Magement of Stage 4 Infected foot

 

Infection as a great destroyer of the diabetic foot and this is particularly the case in the neuroischaemic foot where the blood supply is insufficient to mount a good inflammatory response. Stage 4 is a highly significant staging post on the road to amputation for both neuropathic and neuroischaemic feet, and is usually involved in the final common pathway to amputation: more people undergo major amputation because of combined diabetes and infection than for all other causes.  Surprisingly 85% of major amputations in people with diabetes begin with a ‘clean’ ulcer

Spectrum of clinical presentations There are three distinct stages in the natural history of infection in the diabetic foot. Each of these entities is distinguished by virtue of the treatment it needs:

  • Localized infection
  • Spreading infection
  • Severe infection.

Localized infection

 

This refers to infection in the ulcer bed or immediately surrounding skin. This may present with purulent discharge and surrounding erythema, but often the classical signs of infection are diminished by the presence of neuropathy and ischaemia. Thus, the signs of infectionmay be very subtle. Galen’s classical signs and symptoms of redness, heat, pain and loss of function may not be  evident. However, early warning signs of infection and signs of deterioration should be searched for with great assiduity in all diabetic foot patients especially those with breaks in the skin.If the practitioner waits for florid advanced signs of infection to develop then valuable time is lost. Physician must act early upon the initial signs of infection. Local signs that an ulcer has become infected include any or all of the following:

  • Pain
  • Base of the ulcer changes from healthy pink granulations to yellowish or grey tissue
  • Increased friability of granulation tissue
  • Increased amount of exudate
  • Exudate changes from clear to purulent
  • Unpleasant smell
  • Sinuses develop in an ulcer
  • Edges may become undermined so that a probe can be passed under the skin Bone or tendon becomes exposed in the base of the ulcer or can be reached if a probe is passed along a sinus.

Where there is erythema of surrounding skin there will usually also be local signs of infection as described above. Localized erythema, warmth and swelling are usually associated with ulceration lthough the portal of entry of infection may be a corn, callus, blister, fissure, a problem beneath a nail, or any other skin break. In the darkly pigmented foot, cellulitis can be difficult to detect, but careful comparison with the other foot may reveal a tawny hue. Patients with retinopathy may not see the erythema of cellulitis. In localized infection, the colour alone of surrounding skin may have changed, becoming pink or red, but the texture of the surrounding skin does not change. In most cases of localized infection, oral antibiotics are sufficient and patients do not usually need admission to hospital.

Spreading infection

 

Sepsis has progressed to give signs of spreading infection emanating from the ulcer such as diffuse spreading erythema, oedema, lymphangitis and lymphadenitis and in addition, there will usually be local signs of infection as described above. In the erythematous skin, wrinkles disappear, and when the infection is resolving there is scaling. The portal of entry of infection may be a corn, callus,blister, fissure or any other skin break. This condition should be treated with systemic antibiotics. It can sometimes be treated with intramuscular antibiotics and bedrest at the patient’s home under close surveillance by relatives and frequent visits from the community nurse. However, where the cellulitis is extensive, or in the ischaemic foot, intravenous antibiotics and hospital admission will be needed for patients with spreading infection.

 

Severe infection

 

This refers to ulcers with extensive deep soft tissue infection and also infected feet with blue or purple discolouration of tissues. These people need intravenous antibiotics, immediate hospital admission and an urgent surgical opinion regarding the necessity of surgical drainage and, if the foot is neuroischaemic, appropriate assessments of the possibility of vascular reconstruction. This stage may also be associated with septicaemia, with the patient presenting with hypotension and organ failure.

In the presence of neuropathy pain and throbbing  may be absent, but if present this is a danger sign, usuallyindicating serious infection with pus within the tissues.Palpation may reveal fluctuance, suggesting abscess formation. There may be bulging of the plantar surface of the foot. Discrete abscesses are relatively uncommon in the infected diabetic foot. Often there is a generalized sloughing of the ulcer and surrounding subcutaneous tissues, which eventually liquefy and disintegrate. In late infection there is swelling and the tissues may be sloughing and breaking down and blistered, or fluctuant, and often never recover but become necrotic and need surgical removal.

Severe infection can also present as a blueish-purple discolouration when there is inadequate supply of oxygen to the soft tissues. This is caused by increased metabolic demands of infection and a reduction of blood flow to the skin, secondary to a septic vasculitis of the cutaneous circulation. Purple blebs may indicate subcutaneous necrosis. Blue discolouration can occur in both the neuropathic and also the neuroischaemic foot, particularly in the toes, and in the neuroischaemic foot must not be automatically attributed to worsening ischaemia.

