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Paul Auwaerter, M.D.
02-04-2011
- Diabetes is commonly associated with an increased risk of certain infections; however, good data to support this contention is often slim.
- According to Boyko and Lipsky (ref contains review of epidemiological data and risks), "probable" means data support the association, "possible" means presence or absence of the association cannot be confirmed from available information and "doubtful" indicates that data does not support a link.
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Probable increased risk of infection: asymptomatic bacteruria, lower extremity infections, increased post-surgical infections after sternotomy or total hip replacement, Group B streptococcal infections and reactivation TB in American Indians.
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Possible increased risk of infection: genitourinary infections such as bacterial cystitis, pyelonephritis, candidal vaginitis; respiratory tract infections including pneumonia, influenza, chronic bronchitis, primary or reactivation TB, zygomycete infections (e.g., mucormycosis), malignant otitis media; Fournier's gangrene.
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Doubtful increased risk of infection: S. aureus infections, chronic sinusitis.
- Over incidence of infections associated with diabetes mellitus (DM) difficult to discern based on available data. In US, 10% of all hospital discharges have a DM diagnosis and therefore DM patients admitted more commonly than non-diabetic pts.
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Diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (HHS): infection is leading precipitant with pneumonia and UTIs most common reasons.
- GU infections: bacteruria 2-4x higher in DM. Less data supports increase risk of UTI or pyelonephritis, but likely higher in both women and men. In case reports of emphysematous cystitis, a majority have DM. Candidal UTI, especially C. glabrata, frequently cited as common in DM, but slender data support this association. Commonly believed that candidal vulvovaginitis more common in DM, but no data support this notion.
- Lower extremity (LE) infections more common, including diabetic foot infection, cellulitis and osteomyelitis. Amputation in DM 15x > non-DM.
- Surgical site infections: studies suggest higher rates of sternal wound infections after CABG requiring re-do sternotomy and also saphenous vein graft harvest site infections. Total hip infection rates are also higher in diabetes compared to nodiabetes. Although some studies looking at a broad range of surgical procedures find increased rates of infections (10.7% v 1.8%) other studies found similar rates regardless of status.
- Most convincing data suggests that higher risk for tuberculosis occurs in American Indians with diabetes.
- Group B streptococcal infections: case series have described DM occuring in 9.4%-45.8% of pts.
- Respiratory: S. pneumoniae leading cause of pneumonia but true for most series of community-acquired infection. Mortality for pneumonia or influenza higher inDM patients based upon several studies.
- Zygomycoses (includes Mucor, Rhizopus, Cunninghamella and Absidia fungal species) case series have high rates in DM (up to 70%) and DKA is said to be a special risk factor.
- Necrotizing fasciitis/Fournier's gangrene: diabetes is the most common listed co-morbidity in case series (approximately 10% of patients).
- GU infections: asymptomatic bacteruria defined as >105 organisms/ml in two consecutive urine specimens with or without presence of WBCs. Cystitis or pyelonephritis defined by symptoms and urinalysis: leukocyte esterase (+), nitrite (+), urine with > 10 WBC/hpf, culture >105 organisms per ml. Emphysematous complicated UTI (cystitis or pyelonephritis) with gas seen in renal or bladder structures.
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DKA: leukocytosis of 10,000-15,000 mm3 common and may not indicate infection, if >25,000 mm3 or >10% bandemia consider due to infection until proven otherwise.
- Rhinocerebral zygomycosis: invasive sinusitis in patient usually with eschar present. Obtain sinus CT or MRI along with otolaryngology consultation. Definitive diagnosis by showing hyphae invading tissue + culture.
- Malignant otitis externa: high prevalence of diabetes in case reports. Etiology mostly due to Pseudomonas aeruginosa or Aspergillus species. Historically with high mortality, although this now much lower with effective antibiotic therapy and imaging studies.
- Severe, necrotizing soft tissue infections: necrotizing fasciitis, Fournier's gangrene may present fulminantly (as in type II Group A streptococcal infection ) within 24 hours of onset or more slowly over 2-5 days as in mixed aerobic/anaerobic pathogens typically of type I infections. Pain may be out of proportion to physical findings. Skin discoloration, bullae and thin/foul discharge (not pus) develop routinely without intervention.
