reduced organ-support-free days and mortality nor increased the rates of DKA or acute kidney injury [144].

Optimizing medication safety: drug interaction and toxicity monitoring

People with diabetes often have multiple comorbidities and are exposed to polypharmacy; as such, they require vigilant monitoring to avoid drug–drug interactions and toxicities. For example, an impaired renal function in chronic kidney disease necessitates antibiotic dose reductions or extended dosing intervals; the risk of acute kidney injury is further increased by nephrotoxic agents (e.g., aminoglycosides and vancomycin). Rifampicin, a potent cytochrome P450 inducer, accelerates sulfonylurea metabolism and possibly compromises glycemic control. Likewise, drugs such as ethambutol (optic neuropathy) and isoniazid (peripheral neuropathy) can exacerbate visual and sensory deficits in patients already affected by diabetic retinopathy or neuropathic complications.

Antimicrobial stewardship: avoidance of overtreatment

Given that people with diabetes are more likely to harbor multidrug-resistant pathogens and experience worse outcomes from infections than normal individuals, it is essential to adhere to the principles of antibiotic stewardship using the narrowest effective spectrum, the shortest effective duration, and optimal de-escalation based on culture results.

For example, the treatment of asymptomatic bacteriuria in diabetes does not reduce the risk of subsequent symptomatic UTI or pyelonephritis. Accordingly, the IDSA and European guidelines recommend against screening for or treating asymptomatic bacteriuria in people with diabetes outside of pregnancy [70,145]. Similarly, prophylactic antibiotics for uninfected diabetic foot ulcers do not improve ulcer healing or prevent infection. Therefore, IDSA diabetic foot infection guidelines advise against routine antimicrobial use in uninfected ulcers [119].

VACCINE RECOMMENDATION FOR ADULTS WITH DIABETES

A large primary care cohort study and randomized trials have failed to show that intensive glycemic control or weight reduction decreases infection rates in people with diabetes [34,142]. Some common infections are preventable through vaccination, and international guidelines recommend routine immunization, including annual seasonal influenza, pneumococcal, SARS-CoV-2, hepatitis B in younger adults, recombinant herpes zoster vaccine (≥50 years), and a tetanus, diphtheria and acellular pertussis (Tdap or Td) booster every 10 years for adults with diabetes (Table 3). Although vaccine uptake varies between countries, efficacy in people with diabetes is comparable with or sometimes greater than that in the general population. For instance, influenza vaccination in a Danish cohort is associated with a 15% reduction in all-cause mortality and a 16% reduction in cardiovascular mortality [146]; and a Canadian study has demonstrated a 31% lower stroke incidence post-vaccination in people with diabetes versus 17% in those without diabetes [147]. Similarly, randomized trials and real-world data indicate that COVID-19 vaccines provide equivalent protection against infection and severe outcomes in people with and without diabetes [148]; three doses of these vaccines reduce COVID-19-related mortality by 95% and hospitalization/ICU admission by 85% to 95% in a Hong Kong cohort of patients with diabetes [149].

Key vaccine recommendation for adults with diabetes

CONCLUSIONS

People with diabetes face a markedly increased burden of infectious diseases driven by chronic hyperglycemia-mediated immune dysfunction, microvascular and neuropathic complications, and a tissue environment that favors microbial proliferation, biofilm formation, and antibiotic tolerance. Epidemiologic studies consistently report 2- to 4-fold increased risks of both common infections (urinary and respiratory tract) and life-threatening syndromes, such as emphysematous cholecystitis and necrotizing fasciitis. Hyperglycemia impairs neutrophil chemotaxis, oxidative burst, complement activation, and epithelial barrier integrity; it also promotes resistant organisms and complicates treatment. High-risk presentations in diabetes, including malignant otitis externa and rhino-orbital-cerebral mucormycosis, demand heightened clinical vigilance and prompt, aggressive management.

Therapeutic principles generally mirror those for the nondiabetic population but require tailored considerations. Effective care hinges on individualized glycemic targets, antimicrobial dosing tailored for renal function and drug interactions, strict antimicrobial stewardship to curb resistance, and prompt debridement alongside multidisciplinary collaboration as appropriate to optimize source control and patient outcomes. Preventive strategies include comprehensive vaccination (influenza, pneumococcus, SARS-CoV-2, hepatitis B, herpes zoster, and Tdap/Td) and regular foot surveillance with offloading to avert ulceration. Future efforts should standardize infection case definitions, integrate infectious disease endpoints into diabetes trials, and explore hyperglycemia-driven pathways and microbiome interventions to further mitigate infection-related risks.

Notes

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

FUNDING

None

ACKNOWLEDGMENTS

None

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Fig. 1.

Fig. 1.