Systemic symptoms and signs may be present in the patient with late infection whose foot has extensivediffuse cellulitis, deep soft tissue infection or blue discolouration. Signs of severe infection may include drowsiness, shivering, tachycardia, hypotension, reduced body temperature (< 35°C) or high fever (> 40°C).However, systemic signs and symptoms are notoriously absent in many severe infections of the diabetic  foot. Among patients hospitalized for late infections only 12–35% have significant fever and only 50% of episodes of severe cellulitis will provoke a fever or leucocytosis. However, when a fever is present it usually indicates a severe infection, and the deep spaces of the foot are usually involved with tissue necrosis, severe cellulitis and  possible bacteraemia. Severe infections are often polymicrobial and bothGram-positive and Gram-negative organisms are present together with anaerobes. Severe subcutaneous infection by Gram-negative and anaerobic organisms produces gas, which may be detected by palpating crepitus on the lower limb and can be seen on X-ray. The presence of gas does not automatically mean that the classical gas gangrene organism Clostridium perfringens is present.

Osteomyelitis

Clinically, osteomyelitis may be suspected when a sterile probe inserted into the base of the ulcer penetrates to bone. This may happen in an apparently clean, uninfected ulcer, but osteomyelitis must still be suspected. X-ray and magnetic resonance imaging (MRI) are helpful in the diagnosis of osteomyelitis, which may be confirmed in theory by a positive bone culture or bone biopsy showing bone death, inflammation and repair.

Ischaemia and cellulitis

In the neuroischaemic foot, it may be difficult to differentiate between the erythema of cellulitis and the redness of ischaemia. It is helpful to elevate the leg. The redness of ischaemia is usually cold and is most marked on dependency: it will disappear upon elevation of the limb, whereas cellulitis will remain. The erythema associated with inflammation is warm, although a very ischaemic foot may become deceptively warm when it is infected.

Investigations

Microbial investigations

It is important to make a microbiological diagnosis and ascertain the organisms that are responsible for the infection. This involves either taking a deep ulcer swab or tissue scrapings after debridement. It is preferable to obtain a tissue specimen and this is relatively straightforward in a neuropathic foot. However,  in a neuroischaemic foot, taking a tissue specimen is more difficult, especially when tissue perfusion is severely limited. In these circumstances, an ulcer swab taken after debridement is acceptable and can still give valuable results.

The ulcer is debrided of surrounding callus and superficial slough,The ulcer is washed out with sterile normal saline. The base of the wound is then scraped with a scalpel blade and the scrapings sent for culture without delay. If scraping is not possible then a deep swab is taken from the base of the ulcer. If the patient subsequently undergoes operative debridement, then deep infected tissue rather than a swab should be sent to the laboratory. Bone fragments removed by debridement should be sent for culture. Blood cultures should also be taken if there is fever and systemic toxicity.

Laboratory investigations Blood should be taken for:

  • Full blood count
  • Urea, creatinine and electrolytes
  • Liver function tests
  • C-reactive protein (CRP).

Although the white blood count is only raised in 50% of infections, CRP is nearly always elevated in diabetic foot infections and is a valuable guide to the severity of infection and a useful way of judging a positive response to treatment.

Radiological investigations

With all the above presentations of infection, it is important to X-ray the foot to detect

  • Signs of osteomyelitis
  • Gas in the deep tissues
  • Radio-opaque foreign body.

In the initial stages of osteomyelitis, X-ray may be normal. Signs of osteomyelitis such as localized loss of bone density or cortical outline may not be apparent for at least 14 days. MRI may be useful to look for the presence of osteomyelitis and also to detect collections of fluid in the foot. Intravenous injection of gadolinium-containing con- trast agent heightens the sensitivity of the diagnosis of these clinical features. However, this contrast should not be used in patients with renal failure. The sequences employed in MRI for detection of soft tissue and bony abnormalities may include T1, short tau inversion recovery (STIR) and postgadolinium with fat suppression.

T1 sequence

This shows pathology in specific anatomy. Bone marrow which is normal is bright, and abnormal marrow is dark.

STIR sequence

Normal marrow is dark. Abnormal marrow is bright. Fluid collections become bright.

Postgadolinium with fat suppression sequence

Gadolinium concentrates in areas of inflammation and results in a hyperintense signal on T1 images. As fat is hyperintense on T1 sequence, images are acquired using a fat suppression technique. Normal marrow in the foot is predominantly composed of fat. Thus it is hypointense on the fat-suppressed images. Any bright or high signal after injection of gadolinium with fat suppression technique applied represents a focus of inflammation. The main MRI finding in osteomyelitis is an abnormal marrow signal which is dark on T1 images and bright on STIR images. After injection of gadolinium the abnormal marrow enhances as shown by a bright focus on the fat suppressed T1 images. Further signs of osteomyelitis include cortical disruption and periosteal reaction. An MRI which is negative excludes osteomyelitis. An abscess presents as a focal low T1 signal but a high STIR lesion. Following the injection of gadolinium on fat suppressed T1 images there is a low signal in the centre of the abscess.

