David Levy, MD, FRCP
Infections in patients with diabetes are a persistent trap for both the inexperienced and world-wise physician. Whenever someone with diabetes presents unwell, always consider the possibility of infection. High blood glucose levels predispose to some acute infections, especially postoperatively, but other mechanisms are involved, for example the effects of long-standing hyperglycemia on small and large blood vessels and on the nervous and immune systems. However, among common infections, only candidal and staphylococcal infections of the skin and mucosa seem to be ‘specific’ to poorly controlled diabetes….
There are countless case reports of unusual infections in diabetes, but few well-controlled prospective studies or RCTs. While there is a reasonable evidence base for treatment of diabetic foot infections, infections elsewhere remain a real diagnostic and treatment challenge.
Diabetes and the chronic low-grade infection of periodontal disease are linked in both directions: diabetes has an adverse effect on periodontal health, and periodontal disease seems to be associated with poor glycemic control and diabetes complications, especially macrovascular disease. Demonstrating the latter link and establishing improved glucose control and a lower risk of complications with improved dental hygiene is difficult.
Types of infections
- Common infections are also common in diabetes, though it is still controversial whether chest and urinary tract infections are in fact more common in people with well-controlled diabetes compared with non-diabetic individuals.
- Common infections occurring in unusual sites, especially staphylococcal infections (see below).
- Unusual infections occurring in unusual sites: some serious but rare infections seem mostly to occur in people with diabetes (e.g. rhinocerebral mucormycosis, ‘malignant’ otitis externa and Fournier’s gangrene); the whole urinary tract and the limbs are susceptible to invasive gas-forming organisms. Pyrexia of unknown origin in someone with diabetes is a real challenge. Fortunately, new imaging techniques, especially fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/computed tomography (CT), will be of great diagnostic help in these cases (though hyperglycemia requires correction for efficient PET scanning results).
Methicillin-resistant Staphylococcus aureus and Clostridium difficile infections
These two organisms are responsible for serious, usually hospital-acquired, infections. MRSA is present in about 30–40% of diabetic foot ulcers in the UK, higher than the reported prevalence in South Asia (10%) but lower than that in other European countries, for example Greece (80%) . Nasal MRSA carriage predisposes to foot infections, and community-acquired MRSA infections in patients not previously treated with antibiotics is probably increasing. The role of MRSA in ulcers that are not clinically infected is not known, but in animal studies the organism itself has increased procoagulant and proinflammatory properties compared with sensitive MRSA, and these characteristics are compatible with the clinical course of serious MRSA infections.
Diabetes itself does not seem to be associated with an increased risk of either antibiotic-associated diarrhoea or C. difficile infections, but foot ulcer patients are more likely to be treated for prolonged periods with antibiotics associated with C. difficile infections (cephalosporins, quinolones and clindamycin).
The high incidence of these infections has led to more restrictive hospital antibiotic guidelines for acute infections. In general, penicillins, vancomycin and gentamicin are emphasized over the broader-spectrum quinolones and cephalosporins. Clindamycin, while being associated with a higher risk of C. difficile, is nevertheless a narrow-spectrum antibiotic and on balance its use is encouraged. Follow local hospital policies for inpatient treatment, but wherever care is given to these threatened patients, antibiotic therapy must always be appropriate for the severity of the infection; in particular bear in mind the high risk of limb loss in severe diabetic foot infections.
Advanced autonomic neuropathy may impair the perception of pleuritic pain. Most surveys do not indicate a higher mortality for people with diabetes from general community-acquired pneumonias, but these studies may conceal a worse out-of-hospital mortality rate. Specifically, pneumococcal and influenzal infections are not more common (though bacteremic pneumococcal infection may be), but carry a greater morbidity and mortality, highlighting the need for widespread immunization in diabetic patients. Infections with some organisms are more common in diabetes, for example:
- Staphylococcus aureus;
- Mycobacterium tuberculosis (increasingly recognized link between both type 1 and type 2 diabetes and tuberculosis in high-prevalence areas, but even in developed countries diabetes seems to carry a greater risk of treatment resistance and death);
- Gram-negative organisms, especially Klebsiella pneumonie, particularly associated with empyema.
Infections after surgery
Coronary bypass surgery
Because this is a common and standard procedure, much of the epidemiological work on postoperative infections has been carried out in bypass patients. Lessons are probably generalizable to other forms of surgery.
Poorly controlled diabetes (e.g. HbA1c > 8.5%, 69 mmol/mol, or admission glucose > 9.2 mmol.L, 166 mg/dL) predicts increased risk of major superficial and deep infections (including mediastinitis, thoracotomy site, septicemia and vein harvest site) after coronary bypass surgery. Diabetes, renal failure and obesity (BMI 30–40) each carry a similar risk; the cumulative risk may therefore be very high in some patients. Bilateral internal thoracic artery grafts and associated ischemia may contribute to chronic sternal wound infections in people with diabetes or chronic heart failure. Negative-pressure dressings and possibly hyperbaric oxygen therapy (see below) may be of value in treating these uncommon but very severe infections. Diabetes does not appear to be a risk factor for infections of implanted pacemakers or cardioverter-defibrillators. Although there is strong epidemiological evidence for a close relationship between glycemic control and surgical outcomes, there are no large-scale trial data, nor are there likely to be.
Lower limb total joint replacement surgery
Poor preoperative glycemic control in patients having total hip and knee replacement is associated with urinary tract and wound infections. Associated postoperative risks (ileus, stroke, postoperative hemorrhage and transfusion) contribute to delayed discharge and increased risk of death . Patients with diabetes more frequently require hip replacement revision surgery as a result of deep infection, especially if they have cardiovascular complications.
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David Levy, MD, FRCP, Consultant Physician, Gillian Hanson Centre, Whipps Cross University Hospital; Honorary Senior Lecturer
Queen Mary University of London London, UK
This edition first published 2011, © 2011 by David Levy. 1st edition 1998 (Greenwich Medical Media/Cambridge University Press) 2nd edition 2006 (Altman Publications)