Skin and Soft tissue Infection - Including Cellulitis, Surgical Wound Infections and Necrotising Infections (Fasciitis) in Adults

Publication: 01/08/2009  --
Last review: 01/05/2018  
Next review: 01/05/2021  
Clinical Guideline
CURRENT 
ID: 1597 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Management of Skin and Soft tissue Infection - Including Cellulitis, Surgical Wound Infections and Necrotising Infections (Fasciitis) in Adults

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  • Treatment Algorithm
  • Summary
    Skin and Soft tissue Infection - Including Cellulitis, Surgical Wound Infections and Necrotising Infections (Fasciitis) in Adults

    Diagnosis 

    History

    Examination

    • Carry out severity assessment – follow algorithm
    • If there is skin necrosis, purpura, blisters, loss of sensation, severe pain or features of systemic sepsis – consider necrotising soft tissue infection, see Non-antimicrobial treatment
    • Bilateral/symmetrical inflammation of lower limb skin is not usually caused by infection
    • Alternative diagnoses to consider: varicose eczema (Stasis Dermatitis), erythema nodosum, inflammatory reactions e.g. insect bites, deep vein thrombosis, pyoderma gangrenosum, septic arthritis.

    Investigations

    • Blood cultures prior to starting antibiotics in any patient likely to receive intravenous antibiotics or with features of systemic infection
    • Aspirates of fluid filled lesions (blisters, pustules, collections) for microbiological investigation.
    • Wound swabs from surgical incisions, abscesses or ulcerated lesions if involved in skin infection, for microbiological investigation.
    • FBC, CRP, U&E, LFTs (pre-op work-up or if intravenous antimicrobials may be required).

    Non-antimicrobial treatment

    • If necrotising soft tissue infection suspected, refer to in-house surgical team immediately - follow algorithm
    • Draw around the edge of the abnormal skin/erythema with a permanent marker and write date and time on patient's skin
    • Treat as per severe sepsis protocol if appropriate (link)
    • Drain any collections of pus in an appropriate environment.
    • Provide analgesia (disproportionate pain raises the possibility of necrotising fasciitis)
    • Elevate the affected part, if practical

    Antimicrobial treatment

    Use severity assessment (algorithm) to guide treatment pathway:

    • Empirical inpatient intravenous antimicrobial regimens for: non-surgery related skin and soft tissue infection (Part A) and surgical site infection (Part B). (Table 1).
    • Empirical community intravenous antimicrobial regimens (Table 2).
    • Empirical oral antimicrobial regimens (Table 3).
    • Once organism confirmed, See table 4 for Organism-specific (directed) antimicrobial regimens

    Referrals

    • PLASTICS
      Hand/upper limb abscesses, necrotising soft tissue infection (fasciitis) at LGI site.
    • ORTHOPAEDICS
      Abscess of Lower limb, foot (non diabetic) and involving a joint.
    • GENERAL SURGERY
      Abscess of trunk, groin (Non-IVDU and no vessel involvement).
      Breast abscess out of hours (in hours, direct referral to breast team).
      Necrotising soft tissue infection (fasciitis) at SJUH site.
    • VASCULAR
      Groin abscess in IVDU if vessel involvement.
      Diabetic feet with osteomyelitis/gas on plain films - cellulitis as per Diabetic feet guidelines.
    • ENT
      Abscess of ears.
    • MAX FAX
      Abscess of head or neck or facial cellulitis.
    • GYNAECOLOGY
      Labial/Bartholin's abscess.

    • Relapsing/recurrent infection discuss with Microbiology or Infectious Diseases
    • Orbital cellulitis (see separate guideline) – ophthalmology
    • Surgical site infection – refer to team that operated (link to appendix 2)

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    Background

    Cellulitis is an acute spreading infection of the skin which may extend to involve the subcutaneous (soft) tissues. Skin and soft tissue infections include cellulitis associated with ulcers, traumatic wounds, surgical wounds and necrotising soft tissue infections.  Infections range in severity from the mild lesions that resolve spontaneously to severe life-threatening infection, such as necrotising fasciitis (see below).

    The most common causes are Group A streptococci (Streptococcus pyogenes) and Staphylococcus aureus but other pathogens can be involved in particular clinical situations. For example, cellulitis caused by Group B, C or G streptococci are more common in diabetic patients or those with previous radiotherapy or surgery for cancer.1 Anaerobes including Clostridium species can cause soft tissue infections in dirty wounds or in intravenous drug users.

