Infectious complications of the diabetic foot

Bob Pelz, MD PhD

I have no relevant disclosures

Epidemiology

• 15% of diabetics develop ulcers, 6% require hospitalizaitons

• Over half of ulcers become infected• 20-66% of infected ulcers involve

bone

Spectrum of infections

• Cellulitis• Abscess• Osteomyelitis

Differential diagnosis

• Non-infected neuropathic ulcer• Fracture• Ischemia• Embolization, vasculitis, stasis ulcer,

carcinoma

Evaluation overview

Pathogenesis

• Sensory neuropathy– Trauma, deformity

• Autonomic neuropathy– Diminished sweat, dry, cracked skin

• Hyperglycemia– Decreased neutrophil function

• Arterial disease

Pathogenesis

Challenges in Diagnosis of Osteomyelitis

• Neuropathic changes may resemble infection on MRI, other images

• Superficial cultures correlate poorly with deep organisms, and may not reflect deep infection at all

• Radiographic signs absent early• Bone biopsy invasive, expensive,

inaccurate

Diagnosis of Osteomyelitis• Labs: ESR > 70• Radiology– MRI, Labeled wbc, plain film

• Probe to Bone• Bone biopsy for histopathology, Cx• Surface cultures• Wound > 2 cm2

Plain radiographs

• Cheap and often very helpful• Moth-eaten necrotic bone is dead

and requires surgery

Probe-to-bone

• Grayson, JAMA 1995. 75 inpatients, 66% with osteomyelitis– “On gentle probing, the evaluator detected

a rock-hard, often gritty structure without the apparent presence of any intervening soft tissue”

– Gold standard- histo or clinical + radiology– Sens/spec/PPV/NPV: 66,85,89,56%

Probe to Bone• Lavery et al (Diab. Care 2007): 247 outpts, 12% with OM.– S / S / PPV / NPV=87 / 91 / 57 / 98.

• Shone, et al Diab Care 2006– Sensitivity / Specificity 0.38 / 0.91

• Aragon-Sanchez, Diab Med 2011 PTB or X ray +. Gold standard = Bx with path showing osteo– Sens / Spec 0.97 / 0.92. LR +/- 12.8 / 0.02– 85% of those with pos path had pos Cx

• With exposed bone or positive probe to bone, IDSA guidelines (2004) say X- ray not needed

Bone Bx• Gold standard in most studies• Open Bx more accurate than needle– 31 pts, both needle and open (Seneville, CID 2009)

– 23.9% correlation between open Bx and needle Biopsy Cx• Highest with Staph aureus (46.7%)

– 41.7 correlation between swab Cx and biopsy culture• 82.3 for Staph aureus

Bone Biopsy• Weiner (J Foot Ankle Surg 2011) 44 pts with clinical

osteo.– Just as likely for Bx to be pos by micro as by histo

• Pos Cx rate low- 34% of 41 histologic osteomyelitis – 4 pos Cx in 34 histo-neg pts (Wu et al AJR 2007)

• White, et al (Radiology 1995) Culture swab sensitivity 42%. 50% of histo-positive Bx had positive Cx– Should send Bx specimens for both Cx and histo

Superficial cultures, pitfalls

• Poorly predictive of deep pathogens– 44% of sinus tract Cx contained

organism from surg sample (Mackowiak JAMA 1978)

– 28% concordance, 38% for staph (Zuluaga BMC Infect Dis 2002)

– Twice as many bacteria species isolated by swab than by Bx (Kessler, Diab Med 2005)

Superficial Cx, advantages

• Can often choose ABX to cover all plausible organisms

• Organisms isolated repeatedly and in large numbers likely to be causative

• Useful for detecting MRSA, other MDRO

• Staph aureus likely pathogen if found

Osteomyelitis diagnosis, Meta-analysis

Test LR positive LR Negative

Ulcer > 2cm2 7.2 .48

Positive probe to bone 6.4 .39

ESR >70 11  

Abnormal X ray 2.3  

Positive MRI 3.8 0.14

Butalia, et al. JAMA 2008

Osteomyelitis diagnosis, Meta-analysis

Dinh, MT, CID 2008

Osteomyelitis Treatment

• Aerobic GPCs are the predominant pathogens in diabetic foot infections

• Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections

• Acute infections are often monomicrobial (almost always with aerobic GPC)

Lipsky et al, CID, 2004

Microbiology

Lipsky, et al. CID 2004

Antibiotics• Surgery vs abx vs both.– ABX can’t sterilize dead bone

• IV vs po– Easier to monitor therapy with IV, especially

through RIC or in SNF– IV may be preferable if litigious or unreliable

pt– IV expensive, PICC risks (DVT, infection,

etc.)