However, MRI has notable limitations. MRI of the septic diabetic foot can show a number of false-positive diagnoses.An abnormal marrow signal can be seen with Charcot’s osteoarthropathy and fractures. The acute phase of Charcot’s osteoarthropathy may show the same enhancing marrow oedema that is impossible to separate from osteomyelitis.

MANAGEMENT OF INFECTION

Infection in the diabetic foot needs full multidisciplinary treatment. It is vital to achieve:

  • Microbiological control
  • Wound control
  • Vascular control
  • Mechanical control
  • Metabolic control
  • Educational control.

 

Microbiological control

 

Principles of antibiotic treatment

  • The microbiology of the diabetic foot is unique.Infection can be caused by Gram-positive aerobic, and

Gram-negative aerobic and anaerobic bacteria, singly or in combination

  • As there may be a poor immune response from the diabetic patient, even bacteria normally regarded as skin commensals may cause severe tissue damage. This includes Gram-negative organisms such as Citrobacter, Serratia, Pseudomonas and Acinetobacter. When Gram-negative bacteria are isolated from a deep ulcer swab or curettings they should not, therefore, be regarded as automatically insignificant
  • When a positive culture is found, it is then possible to focus antibiotic therapy according to sensitivities of the bacteria cultured
  • However, at initial presentation it is important to prescribe a wide spectrum of antibiotics for three reasons:

(a) it is impossible to predict the number and type of organisms from the clinical presentation

(b) there is no way of predicting who will develop a rapidly ascending infection which becomes limb- threatening and even life-threatening

(c) diabetic patients are immunosuppressed. The neuropathy and ischaemia of the diabetic foot reduces the local resistance to invading bacteria.

Duration of antibiotic therapy will depend on the clinical progress of the foot and ulcer, tissues involved, severity of the initial infection and also on individual factors relating to the patient.

The route by which therapy is given will depend on the severity of the infection. Use oral therapy for localized infections, intramuscular or intravenous therapy for spreading infections and intravenous therapy for severe infections. Intestinal absorption is unreliable in these  circumstances.

It is important to have a working knowledge of the principal bacteria and their local antibiotic sensitivities including awareness of the prevalence of resistant organisms. However, in every patient, individual sensitivities of each organism isolated on culture should be sought to guide rational antibiotic therapy.

Staphylococcus aureus

This is the commonest pathogen in the diabetic foot and flucloxacillin is the ideal treatment. Clindamycin can also be used but beware of antibiotic-induced colitis especially in the elderly and postoperative patients. Erythromycin may increase the risk of myositis from statin therapy. When taking erythromycin, patients should be advised to stop their statin therapy temporarily.

Methicillin-resistant Staphylococcus aureus (MRSA)

MRSA is associated with the whole spectrum of clinical presentations of diabetic foot infections and commonly occurs in patients who have been in hospital. It can be simply a commensal with no signs of invasive infection but it can also cause severe infections, osteomyelitis and bacteraemia. The frequency of MRSA infections is increasing in the diabetic foot. However, MRSA infections are not necessarily more pathogenic than conventional Staphylococcus aureus  infections. They do frequently cause more extensive tissue destruction because they are often not diagnosed until late These MRSA do not have the multi-resistance of the hospital-acquired MRSA but nevertheless can rapidly progress to severe infections. Approximately two-thirds possess the Panton-Valentine leukocidin (PVL) toxin, which acts to form pores in the cell membrane of mononuclear cells and polymorphonuclear cells and can lead to severe tissue necrosis. Also beware that one-third of hospital-acquired MRSA can express the PVL toxin. MRSA can lead to invasive infection and in these circumstances it is best to give vancomycin intravenously with dosage to be adjusted according to serum levels, or teicoplanin. These antibiotics may need to be accompanied by either sodium fusidate or rifampicin orally. Linezolid is also active against MRSA and has good soft tissue and bony penetration. It is well absorbed. It is necessary, however, to check the platelet count regularly as there may be some marrow suppression with this antibiotic. Courses should not exceed 28 days. The combination of antibiotics quinupristin and dalfopristin can be used when an MRSA infection has not responded to other antibacterials. Daptomycin and tigecycline may also be used in MRSA infections. MRSA can also be treated with clindamycin but sensitivity needs to be confirmed as MRSA resistance to clindamycin has emerged. If MRSA is isolated in localized infections, oral therapy can be given with two of the following: sodium fusidate 500 mg tds, rifampicin 300 mg tds, trimethoprim 200 mg bd or doxycycline 100 mg daily, according to sensitivities.