    The aetiology of surgical wound infections varies with type and site of surgery e.g. for pelvic-abdominal surgery it often includes Gram-negative bacilli (e.g. coliforms like Escherichia coli) and anaerobes which has important implications for empirical therapy.

    Other less common organisms may be associated with specific risk factors or environmental exposure such as Pasteurella multocida infection following cat bites or Capnocyophaga canimorsus infection following dog bites and Vibrio vulnificus infection following sea water exposure, Aeromonas infection following fresh water exposure and Mycobacterium marinum infection in aquarium keepers. It is important to ensure such risk factors are elicited because it may affect empirical treatment contact microbiology for advice.

    Necrotising soft tissue infection and fasciitis
    Necrotising fasciitis is a life and limb-threatening surgical emergency, with a high mortality rate. It is a rapidly progressive soft-tissue infection, primarily involving the fascia but also adjacent tissues, leading to necrosis. Patients with necrotising fasciitis require immediate resuscitation and aggressive surgical debridement. True necrotising fasciitis is uncommon.

    There is a spectrum of necrotising soft tissue infections, such as necrotising myositis or necrotising vasculitis, which may have an identical presentation and clinical course with features of pain, erythema, swelling, and systemic inflammatory response. Toxins released by the causative organism(s), in addition to pro-inflammatory mediators, allow rapid progression of the infection along tissue planes. Perforating blood vessels that supply the skin and subcutaneous tissues from deeper layers (‘perforators’) thrombose, leading to necrosis of the tissue involved.

    Although clinical examination often provides a diagnosis, surgery may be necessary to confirm this, by visualising the fascial layer and obtaining tissue for microbiological and histological analysis. Necrotising fasciitis involving the perineum and external genitalia is called Fournier’s gangrene.

    “Type 1” necrotising fasciitis is a necrotising soft tissue infection caused by mixtures of bacteria (polymicrobial) usually including both Gram-positive and Gram-negative bacteria including anaerobes. These mixed infections often occur in areas of the body usually colonised by faecal flora, or affect the abdominal wall or affect patients with leg ulcers and poor general health. Fournier’s gangrene is a form of type 1 necrotising fasciitis that affects the male genitals and perineum. It is more common in diabetics, alcoholics the malnourished and immunosuppressed.

    “Type 2” necrotising fasciitis refers to necrotising soft tissue infections caused by single organisms (monomicrobial). Group A streptococci are the most common cause while Staphylococcus aureus accounts for a small number of cases. A primary portal of entry is not usually apparent and the legs are most commonly affected.

    Cellulitis associated with septic arthritis should be managed according to the Guidelines for management of septic arthritis of native joints in adults.

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    Clinical Diagnosis

    Recommendations:

    • Assess local symptoms/signs. Symptoms of cellulitis usually begin with local tenderness, pain and redness of the skin, which may develop and intensify rapidly. Affected skin is tender to touch.
    • Assess systemic symptoms/signs of infection such as general malaise, fever, sweats and chills, measure the National Early Warning System (NEWS) score
    • Identify any history of previous surgery or trauma to the skin (e.g. laceration, puncture wound, insect or animal bite) or other lesions (e.g. tinea pedis, furuncle, ulcer) that might predispose to the development of cellulitis. NB. these are not always apparent.
    • Assess for risk factors associated with treatment failure or adverse outcome according to Box 1.
    • Misdiagnosis is common, in patients who are systemically well where the diagnosis is unclear, consider dermatology referral or watchful waiting.
      [Evidence level D]

    Box 1. Risk factors associated with treatment failure or adverse outcome.2
    Evidence level C

    1. Cellulitis affecting face or perineum
    2. Frail/aged >80
    3. Previous splenectomy
    4. Chronic renal or liver disease
    5. Immunocompromise
    6. Alcohol abuse
    7. Treatment failure in the community
    8. Diabetes mellitus
    9. Chronic venous insufficiency
    10. Morbid obesity

     

    Assess risk factors for specific pathogens that will affect empirical therapy according to Box 2.
    Evidence level C

    Box 2. Risk factors for unusual or problematic pathogens that will require a change in empirical therapy [Adapted from.2]

    Risk factor

    Unusual/problematic organism to consider

    Recent pelvic-abdominal surgery (certain procedures)

    Gram-negative bacilli and anaerobes

    MRSA risk factors

    Meticillin-resistant Staphylococcus aureus

    Injecting drug use (IV, subcutaneous)

