Diagnosis and treatment of infected skin ulcers

Richard Everts Infectious Diseases Physician/Microbiologist Nelson Bays Primary Health

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).

Not infection Infection

Harmless contamination ↓ Colonisation ↓ Heavy colonisation – mild immune reaction ↓ Invasive disease – major immune reaction

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).

Not infection Infection

Harmless contamination ↓ Colonisation ↓ Heavy colonisation – mild immune reaction ↓ Invasive disease – major immune reaction

Immune reaction  Cytokines, dilated blood vessels, leaky capillaries,

migration of cells, debris

Pain

Swelling

Lymphangitis Malaise

Fever

Redness

Pus

Lymphadenitis 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

Colonisation

Thanks to Susie Wendelborn

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

WARNING: LOW-DATA TOPIC

 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

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 Coliforms (E. coli, Klebsiella etc.)

Coagulase-negative staphylococci

Anaerobes

Staphylococcus aureus or Group A streptococcus (Streptococcus pyogenes)

Colonisation

Microscopy: No leucocytes seen Moderate GPC seen Culture: Heavy growth of normal skin flora

Colonisation (but need to watch!)

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

Heavy colonisation – may be contributing to non-healing

Microscopy: Scanty leucocytes Scanty GNB Occasional GPC Culture: (1) Heavy growth of E. coli

Colonisation

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

Infection

Microscopy: Moderate leucocytes Moderate GPC Culture: (1) Heavy growth of Staphylococcus aureus (2) Scanty growth of skin flora

Infection (S. aureus) and heavy colonisation (coliforms) – with symptoms (pain) and complications (graft failure, not healing)

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

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

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Choice of systemic antibiotic

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Empiric – cover S. aureus and beta-haem strep – e.g., flucloxacillin Targeted

Route and dose of systemic antibiotic

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Symptoms and signs of invasive infection

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

Treatment of heavy colonisation  What evidence is there for doing this?

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. 1.

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