Practice Essentials
Diabetes increases susceptibility to various types of infections. The most common sites of infection in diabetic patients are the skin and urinary tract.
Ear, Nose, and Throat Infections
Malignant otitis externa and rhinocerebral mucormycosis are 2 head-and-neck infections seen almost exclusively in patients with diabetes.
Malignant or necrotizing otitis externa principally occurs in diabetic patients older than 35 years and is almost always due to Pseudomonas aeruginosa. [1] Infection starts in the external auditory canal and spreads to adjacent soft tissue, cartilage, and bone. Patients typically present with severe ear pain and otorrhea.
Rhinocerebral mucormycosis collectively refers to infections caused by various ubiquitous molds. [2] Invasive disease occurs in patients with poorly controlled diabetes, especially those with diabetic ketoacidosis. Organisms colonize the nose and paranasal sinuses, spreading to adjacent tissues by invading blood vessels and causing soft tissue necrosis and bony erosion.
Urinary Tract Infections
Patients with diabetes have an increased risk of asymptomatic bacteriuria and pyuria, cystitis, and, more important, serious upper urinary tract infection. [3, 4] Intrarenal bacterial infection should be considered in the differential diagnosis of any patient with diabetes who presents with flank or abdominal pain.
Pyelonephritis makes control of diabetes more difficult by causing insulin resistance; in addition, nausea may limit the patient's ability to maintain normal hydration. Treatment of pyelonephritis does not differ for patients with diabetes, but a lower threshold for hospital admission is appropriate.
Skin and Soft Tissue Infections
Sensory neuropathy, atherosclerotic vascular disease, and hyperglycemia all predispose patients with diabetes to skin and soft tissue infections. These can affect any skin surface but most commonly involve the feet.
Bullosis diabeticorum is a spontaneous, noninflammatory, blistering condition of acral skin that is unique to patients with diabetes mellitus. Blisters in this disease typically heal spontaneously, within 2-6 weeks, but secondary infection may develop.
Other Infections
Contiguous spread of a polymicrobial infection from a skin ulcer (particularly a chronic ulcer) to adjacent bone is common in patients with diabetes.
Although cholecystitis is probably no more common in patients with diabetes than in the general population, severe, fulminating infection, especially with gas-forming organisms, is more common.
The incidences of staphylococcal and Klebsiella pneumoniae infections are greater in people with diabetes than in people without diabetes, and cryptococcal infections and coccidioidomycoses are more virulent in patients with diabetes. Also, diabetes is a risk factor for reactivation of tuberculosis.
Overview
Infections cause considerable morbidity and mortality in patients with diabetes mellitus. Infections may precipitate metabolic derangements, and conversely, the metabolic derangements of diabetes may facilitate infection.
Hyperglycemia and acidemia exacerbate impairments in humoral immunity and polymorphonuclear leukocyte and lymphocyte functions but are substantially reversed when pH and blood glucose levels return to normal. [5] Although the exact level above which leukocyte function is impaired is not defined, in vitro evidence suggests a blood concentration of 200 mg/dL as a possible threshold. [6]
Patients with long-standing diabetes tend to have microvascular and macrovascular disease with resultant poor tissue perfusion and increased risk of infection. Moreover, the ability of the skin to act as a barrier to infection may be compromised when the diminished sensation of diabetic neuropathy results in unnoticed injury.
Diabetes increases susceptibility to various types of infections. The most common sites are the skin and urinary tract. Dermatologic infections that occur with increased frequency in patients with diabetes include staphylococcal follicular skin infections, superficial fungal infections, cellulitis, erysipelas, and oral or genital candidal infections. Lower urinary tract infections and acute pyelonephritis are seen with greater frequency.
A few infections, such as malignant otitis externa, rhinocerebral mucormycosis, and emphysematous pyelonephritis, occur almost exclusively in patients with diabetes. Infections such as staphylococcal sepsis occur more frequently and are more often fatal in patients with diabetes than in other individuals. In contrast, infections such as pneumococcal pneumonia have the same effect on patients with diabetes as they do on other persons. [7]
Ear, Nose, and Throat Infections
As previously mentioned, malignant otitis externa and rhinocerebral mucormycosis, 2 head and neck infections that are associated with high rates of morbidity and mortality, are seen almost exclusively in patients with diabetes.