Streptococcus group A, B, C, E, F and G

Streptococcus group B is the commonest and can cause severe infection in the diabetic foot although C, E, F and G can infect the foot.  Streptococcus group A rarely causes infection but when it does it causes a severe blistering  cellulitis and tissue destruction. The Streptococcus milleri group of organisms are beta haemolytic streptococci that can cause abcesses in the foot. Streptococci can be treated with amoxicillin. Clindamycin, rifampicin and erythromycin may also be also active against streptococci.

Enterococcus

Enterococcus faecalis is rarely pathogenic. It may be selected out by cephalosporin treatment. If it is causing definite infection then it may be treated with amoxicillin. Enterococcus faeciummay need vancomycin.

Anaerobes

These are commonly found in deep infections but anaerobes are also a feature of many chronic wounds even when they are superficial. They are associated with necrotic wounds. Anaerobes can act synergistically with Gram-positive and Gram-negative aerobes to cause severe tissue destruction.

Metronidazole is the treatment of choice. Clindamycin and co-amoxiclav (amoxicillin/clavulanic acid) also have anti-anaerobic activity. Meropenem, piperacillin/ tazobactam and ertapenem are also active against anaerobes.

Gram-negative organisms

Klebsiella, Escherichia coli, Proteus, Enterobacter, Citrobacter, Serratia and other Gram-negative bacteria can be definitely pathogenic in the diabetic foot especially when they are in a pure growth or as part of a polymicrobial deep infection. Oral agents that are available to treat Gram-negatives are ciprofloxacin and trimethoprim. Parenteral agents include ceftazidime, aminoglycosides, meropenem, piperacillin/tazobactam, ticarcillin/clavulanate, tigecycline and ertapenem. It is crucial to obtain sensitivity patterns with Gram-negative organisms and not depend on empirical therapy alone. Recently, Gram-negative bacteria have acquired various resistance patterns through the development of certain enzymes and this is relevant to the choice of antibiotic therapy.

Organisms have developed extended-spectrum beta lactamases which are known as ESBLs. By this means, they have developed resistance to extended-spectrum (third generation) cephalosporins (e.g. ceftazidime, cefotaxime, and ceftriaxone) but not to carbapenems (e.g. mero- penem or imipenem). ESBL enzymes are most commonly produced by two bacteria: Escherichia coli and Klebsiella pneumoniae. Another group of lactamases are AmpC  β-lactamases, which are typically encoded on the chromosomes of many Gram-negative bacteria including Citrobacter, Serratia and Enterobacter species where expression is usually inducible.

Pseudomonas

There are many members of the genus  Pseudomonas.Pseudomonas aeruginosa is an important human opporunist bacterium in the diabetic foot. It can be responsible for a spectrum of presentations from superficial colonization of ulcers to extensive tissue damage, including osteomyelitis, septic arthritis and bacteraemia. It may be  sensitive to ciprofloxacin as an oral agent. Otherwise parenteral therapy is necessary and includes ceftazidime, aminoglycosides, meropenem, piperacillin/tazobactam, and ticarcillin/clavulanate.

Antibiotics used mainly against Gram-positive organisms

Amoxicillin

This antibiotic is active against streptococci but is inactivated by penicillinases that are produced by  Staphylococcus aureus and by Gram-negative bacteria such asEscherichia coli.

Co-amoxiclav

This is a combination of amoxicillin and clavulanic acid.The latter is a beta lactamase inhibitor, thus widening thespectrum of activity of co-amoxiclav against beta lactamase producing bacteria that are resistant to amoxicillin including staphylococci, anaerobes and Gram-negative bacteria. The risk of liver toxicity is six times greater with amoxiclav compared with amoxicillin.

Flucloxacillin

This antibiotic is not destroyed by pencillinases and thus it is effective against penicillin-resistant staphylococci. When given intravenously, its dosage may be increased to 2 g qds in staphylococcal bacteraemia or osteomyelitis.

Erythromycin and clarithromycin

They have a similar spectrum to penicillin and are thus useful against staphylococci and streptococci in patientswho are allergic to penicillin. There is an increased risk of myositis and rhabdomyolysis if the patient is on  statin therapy. Thus, statin therapy should be stopped for the duration of erythromycin therapy. If the patient develops intolerance to erythromycin, particularly gastrointestinal side-effects, then clarithromycin may be used.

Fucidin

This is active against penicillin-resistant staphylococci. It has good bone penetration and is useful in osteomyelitis. Resistance to it develops quickly if it is given alone and therefore it should be given with another antistaphylococcal agent. It is useful in combination therapy to treat MRSA infections. Liver function should be monitored if therapy is prolonged and it should be given with caution in patients with liver disease.

