ANTIBIOTICS WITHIN THE MANAGEMENT of Diabetic foot

Nice 28-29avril2005 ABDULMASSIH Bassam MD Endocrinologist

Definition of a Diabetic Foot infection Epidemiology Pathogenesis of a Diabetic Foot Infection classification Assessment Microbiology Principle of antibiotic treatment

Definition of a Diabetic Foot Infection(1)

No generally-accepted definition Foot infections in diabetics can be ulcer- or non-ulcer related Anatomic location of primary site Depth of infection (skin/soft tissue vs. bone/joint) Isolation of pathogenic bacteria from an appropriate culture specimen

Definition of a Diabetic Foot Infection(2)

entrance ,growth ,metabolic activity and ensuing pathophysiologic effects of microorganisms in the tissues of a patient Purulent discharge from the ulcer Signs of inflammation around the ulcer Systemic signs (fever-leukocytosis) The manifestation of the inflammatory signs depends on intact nervous and vascular system

Epidemiology

life time risk of DM patient : 15% 14-20% will need amputation 1 leg is lost every 30 sec. More than 80% are potentially preventable Site of foot ulcers: toes: 51% plantar metatarsal head: 28% dorsum of foot: 14% multiple ulcers: 7%

Pathogenesis of diabetic foot infection triangle of devil

infection

Bad sensation

Bad perfusion

Classification Systems for Diabetic Foot Infections

Classification systems Severity of Infection Foot Ulcer (Wound)

No generally-accepted classification Differ in criteria & complexity Require validation for clinical trials

Classification Systems for Severity of Diabetic Foot Infections

Limb-threatening vs. non-limb threatening Mild, moderate, severe

Classification Systems for Diabetic Foot Ulcers

Wagner Univ. of Texas Depth-ischemia class.

Wagner Classification
0- Intact skin (may have bony deformities. 1- Localized superficial ulcer. 2- Deep ulcer to tendon, bone, ligament or joint. 3- Deep abscess or osteomyelitis. 4- Gangrene of toes or forefoot. 5- Gangrene of whole foot.
Wagner FW: The diabetic foot and amputations of the foot. In Surgery of the Foot. 5th ed. Mann, R editor. St Louis, Mo. The C.V. Mosby Company.

Small ulcer with big problem

Depth- ischemia classification

Grade 0 no skin change

Grade 2 exposed tendon, joint

Grade A no ischemia

Grade C partial gangrene

Grade 1 superficial ulcer Grade 3 bone exposure Grade B ischemia, no gangrene Grade D complete gangrene

Management based classification structure damage

Extention of infection

Perfusion of the foot

Good Moderate Poor Able to correction or not

Skin Subcutaneous tissues Muscle and tendon Bone Articulation

Multidisciplinary team

1-Diabetologist 2-Vascular surgeon 3-Orthopedics 4-Infection disease 5-Plastic surgeon 6-Podiatrician

Six intervention demonstrate efficacy in diabetic foot management

1- off loading 2- Debridement and drainage 3- wound dressing 4- appropriate use of antibiotic 5- revascularization 6- limited amputation

Baseline Assessments
1-Extension of infection 2-Vascular assessment 3-General diabetes assess.

Laboratory

hematology chemistry HgbA1C C-Reactive Protein Wound, tissue, and blood cultures

Wound or ulcer dimensions X ray imaging MRI Isotope scan Doppler Pulse oxygenation measurement (toe) Arteriography

Diagnosis of osteomylitis is very important

X Ray is positive after 30-50%of bone destruction(2 weeks) MRI CT.Scan 3-phase bone scan Leukocyte scan Guided bone biopsy

Epidemiology Definition of a Diabetic Foot infection Pathogenesis of a Diabetic Foot Infection classification Assessment Microbiology Principle of antibiotic treatment

Microbes and Chronic Wounds

All chronic wounds are contaminated by bacteria. Wound healing occurs in the presence of bacteria. It is not the presence of organisms but their interaction with the patient that determines their influence on wound healing.

Louis Pasteur
The germ is nothing. It is the terrain in which it is found that is everything.

Pasteur, L. (1880) De lattenuation virus du cholera des poules. CR Acad. Sci. 91: 673-680.

Definitions
Wound contamination: the presence of non-replicating organisms in the wound. Wound colonization: the presence of replicating microorganisms adherent to the wound in the absence of injury to the host. Wound Infection: the presence of replicating microorganisms within a wound that cause host injury.

Microbiology of Wounds

The microbial flora in wounds appear to change over time.

Early acute wound; Normal skin flora predominate. S. aureus, and Beta-hemolytic Streptococcus soon follow. (Group B Streptococcus and S. aureus are common organisms found in diabetic foot ulcers)

Microbiology of Wounds

After about 4 weeks

Facultative anaerobic gram negative rods will colonize the wound. Most common ones= Proteus, E. coli, and Klebsiella.

As the wound deteriorates deeper structures are affected. Anaerobes become more common. Oftentimes infections are polymicrobial (4-5).

Microbiology of Wounds

In summary: early chronic wounds contain mostly gram-positive organisms. Wounds of several months duration with deep structure involvement will have on average 4-5 microbial pathogens, including anaerobes (see more gram-negative organisms).

How do you know when a wound is infected?

This can be very difficult. A continuum exists between when pathogens colonize the wound and then start to cause damage. There is no absolutely foolproof laboratory test that will aid in this diagnosis.

How do you know when a wound is infected?