Malignant otitis externa
Malignant or necrotizing otitis externa principally occurs in patients with diabetes who are older than 35 years and is almost always due to Pseudomonas aeruginosa. [1] The term malignant otitis externa has been applied to several different clinical entities—severe otitis externa, perichondritis, and temporal bone osteomyelitis—which may coexist.
Infection starts in the external auditory canal and spreads to adjacent soft tissue, cartilage, and bone. Patients typically present with severe ear pain and otorrhea. Fever may be absent. Although patients often have preexisting otitis externa, progression to invasive disease is usually rapid.
Examination of the auditory canal may reveal granulation tissue, but spread of infection to the pinna, preauricular tissue, and mastoid often makes the diagnosis apparent. Involvement of the cranial nerves, particularly the facial nerve, is common; when infection extends to the meninges, it is often lethal. Computed tomography (CT) scanning or magnetic resonance imaging (MRI) helps to define the extent of disease.
Prompt surgical consultation is mandatory for malignant otitis externa because surgical debridement is often an essential part of therapy. Intravenous (IV) antipseudomonal antibiotics should be started immediately in patients with invasive disease. Diabetic patients with severe otitis externa but no evidence of invasive disease can be treated with an otic antibiotic drop and oral ciprofloxacin; close follow-up is required.
Rhinocerebral mucormycosis
Rhinocerebral mucormycosis collectively refers to infections caused by various ubiquitous molds. [2]
Invasive disease occurs in patients with poorly controlled diabetes, especially those with diabetic ketoacidosis. Organisms colonize the nose and paranasal sinuses, spreading to adjacent tissues by invading blood vessels and causing soft tissue necrosis and bony erosion.
Patients with rhinocerebral mucormycosis usually present with periorbital or perinasal pain, swelling, and induration. Bloody or black nasal discharge may be present. Involvement of the orbits, with lid swelling, proptosis, and diplopia, is common. The nasal turbinates may appear dusky red, ulcerated, or frankly necrotic. Black, necrotic nasal mucosal or palatal tissue is an important clue. The infection may invade the cranial vault through the cribriform plate, resulting in cerebral abscess, cavernous sinus thrombosis, or internal carotid artery thrombosis.
Wet smears of necrotic tissue often reveal broad hyphae and distinguish mucormycosis from severe facial cellulitis. CT scanning or MRI helps to delineate the extent of disease.
Treatment consists of controlling the predisposing hyperglycemia and acidemia, giving IV amphotericin B, and immediate surgical debridement. Until the diagnosis is confirmed, antistaphylococcal antibiotic therapy is appropriate.
Urinary Tract Infections
Patients with diabetes have an increased risk of asymptomatic bacteriuria and pyuria, cystitis, and, more important, serious upper urinary tract infection. Intrarenal bacterial infection should be considered in the differential diagnosis of any patient with diabetes who presents with flank or abdominal pain.
The treatment of cystitis is essentially the same as that in patients without diabetes, except that longer courses of therapy are generally recommended (eg, 7 days for uncomplicated cystitis). Individuals with a neurogenic bladder due to diabetic neuropathy may not empty their bladder well and may require urologic referral.
Treatment of pyelonephritis does not differ for patients with diabetes, but a lower threshold for hospital admission is appropriate. Pyelonephritis makes control of diabetes more difficult by causing insulin resistance; in addition, nausea may limit the patient's ability to maintain normal hydration. The ensuing hyperglycemia further compromises their immune response. Also, patients with diabetes have increased susceptibility to complications of pyelonephritis (eg, renal abscess, emphysematous pyelonephritis, renal papillary necrosis, gram-negative sepsis).
Emphysematous pyelonephritis is an uncommon, necrotizing renal infection caused by Escherichia coli,Klebsiella pneumoniae, or other organisms capable of fermenting glucose to carbon dioxide. [8]
The presentation is usually similar to that of uncomplicated pyelonephritis, and the diagnosis is established by identifying renal gas on a plain radiograph, a CT scan, or an ultrasonogram. Surgery is indicated after diagnosis.
