What s New in the New Diabetic Foot Infection Guidelines?

Transcription

1 What s New in the New Diabetic Foot Infection Guidelines? Benjamin A. Lipsky, MD, FACP, FIDSA, FRCP Professor of Medicine, University of Washington Director, Primary Care Clinic & Antibiotic Research VA Puget Sound Health Care System, Seattle, Washington, USA

2 Web of Science: Diabetic Foot Infections Citations & Publications in Past Decade Published Items/year Citations/year ISI Web of Science March 2012

3 Diabetic LE Complications USA : Rate/1000 diabetic population Hospitalizations Amputations Ulcer, Infection Number of hospital d/c for diabetic patients with peripheral arterial disease (PAD), ulcer/inflammation/infection, or neuropathy as 1 st listed diagnosis CDC, 2012:

4 UW/VAPSHCS There is No Shortage of Diabetic Foot Guidelines! Partial Listing of PubMed Search for Apelqvist J et al. Practical guidelines on the management...[pmid: ] Hinchliffe RJ et al. Specific guidelines on wound care...[pmid: ] Bus SA et al. Specific guidelines on footwear for diabetic...[mid: ] Apelqvist J et al. The development of global consensus...[pmid: ] Steed DL et al. Guidelines for the prevention and treatment...[pmid: ] Orsted HL et al. Best practice recommendations for manage...[pmid: ] Société de Infectieuse de Langue Française. [Management of diabetic foot.. Ollenschläger G et al. [The German Program for Diseases...[PMID: ] Frykberg RG et al. Diabetic foot disorders. A clinical...[pmid: ] Steed DL et al. Guidelines for the treatment of diabetic...[pmid: ] Frykberg RG. A summary of guidelines for managing...[pmid: ] Pinzur MS et al. Guidelines for diabetic foot disorders...[pmid: ] Wraight PR et al. Creation of a multidisciplinary diabetic...[pmid: ] Fabregas B. [Care of the diabetic foot. A multidisciplin...[pmid: ] Matwa P et al. Experiences and guidelines for diabetic...[pmid: ] Schaper NC et al. The international consensus a...[pmid: ] Association of Physicians of India.. Indian diabetes guidelines...[pmid: ] Inlow S et al. Best practices for the prevention of...[pmid: ] Rollins G. Guidelines on diabetic foot diseases...[pmid: ] Frykberg RG et al. Diabetic foot disorders: a cinicall...[pmid: ]

5 Diabetic Foot Infections: Management Guidelines Infection Consensus

6 DFI Guidelines: What a Year! NICE: Diabetic Foot Inpatient Management of People with Diabetic Foot Ulcers and Infection. Clinical Guidelines 119, March 2011; diabetic-foot-problems-cg119 International Working Group on the Diabetic Foot: Expert opinion on the management of infections in the diabetic foot (revised). Lipsky et al, Diab Met Res Rev 2012; Feb;28 Suppl 1:163-78; Infectious Diseases Society of America: Clinical Practice Guidelines for the Diagnosis & Treatment of Diabetic Foot Infections (revised). Lipsky et al, Clin Infect Dis 2012;54[June 15]:e132-73;

7 Is the IDSA DFI Severity Classification Valid? 100% Hospitalization Amputation Prospective study:1666 patients with DFU 75% 50% 25% 00% No Infection Mild Moderate Severe Lavery, et al, Clin Infect Dis, 2007;44:562

8 UW/VAPSHCS Relationship of IDSA Severity to Clinical Severity & Outcomes CRP/2 WBC PMN>75% p< Failure Amputation p< SIRS% Deep Inf Osteo devel Req Surgery Mild Mild Moderate Severe Noel, Lipsky, et al; Ceftobiprole vs Vanco+Ceftazadime for DFI (n=257) 0 Mild Moderate Severe

9 IWGDF Classification Predicts LE Amputation Prospective study Sudan ; 2321 DFU patients 28.5% underwent LE amputation; 65% were toes OR, 95% CI Factor significantly associated with amputation Neuropathy ESRD Ischemia Neuropathy Grade of infection Depth of wound Major amputations Toe amputation Widatalla et al. Int J Diabetes Dev Countries 2009;29:1

