Use of Antibiotics in People with Diabetic Foot Disease: a Consensus Statement

Use of antibiotics in people with diabetic foot disease: A consensus statement

Article points 1. Narrow spectrum Graham Leese, Dilip Nathwani, antibiotics should be used where possible to reduce the risk of meticillin Matthew Young, Andrew Seaton, resistant Staphylococcus aureus and Clostridium difficile infection. Brian Kennon, Helen Hopkinson, 2. The choice of antibiotic agent, and route of Duncan Stang, Benjamin Lipsky, delivery used, in the treatment of the infected diabetic foot should William Jeffcoate, Tony Berendt reflect the severity of the infection. 3. Initial treatment of The authors, on behalf of the Scottish Diabetes Group and the infection of the diabetic Scottish Infectious Diseases Society, provide broad, practical foot is frequently based on targeting the pathogen guidance on the use of antibiotics in people with diabetic foot disease presumed involved. complicated by infection. Recommendations on the most appropriate 4. This guidance assists investigative techniques, antibiotics and likely infecting organisms healthcare professionals are provided. This guidance is dependent on local microbiological treating the infected diabetic foot until epidemiology and susceptibility patterns, and prescribing microbiological guidelines, and the authors encourage all those managing infection investigations and clinical in the diabetic foot to seek local specialist infection advice, where response shed further light on the nature of necessary, on the use of antibiotics. the infection.

Key words: he following guidance aims to appropriate. Guidance about antibiotic - Antibiotic guidance help healthcare professionals make choice is dependent on local microbiological - Consensus statement decisions about antibiotic agents for epidemiology and susceptibility patterns. - Diabetic foot disease T - Infection the treatment of the infected diabetic foot in However, the consensus group felt that the order to improve patient outcomes. pathogens causing various diabetic foot This is a consensus document based on infections in Scotland are unlikely to vary limited available clinical trial evidence, substantially within Scotland. Therefore, Author details can be review of international guidelines and merit was seen in providing broad, practical found on the last page expert opinion. There may be circumstances guidance on antibiotic choice, subject to of this article. where alternative courses of action are local adaptation when necessary.

62 The Diabetic Foot Journal Vol 12 No 2 2009 General approach to diabetic foot ulcer management The multidisciplinary team Diabetic foot ulcers should be treated by a multidisciplinary footcare team as this managment strategy has been shown to reduce amputation rates. In addition, attention to aggressive treatment of macrovascular risk factors in people with diabetic foot ulcers has been shown to prolong survival.

Re-ulceration Previous ulceration is the strongest predictor for recurrent ulceration and preventative measures need to be addressed following healing. Re-ulceration rates of up to 70% at 5 years have been reported.

Specimens for culture There is some debate over when a culture is necessary. Clinically uninfected ulcers rarely need to be cultured. An acutely infected wound of mild or moderate severity in a person who has not recently been treated with antibiotics does not need to be cultured. Other wounds should almost always be cultured. If a specimen is not taken at presentation of clinical signs, then cultures should be taken if there is clinical failure of empirical antibiotics. Aspiration of purulent secretions, curettage of the post-debridement wound base, punch biopsy and extruded or biopsied bone are the best specimens for culture.

Diagnosing bone infection Inability to touch bone when probing a wound with a sterile metal probe makes osteomyelitis unlikely, with a negative predictive value of approximately 90% (Jeffcoate and Lipsky, 2004). The positive predictive value of a positive probe-to-bone test is around 50%, meaning that half of all ulcers that probe to bone do not have osteomyelitis (Jeffcoate and Lipsky, 2004). If there is clinical suspicion of osteomyelitis plain X-ray is the usual initial investigation of choice. However, it can take 2 weeks before any changes of acute osteomyelitis are seen on plain radiograph and thus serial X-rays may be required to rule out osteomyelitis. If there is Use of antibiotics in people with diabetic foot disease: A consensus statement

