1. Diabetic foot infection
Dr Paul Chadwick
Consultant Microbiologist
Salford Royal Hospital

2. Case History
A 76 year old man was admitted as an emergency with a red and swollen right foot
Apyrexial and haemodynamically stable
Diagnosed with type 2 diabetes two years earlier
Oral hypoglycaemic therapy: blood sugar control moderate

3. Investigations
X-ray of the foot showed changes consistent with both osteomyelitis and soft tissue infection
C-reactive protein 219 mg/l (<10mg/l)
Neutrophils 19.2 x109/l (4-11 x109/l)
Plasma glucose 24.6 mmol/l (3-6 mmo/l).

4. X-ray changes include destruction of the metatarso-phalangeal joint of the great toe associated with lucencies within the soft tissues extending across the second third and fourth toes and irregularity of the head of the second and third metatarsals suggesting associated fracture.
Illustration reproduced with permission from Clinical Publishing Ltd, Oxford

5. Diagnosis & Initial management
Moderate diabetic foot infection
limb-threatening
critical ischaemia not present
Treated empirically with IV vancomycin and piperacillin/tazobactam

6. Microbiological investigation
Polymicrobial infection
Gram stain of pus showed neutrophils, Gram positive cocci and Gram positive bacilli
Enterocoocci and alpha-haemolytic Streptoccoci were isolated from pus
At least five different species comprising Gram positive cocci and Enterobacteria were cultured from superficial swabs.

7. Surgical Intervention
On day 4 debridement was undertaken to remove infected bone and soft tissue
Enterococcus faecalis, Propionobacterium sp. and Escherichia coli were isolated from deep pus and tissue samples.

8. Further management
On day 7 antimicrobial therapy was changed to oral amoxicillin plus ciprofloxacin.
4 weeks of antimicrobial therapy were given in total
Ongoing wound and foot care was provided by the Podiatry team

9. Diabetic foot infection
Most common reason for diabetes-related admission to hospital
High morbidity – may result in amputations

10. Why does DFI occur?
Foot ulceration is the major factor and occurs secondary to peripheral neuropathy and/or vascular insufficiency (neuro-ischaemic foot ulceration)
Hyperglycaemia and other metabolic disturbances contribute through immunological (e.g. neutrophil) dysfunction and poor wound healing

11. Prevention of DFI Appropriate foot care/pressure relief
Podiatry services
Good glycaemic control
Specialist diabetes services

12. CID 2004; 39:

14. Multidisciplinary Foot-care Team
Physician
Podiatrist
Medical Microbiologist/ID Physician
Vascular surgeon
Foot surgeon
Radiologist
Essential to have interested specialists who can be accessed quickly to provide optimal care and avoid unnecessary amputation

15. Microbiological Samples
Samples should be collected following cleansing and debridement
Deep soft tissue samples should be obtained from the base of an ulcer by curettage, or at surgery
Bone biopsy (including histopathological examination) is important in establishing a diagnosis of osteomyelitis
Samples should be transported without delay to the laboratory and cultured under both aerobic and anaerobic conditions.

16. Microbiological pathogens
Infection is typically polymicrobial where ulceration is present
Aerobic Gram positive cocci
Staphylococcus aureus
Β-haemolytic streptococci
Enterococci
Enterobacteriaceae
Obligate anaerobes
(Nonfermentative Gram negative rods)
(Candida spp.)

17. Diagnosis and Assessment
DFI is diagnosed clinically by signs and symptoms of inflammation
Infections are categorized as mild, moderate or severe, on the basis of clinical and laboratory features
Assessment is made as to whether an episode is life or limb threatening
Categorization helps to guide appropriate clinical management

18. Mild infection Purulent or inflamed wound present
Limited to skin and superficial soft tissues
Inflammation extends <2cm from wound
Not systemically unwell
Treatment usually by oral route
e.g. flucloxacillin, doxycycline, clindamycin
Microbiological sampling not routinely required for mild infection unless recent antimicrobial therapy or previous antibiotic-resistant organisms
Therapy aimed against aerobic GPC is usually adequate for mild infections

19. Moderate infection
Purulent or inflamed wound present in a patient who is systemically well and/or one of the following
inflammation extends >2cm from wound
lymphangitis
spread beneath superficial fascia
abscess formation
necrosis or gangrene
involvement of muscle, tendon, joint or bone
Treatment by oral or parenteral routes according to clinical assessment and choice of agent

20. Moderate infection Treatment options include amoxicillin/clavulanate
clindamycin + ciprofloxacin
rifampicin + levofloxacin
piperacillin/tazobactam
ertapenem
NB. Choices influenced by local policy with consideration of local issues such as C. difficile and MRSA incidence
Add glycopeptide, linezolid or daptomycin if MRSA infection is suspected or infection is life/limb-threatening
Therapy aimed against aerobic GPC may be adequate for moderate infections in patients who have not received prior antibiotics