Doxycycline

This antibiotic can be used in treating MRSA infections. It should be used with caution in patients with hepatic impairment.

Rifampicin

This is active against staphylococci and streptococci and has good soft tissue and bone penetration. Patients should be warned that if they develop nausea, vomiting or malaise they should report this immediately as it may reflect liver dysfunction, which is a well described but rare side-effect of rifampicin therapy. It should be given with caution in patients with existing liver disease. Patients should be warned that their body secretions will turn red. Rifampicin should not be given alone because resistance can develop rapidly.

Clindamycin

This has very good soft tissue and bone penetration and is active against staphylococci, streptococci and anaerobes including Bacteroides fragilis. However, historically it has been linked with antibiotic-associated colitis caused by Clostridium difficile infections although this can occur with many antibiotics.

Vancomycin

This is usually given intravenously. It is active against Gram-positive organisms and is usually used for MRSA infections. Blood levels should be monitored and trough levels should be less than 15 mg/L.

Teicoplanin

This is a glycopeptide antibiotic which is active againstGram-positive organisms including MRSA. It can be given intravenously but also intramuscularly. This is a convenient therapy to be given at home.

Linezolid

Linezolid is active against Gram-positive organisms, including MRSA and vancomycin-resistant enterococci. It can be given orally or intravenously. It may cause marrow suppression and regular platelet counts are advisable. It should not be given for more than 28 days.

Daptomycin

This is a lipopeptide antibacterial active against Gram-positive organisms including MRSA. It is given intravenously and has good soft tissue penetration. Weekly creatine phosphokinase levels should be monitored.

Quinupristin/dalfopristin

This is a combination of two antibiotics, quinupristin and dalfopristin, which work synergistically against Gram-positive organisms including MRSA.

Trimethoprim

It has reasonable soft tissue penetration and is active against Gram-positive and -negative bacteria. It is also useful in combination therapy against MRSA.

Antibiotics used mainly against Gram-negative organisms

Ciprofloxacin

This is useful against Gram-negative organisms and  has good soft tissue and bone penetration. It has only moderate activity against Gram-positive organisms. It is relatively well tolerated but occasionally can give neurological side-effects and can rarely predispose to hypoglycaemia in certain patients.

Septrin

This is a combination of trimethoprim and sulphmethoxazole. This is occasionally used to treat resistant Gram-negative organisms such as  Stenotrophomonas  maltophilia but should only be used if other antibiotics against Gram-negative organisms are not appropriate.

Ceftriaxone

This is a useful antibiotic that can be given either intravenously or intramuscularly when it is administered as 1 g in 3.5 mL of 1% lidocaine. It needs to be given only once a day. This can be given in the community on a once daily basis. It has a wide spectrum of activity but is not active against MRSA or Pseudomonas.

Ceftazidime

This is useful as an initial agent to cover Gram-negative infections as it is usually active against  Pseudomonas.  If the dosage is not reduced in renal impairment, then  the patient may develop muscular twitching and even  fits.

Piperacillin/tazobactam

This antibiotic is given intravenously. It has a wide spectrum of activity including Gram-positive and Gram- negative organisms such as Pseudomonas and anaerobes. It may be useful against bacteria with extended-spectrum beta lactamases.

Ticarcillin/clavulanic acid

This is given intravenously and is active against Pseudomonas, and other Gram-negative bacteria including Proteus spp. and Bacteroides fragilis. Imipenem with Cilastin It is a carbapenem with broad-spectrum activity against Gram-positive and Gram-negative organisms including anaerobes. Imipenem is partly inactivated in the kidney and this is blocked by cilastin. It should be used with caution in renal failure as it may cause fits.

Meropenem

This also has a wide spectrum of activity including usually Pseudomonas. Meropenem is given intravenously and has less frequently caused central nervous system side-effects including fits compared with imipenem. It is also useful against bacteria with ESBLs.

Ertapenem

This is given once daily and is useful against Gram-positive and Gram-negative organisms and also anaerobes. In a recent study it was shown to be equivalent in action with piperacillin/tazobactam in treating infected diabetic feet. It is not active against Pseudomonas or against Acinetobacter. It is useful against bacteria with ESBLs and AmpC-producing Gram-negative bacteria. It may be given intramuscularly as 1 g diluted with 3.2 mL of 1% lidocaine.

Tigecycline

This is a broad-spectrum glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. It is useful in infections caused by Gram-positive organisms, including MRSA, Staphylococcus aureus, vancomycin-resistant enterococci, streptococci, Gram-negative organisms including those with ESBLs and anaerobes including Bacteroides fragilis. Strains of Proteus spp. and Pseudomonas aeruginosamay be resistant.

Aminoglycosides.