Page points ongoing concern of osteomyelitis and it cannot be Neuropathy, Bacterial Infection, and Depth) score 1. If you suspect diagnosed using X-ray, secondary investigations (Ince et al, 2008), the PEDIS (Perfusion, Extent/ osteomyelitis, plain of choice are (in order of preference): size, Depth/tissue loss, Infection, Sensation) score X-ray is the usual initial l Magnetic resonance imaging (MRI). (Schaper, 2004). The Scottish Care Information investigation of choice. l Isotope white cell scan. – Diabetes Collaboration electronic ulcer 2. The presence and severity l Triple phase bone scan (highly sensitive at management programme is based on the Texas of infection should be diagnosing osteomyelitis, but is not specific, classification system. classified according to one and can remain positive for >1 year). of the recognised systems. Imaging options may be dictated by the local Classification of infection 3. Antibiotic choice is availability of imaging equipment. It is recommended that the presence and severity dependent on local of infection be classified according to the IDSA microbiological Loose bone system (Table 1) or the PEDIS system developed susceptibility and epidemiology. Loose bone extruded from an ulcer, or any bone by the International Working Group for the debrided, should be sent for bone culture and Diabetic Foot. 4. Initial antibiotic microbiological assessment. The extrusion of a treatment is frequently General principles of antibiotic use empirical, based on the bone fragment (sequestrum) is highly suggestive presumed pathogen. of underlying osteomyelitis, although the Antibiotic choice is primarily dependent on infection may have arrested coincident to the causative pathogens and epidemiology. However, 5. In light of international concerns over Clostridium passage of the sequestrum. treatment with antibiotics often needs to be difficileand meticillin- commenced before culture and sensitivity results resistant Staphylococcus “Sausage” digit are available. Thus initial therapy is usually aureus, narrow-spectrum The presence of a red, swollen “sausage”-shaped empirical, and based on the local epidemiological antibiotic therapy should digit is suggestive of osteomyelitis, but can be the information and local susceptibility data. As the be used wherever possible. result of other foot problems (e.g. fracture). pathogens in diabetic foot infections do not vary significantly in different parts of Scotland, the Differential diagnosis authors offer practical guidance on antibiotic use. Differentiating between osteomyelitis and Charcot These recommendations are, however, subject foot can be difficult. Diagnosis is based on a good to circumstances related to local epidemiology history and physical examination, and is assisted and prescribing policy. Direct contact with by obtaining supplementary investigations such local specialists may be necessary for advice on as X-ray, MRI, and possibly isotope white cell and specialised use of these, or other, antibiotics. triple phase bone scans. It is important to note Initial antibiotic treatment is frequently that osteomyelitis and Charcot foot frequently empirical, based on the presumed pathogen occur simultaneously. Osteomyelitis most often (Table 2). This guidance is of value until affects the forefoot and heel, while Charcot neuro- microbiological investigations and clinical arthropathy usually affects the forefoot or ankle. response shed further light on the nature of the infection, where available. In light of international Prophylactic antibiotic use concern over Clostridium difficile infection Antibiotics should be used only in those who associated with certain antibiotics (especially have clinical signs of infection (i.e. “mild”, clindamycin, co-amoxiclav, cephalosporins “moderate” or “severe” in the Infectious Disease and quinolones) and the risk of meticillin- Society of America [IDSA] infection grading resistant Staphylococcus aureus (MRSA) infection system; see Table 1). (associated with co-amoxiclav, cephalosporins, quinolones and macrolides), narrow-spectrum Foot ulcer classification antibiotic therapy should be used wherever Various ulcer classification schemes are used. possible. C. difficile is a particular risk for people The primary ones are the Wagner score (Wagner, aged >65 years and for inpatients. Adjustment 1981), the University of Texas system (Lavery of therapy based on microbiology results, et al, 1996), the SINBAD (Site, Ischaemia, when available and clinical response to

64 The Diabetic Foot Journal Vol 12 No 2 2009 Use of antibiotics in people with diabetic foot disease: A consensus statement