    Anaerobes (Clostridium sp.), MRSA, Gram-negative bacilli

    Human bite

    Eikenella corrodens, anaerobes

    Dog or cat bite

    Capnocytophaga canimorsus, Pasteurella multocida

    Sea water exposure of affected skin in previous week

    Vibrio vulnificus

    Fish tank water exposure (fish keeper)

    Mycobacterium marinum

    Fresh water exposure of affected skin in previous week

    Aeromonas hydrophila

     

    Evidence review/justification
    There are no pathognomonic signs nor reliable diagnostic test for cellulitis. The involved area of skin is usually red, hot, swollen and tender. The borders are not usually elevated or sharply demarcated but can be in streptococcal infection that is confined to the dermis (a condition known as erysipelas). Bilateral leg cellulitis, whilst not impossible, is very rare. Varicose eczema is a much more likely cause of bilateral inflammation of the lower legs.

    Misdiagnosis is common and a frequent cause of unnecessary antibiotics and admission to hospital.3 Other conditions that can present with inflamed skin include: varicose eczema (Stasis Dermatitis), erythema nodosum, inflammatory reactions e.g. insect bites, deep vein thrombosis, pyoderma gangrenosum, septic arthritis

    Regional lymphadenopathy, often associated with lymphangitis, is common. Small patches of overlying skin may blister or undergo necrosis.

    Local abscesses can occur so assess for fluctuance.

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    Severity Assessment

    The management of cellulitis depends on the severity of illness which should be assessed according to both physiological measurement and localised signs:

    Recommendations

    • Measure the National Early Warning System (NEWS) score.
      Evidence level C
    • Assess for localised signs of severe infection including necrotising fasciitis:
      1. patient is experiencing pain that appears disproportionate to the severity of the cellulitis (e.g. unable bear weight on an affected leg)
      2. crepitus is present
      3. haemorrhagic blisters present
      4. extensive limb involvement or rapid progression of cellulitis Evidence level C

    Evidence review/justification

    Note that the NEWS score is just a guide; it has not been formally evaluated as predictor in skin and soft tissue infection. If a patient does not have a high NEWS score but appears ill, seek senior advice. Interpretation may be difficult in older patients, seek advice from the elderly care team if in doubt.

    A Laboratory Risk Indicator in Necrotising Fasciitis (LRINEC) score was developed to help distinguish between necrotising fasciitis and severe cellulitis or other soft tissue infections.4 It relies on a series of biochemical parameters to calculate a likelihood of a patient suffering from necrotising fasciitis (see below). However, it does NOT RULE OUT necrotising fasciitis, with a sensitivity of just 43% in a recent UK evaluation. Therefore, if there is clinical suspicion of necrotising fasciitis, refer to the in-house surgical team immediately for surgical exploration and debridement (see pathway on following page).

    LRINEC comprises:
    CRP >150mg/L: 4 points,
    WCC <15 x106/mm2: 0 points, 15-25 x106/mm2: 1 point, >25 x106/mm2: 2 points.
    Haemoglobin >13.5g/dL: 0 points, 11-13.5g/dL: 1 point, <11g/dL: 2 points.
    Sodium <135mmol/L: 2 points, Creatinine >141umol/L: 2 points, Glucose >10mmol/L: 1 point

    A score greater than 6 indicates that necrotising fasciitis was likely in the original work, with variable performance in subsequent analyses but a recent systematic review found it was a good predictor (receiver-operator characteristic [ROC] curve of 0.927.)4-7

    During guideline review there was no consensus on the value of using the LRINEC in clinical practice, so it is included for information only.

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    Investigation

    Recommendations:

    • Two sets of Blood cultures should be taken at different times in all patients with severe sepsis or systemic signs of infection (rigors, chills) or who are likely to be given intravenous antimicrobials. Evidence level D
    • Blood culture should be taken before starting antimicrobials. Evidence level C
    • FBC should be measured at baseline in patients requiring intravenous antimicrobial therapy and repeated according to clinical need.
      Evidence level D
    • CRP should be measured at baseline in patients requiring intravenous antimicrobial therapy and repeated according to clinical need. Evidence level D
    • U&E and LFTs should be measured at baseline in patients requiring intravenous antimicrobials or surgery and repeated according to clinical need. Evidence level D
    • Needle aspirates of fluid filled lesions such as blisters or pustules and wound swabs from abscesses or ulcerated lesions if involved in cellulitis should be sent for culture. Evidence level C
    • Routine needle aspiration of the cellulitic skin edge is not recommended. Evidence level B
    • Deep tissue samples and pus samples (not swabs) should be sent from all patients with necrotising fasciitis.
      Evidence level C
    • X-rays of the affected area are recommended when a metallic foreign body is suspected.2
      Evidence level C
    • Doppler vascular examination should be undertaken in patients with lower limb cellulitis when a deep venous thrombosis is possible.2
      Evidence level C

    Evidence review/justification.