These include amikacin, gentamicin, netilmicin and tobramycin. Gentamicin is the aminoglycoside of choice in the UK. It is active against some Gram-positive organisms and many Gram-negative organisms. Important  side-effects are ototoxicity and nephrotoxicity. These side effects are dose-related and thus extreme care should be taken with dosage. Gentamicin should be administered with strict blood level monitoring and the trough level should be less than 1 mg/L. Antibiotics used against anaerobic organisms

Metronidazole

This is useful against anaerobic bacteria. Patients must be warned not to take alcohol.

 

Indications for surgery

Antibiotics alone may be unable to control infection and it is necessary to decide whether adjunctive surgery is  necessary. In severe episodes of cellulitis, the ulcer may be complicated by extensive infected subcutaneous soft tissue. At this point, the tissue is not frankly necrotic but has started to break down and liquefy. It is best for this tissue to be removed operatively. The definite indications for urgent surgical intervention are:

  • A large area of infected sloughy tissue
  • Localized fluctuance and expression of pus
  • Crepitus with gas in the soft tissues on X-ray
  • Blue or purplish discolouration of the skin.

Management of the three presentations of infection

Treatment is discussed for the three presentations of infection, in neuropathic feet and in neuroischaemic feet, both as initial treatment and follow-up. Infection in the neuroischaemic foot is often more serious than in the neuropathic foot which has a good arterial blood supply. Also, patients with neuroischaemic feet often have cardiac and renal complications which impair the response to infection.

Localized infection

Neuropathic feet

Initial plan. We give amoxicillin 500 mg tds, flucloxacillin 500 mg qds and metronidazole 400 mg tds because streptococci, staphylococci and anaerobes are the most likely organisms. Anaerobes are a common feature of superficial as well as deep infections, but may not always be isolated because of restriction on the length of time of incubation of cultures. If the patient is allergic to penicillin, substitute clarythromycin 500 mg bd foramoxicillin.

When the ulcer extends deeply to fascia or tendon,  add either ciprofloxacin 500 mg bd or trimethoprim

200 mg bd to cover Gram-negative organisms. Send a deep swab or curettings for culture. It is important to know the organisms that are causing the infection so that antibiotics can be used accurately to target the causative organism.

Follow-up plan.

If no signs of infection and no organisms are isolated,  stop antibiotics. If no signs of infection are present but organisms (after od once daily) are isolated,  focus antibiotics and review the patient in 1 week. If signs of infection are present but no organisms are isolated, we continue antibiotics as above. If signs of infection are present and organisms are isolated,  focus antibiotics according to sensitivities. If MRSA is grown, but there are no signs of infection use topical mupirocin 2% ointment if sensitive. Patients should undergo an MRSA eradication protocol to remove it from carrier sites . If MRSA is isolated with signs of infection, oral therapy with two of the following should be given: sodium fusidate 500 mg tds, rifampicin 300 mg tds, trimethoprim 200 mg bd or doxycycline  100 mg daily, according to sensitivities.In this follow-up plan, the difficult decision is when there are no signs of infection present but organisms are isolated. Some organisms may be commensals; however, if there are Gram-positive organisms or anaerobes or a pure growth of Gram-negative organisms regard this as a significant result and microbiological evidence of infection.

 

MRSA eradication protocol

Barrier nurse

Topical protocol for 5 days

Mupirocin 2% nasal ointment every 8 h. If MRSA resistant to mupirocin, then use chlorhexidine hydrochloride cream every 8 hours

Tricolsan 2% liquid soap for body and hair washing once daily

2 days protocol free

Repeat swabs three times at 48-hour intervals

If MRSA negative, no further treatment necessary

If MRSA positive, re-treat with 5 days topical protocol and repeat swabs at 48-hour intervals until three sets of negative swabs are obtained.

 

Neuroischaemic feet

Initial plan. Regardless of the depth of the wound  aim to cover aerobic Gram-positive, aerobic Gram-negative and anaerobic infections, and thus we give amoxicillin 500 mg tds, flucloxacillin 500 mg qds, metronidazole 400 mg tds and ciprofloxacin 500 mg bd or trimethoprim 200 mg bd. If the patient is allergic to penicillin,  substitute clarithromycin 500 mg bd for amoxicillin and flucloxacillin. Use this therapy for both superficial and deep infections because Gram-negative organisms may be a feature of infections in the ischaemic foot whether the ulcer is superficial or deep. Send deep swabs or tissue (where possible) for the reasons already described above.

Follow-up plan.

If there are no signs of infection and no organisms are grown,  consider stopping antibiotics. However, if the patient is severely ischaemic, with pres sure index below 0.5,  continue antibiotics until the ulcer is healed.

If there are no signs of infection but organisms are present,  focus the antibiotics according to sensitivities.