10 Have DFI Guidelines Been Found to be Useful? Outcome of Implementing DFI Guidelines in France 2003 audit of microbiological assessment of DFI Many clinically uninfected wounds cultured Most cultures collected by suboptimal techniques Frequently isolated MDROs (especially MRSA) Isolated many low-virulence (likely colonizing) species Developed & implemented IDSA-based guidelines emphasizing appropriate wound culture methods Re-audited clinical & micro data on 405 pts Micro lab workload; inappropriate antibiotics Cost saving from both of > 231,000 Sotto et al, Diabetologia 2010 ;53:2249

11 UK NICE Guidelines

12 NICE: Inpatient Management Diabetic Foot Problems Initial Evaluation & Assessment (CG 119) Examine for evidence of systemic or local (foot) infection, as well as other foot complications Refer patient to multidisciplinary team w/n 24 hours Obtain plain X-rays (R/O osteo, Charcot, foreign body) Obtain urgent advice from appropriate specialist if Signs of systemic sepsis Evidence of deep-seated infection

13 NICE: Inpatient Management Diabetic Foot Problems Antibiotics for Diabetic Foot Infection Antibiotic treatment is crucial to treat diabetic foot infections but evidence inconclusive & of low quality, precluding recommendations on individual agents Each hospital should have antibiotic guidelines for Rx DFI; MRSA Rx based on local/national guidance Don t delay antibiotic Rx for suspected osteomyelitis pending MRI results Start empirical antibiotic Rx based on severity; definitive regimen should be informed by microbiology results

14 NICE: Inpatient Management Diabetic Foot Problems Antibiotics for Diabetic Foot Infection Select antibiotics with lowest acquisition cost appropriate for the clinical situation & severity Use antibiotics with activity against: Gram + organisms for mild infections Both Gram + & Gram - (± anaerobic bacteria) for moderate /severe infections Route of administration should be: oral for mild infections oral or IV (based on clinical situation) for moderate IV initially for severe infections then reassess Don t give prolonged Rx for mild soft tissue infections

15 IWGDF Revised Guideline on DFI

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17 IWGDF DFI Guidelines: Table of Contents Introduction Pathophysiology Classification Diagnosis Soft tissue infection Osteomyelitis Clinical evaluation Probe-to-bone test Blood tests Imaging studies Plain radiography Magnetic resonance Nuclear medicine Other imaging studies Bone biopsy Assessing severity Microbiological considerations When to send specimen How to obtain specimen Interpreting culture result Bone infection Treatment Antimicrobial therapy Indications for therapy Route of therapy Choice of antibiotics Duration of therapy Wound care Treating osteomyelitis Adjunctive therapies Outcome of treatment Developing country issues

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19 Common Imaging Features of DF Osteomyelitis Table 2

20 Clinical Characteristics Suggesting a More Serious Diabetic Foot Infection (Table 3A) Wound specific -Wound: -Cellulitis: Penetrates into subcutaneous tissues, e.g. fascia, tendon, muscle, joint, bone Extensive (>2 cm), distant from ulceration, or rapidly progressive -Local signs: Severe inflammation, crepitus, bullae, marked induration, discoloration, necrosis/ gangrene, ecchymoses, or petechiae General

21 Clinical Characteristics Suggesting a More Serious Diabetic Foot Infection (Table 3A) Wound Specific General -Presentation: -Systemic signs: Acute or rapidly progressive Fever, chills, hypotension, confusion, volume depletion, -Laboratory tests: Leukocytosis, severe or worsening hyperglycemia, acidosis, azotemia, electrolyte abnormalities -Complicating features Presence of a foreign body (accidental or surgically implanted), puncture wound, abscess, arterial or venous insufficiency, lymphedema -Current treatment: Progression while on presumably appropriate antibiotic therapy

22 Factors Suggesting Hospitalization May be Necessary (Table 3B) Severe infection (see Table 3A) Metabolic instability IV Rx needed (& not available/appropriate as outpt) Diagnostic tests needed not available as outpatient Critical foot ischemia present Surgical procedures (more than minor) required Failure of outpatient management Patient unable/unwilling to comply with outpt Rx Need for complex dressing changes

