Treating skin and soft tissue and bone and joint infections in acute and opat settings
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Treating skin and soft tissue and bone and joint infections in acute and OPAT settings. Andrew Seaton Infectious Diseases Consultant and Lead Doctor Antimicrobial Management Team, Brownlee Centre Gartnavel General Hospital NES Training Day to support Antimicrobial Pharmacists

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Treating skin and soft tissue and bone and joint infections in acute and opat settings

Treating skin and soft tissue and bone and joint infections in acute and OPAT settings

Andrew Seaton

Infectious Diseases Consultant and Lead Doctor Antimicrobial Management Team,

Brownlee Centre

Gartnavel General Hospital

NES Training Day to support Antimicrobial Pharmacists

Friday 30 August 2013


Cellulitis

Cellulitis

Cellulitis vs Erysipelas

Risk factors: Previous cellulitis, lymphoedema, DM, Obesity, varicose excema, insect bites (summer), tinea pedis….

Usually caused by:

Beta haemolytic Streptococci Gp A>> Gps B, C, G

Staphylcoccous aureus

Rarely Gram negatives (immunocompromised)


Cellulitis first line antibiotic management

Cellulitis: First line antibiotic management

Flucloxacillin (vs MSSA, BHS (most))

Oral 7 days if mild

IV-IVOST if moderately severe 7-10 days total

IVOST when significant reduction in heat, erythema and swelling

Should Ben Pen be added?

Penicillin allergic

Clarithromycin or Clindamycin (PO)

Vancomycin (IV)


How is severity assessed

How is severity assessed?

  • Extent, speed of progression and presence of systemic inflammatory response


Treating skin and soft tissue and bone and joint infections in acute and opat settings

  • Abrupt onset fever, rigors and confusion ++

  • Rapidly progressive Cellulitis of leg

  • BP 80 systolic, HR 140,Temp 39.80C


Treating skin and soft tissue and bone and joint infections in acute and opat settings

  • Abrupt onset fever, rigors and confusion ++

  • Rapidly progressive Cellulitis of leg

  • BP 80 systolic, HR 140,Temp 39.80C


Severe gas sepsis

Severe GAS Sepsis

  • “Eagle effect”

    • Static growth phase

    • Failure to produce PBPs

    • Exotoxin: STSP


28 day mortality sepsis severity patients suspected of bacteraemia

28 day Mortality & Sepsis SeverityPatients suspected of bacteraemia

Jones & Lowes, QJM 1996


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Mortality Risk and time to initiation of effective therapy


Necrotising fasciitis

Necrotising Fasciitis

Usually caused by:

Beta haemolytic Streptococci Gp A>> Gps B, C, G

Staphylcoccous aureus

Rarely Gram negative organisms

Pain out with appearance

Masked by NSAIDs

Rapidly progressive with multiorgan failure


Management of severe rapidly progressive sstis

Management of severe/ rapidly progressive SSTIs

SEPSIS 6, Fluid resuscitation and inotropes

HDU setting

Antibiotic considerations:

Cover: BHS, Anaerobes, Staph aureus and Gram –ves

Cidality: Beta lactam based regimen

Toxin production/ EAGLE effect: Clindamycin

Immunoglobulin (GAS)

SURGERY


Treating skin and soft tissue and bone and joint infections in acute and opat settings

MRSA carrier.

not getting better on VANCOMYCIN

Why not?


Surgical site infections

Surgical Site Infections


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Diabetic with forefoot cellulitis

Not getting better on FLUCLOXACILLIN

Why not?


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Drug users:

MSSA and GAS most usually

Cellulitis, deep SSTIs, Abscesses,

Vascular infections, DVTs and bacteraemia


Opat and sstis

OPAT and SSTIs


Opat evidence in ssti

OPAT Evidence in SSTI

  • 2 RCTs of OPAT: 1999 (n=100, variety) and 2004 (n=200, SSTI).

    • Mainly Cefazolin BD

  • RCTs of new antimicrobials includes OPAT Rx pts

Corwin et al BMJ doi 10.1136/bmj.38309.447975.EB;

Board et al Aust N Z J Public Health 2000; 24:305


When to consider opat

When to consider OPAT

  • Non-life-threatening SSTI amenable for home care and requiring i.v. therapy

  • Admission avoidance or early discharge

  • Exclusions:

    • The system

      • Lack of facility/ system for FU/ emergency cover

    • The infection

      • Sepsis syndrome

      • Rapidly progressive/ progression not clear

    • The patient

      • Unstable co-morbidity

      • Psycho-social


Good practice recommendations

Good Practice Recommendations

4.1 Patients with superficial skin and soft tissue infection should be reviewed daily by the OPAT team to optimize speed of intravenous to oral switch.


Patient group direction for sstis

Patient group direction for SSTIs

‘Patient group’: non-life-threatening cellulitis amenable for home care and requiring i.v. therapy

Uniform therapeutic management

Suitable protocol in place

Exclusions

Prior physician review

Indications for specialist review

Indications for IVOST

Trained, experienced staff

Approved by ADTC

IVOST, i.v. antibiotic – oral switch therapy

Seaton RA et al. J Antimicrob Chemother 2005;55:764–767


Opat treatment pathway for sstis empiric antibiotic choice

OPAT treatment pathway for SSTIs: empiric antibiotic choice

History of MRSA

or Beta-lactam allergy?

