Advertisement

Post-treatment Leukocytosis Predicts an Unfavorable Clinical Response in Patients with Moderate to Severe Diabetic Foot Infections

  • Adam E. Fleischer
    Correspondence
    Address correspondence to: Adam E. Fleischer, DPM, MPH, FACFAS, Assistant Professor, Departments of Radiology and Surgery, Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, 3471 Green Bay Road, North Chicago, IL 60064.
    Affiliations
    Assistant Professor, Departments of Radiology and Surgery, Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, IL; Director of Research, Podiatric Surgical Residency Training Program, Advocate Illinois Masonic Medical Center, Chicago, IL
    Search for articles by this author
  • James S. Wrobel
    Affiliations
    Associate Professor, Department of Medicine and Director, Scholl’s Center for Lower Extremity Ambulatory Research (CLEAR), Rosalind Franklin University of Medicine and Science, North Chicago, IL
    Search for articles by this author
  • Andrea Leonards
    Affiliations
    Chief Resident, Podiatric Surgical Residency Training Program, Advocate Illinois Masonic Medical Center, Chicago, IL
    Search for articles by this author
  • Scott Berg
    Affiliations
    Fourth Year Podiatric Medical Student, Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, IL
    Search for articles by this author
  • Daniel P. Evans
    Affiliations
    Professor and Chair, Department of Radiology, Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, IL
    Search for articles by this author
  • Robert L. Baron
    Affiliations
    Professor and Former Chair, Department of Radiology, Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, IL
    Search for articles by this author
  • David G. Armstrong
    Affiliations
    Professor of Surgery and Director of Southern Arizona Limb Salvage Alliance (SALSA), University of Arizona College of Medicine, Tucson, AZ
    Search for articles by this author

      Abstract

      Our aim was to determine whether post-treatment laboratory values could help to predict the clinical response in patients with advanced diabetic foot infections. One hundred and three consecutive patients hospitalized for moderate or severe diabetic foot infections at a large, university-affiliated hospital were identified and their records retrospectively reviewed. Definitive therapy during each patient’s hospital course was defined as any foot surgery when additional major surgery was not anticipated or when a course of deep soft tissue and/or bone culture-specific antibiotics had been initiated. The clinical response was assessed at 90 days after the start of definitive therapy. A poor response was recognized as persistent infection at the initial or a contiguous site or when unplanned revision surgery or amputation was subsequently required. The peripheral white blood cell count, neutrophil count, erythrocyte sedimentation rate, and C-reactive protein levels measured shortly after initiating definitive therapy (i.e., post-treatment) were examined for their association with the clinical response using logistic regression models. A total of 38 patients with the complete compliment of laboratory and clinical follow-up aged 59.7 ± 12.3 years with a diabetes duration of 13.3 ± 9.1 years were included. Leukocytosis, defined as a white blood cell count >11,000 cells/μL, observed an average of 3 ± 1.4 days after treatment, was the single most important marker for predicting a poor clinical response, and the only significant study variable in both univariate and multivariate analyses (multivariate odds ratio 9.7, 95% confidence interval 1.0 to 92, p = .048). We conclude that leukocytosis observed shortly after initiating definitive therapy is predictive of an unfavorable clinical response by 90 days.

      Level of Clinical Evidence

      Keywords

      To read this article in full you will need to make a payment

      References

        • Cavanagh P.
        • Lipsky B.A.
        • Bradbury A.
        Treating diabetic foot ulcers.
        Lancet. 2005; 366: 1725-1735
        • Lipsky B.A.
        • Berendt A.R.
        • Deery H.G.
        • Embil J.M.
        • Joseph W.S.
        • Karchmer A.W.
        • LeFrock J.L.
        • Lew D.P.
        • Mader J.T.
        • Norden C.
        • Tan J.S.
        Diagnosis and treatment of diabetic foot infections.
        Clin Infect Dis. 2004; 39: 885-910
        • Singh N.
        • Armstrong D.G.
        • Lipsky B.A.
        Preventing foot ulcers in patients with diabetes.
        JAMA. 2007; 293: 217-228
      1. US Centers for Disease Control Prevention. Average length of stay (LOS) in days of hospital discharges for nontraumatic lower extremity amputation with diabetes as a listed diagnosis, United States, 1980–2005 [cited 11 September 2008]. Available at: http://www.cdc.gov/diabetes/statistics/lea/fig2.htm. Accessed 24 July 2010.

      2. Kozak LJ, DeFrances CJ, Hall MJ. National Hospital Discharge Survey: 2004 annual summary with detailed diagnosis and procedure data. National Center for Health Statistics. Vital Health Stat Series 13, Issue 162, 2006.