23 Factors that may Influence Choices of Antibiotic Therapy for Diabetic Foot Infections (Table 4) Infection related - Clinical severity of the infection - H/O antibiotic therapy w/n 3 mos - Bone infection (presumed/ proven) Pathogen related - Likelihood of non-gpc pathogen(s) - H/O MDROs colonization/ infection - Local rates of antibiotic resistance Patient related - Allergies to antibiotics - Impaired immunological status - Patient treatment preferences - Renal or hepatic insufficiency - Impaired gastrointestinal absorption - Arterial insufficiency in affected limb - risk MDROs, unusual pathogens Drug related - Safety profile (frequency & severity of AEs) - Drug interaction potential - Frequency of dosing - Formulary availability/ restrictions - Cost considerations (acquisition & administrn) - Approval for indication - Likelihood of inducing C. difficile disease or antibiotic resistance - Published efficacy data

24 Selecting Empiric Antibiotics for DFI (Table 5) Lipsky et al, Diab Met Res Rev 2012;28 Suppl 1:234

25 Figure 1. Approach to the infected diabetic foot pathogen

26 Issues of Importance in Developing Countries Causes of infections: often related to poorly protective or absent footwear Delay in seeking healthcare: related to lack of finances and/or education Use of home remedies of? value/harm Non-prescription antibiotics: over-the-counter (pharmacist), borrowed, expired, short-course Difficulty adhering to prescribed regimen Difficulty in following up with healthcare workers Limited diagnostic and therapeutic modalites

27 Outcome of Treatment Mild infections: Usually resolve with appropriate Rx Moderate/Severe infections: Many require surgical debridement (soft tissue ± bone) or LE amputation (usually partial/minor) With extensive infection LEA rates up to 50-60% (most foot-sparing), but cure in ~80% Recurrence of foot infection in 20-30% ( w/ osteo) Evidence of cure of infection Resolution of signs/symptoms of infection Normalization of inflammatory markers Signs of bone healing on x-ray

28 IDSA DFI Guidelines: Revised Clinical Infectious Diseases 2012;54(12): Published by Oxford University Press on behalf of the Infectious Diseases Society of America DOI: /cid/cis346

29 What s New in the New IDSA Guidelines? New format: 10 questions selected, each with recommendations and evidence summary GRADE system to rank evidence: Strength of recommendation: Strong or Weak Quality of evidence: High, Moderate, Low, Very Low Systematic review of the literature (& limitations) Updated references (345) Recommendations for future work Implementation Regulatory changes Research questions Potential performance measures: outcomes, process

30 Revised IDSA Guideline: The 10 Questions 1. In which diabetic patients with a foot wound should I suspect infection & how should I classify foot wounds? 2. How should I assess a diabetic patient presenting with a foot infection? 3. When should I request a consultation for a patient with a DFI, & from whom? 4. Which patients with a DFI should I hospitalize, & what criteria should they meet before discharge? 5. When and how should I send specimen(s) for culture from a patient with a diabetic foot wound?

31 Diabetic Foot Infection: Revised IDSA Guideline 6. How should I initially select, and when should I modify, an antibiotic regimen for a DFI? 7. When should I consider imaging studies to evaluate a DFI, and which should I select? 8. How should I diagnose and treat osteomyelitis of the foot in a patient with diabetes? 9. In which patients with a DFI should I consider surgical intervention & what procedures may be appropriate? 10. What type of wound care techniques and dressings should I use for a patient with a diabetic foot wound?

32 IDSA/IWGDF Classifications DFI Table 2 Erythema >0.5 cm to 2 cm around ulcer

33 Table 3 DFI Wound Score Lipsky et al Wound Repair Regen 2009;17:671

34 Interpretation of Results of Ankle Brachial Index Table 4

35 Collecting Specimens for Culture From Wounds Table 5

36 Antibiotic Selection Overview: Consideratons Table 6 -positive

37 Consider Empirical Anti-MRSA Rx if History of MRSA infection/colonization in past year Local % S. aureus clinical isolates that are methicillin-resistant) is high (~50% for mild, 30% for moderate soft tissue infection Infection is sufficiently severe that failing to empirically cover MRSA while awaiting definitive cultures would pose unacceptable risk of failure For suspected osteomyelitis, obtain specimen of bone for culture for most cases in which MRSA posible

