Richard Everts

Infectious Diseases Physician/Microbiologist

Nelson Bays Primary Health

Diagnosis and treatment

of infected skin ulcers

Diagnosis

What is infection?

Disease presents as a continuum or spectrum of

symptoms, signs and other features

E.g. Asthma, mental illness

Neisseria meningitidis

Asymptomatic bacteriuria

What is infection?

A point in the continuum from harmless

contamination to invasive disease at which the

patient has symptoms, signs or complications/

problems (e.g. poor healing).

Harmless contamination

↓

Colonisation

↓

Heavy colonisation – mild immune reaction

↓

Invasive disease – major immune reaction

Not infection

Infection

What is infection?

A point in the continuum from harmless

contamination to invasive disease at which the

patient has symptoms, signs or complications/

problems (e.g. poor healing).

Harmless contamination

↓

Colonisation

↓

Heavy colonisation – mild immune reaction

↓

Invasive disease – major immune reaction

Not infection

Infection

Immune reaction

Cytokines, dilated blood vessels, leaky capillaries,

migration of cells, debris

Pain Swelling Redness Pus

Lymphangitis Lymphadenitis

Malaise Fever AbN vital signs CRP rise

What is CRP?

C-reactive protein

Made by the liver in response to any tissue

damage or inflammation

Infection

Trauma

Auto-immune/connective tissue disease (RA, PMR,

Crohn’s disease)

Cancer

A common laboratory test (cost $7-10)

Most strikingly elevated in bacterial infection.

CRP to diagnose infection

CRP = 195 CRP = 13

Harmless

transient

contamination

Thanks to Susie Wendelborn

Colonisation

Colonisation

Swabbing a non-infected ulcer is like

picking your nose in public...

You need to think what you might do

if you find something.

Haemophilus ducreyi

H. ducreyi •Causes chancroid

(STI) in adults

•2007 Auckland: 3

children from

Samoa with skin

ulcers

•2013 PNG: 90

chronic skin ulcers:

42 H. ducreyi; 19

yaws; 12 both

•Identify by PCR,

not culture

Yaws

Infection

Infection

Infection

Infection

Infection

Infection

Why swab an infected ulcer?

If suspect MRSA

Recent previous positive

If flucloxacillin is failing

If there is frank pus.

(And take blood cultures if febrile.)

Skin cancer removed and grafted. Graft broke down.

A little red, goopy, sore, not healing.

Is it infected?

Clinical signs alone?

Which signs? (Thermal imaging?????) Patient

measures temperature? Test CRP?

Taking a sample for culture? If so, how?

Trial of antibiotics? If so, which antibiotic?

Collecting a sample

Tissue best (but hassle, invasive)

Properly collected quantitative swab is

reasonable alternative

‘Expert’ opinion:

Clean site by wiping or irrigating with sterile water or

saline to clear debris and exudate

Debride if necrosis/eschar

Moisten swab first if wound/ulcer-bed dry (??)

Levine method: twirl with pressure on 1 cm2 area

Patricia Bonham. Swab cultures for diagnosing wound infections:

A literature review and clinical guideline.

J Wound Ostomy Continence Nurs 2009; 36(4): 389-95

WARNING:

LOW-DATA TOPIC

Assessing the swab result

Surface swab culture correlates somewhat with

biopsy culture J Trauma 1976; 16:89-94 and many others......

Gram stain microscopy

Lots of white cells?

Lots of pathogenic bacteria?

Culture

Pure or heavy growth?

Pathogen?

Who robbed the bank?

Pseudomonas aeruginosa

Coagulase-negative

staphylococci

Coliforms (E. coli,

Klebsiella etc.)

Anaerobes Staphylococcus aureus or

Group A streptococcus

(Streptococcus pyogenes)

Microscopy:

No leucocytes seen

Moderate GPC seen

Culture:

Heavy growth of normal

skin flora

Colonisation

Microscopy:

No leucocytes

Moderate GNB

Occasional GPC

Culture:

(1) Moderate growth

of mixed coliform

bacilli

(2) Moderate growth

of P. aeruginosa

(3) Scanty growth of

Staphylococcus

aureus

Colonisation

(but need to watch!)