Page points empirical therapy is important in the Specific antibiotic guidance 1. This guidance is management of these risks. Specific clinical symptoms identified during categorised by the severity The choice of antibiotic and the route of careful examination shed light on the likely of infection, and by delivery should reflect the severity of infection microbiology of a diabetic foot ulcer. From whether the person is, or (Table 1). Duration of antibiotic treatment the likely pathology, initial antibiotic therapy is not, antibiotic-naïve. should be adjusted according to the severity of can be decided on with some degree of 2. Mild infections of the infection and should be guided by monitoring confidence – although there will on occasion be diabetic foot in an clinical improvement. In general, the duration circumstances suggesting different selections. antibiotic-naïve person of antibiotic therapy should be kept to a We emphasise the importance of getting good are likely to be caused by Staphylococcus aureus minimum. Antibiotic therapy is used only to quality specimens (see page 64 for a guidance or beta-haemolytic treat evidence of infection, not to heal a wound, on specimens for culture) for microbiological streptococci. which typically takes much longer. investigation, and close liaison with local 3. A microbiological culture Allergies to antibiotics include skin rashes and infection specialists. should be taken if the anaphylaxis, but do not include minor side-effects This guidance is categorised by the severity of presence of an unusual such as nausea. infection, and by whether the person is, or is not, organism is suspected, or Enterococci, Pseudomonas and anaerobes are antibiotic-naïve. The primary choice of antibiotic, if initial treatment fails, frequently isolated from diabetic foot wounds, and alternatives, for use in people with diabetic in a mild infection. but often represent colonising, rather than foot infections are provided and discussed. A infecting, organisms. If, however, there is a summary of the guidance is provided in Table 3. chronic, persisting infection, or they are the predominant organisms, they may represent Mild infection (IDSA) or PEDIS 2 pathogens and need targeted treatment. in an antibiotic-naïve person Likely pathogens Table 1. Grading the severity of diabetic foot infection (based on the l S. aureus (and sometimes coagulase-negative Infectious Disease Society of America classification system; staphylococci) or beta-haemolytic streptococci. Lipsky et al, 2004) l If the person has recently been treated with antibiotics, enterococci and gram-negative rods GRADE 1 NO INFECTION are more likely to be present.

No purulence or signs of infection. Note u Take a microbiological culture if the presence of GRADE 2 MILD INFECTION an unusual organism is suspected, or if initial No systemic illness and evidence of either: (a) pus (purulent treatment fails. secretions) or (b) two or more signs or symptoms of inflammation (i.e. erythema, warmth, pain, tenderness, induration). Any cellulitis Antibiotics <2 cm around the wound. Infection is confined to the skin or Primary subcutaneous tissue. No evidence of systemic infection. l Oral flucloxacillin 1 g four times a day (qds). – Assuming that the first course of GRADE 3 MODERATE INFECTION flucloxacillin was given in high dose and for a full 5–7 days, a second course is Either: (a) lymphatic streaking, deep tissue infection (involving rarely effective if the first was unsuccessful. subcutaneous tissue, fascia, tendon, bone) or abscess, or (b) cellulitis – There is an increased prevalence of >2 cm. No evidence of systemic infection. resistant organisms after the first exposure to flucloxacillin. GRADE 4 SEVERE INFECTION

Any infection accompanied by systemic toxicity (fever, chills, shock, Oral alternatives l vomiting, confusion, metabolic instability). The presence of critical Doxycyline 100 mg twice a day (bd), or l ischaemia of the involved limb may make the infection severe. Clindamycin 300–450 mg qds, if the person is allergic to, or intolerant of, flucloxacillin.

66 The Diabetic Foot Journal Vol 12 No 2 2009 Use of antibiotics in people with diabetic foot disease: A consensus statement

Page points Treatment duration Oral alternatives l 1. A good quality u Treat for 5–7 days. Adjust therapy in light Co-trimoxazole 960 mg bd, or microbiological culture of clinical response and microbiological l Co-amoxiclav 625 mg three times a day (tds). is particularly helpful. culture and sensitivity results. 2. People with chronic Allergic to penicillins infections, especially Moderate infection (IDSA) or PEDIS l Clindamycin (oral, 300–450 mg qds; if they have received 3 in an antibiotic-naïve person IV, 450–600 mg qds), or antibiotics previously, Likely pathogens l Co-trimoxazole 960 mg bd. often have polymicrobial l S. aureus or beta-haemolytic streptococci. infections, including l aerobic gram-negative Obligate anaerobes are often associated with Addition bacilli among the flora. limb ischaemia, gangrene, necrosis or wound l Add oral metronidazole 400 mg tds if odour and must also be addressed. anaerobes are suspected (unless using clindamycin, which has anaerobic cover). Note u A good quality microbiological culture Moderate infection (IDSA) or PEDIS 3 can be particularly helpful in this in a person who is not antibiotic-naïve circumstance. See page 63 for guidance on Likely pathogens specimens for culture. l People with chronic infections, especially Antibiotics if they have received antibiotics previously, Primary often have polymicrobial infections, l Oral flucloxacillin 1 g qds, or including aerobic gram-negative bacilli l Intravenous (IV) flucloxacillin 1 g qds. among the flora.