Yes

No

Ceftriaxone ▼Clindamycin

or

Flucloxacillin

Teicoplanin

Clindamycin*

*If Beta-lactam allergy or sensitive MRSA


Nurse led mx for opat sstis

Nurse-led Mx for OPAT SSTIs

Comparison of patients pre- and post-introduction of a nurse-led management protocol

  • Protocol management was associated with reduced duration of outpatient i.v. therapy (from 4 to 3 days, P=0.02)

Seaton RA et al. J Antimicrob Chemother 2005;55:764–767


Treating skin and soft tissue and bone and joint infections in acute and opat settings

SSTI: Median duration of OPAT (days)

Nurse-led IVOST

Linear time trend in log (OPAT days)

Estmate 0.904 (0.886-0.922) p<0.0001

Seaton RA et al, IJAA, 2011


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Common OPAT Antibiotics in SSTI

*Switch of antibiotic, progression of infection or readmission

Seaton RA et al, IJAA 2011


Factors associated with opat failure in ssti n 963

Factors Associated with OPAT Failure* in SSTI (n=963)

*Switch of antibiotic, progression of infection or readmission

Seaton RA et al, IJAA 2011


Opat ssti factors associated with increase in duration of opat

OPAT SSTI: Factors Associated with increase in duration of OPAT

* Estimates: percentage change in number of days in OPAT: for example, an estimate of 1.10 means that, on average, a variable is associated with a 10% increase in the number of days of treatment.

Seaton RA et al, IJAA 2011


Opat ssti antibiotic therapy

OPAT SSTI: Antibiotic therapy

  • Nurse led IVOST effective and associated with reduced duration of IV Rx

  • OPAT failure and Teicoplanin

    • confounded by another variable?

    • Teicoplanin less effective / more adverse events?

    • Less subject to daily IVOST review therefore longer therapy?

  • Alternative therapies when ceftriaxone contraindicated


65 yr old female diabetic

65 yr old female diabetic

Bilateral amputee with recent admission with ?UTI

Readmitted 2/52 post discharge with fever, fatigue, headache and confusion

Temp 39

HR 120

BP 134/90

WCC 16

Urinalysis; glycosuria


Treating skin and soft tissue and bone and joint infections in acute and opat settings

GAS, Pneumococcus, Meningococcus, other Strep sp

MSSA

Gram negs


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Gram positive cocci on blood culture @ 24 hours


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Continue empirical Rx until confirmed and assuming clinical repsonse

S. aureus confirmed (MSSA)

Where is it coming from and what are the dangers?


Bone and joint infection

Bone and joint Infection


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Bone and joint Infection

  • Diversity of presentations

  • Managed by many specialties

  • About 1m Implants/annum world wide

    • 0.5% of THR

    • 0.5-2% of other PJs

  • BJI in Glasgow; >500 per year


Classification of osteomyelitis

OM due to contiguous spread

Eg Trauma, Surgery or joint replacement

OM due to vascular insufficieny

Eg Following Soft tissue infection in a diabetic (associated neuropathy)

Haematogenous OM

EgDiscitis

Onset

Acute; Days – weeks

Chronic; Months - years

Classification of Osteomyelitis

Lew and Waldvogel, Lancet 2004; 364369


Likely organisms

Likely Organisms

  • Device related

    • Coagulase negative Staphylococci > Staph aureus > Enterococci (sub-acute)

    • Staph aureus, BHS, Gram negatives (acute)

  • Non device related

    • Staph aureus, BHS

    • Gram negatives


How do bugs get in

How do bugs get in?

  • Through the skin or wound

    • Health care workers

    • Environment

  • From the Blood stream

    • Community

    • Cannulae / Catheters

  • Via surgery

    • Asepsis

    • Foreign material


Mechanism of disease the bone

Mechanism of disease:The bone

  • Acute suppurative inflammation

  • Micro-organism embedded

  • Tissue necrosis and destruction of bone trabeculae and matrix

  • Vascular channels compressed and obliterated


Pathogenesis host and micro organisms

Pathogenesis: Host and micro-organisms

  • Staphylococcus aureus

    • Most common and important

    • Virulence through extracellular and cell-associated factors:

      • Attachment: Adhesins allow attachment to extracellular matrix proteins

      • Evading the host defence; Protein A, some toxins, capsular polysaccharide

      • Promote invasion or tissue penetration: Exotoxins and hydrolases


Pathogenesis host and micro organisms1

Pathogenesis: Host and micro-organisms

  • Staphylococcal species

    • Capacity to colonise and persist

    • Promote own uptake by endothelial and endocytic cells and can survive within osteoblasts

    • Can exist in metabolically altered status as small colony variants


Pathogenesis host and micro organisms2

Pathogenesis: Host and micro-organisms

  • Staphylococcal species

    • May persist in biofilm (“Slime”)