        • Eneroth M.
        • Apelqvist J.
        • Stenstrom A.
        Clinical characteristics and outcome in 223 diabetic patients with deep foot infections.
        Foot Ankle Int. 1997; 18: 716-722
        • Akanji A.O.
        • Famuyiwa O.O.
        • Adetuyibi A.
        Factors influencing the outcome of treatment of foot lesions in Nigerian patients with diabetes mellitus.
        Q J Med. 1989; 73: 1005-1014
        • Pittet D.
        • Wyssa B.
        • Herter-Clavel C.
        • Kursteiner K.
        • Vaucher J.
        • Lew P.D.
        Outcome of diabetic foot infections treated conservatively: a retrospective cohort study with long-term follow-up.
        Arch Intern Med. 1999; 159: 851-856
        • Benotmane A.
        • Mohammedi F.
        • Ayad F.
        • Kadi K.
        • Azzouz A.
        Diabetic foot lesions: etiologic and prognostic factors.
        Diabetes Metab. 2007; 26: 113-117
        • Diamantopoulos E.J.
        • Haritos D.
        • Yfandi G.
        • Grigoriadou M.
        • Margariti G.
        • Paniara O.
        • Raptis S.A.
        Management and outcome of severe diabetic foot infections.
        Exp Clin Endocrinol Diabetes. 1998; 106: 346-352
        • Grayson M.L.
        • Gibbons G.W.
        • Habershaw G.M.
        • Freeman D.V.
        • Pomposelli F.B.
        • Rosenblum B.I.
        • Levin E.
        • Karchmer A.W.
        Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients.
        Clin Infect Dis. 1994; 18: 683-693
        • Criado E.
        • De Stefano A.A.
        • Keagy B.A.
        • Upchurch Jr., G.R.
        • Johnson Jr., G.
        The course of severe foot infection in patients with diabetes.
        Surg Gynecol Obstet. 1992; 175: 135-140
        • Lipsky B.A.
        • Sheehan P.
        • Armstrong D.G.
        • Tice A.D.
        • Polis A.B.
        • Abramson M.A.
        Clinical predictors of treatment failure for diabetic foot infections: data from a prospective trial.
        Int Wound J. 2007; 4: 30-38
        • Lipsky B.A.
        A report from the international consensus on diagnosing and treating the infected diabetic foot.
        Diabetes Metab Res Rev. 2004; 20: S68-S77
        • Malay D.S.
        • Margolis D.J.
        • Hoffstad O.J.
        • Bellamy S.
        The incidence and risks of failure to heal after lower extremity amputation for the treatment of diabetic neuropathic foot ulcer.
        J Foot Ankle Surg. 2006; 45: 366-374
        • Crosby L.A.
        • Powell D.A.
        The potential value of the sedimentation rate in monitoring treatment outcome in puncture-wound-related Pseudomonas osteomyelitis.
        Clin Orthop Rel Res. 1983; 188: 168-172
        • Unikila-Kallio L.
        • Kallio M.J.T.
        • Peltola H.
        The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis: a comparison with the usefulness of the erythrocyte sedimentation rate and the white blood-cell count.
        J Bone Joint Surg. 1994; 76: 848-853
        • Khan M.H.
        • Smith P.N.
        • Rao N.
        • Donaldson W.F.
        Serum C-reactive protein levels correlate with clinical response in patients treated with antibiotics for wound infections after spinal surgery.
        Spine J. 2006; 6: 311-315
        • Nilsdotter-Augustinsson A.
        • Briheim G.
        • Herder A.
        • Ljunghusen O.
        • Wahlström O.
        • Ohman L.
        Inflammatory response in 85 patients with loosened hip prostheses: a prospective study comparing inflammatory markers in patients with aseptic and septic prosthetic loosening.
        Acta Orthop. 2007; 78: 629-639
        • Owens C.D.
        • Ridker P.M.
        • Belkin M.
        • Hamdan A.D.
        • Pomposelli F.
        • Logerfo F.
        • Creager M.A.
        • Conte M.S.
        Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery.
        J Vasc Surg. 2007; 45: 2-9
        • Rabjohn L.
        • Roberts K.
        • Troiano M.
        • Schoenhaus H.
        Diagnostic and prognostic value of erythrocyte sedimentation rate in contiguous osteomyelitis of the foot and ankle.
        J Foot Ankle Surg. 2007; 46: 230-237
        • Dupont C.
        • Rodenbach J.
        • Flachaire E.
        The value of C-reactive protein for postoperative monitoring of lower limb arthroplasty.
        Ann Readapt Med Phys. 2008; 51: 348-357
        • Lavery L.
        • Armstrong D.G.
        • Harkless L.B.
        Classification of diabetic foot wounds.
        J Foot Ankle Surg. 1996; 35: 528-531
        • Armstrong D.G.
        • Lavery L.A.
        • Harkless L.B.
        Validation of a diabetic wound classification system: the contribution of depth, infection, and ischemia to risk of amputation.
        Diabetes Care. 1998; 21: 855-859
        • Concato J.
        • Feinstein A.R.
        • Holford T.R.
        The risk of determining risk with multivariable models.
        Ann Int Med. 1993; 118: 201-210
        • Hosmer D.W.
        • Lemeshow S.
        Applied Logistic Regression.
        John Wiley & Sons, New York1989
        • Greenland S.
        Basic methods for sensitivity analysis of biases.
        Int J Epidemiol. 1996; 25: 1107-1116
        • Armstrong D.G.
        • Lavery L.A.
        • Sariaya M.
        • Ashry H.
        Leukocytosis is a poor indicator of acute osteomyelitis of the foot in diabetes mellitus.
        J Foot Ankle Surg. 1996; 35: 280-283
        • Jeandrot A.
        • Richard J.L.
        • Combescure C.
        • Jourdan N.
        • Finge S.
        • Rodier M.
        • Corbeau P.
        • Sotto A.
        • Lavigne J.P.
        Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study.
        Diabetologia. 2008; 51: 347-352
        • Fleischer A.E.
        • Didyk A.A.
        • Woods J.B.
        • Burns S.E.
        • Wrobel J.S.
        • Armstrong D.G.
        Combined clinical and laboratory testing improves diagnostic accuracy for osteomyelitis in the diabetic foot.
        J Foot Ankle Surg. 2009; 48: 39-46
        • Akinci B.
        • Yener S.
        • Yesil S.
        • Yapar N.
        • Kucukyavas Y.
        • Bayraktar F.
        Acute phase reactants predict the risk of amputation in diabetic foot infection.
        J Am Podiatr Med Assoc. 2011; 101: 1-6
        • Wrobel J.S.
        • Mayfield J.A.
        • Reiber G.E.
        Geographic variation of lower-extremity major amputation in individuals with and without diabetes in the Medicare population.
        Diabetes Care. 2001; 24: 860-864