Table 2. Likely infecting organisims of the diabetic foot and the primary and alternative antibiotic therapies suggested for treatment.

LIKELY PATHOGEN ANTIBIOTIC THERAPY

PRIMARY ALTERNATIVES

Staphylococcus aureus l Penicillinase-resistant l Doxycycline, or penicillin l Clindamycin. (e.g. flucloxacillin)

Meticillin-resistant l Vancomycin, l Rifampicin with either: Staphylococcus aureus l Teicoplanin, or – Trimethoprim, l Discuss other – Doxycycline, or options with an – Fusidic acid, infection specialist. l Co-trimoxazole, or l Linezolid.

Beta-haemolytic streptococcus l Amoxicillin. l Clindamycin.

Enterococcus l Amoxicillin, or l Vancomycin, or l Co-amoxiclav. l Linezolid.

Pseudomonas l Quinolones (e.g. high- l Piperacillin-tazobactam, (gram-negative bacillus) dose ciprofloxacin). or l Meropenem. Anaerobes l Metronidazole. l Clindamycin.

68 The Diabetic Foot Journal Vol 12 No 2 2009

1/6/09 10:19:27

†‡

, or

†

†‡

IVteicoplanin.

l l

HomeIV service

if MRSA infection

†‡

Oraltherapy inappropriate.

SEVEREINFECTION

mg/L). concentration15–20 of

suspected(aim trough a for vancomycin

AddIV vancomycin

dailyif required.

infectionsuspected.

IVvancomycin.

Ciprofloxacin500–750 mg bd and

IVciprofloxacin 400mg bd and IVciprofloxacin 400mg bd and

Ifosteomyelitis is present, treat at for

IVantibiotics may be switched oral to

IVco-amoxiclav tds, g 1.2 IVpiperacillin/tazobactam tds, g 4.5

Anyinfection accompanied systemic by with the Treatment following agents

Rifampicin 300 mg bd (with either: Linezolid 600 mg bd. Rifampicin 600 mg bd, or Sodium fusidate 500 mg tds.

clindamycin300–450 mg qds.

– Add – IV vancomycin if MRSA

metronidazole400 mg tds, or

IVmetronidazole 500 mg tds. metronidazole500 mg tds,

or discontinued or as appropriate.

shouldbe reviewed and continued

least4–6 weeks, after which treatment

preparationsafter an interval. appropriate

limbmay make the infection severe.

mg bd,100 fusidic or acid 500 mg tds) presencecritical of ischaemia the of involved continueddiscontinued or as appropriate.

confusion,metabolic instability). The whichtreatment should be reviewed and – Add – gentamicin 5–7 mg/kg once –

toxicity (fever, chills, toxicity(fever, shock, vomiting, days, isrecommended after 10–14 for

trimethoprim 200 mg bd, doxycycline

l l

Primary

l l

Oralswitch

l l l

If allergic If to penicillin l l

If allergic to penicillin, or concern about renal function function renal about concern or penicillin, to allergic If

l l NOTE:

Primary

l l l

Primary Oral switch† l l Osteomyelitis MRSA infection of bone, add either: l l

†‡

, or

†

if MRSA

†‡

†

IVteicoplanin.

l l HomeIV service

†‡

Staphylococcusaureus

anaerobessuspected.

MODERATE INFECTION MODERATE

IVvancomycin.

Ciprofloxacin500–750 mg bd and

IVgentamicin†‡ and IV metronidazole

IVciprofloxacin 400mg tds and IV

Clindamycinmg qds, 450

Ifosteomyelitis is present, treat at for Co-amoxiclavmg tds, 625 or

Co-trimoxazole960 mg bd, Co-trimoxazole960 mg bd.

IVantibiotics may be switched oral to Co-amoxiclavmg tds, 625 or No evidence No systemic of infection.

