Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities
- Amy C Weintrob, MD
Amy C Weintrob, MD
- Associate Professor of Medicine
- The George Washington University and Veterans Affairs Medical Center
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
Diabetic foot infections are associated with substantial morbidity and mortality . Important risk factors for development of diabetic foot infections include neuropathy, peripheral vascular disease, and poor glycemic control. In the setting of sensory neuropathy, there is diminished perception of pain and temperature; thus, many patients are slow to recognize the presence of an injury to their feet. Autonomic neuropathy can cause diminished sweat secretion resulting in dry, cracked skin that facilitates the entry of microorganisms to the deeper skin structures. In addition, motor neuropathy can lead to foot deformities, which lead to pressure-induced soft tissue damage. Peripheral artery disease can impair blood flow necessary for healing of ulcers and infections. Hyperglycemia impairs neutrophil function and reduces host defenses. Trauma in patients with one or more of these risk factors precipitates development of wounds that can be slow to heal and predispose to secondary infection.
The microbiology, clinical evaluation, diagnosis, and management of diabetic foot infections will be reviewed here. The general evaluation of the diabetic foot and management of uninfected diabetic foot lesions are discussed separately. (See "Evaluation of the diabetic foot" and "Management of diabetic foot ulcers".)
OVERVIEW OF APPROACH TO THE PATIENT
In 2012, the Infectious Disease Society of America updated guidelines on the diagnosis and management of diabetic foot infections, which were originally published in 2004 . Practical guidelines are also published regularly by the International Working Group on the Diabetic Foot . The information reviewed in this topic is largely consistent with these guidelines.
The evaluation of a patient with a diabetic foot infection involves three key steps: 1) determining the extent and severity of infection, 2) identifying underlying factors that predispose to and promote infection, and 3) assessing the microbial etiology.
The clinical history should focus on the details related to recent trauma, the duration of the current lesion(s), associated systemic symptoms, and prior treatment, if any. Mechanical factors that may predispose to the formation of an ulcer should be noted, and the history of blood glucose control should be assessed. Evidence of systemic toxicity should also be carefully noted.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Caputo GM, Cavanagh PR, Ulbrecht JS, et al. Assessment and management of foot disease in patients with diabetes. N Engl J Med 1994; 331:854.
- Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132.
- Bakker K, Schaper NC, International Working Group on Diabetic Foot Editorial Board. The development of global consensus guidelines on the management and prevention of the diabetic foot 2011. Diabetes Metab Res Rev 2012; 28 Suppl 1:116.
- Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2004; 39:885.
- Jeandrot A, Richard JL, Combescure C, et al. Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study. Diabetologia 2008; 51:347.
- Uzun G, Solmazgul E, Curuksulu H, et al. Procalcitonin as a diagnostic aid in diabetic foot infections. Tohoku J Exp Med 2007; 213:305.
- Mutluoğlu M, Uzun G, İpcioğlu OM, et al. Can procalcitonin predict bone infection in people with diabetes with infected foot ulcers? A pilot study. Diabetes Res Clin Pract 2011; 94:53.
- Karchmer AW, Gibbons GW. Foot infections in diabetes: evaluation and management. Curr Clin Top Infect Dis 1994; 14:1.
- Embil JM, Trepman E. Microbiological evaluation of diabetic foot osteomyelitis. Clin Infect Dis 2006; 42:63.
- Wheat LJ, Allen SD, Henry M, et al. Diabetic foot infections. Bacteriologic analysis. Arch Intern Med 1986; 146:1935.
- Sapico FL, Witte JL, Canawati HN, et al. The infected foot of the diabetic patient: quantitative microbiology and analysis of clinical features. Rev Infect Dis 1984; 6 Suppl 1:S171.
- Lipsky BA, Pecoraro RE, Larson SA, et al. Outpatient management of uncomplicated lower-extremity infections in diabetic patients. Arch Intern Med 1990; 150:790.
- Joseph WS, Axler DA. Microbiology and antimicrobial therapy of diabetic foot infections. Clin Podiatr Med Surg 1990; 7:467.
- Urbancic-Rovan V, Gubina M. Bacteria in superficial diabetic foot ulcers. Diabet Med 2000; 17:814.