If signs of infection are present but no organisms are grown,  continue to give broad-spectrum antibiotics asabove.

If signs of infection are still present and organisms are grown, focus the antibiotics according to sensitivities.

If MRSA is isolated with signs of infection, oral therapy with two of the following is given: sodium

fusidate 500 mg tds, rifampicin 300 mg tds, trimethoprim 200 mg bd or doxycycline 100 mg daily, according to sensitivities.

If there is surrounding erythema then it should be traced to allow early recognition of extension of erythema,which indicates that antibiotic therapy needs adjustment.

 

Spreading infection

Neuropathic feet and neuroischaemic feet

Initial plan. In an ideal world these patients would be admitted to hospital and given intravenous antibiotic therapy as follows: amoxicillin 500 mg tds, flucloxacillin 500 mg qds, metronidazole 500 mg tds and ceftazidime  1 g tds. For patients who are allergic to penicillin  substitute clarythromycin 500 mg bd for amoxicillin and flucloxacillin. The reason for this regime is because spreading infections are often polymicrobial. Other broad-spectrum parenteral therapies which may also be used, depending on local antibiotic policies,

include:

  • Ciprofloxacin and clindamycin
  • Ticarcillin/clavulanate
  • Piperacillin/tazobactam
  • Meropenem
  • Ertapenem
  • Tigecyline.

If admission to hospital is not possible then a useful therapy is intramuscular ceftriaxone 1 g in 3.5 mL of 1% lidocaine once daily together with metronidazole either 1 g rectally tds or 400 mg tds orally. Ceftriaxone is a useful wide-spectrum antibiotic with a prolonged period of activity making it suitable for once a day administration. This regime is suitable for neuropathic and neuroischaemic patients, but anticoagulant therapy is a contraindication to intramuscular injections. Other useful intramuscular antibiotics include teicoplanin to treat Gram-positive organisms including MRSA and imipenem with cilastatin and ertapenem to treat Gram-positives, Gram-negatives and anaerobes.

Osteomyelitis

Osteomyelitis can complicate any of the above infective presentations.

Initial treatment

  • Usually antibiotics will be given for the associated soft tissue infection
  • When soft tissue infection is not present but a diagnosis of osteomyelitis is made clinically, an empirical regime with good bone penetration should be given such as rifampicin 300 mg tds and ciprofloxacin 500 mg bd

Follow-up plan

  • Antibiotics should be given for at least 12 weeks. Parenteral therapy has in the past been given for up to 6 weeks followed by oral therapy for 6 weeks. However, it may be possible to limit the parenteral therapy to 2 weeks and follow this with appropriate oral antibiotics for up to 10 weeks (if the infected bone is resected then a shorter course of antibiotics such as 4 weeks may be necessary). Conservative therapy is often successful, and is associated with resolution of cellulitis and healing of the ulcer.
  • However, if, after 3 months treatment, the ulcer persists, with continued probing to bone that is fragmented on X-ray, consider resection of the underlying bone, which may entail toe amputation or removal of a metatarsal head.

Vascular control

It is important to explore the possibility of revascularization in the infected neuroischaemic foot. Improvement of perfusion will not only help to control infection, but will also promote healing of the wound if operative debrideent is necessary.

Angiography

Initially, duplex angiography should be carried out to detect the presence of stenoses or occlusions which may be amenable to angioplasty or bypass. Duplex angiography is proficient at looking at the iliac, femoral and popliteal arteries, but it is sometimes difficult to obtain good views of the infrapopliteal arteries and foot arteries because of the excessive calcification in the diabetic patient. If duplex angiography is not available then MRI or CT angiography may be used to demonstrate infra- popliteal vessels and also for delineating the aortoiliac  circulation.

Angioplasty

When non-invasive angiography reveals lesions that are amenable to angioplasty in the femoral and popliteal arteries, then down stream transfemoral angiography is performed followed by angioplasty. The infrapopliteal arteries are also visualized and appropriate lesions angioplastied. Angioplasty is possible at several levels of the leg arterial system to obtain straight-line flow to the foot. It is indicated for the treatment of isolated or multiple stenoses as well as short segment occlusions less than 10 cm  in length in iliac, femoral and tibial arteries. Recent progress has resulted in long occlusions being satisfactorily angioplastied, either using long balloons or the technique of subintimal angioplasty, with the catheters inserted  into the subintimal plane. The aim is to improve the arterial circulation, achieve straight-line flow to the foot and bring about an increased blood supply to the site of ulceration and infection . Although the foot pulses may not be restored,there is usually a notable increase in the transcutaneous oxygen tension.

Angiography and angioplasty are safe procedures with few complications so long as appropriate precautions are taken. Investigations should include:

  • A recent full blood count, including a platelet count
  • Blood coagulation indices
  • Serum electrolytes and creatinine
  • Blood grouping.