Oralfluxcloxacillin MSSA qds g 1 (for or IVco-amoxiclav tds. g 1.2

clindamycin300–450 mg qds. Treatment with the Treatment following agents is

Rifampicin 300 mg bd (with either: Linezolid 600 mg bd. Rifampicin 600 mg bd, or Sodium fusidate 500 mg tds.

metronidazole400 mg tds, or

infectionsuspected).

ifMRSA infection suspected), or 500mg IV tds (add vancomycin

Add – metronidazole 400 mg tds if metronidazole500 mg IV tds (add vancomycin discontinuedas appropriate.

shouldbe reviewed and continued or

least4–6 weeks, after which treatment

preparationsafter an interval. appropriate

tendon, fascia, tendon, abscess, or bone or mg bd,100 fusidic or acid 500 mg tds) asappropriate.

infectioninvolving subcutaneous tissue, beta-haemolyticstreptococci). shouldbe reviewed and continued discontinued or

Lymphaticstreaking, deep tissue recommended5–7 for days, after which treatment

trimethoprim 200 mg bd, doxycycline

Cellulitis cm, and >2

l l

Primary

l l

Alternativeoral switch

l l

Alternatives

l l

l l l

l l l l

Alternatives l l l l

Primaryoral switch

Primary l l l

Primary l l

Oral switch† l l Osteomyelitis MRSA infection of bone, add either: l l

Note concerns Note about linezolid toxicity with protracted therapy.

; MSSA=meticillin-sensitive ;

Staphylococcusaureus

Monitor serum Monitor concentration;

†

‡

MILDINFECTION

Doxycyclinemg bd, 100 or

Clindamycin300–450 mg qds.

Oralflucloxacillin qds. g 1 Doxycyclinemg bd, 100 or

Treatment with the Treatment following agents is

or discontinued or as appropriate.

treatmentshould be reviewed and continued

No evidence No systemic of infection.

recommended5–7 for days, after which

confined to skin or subcutaneous tissue, and

Anycellulitis <2 cm around the wound

pain,tenderness, induration,

Pustwo or of: erythema, more or warmth,

Clindamycin 300–450 mg qds.

l l

Alternatives

l l

l l l

Primary Primary l l

Symptoms Treatment duration Treatment Antibiotic–na MRSA ï Not antibiotic–na Not ve

ï ve

Requiresmonitoring for complications;

†

IV=intravenous;MRSA=meticillin-resistant

Dosingfrequencies: bd=twice day; a qds=four times day; a tds=three times day. a Table 3. Summary 3. Table guidance of antibiotics on the for treatment infection of in the diabetic foot. Leese_summary_v4.indd 1

1/6/09 10:19:27

†‡

, or

†

†‡

IVteicoplanin.

l l

HomeIV service

if MRSA infection

†‡

Oraltherapy inappropriate.

SEVEREINFECTION

mg/L). concentration15–20 of

suspected(aim trough a for vancomycin

AddIV vancomycin

dailyif required.

infectionsuspected.

IVvancomycin.

Ciprofloxacin500–750 mg bd and

IVciprofloxacin 400mg bd and IVciprofloxacin 400mg bd and

Ifosteomyelitis is present, treat at for

IVantibiotics may be switched oral to

IVco-amoxiclav tds, g 1.2 IVpiperacillin/tazobactam tds, g 4.5

Anyinfection accompanied systemic by with the Treatment following agents

Rifampicin 300 mg bd (with either: Linezolid 600 mg bd. Rifampicin 600 mg bd, or Sodium fusidate 500 mg tds.

clindamycin300–450 mg qds.

– Add – IV vancomycin if MRSA

metronidazole400 mg tds, or

IVmetronidazole 500 mg tds. metronidazole500 mg tds,

or discontinued or as appropriate.

shouldbe reviewed and continued

least4–6 weeks, after which treatment

preparationsafter an interval. appropriate

limbmay make the infection severe.

mg bd,100 fusidic or acid 500 mg tds) presencecritical of ischaemia the of involved continueddiscontinued or as appropriate.

confusion,metabolic instability). The whichtreatment should be reviewed and – Add – gentamicin 5–7 mg/kg once –

toxicity (fever, chills, toxicity(fever, shock, vomiting, days, isrecommended after 10–14 for

trimethoprim 200 mg bd, doxycycline

l l

Primary

l l

Oralswitch

l l l

If allergic If to penicillin l l

If allergic to penicillin, or concern about renal function function renal about concern or penicillin, to allergic If

l l NOTE:

Primary

l l l

Primary l l l

Oral switch† l l Osteomyelitis MRSA infection of bone, add either: l l

†‡

, or

†

if MRSA

†‡

†

IVteicoplanin.

l l HomeIV service

†‡

Staphylococcusaureus

anaerobessuspected.