- Rhinocerebral zygomycosis: sinus complaints, eschar of the palate that may invade bone, brain and yield cranial nerve palsies.
- Malignant otitis externa: otalgia, ear canal erythema or eschar. May cause facial nerve paralysis w/ progression to involve CN IX, X, XI and XII +/- skull osteomyelitis.
- Group B streptococcal (GBS) infections: higher risk due to diabetes seen with skin/soft tissue infections, bone/joint infections and UTIs--often with concomitant bacteremia.
- GU: if patient without symptoms this is asymptomatic bacteruria regardless of whether leukocytes are present or absent in urine.
- GU infections: asymptomatic bacteruria = no antimicrobial treatment needed. Uncomplicated UTI treated for longer course in DM (i.e. 7 days-10 days), otherwise similar to non-DM (i.e. nitrofurantion 50-100 mg PO daily, amoxicillin-clavulanate 500/125 mg PO twice daily, or trimethoprim-sulfamethoxazole DS 1 tab PO daily)
- Candidal vulvovaginitis: topical suppositories first-line therapy [e.g. OTC: clotrimazole, butoconazole, miconazole, tioconazole] or topical nystatin 100,000U/d, use short course (1-3d) for mild sx, >7-14d if severe, recurrent or abnormal host. Systemic therapy: fluconazole 150mg PO single dose (wait 3d for response). Boric acid 600mg gel capsule intravaginal daily x 14d effective especially for non-albicans species or refractory infections.
- LE infections: see diabetic foot ulcers, osteomyelitis, cellulitis modules. Cellulitis treated with agents to cover staphylococcal +/- MRSA and Gram negative bacteria (i.e. cephalexin 500 mg PO four times daily, amoxicillin/clavulanate 875mg-1000mg PO twice daily or clindamycin 300 mg PO three times daily for 14 days).
- Pneumonia: guidelines for community-acquired pneumonia or hospital-acquired pneumonia do not distinguish diabetes from non-diabetes. Influenza-related mortality may be higher in DM and is considered a high-risk condition for which antiviral treatment should be considered.
- Rhinocerebral zygomycosis: surgical debridement critical, performed on an emergent basis. Antifungal therapy traditionally polyene-based (liposomal amphotericin 5mg/kg IV q24h) but posaconazole and combination therapy (caspofungin and lipid amB) reported to have role in salvage therapy or yield improved outcomes over historical cohorts treated with polyene alone. Fluconazole, voriconazole and echinocandin monotherapy ineffective. Need to correct underlying acidosis and hyperglycemia if present.
- Malignant otitis externa: irrigation, toilet, ear wick and topical antibiotic therapy (see otitis externa module). Oral systemic therapy typically used in addition to topical: ciprofloxacin 500mg PO twice-daily x 10-14 d. Refractory infection or resistant organisms may require parenteral antipseudomonal drugs guided by sensitivity data from culture. Role of surgery unclear.
- GBS: treatment depends on location of infection, penicillin preferred therapy (see Streptococcal species module).
- The best studies documenting decreased wound infection rates with achieving optimal glucose control have been done in the post-CABG patient population.
- Diabetes is often cited as increasing the risk of infection for many conditions; however, data truly linking a diabetic condition to infectious risk is absent for most conditions.
- Hyperglycemic state appears to affect the function of neutrophils with impairment of phagocytosis, chemotaxis/migration as well as intracellular lysis of organisms.
- Other predisposing factors may include abnormal tissue perfusion including peripheral vascular disease and microcirculatory abnormalities.
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Peripheral neuropathy due to diabetes is clearly a risk for diabetic foot infection.
- Patients with abnormal bladder function due to neuropathy are at higher risk of UTI.
- Boyko EJ, Lipsky BA.;
Infection and Diabetes, Chapter 22;
Diabetes in America. ;
2006; Vol.
2nd edition; pp.
485-499;
Rating:
Basis for recommendation Note:
http://diabetes.niddk.nih.gov/dm/pubs/america/index.htm
Comments:Authors canvass available literature to establish whether there is an association with infections commonly considered to be more common in the setting of diabetes. There are some surprising findings, such as insufficient evidence to strongly link rhinocerebral mucormycosis to diabetes or DKA--although this may reflect the available data rather than a true lack of an association. Some studies that support a link date to the 1970's or earlier and relevance in the modern era may be questioned.
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