    Blood Cultures are positive in only 2-5% of cases of erysipelas cellulitis and have not been deemed to be cost effective if used in all patients8,9 hence Blood cultures should be restricted to those with more severe infection according to criteria above.

    NB In groin-injecting intravenous drug users Blood cultures should not be taken via a groin sinus. Blood cultures should not be taken by the patient.

    C-reactive protein (CRP) is raised in more severe cellulitis; it is part of the Laboratory Risk Indicator in Necrotising Fasciitis (LRINEC) score and can be a useful adjunct to clinical observation in assessing response to therapy.

    Renal & liver function may influence choice and dose of antimicrobials as well as fluid balance, nutritional support etc.

    Needle aspiration from the centre or advancing edge of a cellulitic lesion with culture of the aspirate has a poor success rate in determining the pathogen (10-30%)10 and cannot be recommended as a routine.11 It should be considered when unusual pathogens are suspected or when initial antimicrobial therapy has failed.

    Ultrasound scanning or magnetic resonance imaging may be required to identify drainable collections or evidence of necrotising infection or radiolucent foreign bodies.2
    Evidence level C

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    Treatment

    General Principles
    The need for admission, the need for various investigations, the choice of antimicrobial therapy and the route of administration antimicrobials should be influenced by the severity of infection, the presence of risk factors for an adverse outcome and risk factors for specific pathogens. An algorithm to guide the appropriate treatment pathway is included. As with all guidelines, this is no substitute for clinical judgment and if there are concerns about the appropriateness of a suggested pathway these should be discussed with a senior colleague.

    If the national early warning score (NEWS) is ≥5, patients require hospitalisation, management according to severe sepsis guidelines and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1).
    Evidence level D

    Patients with local signs of severe infection including necrotising infection require admission, urgent surgical assessment because they may need debridement of the affected area and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1).
    Evidence level C

    Patients with NEWS score 2-4 and/or risk factors for a poor outcome (Box 1) will initially require admission and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1).
    Evidence level D

    Patients with risk factors for a poor outcome (Box 1) and a NEWS score 0-1 or systemic symptoms of infection may initially require admission and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1) or, selected cases may be treated in the community according to empirical community intravenous antimicrobial regimens (Table 2), where this service is available.
    Evidence level D

    Patients with NEWS score 0-1, no systemic symptoms of infection and non-severe local infection can usually be managed with oral antimicrobials on an outpatient basis according to empirical oral antimicrobial regimens (Table 3)
    Evidence level C

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    Non-Antimicrobial Treatment

    Recommendations:

    • Draw around the edge of the abnormal skin/erythema with a permanent marker and write date and time on patient's skin. Evidence level D.
    • For non-severe surgical site infection, remove sutures at affected site and dress. Evidence level C
    • Drain collections of pus/debride necrotic tissue. Evidence level C
    • Ensure adequate analgesia, N.B. disproportionate pain should raise the possibility of deep soft tissue infection.
    • Elevate the affected part, if practical. Evidence level D
    • If NEWS is ≥5 or 3 in one parameter, patients require assessment and management according to sepsis guidelines and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1).
      Evidence level D
    • Patients with local signs of severe infection including necrotising infection require admission, urgent assessment by the in-house surgical team because they may need debridement of the affected area and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1).
      Evidence level C
    • Patients with NEWS score 2-4 and/or risk factors for a poor outcome (Box 1) will initially require admission and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1).
      Evidence level D
    • Patients with risk factors for a poor outcome (Box 1) and a NEWS score 0-1 or systemic symptoms of infection may initially require admission and treatment according to empirical inpatient intravenous antimicrobial regimens (Table 1) or, selected cases may be treated in the community according to empirical community intravenous/oral antimicrobial regimens (Table 2), where this service is available.
      Evidence level D
    • Patients with NEWS score 0-1, no systemic symptoms of infection and non-severe local infection can usually be managed with oral antimicrobials on an outpatient basis according to empirical oral antimicrobial regimens (Table 3)
      Evidence level C

    Evidence review/justification

    General Principles
    The need for admission, the need for various investigations, the choice of antimicrobial therapy and the route of administration antimicrobials should be influenced by the severity of infection, the presence of risk factors for an adverse outcome and risk factors for specific pathogens. An algorithm (see Appendix 1) to guide the appropriate treatment pathway is included. As with all guidelines, this is no substitute for clinical judgment and if there are concerns about the appropriateness of a suggested pathway these should be discussed with a senior colleague.