MODERATE INFECTION MODERATE

IVvancomycin.

Ciprofloxacin500–750 mg bd and

IVgentamicin†‡ and IV metronidazole

IVciprofloxacin 400mg tds and IV

Clindamycinmg qds, 450

Ifosteomyelitis is present, treat at for Co-amoxiclavmg tds, 625 or

Co-trimoxazole960 mg bd, Co-trimoxazole960 mg bd.

IVantibiotics may be switched oral to Co-amoxiclavmg tds, 625 or No evidence No systemic of infection.

Oralfluxcloxacillin MSSA qds g 1 (for or IVco-amoxiclav tds. g 1.2

clindamycin300–450 mg qds. Treatment with the Treatment following agents is

Rifampicin 300 mg bd (with either: Linezolid 600 mg bd. Rifampicin 600 mg bd, or Sodium fusidate 500 mg tds.

metronidazole400 mg tds, or

infectionsuspected).

ifMRSA infection suspected), or 500mg IV tds (add vancomycin

Add – metronidazole 400 mg tds if metronidazole500 mg IV tds (add vancomycin discontinuedas appropriate.

shouldbe reviewed and continued or

least4–6 weeks, after which treatment

preparationsafter an interval. appropriate

tendon, fascia, tendon, abscess, or bone or mg bd,100 fusidic or acid 500 mg tds) asappropriate.

infectioninvolving subcutaneous tissue, beta-haemolyticstreptococci). shouldbe reviewed and continued discontinued or

Lymphaticstreaking, deep tissue recommended5–7 for days, after which treatment

trimethoprim 200 mg bd, doxycycline

Cellulitis cm, and >2

l l

Primary

l l

Alternativeoral switch

l l

Alternatives l l

l l l

l l l l

Alternatives l l l l

Primaryoral switch l

l l l

Primary Primary l l

Oral switch† l l Osteomyelitis MRSA infection of bone, add either: l l

Note concerns Note about linezolid toxicity with protracted therapy.

; MSSA=meticillin-sensitive ;

Staphylococcusaureus

Monitor serum Monitor concentration;

†

‡

MILDINFECTION

Doxycyclinemg bd, 100 or

Clindamycin300–450 mg qds.

Oralflucloxacillin qds. g 1 Doxycyclinemg bd, 100 or

Treatment with the Treatment following agents is

or discontinued or as appropriate.

treatmentshould be reviewed and continued

No evidence No systemic of infection.

recommended5–7 for days, after which confined to skin or subcutaneous tissue, and

Anycellulitis <2 cm around the wound

pain,tenderness, induration,

Pustwo or of: erythema, more or warmth,

Clindamycin 300–450 mg qds.

l l

Alternatives

l l

l l l

Primary l l

Primary

Symptoms Treatment duration Treatment Antibiotic–na MRSA ï Not antibiotic–na Not ve

ï ve

Requiresmonitoring for complications;