The patient should not be dehydrated. Start an insulin sliding scale together with intravenous fluids before the procedure. Dopamine is no longer used to protect kidney function but it is important to keep the patient hydrated with intravenous fluids prior to the procedure. Patientswith impaired renal  function should be prescribed N-acetylcysteine 600 mg bd 24 hours before the procedure and on the day of the procedure. If the patient has previously been on warfarin then this must be stopped at least 3 days prior to the procedure and the patient changed to intravenous heparin. The  heparin infusion is stopped 2 hours before the procedure. Metformin should be stopped 2 days before the procedure and restarted 2 days after the procedure. If the angiogram is required as an emergency, it may be necessary to give vitamin K to counteract the effect of the warfarin therapy.

Post-angiography, patients should be monitored closely, recording blood pressure and pulse. A rare  complication is bleeding from the femoral artery injection site, which may not be immediately apparent. The pulse rate may not respond in the usual way to loss of intravascular volume because of autonomic neuropathy, therefore tachycardia may not be present. However, blood pressure will drop and an urgent blood count together with cross-matching for at least 6 pints of blood should be performed. Full resuscitation should immediately be carried out with haemodynamic monitoring.

Most cases of bleeding resolve with blood replacement and tamponade themselves off spontaneously. A mass may become palpable in the lower abdomen but this may not appear until 5–6 hours after the procedure. Earlier diagnosis may be made with an ultrasound examination of the abdomen. Continued hypotension despite adequate blood replacement is an indication for surgical exploration.

Post-angioplasty it may be advisable to give heparin if  a long occlusion has been treated. It is best to give unfractionated heparin intravenously. If there is any postprocedure bleeding over the subsequent few hours from the femoral artery injection site, this can be exacerbated by heparin. Unfractionated heparin can be easily stopped if given intravenously; however, low molecular weight heparin given subcutaneously is difficult to reverse and we have had one case of severe post procedure bleeding in these circumstances. In patients with impaired renal function, serum creatinine may rise after the procedure, and should be checked after 48 hours. There may be a mild rise of serum creatinine of 50 mmol/L (0.57 mg/dL) but this falls gradually over the subsequent 10 days, but should be carefully monitored. In some cases renal impairment may be severe and renal support in the form of dialysis needed. Following angioplasty, both lower limbs should be carefully observed to detect the presence of unexpected ischaemia or emboli. Trash foot is described after angioplasty but is notably rare. The limbs should be observed for the development of a pale cold periphery which might indicate significant arterial damage either at the femoral injection site or the angioplasty site.

Mechanical control

Patients with extensive cellulitis should not walk. They should be on bed rest and use crutches or wheelchair for trips to the bathroom. Every step taken will spread infection. Heels must be protected with a pillow/foam wedge under the calves to keep the patient’s heels clear of the mattress when he is in bed. Special mattresses should be provided to prevent decubitus ulcers. If he slides down the bed he risks pressure lesions from the bed end. Long periods on the operating table can lead to heel blistering and heel necrosis, and patients who go to theatre should have their heels regularly protected. It is possible to off-load postoperative wounds in the neuropathic foot with a removable bivalved cast or indowed cast which enable wound inspection. Pressure-relieving ankle–foot orthoses (PRAFOs) are increasingly used as heel off-loaders in both classes of foot. After operative debridement in the neuroischaemic foot, non-weightbearing is advised until the wound is healed.

Metabolic control

It is important to make sure that there are no systemic,metabolic or nutritional disturbances to impair the response to infection and retard healing of wounds. In severe infections, considerable metabolic decompensation may occur. Full resuscitation is urgently required with intravenous fluids and intravenous insulin sliding scale which is often necessary to achieve good blood glucose control whilst the patient is infected. This is followed by a basal-bolus regimen of three times a day short-acting insulin before meals and long-acting insulin at night. Total dose of insulin (units) = 0.5 × body weight (kg), split 2/3 as bolus and 1/3 as basal. These are complex patients. Cardiac and renal function should be assessed and any impairment should  be managed carefully. Echocardiography will identify patients with left ventricular dysfunction. This is expressed as the ejection fraction and a value less than 35% increases the risk of non-cardiac surgery. Close observation and monitoring of these systems is essential to maintain correct electrolyte and fluid balance, especially postoperatively. Neuroischaemic patients should be regularly taking statins, angiotensin-converting enzyme (ACE) inhibitors and antiplatelet agents and these should be continued if the patient is admitted to hospital. Aspirin should not be stopped before angiography or angioplasty although if the patient is taking aspirin and clopidogrel, the latter should be stopped. High blood glucose is associated with reduced white cell function, which improves when the blood glucose is lowered.