    Hyperbaric oxygen therapy has been used as a component of therapy for necrotising fasciitis but remains controversial. Facilities are not available in Leeds and early surgery is the priority and hyperbaric oxygen if considered necessary will be coordinated through plastic surgery.

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    Empirical Antimicrobial Treatment

    NB. Antimicrobials should not be started until after blood cultures have been taken.

    Recommendation: use algorithm (Appendix 1) to assess severity and the need for empirical intravenous or oral therapy.

    Recommendation: commence empirical treatment of non-surgery related infections according to Table 1, 2, or 3 part A, for surgical site infection use Table 1, 2, or 3 part B.

    Evidence review/justification
    All antibiotics carry risks, including the regimens recommended herein. It is important to review patients who are being treated with antibiotics on a daily basis to monitor response to therapy and for signs of toxicity. The empirical regimens recommended in this guideline should be prescribed for the shortest time possible to reduce the risk of adverse effects. In addition to routine daily review, a day three review should take place to plan modifications to therapy and total duration, based on available information.

    If a patient was initially thought to have necrotising fasciitis but this diagnosis is excluded, consider “de-escalating antibiotic to appropriate cellulitis or SSI regimen.

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin will adequately cover the most common causes of cellulitis (Staphylococcus aureus and streptococci) in most clinical situations and is the “gold standard” against which new agents are compared, except when MRSA infection is suspected. When MRSA is confirmed or suspected, Linezolid electronic Medicines Compendium information on Linezolid or glycopeptide (e.g. Teicoplanin electronic Medicines Compendium information on Teicoplanin ) is considered the “gold standard”; a recent randomized open label study compared Vancomycin with Linezolid electronic Medicines Compendium information on Linezolid therapy for complicated skin and soft tissue infections: 91.5% of patients with cellulitis were cured in both treatment arms.12 Open trials of Teicoplanin electronic Medicines Compendium information on Teicoplanin for SSTI reported rates ranging between 92%13 and 96.8%14 at a low dose of 3mg/kg Teicoplanin electronic Medicines Compendium information on Teicoplanin . Local evidence of treatment failures prompted use of a weight-based Teicoplanin electronic Medicines Compendium information on Teicoplanin dosing regimen (unpublished data). Vancomycin is being largely replaced by Teicoplanin electronic Medicines Compendium information on Teicoplanin because of repeated errors with vancomycin dosing and concerns about toxicity with larger doses. A recent meta-analysis did not find evidence of a difference in outcomes for cellulitis treated with either penicillins or cephalosporins and macrolides and lincosamides (Clindamycin electronic Medicines Compendium information on Clindamycin ).15

    For type 2 necrotising fasciitis (caused by group A streptococci) the addition of Clindamycin electronic Medicines Compendium information on Clindamycin to a cell-wall acting agent has some theoretical benefit, but clinical evidence of effectiveness comes from just three cases of necrotising fasciitis included in a retrospective observation study of invasive group A streptococcal infection in children.16Clindamycin electronic Medicines Compendium information on Clindamycin resistance is not uncommon in streptococci causing this condition. Therefore, high dose intravenous penicillin with Clindamycin electronic Medicines Compendium information on Clindamycin is recommended, once a microbiological diagnosis is confirmed.1

    Exposure to specific environments or conditions puts patients at risk of infection with some less common pathogens that may not respond to empirical Flucloxacillin electronic Medicines Compendium information on Flucloxacillin – see Box-2

    Evidence update

    Although systematic review of the treatment of uncomplicated skin and soft tissue abscesses (SSTAs) after incision and drainage found no evidence of a benefit for the addition of antibiotics for uncomplicated infection,17 a placebo controlled trial found evidence of improved outcomes with the addition of Clindamycin electronic Medicines Compendium information on Clindamycin or Co-trimoxazole electronic Medicines Compendium information on Co-trimoxazole , but the benefit was restricted to those with S. aureus infection.18