38 Antibiotics for DFI: Revised IDSA Guidelines Route & Agent Mild Mod erate /Severe Comments Table 8 Dicloxacillin (po) [* = 1 DFI trial] Requires QID dosing, inexpensive Cephalexin (po)* [Ital=FDA aprvd] Requires QID dosing, inexpensive Clindamycin (po,iv)* t [ t =covers MRSA] GP aer/ana-robes; ±MRSA; D-test Trimeth/Sulfa (po,iv) t [Bold=common] GPC (± streps), GNR, C-A MRSA Amoxicillin/clav(po)* Relatively broad-spectrum Levofloxacin (po,iv)* QD dosing; suboptimal S. aureus Moxifloxacin (po,iv)* QD dosing; better for anaerobes Cefoxitin (IV)* 2 nd gen cephalosporin- for anaerobes Ceftriaxone (IV,IM) 3 rd gen cephalosporin; QD dosing Ampicillin/sulb (IV)* Rel. broad-spectrum, not Ps aerug. Linezolid (po,iv)* t GPs & MRSA; $$; toxicity >2 weeks Daptomycin (IV)* t GPs & MRSA; $$; QD; monitor CK Vancomycin (IV)* t Cheap; MIC creep; monitor for creat Ertapenem (IV)* QD; rel. broad-spect, not Ps aerug. Tigecycline (IV)* t Broad-spect. & MRSA;N/V; efficacy Piperacillin/tazo(IV)* TID/QID; broad-spect. & Ps aerug. Imipenem-cilast (IV)* Broad-spect. & ESBLs; not MRSA

39 Suggested Route, Setting, & Duration of Antibiotic Therapy, by Syndrome (Soft Tissue) Table 11

40 Bone Biopsy for Diabetic Foot Osteomyelitis Courtesy: E. Senneville, MD

41 In Which Situations Is Diagnostic Bone Biopsy Most Recommended? Table 9 Uncertainty regarding the diagnosis of osteomyelitis despite clinical and imaging evaluations; Absence (or confusing mix) of culture data from soft tissue specimens; Failure to respond to empiric antibiotic\therapy; or, Desire to use antibiotic agents that may be especially effective for osteomyelitis but have a high potential for selecting resistant bacteria (eg, rifampin, FQs)

42 Management Suspected DFO If X-ray changes suggestive of osteomyelitis Treat for presumptive osteomyelitis, preferably After obtaining appropriate specimens for culture (consider obtaining bone biopsy, if available) If the radiographs show no evidence of osteomyelitis, Rx antibiotics 2 weeks if soft tissue infection, and Optimal wound care and off-loading Repeat plain x-rays; if negative If wound improving, PTB-, osteomyelitis unlikely If wound not improving or PTB+, further dx studies

43 Approach to Treating Diabetic Foot Osteomyelitis Table 10

44 Approach to Treating DF Osteomyelitis (contin) Table 10 (continued)

45 Suggested Route, Setting, & Duration of Antibiotic Therapy, by Syndrome (DFO) Table 11 (contin.)

46 Surgical Intervention in Diabetic Foot Infections Seek surgical consultation for infection with gas in deeper tissues, abscess, substantial nonviable tissue, necrotizing fasciitis, extensive bone or joint involvement, bullae, neurologic loss, new anesthesia The surgeon should have knowledge of foot anatomy & experience in dealing DFIs Evaluate limb s arterial supply; consider revascularization 4 central spaces

47 Questions to Ask When Dealing With DFI Nonresponse or Recurrence Table 13

48 Questions to Ask When Dealing With DFI Nonresponse or Recurrence Table 13 (contin)

49 Potential Performance Measures for Managing Diabetic Foot Infection Table 14

50 Potential Performance Measures for Managing Diabetic Foot Infection Table 14 (contin.) situations

51 Diabetic Foot Infections: Summary Common, complex and costly problem Classification: based on severity (± ischemia) Culture tissue (rather than swab) specimens Causative organisms: GPC >> GNR > Anaerobes Antibiotic therapy: choosing empiric, definitive Often need debridement, I&D; ± revascularization Osteomyelitis: difficult to diagnosis & to treat Adjunctive measures occasionally helpful Multidisciplinary teams lead to improved outcomes How do we improve implement, audit, study