Microscopy:

Scanty leucocytes

Scanty GNB

Occasional GPC

Culture:

(1) Heavy growth of

E. coli

Heavy colonisation – may be

contributing to non-healing

Microscopy:

No leucocytes

Moderate GPC

Moderate GPB

Scanty GNB

Culture:

(1) Heavy growth of

mixed coliforms

(2) Moderate growth of

Enterococcus spp.

(3) Moderate growth of

anaerobes

Colonisation

Microscopy:

Moderate leucocytes

Moderate GPC

Culture:

(1) Heavy growth of

Staphylococcus aureus

(2) Scanty growth of skin

flora

Infection

Microscopy:

Moderate leucocytes

Moderate GPC

Moderate GNB

Culture:

(1) Heavy growth of

Staphylococcus

aureus

(2) Moderate growth of

mixed coliform bacilli

(3) Moderate growth of

coagulase-negative

staphylococci

Infection (S. aureus) and heavy

colonisation (coliforms) – with

symptoms (pain) and complications

(graft failure, not healing)

Summary - diagnosis

No symptoms or signs of infection –

don’t swab, no need for systemic

antibiotic treatment

Uncertain – consider correctly taken

swab and assess result carefully; or trial

of systemic antibiotic treatment Flucloxacillin > cephalexin/cefazolin >

clindamycin

Obviously infected – swab in selected

cases, give systemic antibiotic

treatment as above.

Treatment

Treatment of infected ulcers

Treat underlying cause.

Invasive disease

Choice of systemic antibiotic

Empiric – cover S. aureus and

beta-haem strep – e.g.,

flucloxacillin

Targeted

Route and dose of systemic

antibiotic

Initially high-dose (IV or

probenecid-boosted)

Duration – varies.

Density of bacterial tissue

invasion correlates with

delayed healing

Antimicrobial Agents and

Chemotherapy 1964; 10: 147

Symptoms and signs of

invasive infection

Treatment of heavy colonisation

What evidence is there for doing this?

1. Surface colonisation correlates somewhat

with tissue invasion on biopsy.

2. Topical antibacterial agents probably improve

healing even in the absence of features of

invasive infection.

Treatment of heavy colonisation

Debride necrotic/devitalised material/eschar

Remove slough/goop (toxins, WC, bacteria)?

Dressings (none better than any other)

Topical antibacterial agents Silver sulphadiazine

Cadexomer iodine

Povidone iodine

Honey

Peroxide

Chlorhexidine

Others.....

Do topical antibacterial products

or dressings kill bacteria?

Kill bacteria in lab? – YES

Kill bacteria on surface of ulcer – YES (for how

long?)

Kill bacteria deep in tissues – YES Chronic pressure ulcers. Test = reduce to < 105/g in biopsy

in 3 weeks. Success rates: SSD (n = 15) 100%; saline

(n=14) 79%; pov-iod (n=11) 64%. J Am Geriatr Soc 1981; 29(5): 232-

Improve signs of infection – YES Chronic wounds (n=34). Test = infection checklist score

change in 4 weeks. Silver alginate dressing 3.3 to 1.3;

control 2.2 to 2.3. Advances in Skin and Wound Care 2012; 25(11): 503-8

Do topical anti-bacterial products

or dressings cause damage?

Allergic reaction? – OCCASIONALLY

Damage cells (e.g. fibroblasts) in-vitro models

SSD – YES

Chlorhexidine – YES

Povidone iodine – YES

But in-vivo??

Anti-microbial resistance – SOME YES

The ultimate test....

Randomised controlled trials of ulcer healing

Requirements:

Independent investigator (publication bias,

assessment of outcome bias etc.)

Ethics approved

Patienti consent, ability to withdraw if choose

Randomised

Reasonable numbers

Objective outcome scoring....

Topical anti-bacterial agents for

venous ulcer healing Cochrane Database Syst Rev 2014

45 RCTs, 53 comparisons, 4486 patients

Poor design - small, high risk of bias, different baseline status,

different duration of treatment....

Overall – difficult to know if effective or not!

Results:

Cadexomer iodine (12 RCT) – likelihood of complete healing

at 4 to 12 weeks improved by RR 2.17 compared with

standard care

No evidence of benefit for povidone iodine (7 RCT), honey (2

RCT) Cochrane review of honey 2015 – may help burns and post-op wounds

Surrogate markers only for silver (12 RCT – size, not %

healed) and peroxide (4 RCT.)

Thanks