    A meta-analysis of trials of recently concluded that treatment with a macrolide or lincosamide for cellulitis or erysipelas has a similar efficacy and incidence of adverse effects as treatment with a beta-lactam.19 A RCT that investigated the addition of Co-trimoxazole electronic Medicines Compendium information on Co-trimoxazole to cephalexin did not demonstrate any benefit,20 while another RCT found no difference between oral Clindamycin electronic Medicines Compendium information on Clindamycin and Co-trimoxazole electronic Medicines Compendium information on Co-trimoxazole .21

    Tedizolid is an oxazolidinone (same class as Linezolid electronic Medicines Compendium information on Linezolid ) which showed non-inferiority to Linezolid electronic Medicines Compendium information on Linezolid in a head-to-head randomised, double-blind, phase 3, non-inferiority trial of treatment for acute bacterial skin and skin-structure infections (ABSSSI).22 And treatment duration as 6 days in the tedizolid vs 10 days in the Linezolid electronic Medicines Compendium information on Linezolid arm. Tedizolid may be recommended on microbiology advice as an alternative to Linezolid electronic Medicines Compendium information on Linezolid .

    A network meta-analysis of randomised controlled trials concluded that tedizolid was superior to vancomycin but no different from other comparator agents in the treatment of MRSA SSTI.23 Another meta-analysis of randomised controlled trials of treatment for ABSSSI found no difference between vancomycin, Daptomycin electronic Medicines Compendium information on Daptomycin , Linezolid electronic Medicines Compendium information on Linezolid , and novel antimicrobial agents including oritavancin, when assessing the early clinical response endpoint.24

    For MRSA surgical site infection, a systematic review concluded that “Linezolid electronic Medicines Compendium information on Linezolid is superior to vancomycin in the eradication of MRSA on the basis of evidence from one small trial that was at high risk of bias,”25 similarly a Cochrane review found that Linezolid electronic Medicines Compendium information on Linezolid was superior to vancomycin but concluded the risk of bias was high.26

    The efficacy of Daptomycin electronic Medicines Compendium information on Daptomycin versus other antibiotics for skin and soft-tissue infections has been assessed in a meta-analysis of randomised controlled trials, which concluded it was at least as effective and may be superior to vancomycin.27

    Oritavancin is a lipoglycopeptide antibiotic (related to glycopeptides) with activity against gram-positive bacteria, it is approved for use in the European Union but on LTHT formulary at present. A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated in two similar RCTs.28,29

    Dalbavancin is also a lipoglycopeptide with a long half-life.30 Although usually used as two doses a week apart, a single 1500-mg infusion of dalbavancin was recently found to be non-inferior to a 2-dose regimen in a RCT for ABSSSI.

    Table 1. Empirical inpatient intravenous antimicrobial regimens for: non-surgery related skin and soft tissue infection (Part A) and surgical site infection (Part B).

    Risk factor

    First choice

    Second choice (e.g. true allergy to first choice)

    Part A non-surgery related skin and soft tissue infection.

    No risk factors for atypical organisms

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin * 2g 6-hourly IV.

    Teicoplanin electronic Medicines Compendium information on Teicoplanin 6mg/kg IV regimen

    Necrotising fasciitis

    Meropenem electronic Medicines Compendium information on Meropenem * 1g 8-hourly IV AND Clindamycin electronic Medicines Compendium information on Clindamycin 600mg 6-hourly IV

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Clindamycin electronic Medicines Compendium information on Clindamycin 600mg 6-hourly iv AND Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin * 400mg 12-hourly IV

    MRSA risk (e.g. previous infection or colonisation with MRSA)

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline)

    Linezolid electronic Medicines Compendium information on Linezolid or Daptomycin electronic Medicines Compendium information on Daptomycin *- discuss with microbiology

    Human, dog, cat bite

    Co-amoxiclav electronic Medicines Compendium information on Co-amoxiclav * 1.2g 8-hourly IV

    Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin * 400mg 12-hourly IV AND Clindamycin electronic Medicines Compendium information on Clindamycin 600mg 6-hourly IV

    Injecting drug use (IV, subcutaneous)

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin * 2g 6-hourly iv AND Metronidazole electronic Medicines Compendium information on Metronidazole 500mg 8-hourly IV or 400mg 8-hourly oral, if absorbing

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Metronidazole electronic Medicines Compendium information on Metronidazole 500mg 8-hourly IV or 400mg 8-hourly oral, if absorbing