52 Guidelines are like a map The Role of Guidelines Implementation is the journey K. Bakker, MD Chair, International Working Group on the Diabetic Foot

53 Teşekkür ederim!

54 Signs of a Possibly Imminently Limb Threatening Infection Table 12

55 When Rx of DFO Fails, Consider Was the original diagnosis correct? Is there residual necrotic/infected bone or surgical hardware that should be resected/removed? Was selected antibiotic regimen likely to cover causative organism(s), achieve adequate bone levels, given for a sufficient duration? Is a noninfectious complication (eg, inadequate offloading, blood supply), not failure to eradicate bone infection, the problem?

56 NICE: Inpatient Management Diabetic Foot Problems Investigating Possible DFI (CG 119) If moderate-severe soft tissue wound infection suspected Send tissue sample from base of debrided wound for microbiological examination If not possible, a superficial swab may provide useful information on the choice of antibiotic therapy

57 NICE: Inpatient Management Diabetic Foot Problems Investigation Possible DFI (CG 119) If moderate-severe soft tissue wound infection suspected Send tissue sample from base of debrided wound for microbiological examination If not possible, a superficial swab may provide useful information on the choice of antibiotic therapy If osteomyelitis suspected but not confirmed by X-ray Order a MRI study If unavailable/contraindicated consider WBC scan For suspected osteomyelitis, do not Exclude by negative X-rays or probe-to-bone alone Diagnose by nuclear medicine bone scans

58 Studies of Antibiotic Rx for DFI Since 2004 Table 7

59 Clinical Classification Diabetic Foot Infection IDSA IWGDF Clinical Manifestations* Severity PEDIS No purulence or inflammation (erythema, pain, warmth tenderness, or induration) Infected but any erythema 2 cm around ulcer & infection limited to skin & superficial subcutaneous tissues Uninfected 1 Mild 2 1 of following: cellulitis >2 cm; lymphangitis; subq spread; deep abscess; gangrene; muscle, tendon, joint or bone involved Moderate 3 Systemic toxicity or metabolic instability *Severity worsened by ischemia Severe 4

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61 Diabetic Foot Infection Guidelines Panels IDSA: Benjamin A. Lipsky (Chair) Anthony R. Berendt ^ Adolph W. Karchmer David G. Armstrong * P Eric Senneville * ^ Paul B. Cornia * G Edgar J. Peters * ^ H. Gunner Deery James C. Pile * H John M. Embil ^ Michael Pinzur * O Warren S. Joseph P IWGDF panel: Benjamin A. Lipsky (Chair) William Jeffcoate D Larry Lavery P Karel Bakker D Vilma Rovan- Urbancic D *New; Non-US; P Podiatrist; O Orthopedist; G Generalist; H Hospitalist; D Diabetol. ^ Also a member of the IWGDF

62 Situations in Which to Consider Non-Surgical Management of Diabetic Foot Osteomyelitis No acceptable surgical target (ie, radical cure of infection would unacceptable functional loss) Patient has limb ischemia caused by unreconstructable vascular disease but wishes to avoid amputation Infection confined to the forefoot, & there is minimal soft tissue loss Patient & healthcare professionals agree that surgical management carries excessive risk or is otherwise not appropriate or desirable

63 Potential Suggested Performance Measures Composition & meeting frequency of DF Teams % patients with DFI see by a multidisciplinary team Waiting times for initial evaluation & referral to the specialist foot care team Time intervals between key management milestones clinical assessment to appropriate imaging, to initiation of treatment, or completion surgery Average and median length of hospital stay for a DFI Frequency of providing appropriate foot care services on discharge from the hospital Existence and use of locally agreed protocols, and evidence of audit of compliance

64 Systematic Review of Effectiveness of Interventions for Managing DFIs: IWGDF 7517 papers; 33 met criteria; 29 RCTs; 4 cohort studies Comparisons antibiotic regimens for skin/soft-tissue ± bone infection: none showed significant difference 2 health economic analyses; 1 w/ small saving for 1 arm No data supported superiority of a particular route of delivery or optimal duration of antibiotic therapy Possible benefit (weak studies): bone culture-guided antibiotics; early surgical intervention; superoxidized water; G-CSF No infection benefit shown for systemic HBO Peters et al, Diabetes Metab Res Rev 2012 Feb;28 Suppl 1:142

65 Characteristics Suggesting a More Serious DFI Wound specific Wound Cellulitis Local signs General Presentation Systemic signs Laboratory tests Complicating features Current treatment Penetrates into subcutaneous tissues Extensive (>2 cm) or rapidly progressive Crepitus, bullae, discoloration, necrosis, gangrene, ecchymoses or petechiae Acute onset or rapidly progressive Fever, chills, hypotension, confusion, volume Leukocytosis, severe hyperglycemia, acidosis, azotemia, electrolyte abnormalities Foreign body, puncture wound, abscess, arterial or venous insufficiency, lymphedema Progression while on apparently appropriate antibiotic therapy Lipsky et al, IWGDF. Diabetes Metab Res Rev 2012;28 Suppl 1:234

66 Management Suspected DFO: continued Repeat X-rays 2 4 weeks after initial radiographs If remain normal but osteomyelitis still possible: Where wound depth is decreasing & PTB negative, osteomyelitis unlikely Where wound not improving or PTB +, consider Additional imaging studies, preferably MRI Bone biopsy for culture and histology Empiric treatment: (based on available cultures) X 2 4 weeks then repeat X-rays

67 Conclusions: Effects of DFI Guidelines Better recognition of clinically infected ulcers Better techniques for obtaining specimens for culture # of cultured wounds in number of bacteria/specimen prevalence colonizers (23% 6%) Decreased prevalence of MDRO (35% 16%) laboratory workload broad-spectrum antibiotic prescriptions COST-SAVINGS 20, ,585

68 Systematic Review of Effectiveness of Interventions for Managing DFIs: IWGDF 7517 papers; 33 met criteria; 29 RCTs; 4 cohort studies Comparisons antibiotic regimens: 12 for skin/soft-tissue, 7 for SSTI + bone infection: none showed difference 2 health economic analyses; 1 w/ small saving for 1 arm No data supported superiority of a particular route of delivery or optimal duration of antibiotic therapy Possible benefit (weak studies): bone culture-guided antibiotics; early surgical intervention; superoxidized water; G-CSF No infection benefit shown for systemic HBO Peters et al, Diabetes Metab Res Rev 2012 Feb;28 Suppl 1:142

69 Systematic Reviews of Antibiotic Therapy RCTs of Treatment Diabetic Foot Inections 18 published RCTs comparing antibiotics Overall observed treatment failure rate: 23% Rates for direct comparison various agents similar Combining patients, failures with carbapenems Failure rates for MRSA (alone or mixed): 35% Rates similar +/- osteomyelitis: 26% Variations in study design, inclusion criteria, definitions of clinical & microbiological endpoints Cannot determine most appropriate regimen Vardakas et al, Diabetes Res Clin Pract 2008;80:344 Crouzet et al Int J Inf Dis 2011;15(9):e601-10

70 Critical Review of Randomized Clinical Trials of Antibiotic Therapy of DFI ( ) From 123 papers found,14 were RCTs 6 double-blind: 2 single-blind; 6 open-label 15 supported by pharmaceutical companies 12 excluded cases with osteomyelitis Duration follow-up: 1 wk to 2 months Discrepancies in study design, inclusion criteria, statistical methodology, & varying definitions of clinical & microbiological endpoints make comparisons difficult Cannot determine most appropriate regimen Crouzet et al Int J Inf Dis 2011;15(9):e601-10

71 IDSA DFI Guidelines: Revised In which diabetic patients with a foot wound should I suspect infection and how should I classify it? 2. How should I assess a diabetic patient presenting with a foot infection? 3. When should I request a consultation for a patient with a diabetic foot infection, and from whom? 4. Which patients with a diabetic foot infection should I hospitalize, and what criteria should they meet before I discharge them? 5. When and how should I obtain specimen(s) for culture from a patient with a diabetic foot wound? Lipsky et al, Clin Infect Dis (in press)

72 IDSA DFI Guidelines: Revised How should I initially select, and when should I modify, an antibiotic regimen for a diabetic foot infection? 7. When should I consider imaging studies to evaluate a diabetic foot infection, and which should I select? 8. How should I diagnose and treat osteomyelitis of the foot in a patient with diabetes? 9. In which patients with a diabetic foot infection should I consider surgical intervention and what type of procedure may be appropriate? 10. What types of wound care techniques and dressings are appropriate for diabetic foot wounds? Lipsky et al, Clin Infect Dis (in press)

73 Randomized Antibiotic Trials for DFI Past 5 yrs Linezolid (vs aminopenicillin/β-lactamase inhibitor) 1 Daptomycin (vs vancomycin or nafcillin) 2 Moxifloxacin (vs pip/tazo or amoxicillin/clavulanate) 3,3a,4a Ertapenem (vs piperacillin/tazobactam) 4 Piperacillin/tazobactam (vs ampicillin/sulbactam) 5 Pexiganan cream (vs oral ofloxacin) 6 Tigecycline (vs ertapenem) 7 Ceftobiprole (vs ceftazidime + vancomycin) 8,8a Clinical cure rates ~70-85% in all; no differences between agents 1 Lipsky et al, Clin Inf Dis 2004;38:17; 4 Lipsky et al. Lancet 2005; 366: Lipsky et al, J Antimicrob Chemother 2005;55:240; 8a Noel et al (in prep) 3 Lipsky et al, J Antimicrob Chemother 2007; 60:370 3a Vick-Fragosos et al, Infection 2009 (epub Sept); 4a Shaper, ECCMID 10 5 Harkless et al, Surg Infect (Larchmt) 2005;6:27; 8 Noel et al CID 2009;46 6 Lipsky et al, Clin Inf Dis 2008;47:1537; 7 Sabol et al, IDSA abst 2009

74 OPIDA: Outcome of Hospitalized DFI Patients Prospective study 291 pts at 38 French hospitals Most wounds on toes/forefoot; mostly moderate ; 50% osteomyelitis; ~60% PAD; mostly GPC (esp. S. aureus) Antibiotics IV in 49%; changed in 56% (mismatch) Outcomes In hospital LEA in 35%; 52% good outcome 1 year after d/c for 150 non-amputated patients: 19% had amputation, 79% had healed wounds Independent risks amputation: toes; severity; osteo PAD: associated w/ poor prognosis; often neglected Overall 48% had LEA (despite specialized DFUs) Richard et al, Diabetes Metab 2011;37:208

75 Treating DFI: Approach Based on Infection Severity Infection Hospitalization Initial Surgery Antibiotic Life/Limb Severity Required Antibiotic Consult Spectrum Threatening Mild No Topical/Oral Rarely Narrow No Moderate Occasionally Oral / IV Often, Broader Occasionally elective (limb) Severe Yes IV Usually, Very Yes & urgent broad (limb & life) Lipsky et al, IDSA revised guidelines, in preparation 2010

76 General Approach to Antibiotic Therapy for Diabetic Foot Infections Initial therapy: often empirical best guess - Can be narrow-spectrum if mild; broad if severe - Alter based on clinical response & culture results - Often do not need to treat all isolates Definitive therapy: to completion of course; based on - Culture & sensitivity results, and - Clinical response to empiric therapy Duration of therapy weeks for mild/moderate - Longer only if slow to respond or bone infection

77 Independent Risk Factors for Adverse Outcomes in Diabetic Foot Infections Prospective study 96 hospitalized patients in Turkey Outcome Associated Factor P value OR 95% CI Resistant bacteria Prev amputation Antibiotic w/n 30 d Osteomyelitis Wound >4.5 cm Amputation Prev foot infection Osteomyelitis Failure of Treatment Resistant bacteria Ertugrul et al, Eur J Clin Microbiol Infect Dis 2012, e-pub Feb 22

78 Expert Panel on Diabetic Foot Infections Benjamin A. Lipsky, Chair Anthony R. Berendt, Vice-Chair Paul B. Cornia, James C. Pile, Edgar J.G. Peters, David G. Armstrong, H. Gunner Deery, John M. Embil, Warren S. Joseph, Adolf W. Karchmer, Michael S. Pinzur, Eric Senneville