One feature is common to all infected chronic wounds; The failure of the wound to heal and progressive deterioration of the wound. Unfortunately, wound infections are not the only reasons for poor wound healing.

How do you know when an ulcer is infected?

The typical features of wound infections:

increased exudate increased swelling increased erythema increased pain increased local temperature Periwound cellulitis, ascending infection, change in appearance of granulation tissue (discoloration, prone to bleed, highly friable).

Methicillin resistant Staph. Au. An increasing problem

Retrospective analysis of 63 swabs from infected foot ulcer Gram+ aerobic 84.2% staph. Au.79% 30.2% MRSA Not related to prior antibiotic usage
( dang and al. diab.med.20;2:159 feb2003)

In a prior study MRSA is associated with previous antibiotic treatment

(tentolouris and al. diab.med.16;9:767sep1999)

141 microbes isolated from 93 diabetic foot ulcer

Study done on syrian population presented in SDA sept2003 B.hammad MD and H.Jammal MD

gram+ coliform Other gramKLIBSELLA PSEUDOMONAS PROTEUS E.COLI ENTEROC. STREP MRSA staph.au.

2 7 6 6 8 19 18 19 19

46

50

40

30

20

10

vanco. bacitracin tecoplanin amox.+clav oxacillin

erythro. ceftriaxone cephadrin lincomycin cipro. genta.

150

100

50

staph sensitivity

fucidic ac.

Epidemiology Definition of a Diabetic Foot infection Pathogenesis of a Diabetic Foot Infection classification Assessment Microbiology Principle of antibiotic treatment

Treatment

Management of infection: 1- antibiotics. 2-Incision and drainage. 3-soft tissue, joint and bone resection 4-amputation

What is the best approach?

1-Oral antibiotic follow up after one week 2-IV antibiotic in the hospital and observation 3-Rapid drainage + IVantibiotic

Bed side surgery

Ischemic foot problem

Self amputation

Should we clean uncomplicated foot ulcer with antibiotics?

44 Clinically uninfected neuropathic foot ulcer Randomized to amoxi+clav vs. placebo 20 days follow-up no difference in outcome
(chantelau and al. diab. Med. 1996 ;13:156-159)

64 new foot ulcer with no clinical evidence of infection Randomized to antibiotics vs. placebo Patients with ischemia and positive ulcer swabs should be considered for early antibiotic treatment
( foster and al. diab. Med.1998;15:suppl.2)

Principles of treatment

Evidence-based regimes

empirical therapy vs specific therapy

Optimal dosage Optimal duration Identification and removal of infective focus Recognition of adverse effects

The -lactams

Penicillins

penicillin V/G, ampicillin, amoxycillin, cloxacillin, ticarcillin, piperacillin

Cephalosporins
1st generation e.g. cefazolin, cefalexin (Keflex) 2nd generation e.g. cefuroxime (Zinacef, Zinnat )

The -lactams
3rd generation e.g. ceftriaxone (Rocephin ), cefotaxime (Claforan ), ceftazidime (Fortum ), cefoperozone (Cefobid ), ceftibuten (Cedax ) 4th generation e.g. cefepime (Maxipime )

Carbapenems

imipenem, meropenem aztreonam

Monobactam

-lactam/-lactamase inhibitor combinations

INHIBITOR Clavulanate Clavulanate Sulbactam Sulbactam Tazobactam

-LACTAM Amoxicillin Ticarcillin Ampicillin Cefoperazone Piperacillin

APPROVED/TRADE NAME Co-amoxiclav, Augmentin Timentin Sultamicillin*, Unasyn Sulperazon* Tazocin, Zosyn

ROUTE PO, IV IV PO*, IV IV IV

Macrolides and Quinolones

Macrolides

erythromycin, clarithromycin (Klacid ), azithromycin (Zithromax )

Quinolones (FQ)

ofloxacin, levofloxacin (Cravit ), Ciprofloxacin (Ciproxin )

Others

Aminoglycosides

gentamicin, amikacin, netromycin* (NA)

doxycyline (Vibramycin ), minocycline vancomycin, teicoplanin

Tetracyclines

Glycopeptides

New: linezolid, ertapenem, moxifloxacin

Bad perfusion

Normal perfusion

ischemic

Non-ischemic

deep swab

superficial

signs of infection No signs of infection swab

Large coverage
Large coverage

Gram+

No antibiotics

Recent and superficial ulcer or cellulitis (non ischemic)

Staph. Au. + strep

Cloxacillin Amoxi+ with -lactamase inhibitors Cefazolin Cephalexin Clindamycin

Deep ulcer or neuroischemic ulcer

polymicrobial: gram positive cocci, gram negative bacilli and anaerobes
-lactam

+ -lactamase inhibitors +amikacin 3rd GC + clindamycin ciprofloxacin + clindamycin Ciprofloxacin + linezolid carbapenems vancomycin if life threatening

most ulcers will heal with the traditional Therapy

For low grade uninfected wounds a form of removable or irremovable offloading device should be a part of any treatment plan. The TCC is the most established; We can not recommend any one dressing over another; Debridement should still be done the old fashioned way but could be facilitated by using Hydrogel or MDT where available; if wounds fail to heal, treating them with a skin graft or adding becaplermin (or the platelet releasate) not been validated as cost effective in any clinical trial. The use of systemic HBO or Iloprost, especially in high grade ulcers with a significant ischaemic element

Diabetic foot successfully treated !!