Skin and Soft Tissue Infections
Sensory neuropathy, atherosclerotic vascular disease, and hyperglycemia all predispose patients with diabetes to skin and soft tissue infections. These can affect any skin surface but most commonly involve the feet. (See Diabetic Foot Infections for complete information on this topic.)
Bullosis diabeticorum is a spontaneous, noninflammatory, blistering condition of acral skin that is unique to patients with diabetes mellitus. Blisters in this disease typically heal spontaneously, within 2-6 weeks, but secondary infection may develop. (See Bullous Disease of Diabetes.)
Cellulitis, lymphangitis, and, most ominously, staphylococcal sepsis can complicate even the smallest wound. Minor wound infections and cellulitis are typically caused by Staphylococcus aureus or hemolytic streptococci. Outpatient treatment of minor infections is appropriate for patients who are reliable, who monitor their blood glucose and urine ketone levels, and who have access to close follow-up.
Treatment with a penicillinase-resistant synthetic penicillin or a first-generation cephalosporin has been effective for the outpatient treatment of minor infections, but the increasing prevalence of community-acquired methicillin-resistant S aureus (CA-MRSA) must now be considered when selecting an antibiotic. Rates of CA-MRSA do not appear to be higher in patients with diabetes than in comparable patients without diabetes.
Necrotizing infections of the skin, subcutaneous tissues, fascia, or muscle can also complicate wounds, particularly cutaneous ulcers. These infections are typically polymicrobial, involving group A streptococci, enterococci, S aureus, Enterobacteriaceae, and various anaerobes. Radiographs of any spreading soft tissue infection in a patient with diabetes should be obtained to look for the soft tissue gas that characterizes necrosis. Gram stains and surface cultures are not helpful.
Surgical debridement is necessary for necrotizing infections. Antibiotic coverage should reflect the range of potential pathogens.
Treatment of diabetic foot ulcers requires management of a number of systemic and local factors, often by a multispecialty team. (For complete information, see Diabetic Ulcers.)
Osteomyelitis
Contiguous spread of a polymicrobial infection from a skin ulcer (particularly a chronic ulcer) to adjacent bone is common in patients with diabetes.
In one study, osteomyelitis was found in the bone under 68% of diabetic foot ulcers, and findings on physical examination and plain radiographs did not help in diagnosing one half of the cases. [9]
Unfortunately, these diagnostic modalities are often the only ones available in the emergency department, and while the diagnosis might be suspected, it might not be established. MRI, if available on an emergent basis, has better sensitivity and specificity in diagnosing osteomyelitis. [10]
Cultures from superficial wound swabs often fail to identify the causative organism. Cultures from biopsy or curettage of the debrided ulcer base are preferred. If osteomyelitis is apparent on physical examination (eg, if the wounds are deep enough to expose tendons or bone), radiography, or MRI, the patient should be admitted for IV antibiotic treatment. If osteomyelitis is suspected but the soft tissue infection or metabolic disturbances do not warrant admission, the patient can be discharged for outpatient workup.
Emphysematous Cholecystitis
Although cholecystitis is probably no more common in patients with diabetes than in the general population, severe, fulminating infection, especially with gas-forming organisms, is more common. The early clinical manifestations of emphysematous cholecystitis are indistinguishable from those of the usual form of cholecystitis.
The diagnosis can be made by finding gas in the gallbladder lumen, wall, or surrounding tissues. Gallstones are present in only approximately 50% of cases. Perforation is common, and, even with immediate surgery, the rate of mortality is high. Infection is typically polymicrobial. Clostridial species are found in more than 50% of cases.
Other Infections
The incidences of staphylococcal and K pneumoniae infections are greater in people with diabetes than in people without diabetes, and cryptococcal infections and coccidioidomycoses are more virulent in patients with diabetes. Also, diabetes is a risk factor for reactivation of tuberculosis. However, a study from Denmark, a country with low tuberculosis burden, found no evidence of association between tuberculosis and dysglycemia. [11]