      • Cells attach to each other and substratum or interface

      • Matrix of extracellular polymeric substance

      • Altered growth, gene expression and protein production

      • Quorum sensing between organisms

      • Inherent resistance to antimicrobials

        • Metabolic alteration

        • Reduced cell division

        • “Layered variation” in phenotype


Bji management

BJI Management

  • Microbiological Dx is essential

  • Imaging: Xray, CT, MRI, Bone scan

  • Acute Presentation

    • Blood cultures / joint aspiration

    • Management of sepsis: empirical therapy

    • Identify and remove foci of infection

  • Sub-acute presentation

    • Sample off antibiotics

    • Empirical Rx after sampling


Principles of antibiotic management

Principles of antibiotic management

  • Combined with surgical management

  • Deliver to site of infection (bone/joint penetration)

  • Activity in biofilm

  • Route of administration: IV (by convention not evidence) initial and consider IVOST

  • Length of Rx: ≥6 weeks BUT dependent on surgical management

  • Cure vs Suppression

  • Maintenance of function


Choice of antibiotic

Choice of Antibiotic

  • Best guess: Glycopeptidevs flucloxacillin

  • Favour Flucloxacillin with Gentamicin if acute presentation

  • Consider 2nd oral agent Rifampicin>Sodium fusidate/ Doxycycline/ TMP/ Pristinamycin

  • Gram negative cover: Ciprofloxacin


Treating skin and soft tissue and bone and joint infections in acute and opat settings

OPAT


When to consider opat1

When to consider OPAT

  • When (prolonged) IV Rx anticipated

  • Ambulant / well supported patient

  • Stable comorbidity

  • Agreed plan between surgical team and OPAT

  • Clear lines of communication

  • No logistic obstacles

  • Usually self/ carer administration


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Distribution of patients within the Glasgow OPAT service (2001-2011)

a. OPAT patient episodes b. OPAT days

Seaton and Barr, EJIM, 2013


Good practice recommendations1

Good Practice Recommendations

3.2 The treatment plan is the responsibility of the OPAT infection specialist, following discussion with the referring clinician. It should include choice and dose, frequency and duration. Should take into account flexibility based on clinical response

3.3 Antimicrobial choice within OPAT should be subject to review by the local antimicrobial stewardship programme


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Relative frequency of first line antimicrobial agent use in Glasgow OPAT service.

Seaton and Barr, EJIM, 2013


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Lamont E et al. J Antimicrob Chemother 2009;doi:10.1093/jac/dkp147


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Lamont E et al. J Antimicrob Chemother 2009;doi:10.1093/jac/dkp147


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Duncan et al, Int J Clin Pharm

DOI 10.1007/s11096-012-9637-z


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Multivariate odds ratio of failing initial OPAT therapy

Mackintosh CL, White H.A, and Seaton R.A, JAC 2011


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Kaplan-Meier survival estimate of time to treatment

failure for all patients per diagnosis

Mackintosh CL, White H.A, and Seaton R.A, JAC 2011


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Association of the initial IV Antibiotic with failure over the follow up period in OPAT BJI (Cox regression)


Outcome @ 28 days

Outcome @ 28 days


Treating skin and soft tissue and bone and joint infections in acute and opat settings

Relative frequency of adverse drug reaction (ADR) types, in all first OPAT episodes over 10 year study period.

Note: An ADR in an individual patient in some instances involved multiple drug reaction types (e.g. rash and fever); each ADR type is counted separately in frequency bars even where they stem from one ADR event.


Adrs infection type and ab used ggc opat

ADRs, Infection Type and AB Used (GGC OPAT)


Oviva study

OVIVA study

  • Randomised to IV vs oral before completion of 1 week of IV Rx

  • Use of bio-available antibiotics with good bone penetration (Rifampicin, Ciprofloxacin, Tetracyclines)

  • Staph aureus bacteraemia excluded (and those in whom only IV Rx available)


Conclusions

Conclusions

  • SSTIs and BJIs: Gram positive infections (MSSA, BHS and CNS)

  • Initial IV therapy is usual standard of care

  • OPAT is useful for both patient groups

  • In SSTI Teicoplanin associated with poorer OPAT outcome cf ceftriaxone

  • Antimicrobial Stewardship principles important in OPAT esp IVOST in SSTI

  • Role of oral therapy in BJI currently being explored


Acknowledgements

Acknowledgements

OPAT Nurses: Lindsay Semple, Claire Vallance, Deepa Matthew, Emma Sharp

Antimicrobial Pharmacist: Fiona Robb

OPAT Medics past and present: David Barr, Chris Duncan, Claire Mackintosh


Current practice gram positive infections

Current Practice: Gram Positive Infections


Clostridium difficile and opat

Clostridium difficile and OPAT

  • 4 per 3,356 UK OPAT episodes (0.1%)

  • 2 per 2,233 Glasgow OPAT episodes (0.05 events per 1000 OPAT patient days)

Chapman et al JAC 2009; 64:1316

Mathews et al JAC 2007; 60: 356

Seaton et al IJAA 2011; 38: 243

Barr et al IJAA 2012; 39: 407


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