IV Antibiotics, MRSAAntibiotic Pro Con

Vancomycin Cheap, safe, active against MRSA

Monitor level. Infusions slow, often BID. Poor bone penetration. Weak antibiotic

Daptomycin Once daily, rapid infusion, good bone penetration

$150ish a dose wholesale

Televancin As for daptomycinCeftaroline Good tissue penetration,

highly activeBID, cost. Spectrum may be overly broad.

IV Antibiotics, MSSAAntibiotic Pro ConNafcillin Most active, narrow

spectrumQ 4 hours or CAD pump

Ceftriaxone Q day. Covers many gram negatives

Least in vitro activity of the 3

Cefazolin Activity between nafcillin and ceftriaxone

Q 8 hours

Oral antibioticsAntibiotic Pro Con

Rifampin Good bone, biofilm penetration. Given with Vanco, FQs, others

Nausea, LFTs. Resistance, drug interactions

TMP/SMX Cheap, good tissue penetration

Allergy, renal issues

Doxycycline/Mino Cheap, good bone penetration

GI issues with doxy. Static, not ‘cidal

Fluoroquinolones Good data when used with rifampin. Good bone penetration

Cipro has poor gram positive activity. C. diff with levo. Tendinopathy

Linezolid Bioavailability about 100%. Up to $100 a tablet. MAOI, low platelets

IV vs PO therapy• IV Cloxacillin vs Bactrim/rif, 50 pts with

surgical Cx, RCT. (Euba AAC 2009) – Relapses no different with 7-9 years f/u

• Gentry, et al (AAC 1991) Ofloxacin vs IV, Bx-confirmed osteo. – 74% vs 86% w/out relapse at 18 month f/u

• Fleroxacin/rif vs IV: 89% vs. 69% cure (Schrenzel, CID 2004)

• Ofloxacin/Rif: Diabetic foot Staph. osteo. 76% relapse free at 22 mo. (Senneville CID 2001)

IV vs PO therapy

• 9/11 osteo cured with Rif/Linezolid vs 9/10 with Rif/Bactrim (Nguyen Clin Micro Infect 2009). Similar cure with infected hardware.

• Linezolid vs Unasyn or vanco (MRSA). 45 sites, 8 countries. (Lipsky, CID

2004) Excluded ischemic feet. 371 pts. Cured osteo in 27/44 Linezolid, 11/16 unasyn. More AEs in L arm, but mild

IV vs PO therapy

• Generally, cure rates with IV and po therapy comparable. Rifampin almost always given.

Duration of therapy

• 4-6 weeks typical, but not based on randomized data

• IV followed by 3 months po if inadequate debridement

Case• 60, dm, h/o right 4th and

5th ray amputations, retinopathy, neuropathy

• 4/27/11- Fever, Acute red, tender foot. – MRI cuboid edema, ?5th

met osteo. No abscess– Cx- Group B Strep– Keflex 1 week– Offloading

Case• 5/10/11 Foot red, 1

week off keflex– X ray- no osteo– CRP- 0.7

• 5/24 pus, CRP=9.7, Cx=GBS, faxed in 20 days doxycycline

• 5/31 erythema better• 7/11 Total contact cast

Case, cont.• 8/1/11 Copious

drainage, necrotic base, +/- PTB despite total contact cast– X ray- still no osteo.– Tagged WBC c/w

osteo– TcPO2 42

Case, cont• To OR, 8/11/11– Path- no osteo, but

possible fracture– Cx- Proteus, enterococcus– 2 weeks keflex– Wound improving with

resection of weight-bearing 5th metatarsal

– Wound healed as of 9/11

Case summary• 8 ID, 3 ortho, 13 wound care encounters over

5 months– 3 X rays, 1 MRI, 1 bone/WBC scan, TCC, surg

• Cellulitis, possible abscess, but osteo never definite clinically, probably never had it despite positive cultures.

• Fracture vs infection• Ulcer due to abnormal weight bearing,

resolved with surgery• Lives with son who is nearly blind

Take-homes

• Diagnosis and management of infected foot ulcers difficult, requires team approach

• Anaerobes, resistant gram negatives not as common as taught. Staph aureus is at least half of infections.

• Swab Cx, probe to bone, X rays useful• Oral therapy likely as good as IV