21. Severe infection
Infection in a patient with evidence of systemic inflammatory response syndrome
IV treatment, at least initially, as an inpatient, e.g.
clindamycin + ciprofloxacin
piperacillin/tazobactam
meropenem or imipenem/cilastatin
Add glycopeptide, linezolid or daptomycin if MRSA infection is suspected or infection is life/limb-threatening
Broad-spectrum therapy pending culture results

22. Duration of Antimicrobial Therapy
Continued until the signs and symptoms of infection have resolved (ulcer may persist)
Mild soft tissue infections 1-2 weeks
Moderate-severe soft tissue 3-4 weeks
Osteomyelitis typically 6 weeks, unless all affected bone is completely removed by surgery (1-2 weeks)
Therapy ≥3 months sometimes required for extensive bone infection e.g. calcaneum
NB. Courses may need to be longer than for non-diabetic patients with cellulitis

23. Antibiotics in DFI Antimicrobial therapy can be challenging!
Consider patient factors (e.g. age, renal function, peripheral vascular disease)
Side effects are common
Gastrointestinal intolerance of oral antibiotics, often to multiple agents
Hypersensitivity reactions (typically skin rashes)
Deterioration in renal function may occur
Deterioration in renal function may be seen with glycopeptides, doxycycline or ciprofloxacin
All hospitals should have an antibiotic guideline for DFI (NICE)

24. Does the patient require surgery?
Surgical intervention is often required. Urgent assessment is needed by a surgeon with expertise in foot surgery where the infection is life- or limb-threatening. Vascular surgery may be needed where there is critical ischaemia.
Excision & drainage
Debridement
Resection +/- reconstruction
Revascularisation
Amputation
Important to get an enthusiastic surgeon on board as part of the multidisciplinary team

25. Wound Care Issues Ongoing debridement of non-viable tissue as required
Dressings to allow daily inspection of wound and to encourage a moist wound-healing environment
Remove pressure from the wound (off-loading)
Debridement with a scalpel can often be undertaken without anaesthetic in patients with a neuropathic foot.
Many wound care products available – limited evidence to favour any particular dressing type.

26. Glucose Control Good blood glucose control should be achieved
To manage the acute infection
To reduce the risk of future foot problems
Involvement of specialist diabetes nurses is helpful

27. Diagnostic Imaging 1
Imaging should always be considered to identify soft tissue abscesses or osteomyelitis
Osteomyelitis is present in 30% DFI
It is important to identify underlying osteomyelitis as this influences the choice, dose, route and duration of antimicrobial therapy, however
There is no single, non-invasive, highly sensitive and specific test for osteomyelitis
MRI is the most accurate of the available radiological tests, but difficult to distinguish infection from Charcot neuropathy

28. Diagnostic Imaging 2
If osteomyelitis is suspected and initial X-ray does not confirm the presence of osteomyelitis, use magnetic resonance imaging (MRI).
If MRI is contraindicated, white blood cell (WBC) scanning may be performed instead
NICE clinical guideline 119

29. Clinical signs of osteomyelitis
The following are associated with osteomyelitis
Inflamed, swollen (‘sausage’) toe
Presence of exposed bone
Positive ‘probe-to-bone’ test

30. Suggests osteomyelitis (but not conclusive)
‘Sausage toe’

31. Osteomyelitis of hallux
Probe to bone?
Bone may either be visible in the base of an ulcer, or it may be possible to touch bone directly using a blunt metal probe. Either is suggestive of osteomyelitis (but not conclusive).

32. X-rays and DFI
Plain X-rays can be negative during the first 2-3 weeks of osteomyelitis
Charcot neuroarthropathy & gout may produce similar appearances
Pragmatic approach where osteomyelitis is suspected but X-rays are negative
treat for osteomyelitis for two weeks then re-Xray
extend the course of therapy if new changes become apparent.

33. Osteomyelitis distal phalanx
Distal phalanx (2 different views) shows bone loss, cortical irregularity and disordered bone architecture, consistent with osteomyelitis. Note 50% of bone has to be lost before this is apparent on plain Xray.

34. MR imaging and DFI Marrow oedema Cortical discontinuity
periosteal reaction
debris
sequestra
soft tissue oedema/induration
joint involvement
ulceration
sinus formation
abscess collection

35. Osteomyelitis of calcaneum, T1 image
Marrow oedema
Sinus
Image courtesy of Dr J Harris, Radiology Department, Salford Royal Hospital

36. Osteomyelitis of 1st metatarsal head, STIR image
Soft tissue oedema
Marrow oedema
Image courtesy of Dr J Harris, Radiology Department, Salford Royal Hospital

37. OPAT and DFI
Outpatient (or home) parenteral antimicrobial therapy may be appropriate as prolonged IV therapy often needed for
Severe infection
Osteomyelitis
MRSA infection
Intolerance of oral agents
No response to oral agents
Examples of drugs used: teicoplanin, daptomycin, ertapenem, meropenem

38. Patient eligibility for OPAT
Medically stable
Appropriate IV access
Home circumstances appropriate
Support
Communications
Facilities

39. PICC lines