spinal epidural abscess: not to be missed

Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford

FDA Anti-Infective Drugs Advisory Committee, FDA Anti-Infective Drugs Advisory Committee, October 2003October 2003

Diabetic foot Diabetic foot infection: what infection: what remains to be remains to be discovered?discovered?Dr. Tony Berendt, BM, BCh, Dr. Tony Berendt, BM, BCh,

FRCPFRCPBone Infection Unit, OxfordBone Infection Unit, Oxford


Take home messages• Despite considerable advances, there is

much we do not know about diabetic foot infection

• Expert consensus guidance does not fully compensate for a dearth of optimally-conducted studies, which have left many unanswered questions

• There is an urgent need for standardised definitions of infection in the diabetic foot– To permit multi-centre studies– To permit comparison between different

studies


Overview Epidemiology and importance of

infection Clinical spectrum Defining diabetic foot infection Diagnosing diabetic foot infection Where has expert opinion got to?

Clinical guidelines Classification scheme for research

purposes


Epidemiology and importance of infection

Clinical spectrum Defining diabetic foot infection Diagnosing diabetic foot infection Where has expert opinion got to?


purposes


Epidemiology 250 million diabetics by 2025 2-5% of diabetics develop foot ulcer

annually Point prevalence of ulceration

estimated at 4-10% 40-60% of all non-traumatic lower

extremity amputations are in diabetics

85% of these preceded by foot ulcerInternational Consensus on the Diabetic Foot, IWGDF, IDF, 1999


Socio-economic importance

Foot problems account for largest number of bed days used by diabetic persons1

Average length of stay if hospitalised and have foot ulcer is 30-40 days (50% longer than if no ulcer)

77% of >75 yrs old undergoing amputation in USA do not return to independent living

Studies have shown it may be cheaper to save a limb than to amputate

1Ramsey 1999 Incidence, outcomes and cost of foot ulcers in patients with diabetes. Diabetes Care 22:382-387


Outcome Author Costs

Primary ulcer healing Bouter (1998) $10,000 (hospital)

Apelqvist (1994) $7,000 (to healing)

Healing with amputation Connor (1987) $14,000 (hospital)

Bouter (1988) $15,000 (hospital)

Bild (1989) $8-12,000 (hospital)

Reiber (1992) $20-25,000 (incl. rehab)

Thompson (1993) $11,000 (hospital)

Apelqvist (1994) $43-65,000 (to healing)

Van Houtum (1995) $14,500 (hospital)

Long term costs (3 years)

Apelqvist (1995)Primary healingHealing with amputation

$16,100-26,700$43,100-63,100


The importance of infection

A major pathway to amputation1

A contributor to soft tissue loss A reason for delayed wound healing A cause of acute or chronic

systemic effects (decompensated diabetes, septicaemia; malaise; cachexia)

1Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation: basis for prevention. Diabetes Care 1990;13: 516-521





purposes


Clinical spectrum With intact soft tissue

Cellulitis Primary musculoskeletal

infection Complicating ulceration

Paronychia Infected ulcer Cellulitis Abscess formation Chronic septic arthritis and

osteomyelitis Necrotising fasciitis, myositis,

gangrene, septicaemia





purposes


Definition of Diabetic foot infection

A: Any infection (as defined by International Consensus) involving the foot (below the malleoli) in a person with diabetes

B: Any infection (as defined by International Consensus) involving the foot (below the malleoli) in a person with diabetes originating in a chronic or acute injury to the soft tissue envelope of the foot, with evidence of pre-existing neuropathy and/or ischaemia1

1Berendt and Lipsky 2003, for FDA AIDAC


Justification• Neuropathy is the dominant cause of skin

breaches in the feet of persons with diabetes• Clinical features of the majority of infections

in diabetics support a “contiguous focus” model

• The presence of ischaemia has a major bearing on the outcome of infection

• Effective foot care services have a proven impact on amputation rates

• No evidence that outcomes in non-neuropathic, non-ischaemic diabetic patients differ from those in non-diabetic patients





purposes


Diagnosis Infection: multiplication and invasion

of pathogens in host tissue, usually with an inflammatory response

Colonisation: non-invasion association of bacteria with a particular site

Contamination: abnormal presence of micro-organisms in a site (or sample)


Diagnosing infection in a diabetic foot ulcer

Clinical Systemic signs of infection Local signs or symptoms of infection Should also suspect if gangrene, necrosis

or foetid odour Laboratory

Specificity depends upon co-morbidities Imaging

Role in identifying collections and osteomyelitis


Controversies over clinical diagnosis

• How to diagnose infection in the context of acute Charcot neuro-osteopathy, gout, and other common comorbidities that can produce inflammation of skin?

• Does ischaemia reduce inflammatory response enough to give false-negative signs?

• Do clinical criteria allow us reliably to distinguish an infected from an uninfected ulcer?