- Sims D, Keating SE, DeVincentis AF. Bacteriology of diabetic foot ulcers. J Foot Surg 1984; 23:149.
- Zubair M, Malik A, Ahmad J. Clinico-microbiological study and antimicrobial drug resistance profile of diabetic foot infections in North India. Foot (Edinb) 2011; 21:6.
- Hatipoglu M, Mutluoglu M, Uzun G, et al. The microbiologic profile of diabetic foot infections in Turkey: a 20-year systematic review: diabetic foot infections in Turkey. Eur J Clin Microbiol Infect Dis 2014; 33:871.
- Ramakant P, Verma AK, Misra R, et al. Changing microbiological profile of pathogenic bacteria in diabetic foot infections: time for a rethink on which empirical therapy to choose? Diabetologia 2011; 54:58.
- Young H, Knepper B, Hernandez W, et al. Pseudomonas aeruginosa: an uncommon cause of diabetic foot infection. J Am Podiatr Med Assoc 2015; 105:125.
- Lipsky BA, Armstrong DG, Citron DM, et al. Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, double-blinded, multicentre trial. Lancet 2005; 366:1695.
- Lipsky BA, Itani K, Norden C, Linezolid Diabetic Foot Infections Study Group. Treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate. Clin Infect Dis 2004; 38:17.
- Shakil S, Khan AU. Infected foot ulcers in male and female diabetic patients: a clinico-bioinformative study. Ann Clin Microbiol Antimicrob 2010; 9:2.
- Tascini C, Piaggesi A, Tagliaferri E, et al. Microbiology at first visit of moderate-to-severe diabetic foot infection with antimicrobial activity and a survey of quinolone monotherapy. Diabetes Res Clin Pract 2011; 94:133.
- Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet 2003; 361:1545.
- Chen SY, Giurini JM, Karchmer AW. Invasive Systemic Infection After Hospital Treatment for Diabetic Foot Ulcer: Risk of Occurrence and Effect on Survival. Clin Infect Dis 2017; 64:326.
- Grayson ML, Gibbons GW, Balogh K, et al. Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients. JAMA 1995; 273:721.
- Newman LG, Waller J, Palestro CJ, et al. Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline. JAMA 1991; 266:1246.
- Butalia S, Palda VA, Sargeant RJ, et al. Does this patient with diabetes have osteomyelitis of the lower extremity? JAMA 2008; 299:806.
- Dinh MT, Abad CL, Safdar N. Diagnostic accuracy of the physical examination and imaging tests for osteomyelitis underlying diabetic foot ulcers: meta-analysis. Clin Infect Dis 2008; 47:519.
- Rajbhandari SM, Sutton M, Davies C, et al. 'Sausage toe': a reliable sign of underlying osteomyelitis. Diabet Med 2000; 17:74.
- Lipsky BA, Peters EJ, Senneville E, et al. Expert opinion on the management of infections in the diabetic foot. Diabetes Metab Res Rev 2012; 28 Suppl 1:163.
- Kapoor A, Page S, Lavalley M, et al. Magnetic resonance imaging for diagnosing foot osteomyelitis: a meta-analysis. Arch Intern Med 2007; 167:125.
- Lavery LA, Armstrong DG, Murdoch DP, et al. Validation of the Infectious Diseases Society of America's diabetic foot infection classification system. Clin Infect Dis 2007; 44:562.
- Gottrup F, Holstein P, Jørgensen B, et al. A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. Arch Surg 2001; 136:765.
- Trautner C, Haastert B, Mauckner P, et al. Reduced incidence of lower-limb amputations in the diabetic population of a German city, 1990-2005: results of the Leverkusen Amputation Reduction Study (LARS). Diabetes Care 2007; 30:2633.
- Hellingman AA, Smeets HJ. Efficacy and efficiency of a streamlined multidisciplinary foot ulcer service. J Wound Care 2008; 17:541.
- Frykberg RG, Zgonis T, Armstrong DG, et al. Diabetic foot disorders. A clinical practice guideline (2006 revision). J Foot Ankle Surg 2006; 45:S1.
- Abdelatif M, Yakoot M, Etmaan M. Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. J Wound Care 2008; 17:108.