Pathophysiological interactions between diabetes mellitus and infection. Chronic hyperglycemia drives low grade inflammation and directly impairs innate and adaptive immunity—diminishing neutrophil chemotaxis, phagocytosis, natural killer (NK) cell function, complement activation, and antigen presentation. Microangiopathy restricts tissue perfusion and antibiotic delivery, while peripheral and autonomic neuropathy increase trauma, skin breakdown, and delay wound repair. Hyperglycemia is also associated with dysbiosis of the skin and gut microbiota, along with enhanced bacterial proliferation, biofilm formation and virulence. Collectively, these factors predispose individuals with diabetes to a wide range of infections, including severe and opportunistic pathogens. TNF-α, tumor necrosis factor-α; IL, interleukin; IFN-γ, interferon γ.

Table 1.

Infections associated with diabetes

Category with clinical implications Examples
Common infections Urinary tract infection
 Occur more frequently with greater severity than in the general population Skin and soft tissue infection
Community-acquired pneumonia
Bone and joint infection
Liver abscess
Surgical site infection
Tuberculosis
Rare, but aggressive infections Rhinocerebral mucormycosis
 Almost entirely confined to people with diabetes Malignant otitis externa
Infected diabetic foot
Panophthalmitis
Fournier’s gangrene

Table 2.

Severity classification system and key recommendations on diagnosing and treating foot infection in a person with diabetes

Severity classification Clinical classification/Definitions Empirical antimicrobial regimen Route/Duration
Uninfected No systemic or local signs No antibiotics None
Mild No systemic manifestations, and Target gram-positive cocci (staphylococci and streptococci) Oral/1–2 weeks
≥2 local signs: erythema >0.5 to <2 cm warmth, tenderness, swelling/induration, purulence  First-generation cephalosporin (cephalexin)
Moderate No systemic manifestations, and erythema extending ≥2 cm from ulcer margin, and/or involving deeper tissues (tendon, muscle, joint, bone) Target gram-positive cocci±gram-negative rods Initially IV→Oral/2–4 weeks (10 days following surgical debridement)
 β-lactam/β-lactamase inhibitor (ampicillin/sulbactam, amoxicillin/clavulanate)
 Second-, third-generation cephalosporin (cefuroxime, cefotaxime, ceftriaxone)
Severe Any foot infection with systemic inflammatory response syndrome (SIRS), as manifested by ≥2 of the following: If recent antibiotic exposures, piperacillin/tazobactam or ertapenem can be considered
 Temperature >38°C or <36°C If macerated ulcer or warm climate, target gram-negatives including Pseudomonas spp.
 Heart rate >90 beats/min If ischemic limb/necrosis/gas forming, target gram positive cocci±gram-negative rods±strict anaerobes
 Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg  β-Lactam/β-lactamase inhibitor (ampicillin/sulbactam, piperacillin/tazobactam)
 White blood cell count >12,000/mm3, <4,000/mm3, or >10% immature (band) forms  Second-, third-generation cephalosporin+clindamycin or metronidazole
 Ertapenem or mero/imipenem
Osteomyelitis Infection involving bone Choose bone-penetrant agent After,
 Resection: 2–5 days
 Minor amputation: 3 weeks
 No surgery: 6 weeks

Table 3.

Key vaccine recommendation for adults with diabetes

Vaccine Indication Schedule Recommendation in Koreaa
Seasonal influenza All Yearly Annual vaccination each autumn (October–November)
Pneumococcal All Based on local guidelines One dose of PCV20, or PCV15 then PPSV23 (1 year apart)
SARS-CoV-2 All Based on local guidelines Recommended
Hepatitis B <60 years of age, ≥60 years of age after discussion with healthcare professionals Two-b or three-dose series Follow general adult three-dose (0, 1, 6 months) series (especially ages 19–59 years)
Herpes zoster (recombinant) ≥50 years Two doses, 2–6 months apart Recommend ≥50 years (per general adult guidance)c
Tetanus, diphtheria and acellular pertussis (Td/Tdap) All One dose followed by booster every 10 years Td or Tdap per adult schedule
Booster every 10 years; Tdap once if never received
Human papilloma virus ≤26 years of age, 27–45 after discussion with healthcare professionals Three doses over 6 months As per routine adult indications (no additional contraindication)
Hepatitis A, MMR, varicella, meningococcal As per routine adult indications (no additional contraindication)

PCV, pneumococcal conjugate vaccine; PPSV, pneumococcal polysaccharide vaccine; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; MMR, measles, mumps, rubella.

a

Korean Society of Infectious Diseases, https://www.ksid.or.kr/content/info/vaccine_info.php,

b

2‑dose series only applies when 2 doses of Heplisav–B are used at least 4 weeks apart. https://www.cdc.gov/vaccines/hcp/imz-schedules/adult-notes.html,

c

In patients without contraindications to live vaccines, the zoster vaccine live (ZVL) may be administered as an alternative to the recombinant formulation.