Diabetic foot infection Dr Paul Chadwick Consultant Microbiologist Salford Royal Hospital

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

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).

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

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

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.

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.

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

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

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

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

CID 2004; 39:885-910

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

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.

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.)

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

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

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

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

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

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

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)

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

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.

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

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

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

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

Suggests osteomyelitis (but not conclusive) ‘Sausage toe’

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).

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.

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.

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

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

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

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

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

PICC lines