- Senneville E, Melliez H, Beltrand E, et al. Culture of percutaneous bone biopsy specimens for diagnosis of diabetic foot osteomyelitis: concordance with ulcer swab cultures. Clin Infect Dis 2006; 42:57.
- Perry CR, Pearson RL, Miller GA. Accuracy of cultures of material from swabbing of the superficial aspect of the wound and needle biopsy in the preoperative assessment of osteomyelitis. J Bone Joint Surg Am 1991; 73:745.
- Mackowiak PA, Jones SR, Smith JW. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. JAMA 1978; 239:2772.
- Chakraborti C, Le C, Yanofsky A. Sensitivity of superficial cultures in lower extremity wounds. J Hosp Med 2010; 5:415.
- Khatri G, Wagner DK, Sohnle PG. Effect of bone biopsy in guiding antimicrobial therapy for osteomyelitis complicating open wounds. Am J Med Sci 2001; 321:367.
- Zuluaga AF, Galvis W, Jaimes F, Vesga O. Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study. BMC Infect Dis 2002; 2:8.
- Tan JS, Friedman NM, Hazelton-Miller C, et al. Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation? Clin Infect Dis 1996; 23:286.
- Chang BB, Darling RC 3rd, Paty PS, et al. Expeditious management of ischemic invasive foot infections. Cardiovasc Surg 1996; 4:792.
- Chantelau E, Tanudjaja T, Altenhöfer F, et al. Antibiotic treatment for uncomplicated neuropathic forefoot ulcers in diabetes: a controlled trial. Diabet Med 1996; 13:156.
- Hirschl M, Hirschl AM. Bacterial flora in mal perforant and antimicrobial treatment with ceftriaxone. Chemotherapy 1992; 38:275.
- Lipsky BA. Evidence-based antibiotic therapy of diabetic foot infections. FEMS Immunol Med Microbiol 1999; 26:267.
- Peters EJ, Lipsky BA, Berendt AR, et al. A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot. Diabetes Metab Res Rev 2012; 28 Suppl 1:142.
- Xu ZR, Ran XW, Xian Y, et al. Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial. J Antimicrob Chemother 2016; 71:1688.
- Lauf L, Ozsvár Z, Mitha I, et al. Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis. Diagn Microbiol Infect Dis 2014; 78:469.
- Grayson ML, Gibbons GW, Habershaw GM, et al. Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients. Clin Infect Dis 1994; 18:683.
- Lipsky BA, Baker PD, Landon GC, Fernau R. Antibiotic therapy for diabetic foot infections: comparison of two parenteral-to-oral regimens. Clin Infect Dis 1997; 24:643.
- Senneville E, Lombart A, Beltrand E, et al. Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care 2008; 31:637.
- Berendt AR, Peters EJ, Bakker K, et al. Diabetic foot osteomyelitis: a progress report on diagnosis and a systematic review of treatment. Diabetes Metab Res Rev 2008; 24 Suppl 1:S145.
- Blume PA, Walters J, Payne W, et al. Comparison of negative pressure wound therapy using vacuum-assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial. Diabetes Care 2008; 31:631.
- Cruciani M, Lipsky BA, Mengoli C, de Lalla F. Are granulocyte colony-stimulating factors beneficial in treating diabetic foot infections?: A meta-analysis. Diabetes Care 2005; 28:454.
- Gough A, Clapperton M, Rolando N, et al. Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection. Lancet 1997; 350:855.
- Cruciani M, Lipsky BA, Mengoli C, de Lalla F. Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections. Cochrane Database Syst Rev 2013; :CD006810.
- OVERVIEW OF APPROACH TO THE PATIENT
- Risk of specific organisms
- - Resistant Staphylococcus aureus
- - Pseudomonas aeruginosa
- - Resistant enteric gram-negative rods
- CLINICAL MANIFESTATIONS
- Diagnosis of underlying osteomyelitis
- DIFFERENTIAL DIAGNOSIS
- DETERMINING SEVERITY OF INFECTION
- Wound management
- - Obtaining samples for culture
- - Surgery
- Antimicrobial therapy
- - Empiric therapy
- Mild infection
- Moderate infection
- Severe infection
- - Targeted therapy
- - Duration of therapy
- Adjunctive therapies
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS