This systematic review analyzed 33 studies involving 6,637 patients to compare treatment regimens for diabetic foot infections. Several studies found early surgical intervention and drainage significantly reduced amputation rates compared to delayed treatment. Meta-analysis was not possible due to heterogeneity. While some individual studies identified statistically significant differences in outcomes, the review concluded no major differences exist between antibiotic regimens in terms of efficacy. Larger, higher quality comparative trials were recommended to help optimize empiric antibiotic selection.

1. By: Flora Blumin, Melissa Connell, Srikanth Venkanhagari, Hae Yoon, John
Chamoun, Jagrutkumar Vyas, Marissa Egipciaco, Dan Do, Camille Zambrana,
Jitenkumar Nathani, Kimberly Regis and Michael Ruden
A systematic review of the effectiveness of
interventions in the management of infection
in the diabetic foot

2. Diabetes Foot Infection
Disease State Overview
Clinical Applicability
Study Design
Results
Evaluation Methods
Discussion/Limitation
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3. • Lifetime risk of developing foot ulcer in DM pts: 15-
25%
• Frequency of infection: 40%-80%
• DFIs account for most common cause of diabetes-
related hospital admission
• Most infections involved soft tissue; however, ~ 20%
progress to osteomyelitis
Diabetic Foot Infections (DFIs)

4. • High glucose levels in the blood provide
nutrients for microorganisms to proliferate
• High glucose levels also affect nerve
conduction, leading to diabetic neuropathy
• DFI typically originate as a wound which
goes undetected due to neuropathy
Diabetic Foot Infections

5. •Skin and Soft Tissue infection
• Early recognition of the area and tissue
involvement could prevent the
progression of the infection
• Osteomyelitis
• Common yet serious complication
associated with DFI
• Delay in diagnosis leads to increased
risk for amputation
Diabetic Foot Infections

6. •Presence of infections: ≥ 2
• Carlor (heat), Rubor (redness), Tumor (swelling), Dolor (pain)
•Infections classification:
• Mild (superficial and limited in size and depth)
• Moderate (deeper or more extensive)
• Severe ( accompanied by systemic signs or metabolic
perturbations)
Diabetic Foot Infections

7. International consensus on the diabetic foot classification of
foot wound infections
Grade 1 • No symptoms, no signs of infection
• Lesion only involving the skin (no subcutaneous tissue lesion or
systemic disorders) with at least two of the following signs:
• Local warmth
• Erythema > 0.5 cm - 2 cm around the ulcer
Grade 2 • Local tenderness or pain
• Local swelling or induration
• Purulent discharge (thick, opaque to white or sanguineous
secretion)
• Other causes of inflammation of the skin must be eliminated (for
example: trauma, gout, acute Charcot foot, fracture, thrombosis,
venous stasis)
• Erythema > 2 cm and one of the findings described above
or
Grade 3 • Infection involving structures beneath the skin and subcutaneous
tissue, such as deep abscess, lymphangitis, osteomyelitis, septic
arthritis or fasciitis
• There must not be any systemic inflammatory response (see
Grade4)
• Regardless of the local infection, in the presence of systemic
signs corresponding to at least two of the following
characteristics:
• Temperature > 39°C or < 36°C
• Pulse > 90 bpm
Grade 4 • Respiratory rate > 20/min
• PaCO2 < 32 mmHg
• Leukocytes > 12 000 or < 4 000/mm3
• 10% of immature leukocytes

8. •Polymicrobial:
•Aerobic gram-positive cocci (i.e
staphylococci)
•Aerobic gram-negative bacilli:
chronic or post treatment
•Obligate anaerobes: ischemic or
necrotic wounds
Diabetic Foot Infections

9. •Appropriate antibiotic therapy
•Surgical drainage
•Debridement and resection of
dead tissue
•Appropriate wound care
•Correction of metabolic
abnormalities
Diabetic Foot Infections

10. • Clinically uninfected wounds should NOT be
treated with antibiotic therapy
• Clinicians select an empiric antibiotic regimen
on the basis of the severity of the infection
• Mild-moderate: antibiotic naïve aerobic GPC coverage
• Severe: Broad spectrum empiric antibiotic therapy,
pending culture results
• Empiric therapy for Pseudomonas aeruginosa is usually
unnecessary except for high risk
• Empiric therapy to MRSA indicated with prior history of
MRSA
Diabetic Foot Infections

11. Diabetes Foot Infection
Disease State Overview
Clinical Applicability
Study Design
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12. •Title: A systematic review of the effectiveness of
interventions in the management of infection in the
diabetic foot
•Authors: E.J. G. Peters, B.A Lipsky, A.R. Berendt,
J.M. Embil, L.A. Lavery, E. Senneville, V. Urbancic-
Rovan, K. Bakker, W.J. Jeffcoate
•Published in Diabetes/Metabolism Research and
Reviews 2012; 28 (Supplement 1): 142-162
Diabetic Foot Infections

13. Article Objective:
Conduct a systematic review to compare
treatment regimens in the management
of diabetic foot infections
Diabetic Foot Infections

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15. •Database used: Pubmed and Embase
•Inclusion Criteria:
•Studies in any language for interventions for treatment of DFIs
•Patient over age of 18 years or older patient with DM
•Eligible studies: RCTs, case control, cohorts, ITS, CBA
•Exclusion Criteria:
•Uncontrolled case series, study with historical control and case
reports
•Studies where patients with DFIs formed part of the total population
were excluded if the data for the subgroup with diabetes were not
separately described
Diabetic Foot Infections

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17. • Methodoligcal quality: Dutch Cochrane
Center scoring list
• Level of evidence: SIGN
• Scoring system:
• ++: high quality, low risk of bias
• +: well conducted, low risk of bias
• - : low quality, high risk of bias
Diabetic Foot Infections

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19. •A total of 29 papers were chosen for review
based on the inclusion criteria. Later, four
papers were identified and added manually to
the review.
•Of the final 33 papers, 29 were randomized
controlled trials and 4 were cohort studies.
•A total of 6, 637 patients were enrolled in a
total of 33 trials.
Diabetic Foot Infections

20. • Blinding:
• 10 double blind study
• 1 assessor blind
• 1 patient blind
• 2 investigator blind
• 6 open blind study
Diabetic Foot Infections

21. • Meta-analysis were not performed due to
heterogeneity of:
• The study designs
• Interventions
• Follow-up
• Outcomes
• The 33 studies were divided into individual topics
and the results with p-values were summarized in
Appendix B
• The researchers provided a descriptive analysis of
the results for various topic
Diabetic Foot Infections

22. • Early surgical intervention
• Health economics
• Topical treatment with antiseptic agents
• Granulocyte-colony stimulating factor
• Procaine plus polyvinyl-pyrrolidone
• Hyperbaric Oxygen Therapy
• Antibiotic Choice Based on Boney biopsy
• Comparison of antibiotic regimens:
• Skin and soft tissue infection alone
• Skin and soft tissue with osteomyelitis infection
Diabetic Foot Infections

23. • Differences found in following studies were statistically
significant
• Tan et al., Faglia et al., Tice et al., Martinez-de jesus et al.,
Piagessi et. al., Erstad and Mclntyre et al. and Lipsky et al.
Diabetic Foot Infections

24. •Tan et al.
• Amputation rate in antibiotic use vs surgical intervention
(27.6% vs. 13.0 %)
•Faglia et al.
• Amputation rate in early vs delayed drainage (1/43 pt vs.
23/63 pt)
•Tice et al.
• Total cost of hospitalization in Ertapenem vs Zosyn use
($356 vs. $503)
Diabetic Foot Infections

25. •Martindez-de jesus et al.
• Odor reduction in superoxide vs other disinfectants (100% vs 25%)
• Surrounding cellulitis reduction in superoxide vs other disinfectant
(81% vs 44%)
•Piaggessi et al.
• Duration of antibiotic use with Dermacyn vs Povidone (10.1 +/- 6.1
weeks vs 15.8 +/- 7.8 weeks)
• Healing rate at 6 month with Dermacyn vs Povidone (90% vs
55%)
• Healing time with Dermacyn vs Povidone (10.5 +/- 5.9 days vs
16.5 +/- 7.1 days)
Diabetic Foot Infections

26. •Erstad and Mclntyre et al.
• Cure rate of symptoms for Cefoxitin vs Unasyn (21% vs 6%)
• Total hospitalization day of Cefoxitin vs Unasyn (12 vs 21)
•Lipsky et al.
• Cure rate in Linezolid vs Augmentin (81% vs 68%) **
• Cure rate in patient without osteomyelitis in Linezolid vs
Augmentin (87% vs 72%) **
** significantly more incidence of anemia, thrombocytopenia and
discontinuation of therapy reported with Linezolid.
Diabetic Foot Infections

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28. •Surgical interventions
• Trial design can pose problems
• Early surgery is accepted yet the trial
evidence to substantiate the benefit is weak
• Two studies may had a high chance of bias
• Use of SIGN criteria for documenting study
quality
• Quality of study design vs. study conduct
Diabetic Foot Infections

29. •Antimicrobial agents
• Number of subjects limits their usefulness
• Marred by the use of small and
heterogeneous populations
• Low score for study design
• Poorly described or had a high risk of bias
• Various choices of treatment in different
countries and settings
Diabetic Foot Infections

30. •Important conclusion
• Emerging observational evidence of gram
negative species
• Impact on the selection of antibiotic regimens
• Possibility to treat selected patients with DFI
in an outpatient setting with oral Abx
• No great difference between antibiotic
regimens with a broad or narrow spectrum of
activity
• Short duration of treatment – even with bone
infection
Diabetic Foot Infections

31. •Future research suggestion
• Robust, well designed, comparative trial
• Help clinicians make an optimal choice of
both empiric and targeted Abx regimen
• Choice of specific agents, the route, and
duration of administration
Diabetic Foot Infections

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33. • No major differences presented in comparison to the
current DFI guidelines produced by the IDSA
• No difference in using a specific antibiotic agent, route of administration, or
duration of therapy in diabetic foot osteomyelitis.
• Treatment duration for soft tissue infection ≈ 2 weeks
• Mild infections – 1-2 weeks
• Moderate to severe infections – 2-3 weeks
• Cost effectiveness
• Comparison of ertapenem vs. Zosyn (Tice et al.)
• Zosyn total costs were slightly higher due to more frequent dosing, including
preparation and administering
• Comparison of ceftriaxone and metronidazole vs.
ticarcillin/clavulanate in skin and soft-tissue infections (Clay et al.)
• Potential cost savings of $61 per patient treated with ceftriaxone and
metronidazole vs ticarcillin/clavulanate
Diabetic Foot Infections

34. Changes to practice settings are
not recommended at this time
Diabetic Foot Infections

35. THANK YOU!