†

IV=intravenous;MRSA=meticillin-resistant

Page points Antibiotics be admitted to hospital for the initial phase 1. As severe infection Primary of management. implies systemic toxicity, l IV co-amoxiclav 1.2 g tds (especially it is generally advised when anaerobes or coliforms are suspected). Antibiotics that people at this level Primary of infection should be Oral switch l IV co-amoxiclav 1.2 g tds. admitted to hospital l 1 for the initial phase of Co-amoxiclav 625 mg tds, or – If necessary, add gentamicin 5–7 mg/kg management. l Co-trimoxazole 960 mg bd. once daily or as per local practice. 2. A good quality microbiological culture Allergic to penicillins Allergic to penicillins or concern about renal should be taken from l IV ciprofloxacin 400 mg tds and IV function severe infections. metronidazole 500 mg tds, or l IV ciprofloxacin 400 mg bd and IV l 1 3. Severe infections IV gentamicin (monitor serum concentration) metronidazole 500 mg tds. in people who are and IV metronidazole 500 mg tds. – Add vancomycin (monitor serum antibiotic naïve are – Add vancomycin (monitor serum concentration) if MRSA infection is usually caused by concentration) to either of the above if suspected. Staphylococcus aureus MRSA infection is suspected. or beta-haemolytic streptococci. Anaerobes, l Choice will depend on the relative risks Treatment duration enterobacteriaceae and of C. difficle infection versus those of u Treat for a minimum of 10–14 days. Pseudomonas aeruginosa renal impairment. Adjust therapy in light of clinical (usually a coloniser response and microbiological culture and rather than the infecting Oral switch options if allergic to penicillins sensitivity results. organism) may also need to be treated. l Oral ciprofloxacin 500–750 mg bd with either: – Oral metronidazole 400 mg tds, or Severe infection (IDSA) 4. If infection with an – Clindamycin 300–450 mg qds. or PEDIS 4 extended-spectrum beta-lactamase- The following guidance is for the treatment of producing pathogen is Treatment duration severe or PEDIS 4 diabetic foot infections in proven, seek specialist u Treat for 5–7 days. Adjust therapy in light of number of circumstances: infection advice. clinical response and microbiological culture l People who have recently received antibiotic and sensitivity results. therapy (i.e. those who have received antibiotic treatment within the preceding 90 days). Severe infection (IDSA) or l People with a proven drug-resistant infection. PEDIS 4 in an antibiotic-naïve person l Those at risk of a drug-resistant infections Likely pathogens (e.g. those who have previous had an l S. aureus or beta-haemolytic streptococci. MRSA colonisation). l Anaerobes, enterobacteriaceae and Pseudomonas l Those infected with an extended-spectrum aeruginosa may also need to be treated. P. beta-lactamase-producing (ESBL) Escherichia aeruginosa is usually a coloniser rather than coli or Klebsiella spp. If infection with an being the infecting organism. ESBL pathogen is proven, seek specialist Notes infection advice. u A good quality microbiological culture should virtually always be taken (see page 63 Notes for guidance). u A good quality microbiological culture u Caution: As Severe or PEDIS 4 infection should always be taken (see page 63 for implies systemic toxicity, it is generally guidance). advised that people at this level of infection u Caution: As Severe or PEDIS 4 infection

1Gentamicin should be given as a high dose, determined by local practice, once daily. Close monitoring of serum levels and renal function will be required. Treatment with gentamicin for >48 hours should only be undertaken with specific advice from an infection specialist.

72 The Diabetic Foot Journal Vol 12 No 2 2009 Use of antibiotics in people with diabetic foot disease: A consensus statement

implies systemic toxicity, it is generally Treatment duration Page point advised that people at this level of infection u Treat for minimum of 10–14 days. Adjust 1. Continuing meticillin- be admitted to hospital for the initial phase therapy in light of clinical response and resistant Staphylococcus of management. microbiological culture and sensitivity results. aureus cover may be required, whether Antibiotics MRSA the person can safely be discharged from Primary If continuing MRSA cover is required, and the hospital will influence l IV piperacillin/tazobactam 4.5 g tds, person can safely be discharged from hospital, the the choice of agent. – Add vancomycin if MRSA infection authors suggest either: is suspected (consult pharmacy for dose, l Outpatient or home parenteral antimicrobial but aim for a trough vancomycin level of therapy (OHPAT) if available (usually 15–20 mg/L). IV teicoplanin). l Oral linezolid 600 mg bd. Note that treatment Penicillin allergy beyond 2 weeks’ duration with this agent needs l IV ciprofloxacin 400 mg bd and IV to be monitored closely as it can be associated metronidazole 500 mg tds. with bone marrow toxicity (particularly Oral switch thrombocytopenia or leucopenia) and lactic l Be guided by microbiology where possible. acidosis, which are usually reversible on – Otherwise try oral ciprofloxacin discontinuation of the drug. 500–750 mg bd and metronidazole l Rifampicin 300 mg bd with either: 400 mg tds. – Oral doxycycline 100 mg bd, Use of antibiotics in people with diabetic foot disease: A consensus statement

Page points – Fusidic acid 500 mg tds, or C-reactive protein and white blood cell counts