79 Change in Format All new IDSA Guidelines must have standardized format ( Question Recommendations Evidence Summary Evidence is now summarized using the BMJ GRADE system Strength of recommendation (High, moderate, weak) Level of Evidence i.e. Strong, Low

80 Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group began in 2000 as informal collaboration to address shortcomings of available grading systems in health care Developed a common, sensible & transparent approach to grading Quality of evidence (high, moderate, low, very low) Strength of recommendations (strong, weak) Many international organizations provided input into the development & are using it

81 Diabetic Foot Infection: Advice, circa 1980s Most diabetic foot ulcers are infected Hospitalize most patients with an infected ulcer Infections are almost always polymicrobial Initial antibiotic therapy should be parenteral Select a broad-spectrum antibiotic regimen Treat for weeks, until the wound heals Resect/amputate all infected bone

82 Diabetic Foot Infections: 2010 Only half of diabetic foot ulcers are clinically infected Only clinically infected ulcers need antibiotic therapy Properly obtained cultures are strongly recommended Likely more organisms that previously thought Narrow-spectrum (for GPCs) agents usually adequate Oral antibiotic therapy generally adequate Relatively short courses of therapy usually sufficient Surgical resection not needed for all osteomyelitis Antibiotics are necessary, but not sufficient

83 Antimicrobial Therapy of DFI by Clinical Situation Type Infection Soft tissue Route Location Duration - Mild Oral Outpatient all 1-2 weeks - Moderate/ - Severe Oral (± init. IV) IV, switch po Outpatient most Inpatient all 2-3 weeks Lipsky et al, IDSA Guidelines, Clin Inf Dis 2004;39:885

84 Antimicrobial Therapy of DFI by Clinical Situation Type Infection Soft tissue Route Location Duration - Mild Oral Outpatient all 1-2 weeks - Moderate/ - Severe Bone Oral (± init. IV) IV, switch po Outpatient most Inpatient all 2-3 weeks - Resected IV or oral Inpatient outpt < 1 week - Debrided IV or oral Inpatient outpt 4-6 weeks - No surgery IV, then oral Outpatient 3 months Lipsky et al, IDSA Guidelines, Clin Inf Dis 2004;39:885

85 Special Concerns in Developing Countries Delayed treatment related to lack of money/access Limited availability of clinical microbiology testing Cost of antibiotics, surgery, adjunctive therapy Over-the-counter (non-prescribed) antibiotic therapy Need to educate patients, family? Need to educate pharmacists Limited specialists (eg, podiatry, vascular surgery) Lack of availability or adherence to wound care Off-loading Dressings

86 Overview: The New Guidelines on Diabetic Foot Infections 2011 IDSA Expert Panel Guidelines: 1 st revision (since 2004) New format: questions & evidence GRADE system: quality & strength recommendations Performance measures IWGDF Expert Opinion: 1 st revision (since 2004) Incorporating IWGDF osteomyelitis review (2008) Informed by systematic review of treatment (2011) Specific guidelines: 2 page consensus document NICE (UK) Inpatient Diabetic Foot Management Newly issued guidelines Will highlight infection section

87 Evaluating a Diabetic Patient with a Foot Wound Check for sensation (monofilament) Check arterial circulation (pulses, Dopplers) Cleanse and debride ulcer (preferably surgically) Evaluate for infection (pus, inflammation); if present obtain appropriate cultures + select antibiotic regimen Probe wound (foreign bodies, bone?) Consider need for: hospitalization; surgery Adequately offload pressure; apply proper dressing Set up appropriate follow-up Educate patient/family about 2º prevention Lipsky et al, IDSA DFI Guidelines, Clin Inf Dis 2004; 39:885

88 Summary of General Approach to Antibiotic Therapy for Diabetic Foot Infections Initial therapy: usually empirical (best guess) -Narrow spectrum for mild, no previous treatment -Broad for severe, previously treated Definitive therapy: evidence based - Based on clinical response & culture results - Often do not need to treat all isolates Duration of therapy weeks for most mild/moderate infections - Longer only if slow to respond or bone infection Adjunctive Tx: Antibiotics necessary but insufficient - Wound care: debridement, off-loading, dressings - HBO, G-CSF, negative-pressure, maggots