Microbiological diagnosis

Easy to interpret Culture of pus from an abscess, or

positive reliable culture from a “sterile site”, e.g. muscle, tendon sheath, bone (if sampled correctly)

Difficult to interpret Culture from an ulcer Culture from necrotic tissue unless

in a closed space


Optimal sampling for diagnostic accuracy

• Poor relationship between superficial and deep microbiology1

• Debride ulcer, expose tissue at base• Aspirate pus if present; curette ulcer base

with sterile instrument• Obtained deep samples though an

uninfected [ideal] or debrided field wherever possible

• Swabs, cultures of sinuses, or of exposed slough/necrosis discouraged2

1Lipsky BA et al 1990 Arch Int Med 150:790-7972International Consensus on the Diabetic Foot, IWGDF, IDF, 1999


Controversies over microbiological

diagnosis• Whether swabs from the base of a debrided ulcer are acceptable

• Whether all microrganisms identified from reliable samples need to be treated

• Whether quantitative microbiology can do any better than clinical judgement in diagnosing actual or incipient infection


Pathogenesis of Staphylococcal infection

Lag Log Post-exponential

Adhesin genes on

Toxin genes off

Quorum sensing


Quorum sensing

Cyclic Cyclic octapeptoctapept

ideideagragr


ideide

ToxinsToxinsRNRNA IIIA III


ideide


Pathogenesis of Staphylococcal infection

Adhesin genes off

Toxin genes on

Planktonic

Mature biofilm

Sessile

Lag Log Post-exponential

Adhesin genes on

Toxin genes off

Quorum sensing


Bioburden, infected and uninfected wounds

• Some evidence that in acute wounds or burns, there is a transition between colonisation and infection at bacterial numbers of c.105/g

• No evidence for this in chronic wounds or diabetic foot

• Some evidence of inter-species interference in Staphylococcal quorum sensing, which might attenuate even high pathogen loads in mixed wound flora





purposes


Clinical guidelines• International Consensus on Diagnosing and

Treating the Infected Diabetic Foot (2003)• Clinical Practice Guidelines for Diabetic

Foot Infections, IDSA (expected 2003)• International, multidisciplinary expert

panels with clinical representation from academia and government health services

• Consensus process• Unable to grade recommendations due to

overall quality of studies and problems of definition


Approach to infection• In view of varied clinical spectrum,

simple clinical classification and approach

• Assessment of whole patient, limb, foot, ulcer

• Assessment of severity of infection– Mild (superficial)– Moderate (limb threatening)– Severe (life threatening)


Uninfected No erythema, purulenceMild 0.5-2 cm erythema

Superficial ulcerationMinimal purulenceUsually monomicrobial

Moderate >2 cm erythema, e.g onto foot from toeDeeper ulceration, more purulenceMay have involvement of bone or joint, with necrosis or gangreneMono- or polymicrobial

Severe Systemic symptomsOften have deep ulceration,gangrene, fasciitis, necrosis, extensive soft tissue or bone involvementUsually polymicrobial


Duration of antimicrobial therapy

No good data Mild 1-2 weeks Moderate 2 to 4 weeks, unless

osteomyelitis Severe: soft tissue up to 4

weeks unless osteomyelitis Osteomyelitis: depends on

degree of resection


Osteomyelitis: antibiotic treatment planning

Bony ablation with no residual infected soft tissue

24-72 hrs

Bony ablation with residual infected soft tissue

2-4 wks

Non-ablative bony resection back to viable but potentially or definitely infected bone

4-6 wks

Retained dead bone min 3 months





purposes


PEDIS: Ulcer classification scheme for research

purposes• Proposed by the International

Consensus on the Management and Prevention of the Diabetic Foot

• Intended to be specific rather than sensitive

• Should allow multi-centre and comparative studies

• Should allow categorisation of cases and description of casemix


PEDIS Classification• Perfusion: Grades 1-3, in line with TASC

– Grade 1 apparently normal; Grade 2 non-critical ischaemia; Grade 3 Critical limb ischaemia

• Extent/Size: In square centimetres. – Report ulcer sizes in study group in quartiles

• Depth/Tissue loss: Grades 1-3– Grade 1 dermis only; Grade 2 subcutaneous tissue,

muscle and tendon; Grade 3 involves bone or joint• Infection: Grades 1-4• Sensation: Grades 1 and 2

– Grade 1 protective sensation present; Grade 2 protective sensation absent


Grade 1 No symptoms of signs of infection


Grade 2 Infection involving the skin and subcutaneous tissue only, without involvement of deeper tissues or systemic signs. At least 2 of:•Local swelling or induration•Local warmth•Local tenderness or pain•Erythema 0.5-2 cm from ulcer margin•Purulent dischargeOther causes of an inflammatory response of skin should be excluded (e.g. gout, acute Charcot neuro-osteopathy, venous stasis, fracture)


Grade 3

Erythema > 2 cm plus one of the items described above (swelling, tenderness, warmth, discharge) or

Infection involving structures deeper than skin and subcutaneous tissues such as abscess, osteomyelitis, septic arthritis, fasciitis.

No systemic inflammatory response signs as described below.


Grade 4

Any foot infection with the following signs of a systemic inflammatory response syndrome (SIRS). This response is manifested by two or more of the following conditions: •Temperature > 38 or < 36°Celsius •Heart rate > 90 beats/min •Respiratory rate > 20 breaths/min •PaCO2 < 32 mmHg •White blood cell count > 12.000 or < 4.000/cu mm •10% immature (band) forms


What needs to be discovered?

• Robust definitions and classification (includes need to rationalise diagnostics)

• Role of antimicrobials in “uninfected” ulcers and in wound healing

• Duration of treatment for soft tissue and bone infection

• Role of surgery in osteomyelitis• Cost effectiveness of limb salvage in

complex ischaemia/soft tissue loss/bone infection


Conclusions• Some progress in general understanding

and in consensus on diagnosis and treatment

• Difficulties in generating highly specific definitions and classifications; potential lack of relationship to “real world”

• PEDIS classification may help identify casemix in studies

• Further development of consensus definitions, e.g. of osteomyelitis, would be valuable

• Changing practice in treatment of osteomyelitis may make inclusion in some trials more possible


Acknowledgements• Ben Lipsky, VA, Seattle• Carl Norden• Karel Bakker, Netherlands• Colleagues at Bone Infection

Unit, Oxford

spinal epidural abscess: not to be missed

Documents