1. Early, local surgery to – Trimethoprim 200 mg bd. may assist in determining the course of the excise infected bone can All these agents can be used to treat people osteomyelitis, but should not be taken more help accelerate healing allergic to penicillins. than once per week. n and reduce the length of time antibiotics are Osteomyelitis required in cases of Early, local surgery to excise infected and osteomyelitis. Graham Leese is a Consultant in Diabetes, Ninewells necrotic bone may help accelerate healing Hospital, Dundee, and Chairman of the Scottish 2. The evidence base for and reduce the length of time that treatment antibiotic choice for Diabetes Foot Action Group; Dilip Nathwani is a osteomyelitis is poor. with antibiotics are required in cases of Consultant in Infectious Diseases, Ninewells Hospital, osteomyelitis (Berendt et al, 2008). The exact Dundee; Matthew Young is a Consultant Physician 3. There is no evidence role of local surgery in treating osteomyelitis and Clinical Lead, Diabetic Foot Clinic, The Royal that intravenous Infirmary, Edinburgh; Andrew Seaton is a Consultant antibiotic therapy is remains controversial. in Infectious Diseases, Gartnavel Hospital, Glasgow; superior to oral therapy Published studies have shown that Brian Kennon is a Consultant in Diabetes, Southern in the treatment of antibiotic therapy without surgery can lead General Hospital, Glasgow; Helen Hopkinson osteomyelitis. to resolution of infection in up to 80% of is a Consultant in Diabetes, Victoria Infirmary, cases of osteomyelitis (Game and Jeffcoate, Glasgow; Duncan Stang is a Podiatrist, Hairmyres 4. Tolerability of oral Hospital, East Kilbride and National Diabetes antibiotics during 2008). The evidence base for antibiotic choice Foot Coordinator; Benjamin Lipsky is Professor of osteomyelitis is a for these infections is poor. However, the Medicine, University of Washington, Seattle, WA, significant issue and group recommends that, in those people who USA; William Jeffcoate is Professor of Endocrinology, therapy may need to be Nottingham University Hospitals NHS Trust, tailored accordingly. show evidence of osteomyelitis, and in all cases where infected bone is not resected, the Nottingham; Tony Berendt is a Consultant Physician, Bone Infection Unit, Nuffield Orthopaedic Centre treatments outlined above should be continued NHS Trust, Oxford. for at least 4–6 weeks, or longer if the clinical response is poor. There is no evidence that IV antibiotic therapy is superior to oral therapy in the treatment of osteomyelitis, although Berendt AR, Peters EJ, Bakker K et al (2008) in certain infections, like those caused Specific guidelines for treatment of diabetic foot osteomyelitis. Diabetes Metab Res Rev by MRSA, IV therapy delivered in the 24(Suppl 1): S190–S1 OHPAT setting enhances compliance and Game FL, Jeffcoate WJ (2008) Primarily non-surgical reduces the duration of hospitalisation. management of osteomyelitis of the foot in diabetes. Diabetologia 51: 962–7 For MRSA-related osteomyelitis there is Ince P, Abbas ZG, Lutale JK et al (2008) Use of the SINBAD some evidence that adding rifampicin classification system and score in comparing outcome of 600 mg bd or sodium fusidate 500 mg tds foot ulcer management on three continents. Diabetes Care 31: 964–7 to the usual therapies can be beneficial. Jeffcoate WJ, Lipsky BA (2004) Controversies in diagnosing Rationalisation of therapy should be discussed and managing osteomyelitis in diabetes. Clin Infect Dis with an infection specialist. 39(Suppl 2): S115–S22 Tolerability of oral antibiotics during Lavery LA, Armstrong DG, Harkless LB (1996) osteomyelitis is a significant issue and therapy Classification of diabetic foot wounds. J Foot Ankle Surg 35: 528–31 may need to be tailored accordingly. Various Lipsky BA, Berendt AR, Deery HG (2004) antibiotics require monitoring of liver function Infectious Diseases Society of America guidelines: tests, full blood counts and or serum levels. diagnosis and treatment of diabetic foot infection. Clin Infect Dis 39: 885–910 If considering linezolid for the treatment Schaper NC (2004) Diabetic foot ulcer classification system of osteomyelitis, the prescriber must be for research purposes: a progress report on criteria for aware of its unlicensed status for including patients in research studies. Diabetes Metab Res 20(Suppl 1): S90–S5 osteomyelitis, and of the risk of bone marrow Rev Wagner Jr FW (1981) The dysvascular foot: toxicity, peripheral or optic neuropathy a system for diagnosis and treatment. and lactic acidosis. Measurement of serial Foot Ankle 2: 64–122

74 The Diabetic Foot Journal Vol 12 No 2 2009