    Sea or fresh water exposure of affected skin in previous week (note place of exposure, presence of trauma and co-morbidity)

    contact microbiology/Infectious Diseases

    contact microbiology/Infectious Diseases

    Fish tank water exposure (fish keeper)

    contact microbiology/Infectious Diseases

    contact microbiology/Infectious Diseases

    Part B Surgical site infection

    Head, face, ear, neck, arm, hand, thorax, breast, spine, leg, foot (excluding surgery involving implants)

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 2g 6-hourly IV

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline)

    Head, face, ear, neck, arm, hand, thorax, breast, spine, leg, foot (where surgery involves implants, excluding hip or knee replacement)

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Gentamicin 7mg/kg regimen IV

    Discuss with microbiology

    Sternotomy

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 2g 6-hourly IV AND Gentamicin 7mg/kg regimen

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Gentamicin 7mg/kg regimen IV

    Abdominal see intra-abdominal infection guideline

    -

    -

    Perineal/genital

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 2g 6-hourly IV AND Gentamicin 7mg/kg regimen IV AND Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 8-hourly orally (or 500mg 8-hourly IV if required).

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Gentamicin 7mg/kg regimen IV AND Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 8-hourly orally (or 500mg 8-hourly IV if required)

    *Adjust doses according to renal function. Where combinations of risk factors exist discuss with Microbiology or Infectious Diseases.

    Table 2. Empirical community intravenous antimicrobial regimens for: non-surgery related skin and soft tissue infection (Part A) and surgical site infection (Part B)

    Risk factor

    First choice

    Second choice (e.g. true allergy to first choice)

    Part A non-surgery related skin and soft tissue infection

    No risk factors for atypical organisms

    Teicoplanin electronic Medicines Compendium information on Teicoplanin * 6mg/kg IV regimen

    Daptomycin electronic Medicines Compendium information on Daptomycin 4mg/kg*- 24-hourly iv

    Necrotising fasciitis (amend when tissue culture results available)

    Community treatment is not usually appropriate.

    Community treatment is not appropriate.

    MRSA risk (e.g. previous infection or colonisation with meticillin-resistant

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline)

    Daptomycin electronic Medicines Compendium information on Daptomycin 4mg/kg*- 24-hourly IV

    Human, dog, cat bite

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin * 500mg 12-hourly orally AND Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 8-hourly orally

    Discuss with Microbiology/Infectious Diseases

    Drug abuse (iv, subcutaneous)

    N/A

    N/A

    Sea or fresh water exposure of affected skin in previous week

    contact Microbiology/Infectious Diseases

    contact Microbiology/Infectious Diseases

    Fish tank water exposure (fish keeper)

    contact Microbiology/Infectious Diseases

    Contact Microbiology/Infectious Diseases

    Part B Surgical site infection

    Craniotomy, face, neck, ear, limb, hand, foot, thoracotomy, breast (excluding surgery involving implants)

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline)

    Daptomycin electronic Medicines Compendium information on Daptomycin 4mg/kg*- 24-hourly IV

    Craniotomy, face, neck, ear, limb, hand, foot, thoracotomy, breast (where surgery involves implants, excluding hip or knee replacement)

    Removal of implant, if infected, (source control) will need consideration. Management to be discussed case-by-case

    Sternotomy

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 500mg 12-hourly orally

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline)) AND Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 500mg 12-hourly orally

    Abdominal see intra-abdominal infection guideline

    -

    -

    Perineal/genital

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 500mg 12-hourly orally

    Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline) AND Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 500mg 12-hourly orally

    *Adjust doses according to renal function. Where combinations of risk factors exist discuss with Microbiology or Infectious Diseases.

    Table 3. Empirical oral antimicrobial regimens

    Risk factor

    First choice

    Second choice (e.g. true allergy to first choice)

    No risk factors for atypical organisms

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 1g 6-hourly orally

    Clindamycin electronic Medicines Compendium information on Clindamycin $ 450mg 6-hourly orally OR Co-trimoxazole electronic Medicines Compendium information on Co-trimoxazole 960mg 12-hourly orally

    Necrotising fasciitis

    N/A

    N/A

    MRSA risk (e.g. previous infection or colonisation with meticillin-resistant

    Linezolid electronic Medicines Compendium information on Linezolid 600mg 12-hourly orally

    Infectious Diseases/Microbiology referral

    Human, dog, cat bite

    Co-amoxiclav electronic Medicines Compendium information on Co-amoxiclav 625mg 8-hourly orally

    Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin * 500mg 12-hourly orally AND Clindamycin electronic Medicines Compendium information on Clindamycin $ 450mg 6-hourly orally

    Drug abuse (iv, subcutaneous)

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 1g 6-hourly orally AND Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 8-hourly orally

    Contact Microbiology/Infectious Diseases

    Sea or fresh water exposure of affected skin in previous week

    Contact Microbiology/Infectious Diseases

    Contact Microbiology/Infectious Diseases

    Fish tank water exposure (fish keeper)

    Contact Microbiology/Infectious Diseases

    Contact Microbiology/Infectious Diseases

    *Adjust doses according to renal function. $ Only use Clindamycin electronic Medicines Compendium information on Clindamycin if patient is under 65 years of age and is not known to have had Clostridium difficile infection previously.

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    Directed Antimicrobial Treatment (when microbiology results are known)

    Antimicrobials should be modified according to culture and sensitivity results, ensuring the selected antibiotic is active against the causative organism and taking into account severity and response to therapy of case.

    Table 4. Recommended directed (when susceptibility results are known) antimicrobial regimens for skin and soft tissue infection

    Organism

    First choice IV

    Second choice IV

    Oral alternative/switch

    Meticillin-susceptible Staphylococcus aureus

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin ## 1g 6-hourly

    Teicoplanin electronic Medicines Compendium information on Teicoplanin * 6mg/kg regimen, ORClindamycin electronic Medicines Compendium information on Clindamycin $ 600mg 6-hourly

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 1g 6-h OR Clindamycin $ 450mg 6-hourly OR Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly OR co-trimoxazole 960mg 12-hourly

    Meticillin-resistant Staphylococcus aureus (MRSA)

    Teicoplanin electronic Medicines Compendium information on Teicoplanin * 6mg/kg regimen

    Clindamycin electronic Medicines Compendium information on Clindamycin $ 600mg 6-h or Daptomycin electronic Medicines Compendium information on Daptomycin 4mg/kg*- 24-hourly IV

    Clindamycin electronic Medicines Compendium information on Clindamycin $ 450mg 6-h OR Linezolid electronic Medicines Compendium information on Linezolid 600mg 12-hourly OR Doxycycline electronic Medicines Compendium information on Doxycycline 200mg 24-hourly

    Group A streptococcus#

    Benzyl penicillin electronic Medicines Compendium information on Benzyl penicillin * 1.2g 4-hourly

    Teicoplanin electronic Medicines Compendium information on Teicoplanin * 6mg/kg regimen

    Amoxicillin electronic Medicines Compendium information on Amoxicillin 1g 8-hourly OR Clindamycin electronic Medicines Compendium information on Clindamycin $ 450mg 6-hourly OR Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly.

    Group B, C, G streptococcus#

    Benzyl penicillin electronic Medicines Compendium information on Benzyl penicillin * 1.2g 4-hourly

    Teicoplanin electronic Medicines Compendium information on Teicoplanin * 6mg/kg regimen

    Amoxicillin electronic Medicines Compendium information on Amoxicillin 1g 8-hourly OR Clindamycin electronic Medicines Compendium information on Clindamycin $ 450mg 6-hourly OR Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly.

    Coliforms, Pseudomonas, anaerobes

    Discuss additional antibiotics with microbiology

    A, Evidence level A. *Adjust doses according to renal function; **in necrotising fasciitis; $ Only use Clindamycin electronic Medicines Compendium information on Clindamycin if patient is under 65 years of age and is not known to have had Clostridium difficile infection previously. #if in pure culture.

    ##The Flucloxacillin electronic Medicines Compendium information on Flucloxacillin dose for directed S. aureus therapy is lower than the empirical regimens. Higher doses are used in empirical regimens partly because of theoretical concerns about reduced susceptibility of streptococci to Flucloxacillin electronic Medicines Compendium information on Flucloxacillin and partly to ensure high tissue levels early in therapy.

    NB. Doses of antimicrobials or choice of antimicrobial agent may need amending on advice from microbiology or Infectious Diseases.

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    Duration of Treatment

    Recommendations:

    • The duration of antimicrobial therapy for cellulitis is guided by the clinical response. Antibiotics can be stopped when there has been clinical resolution of the cellulitis. This resolution normally takes between 1-2 weeks, although resolution may happen before or after this time period. (NB there may be residual skin discolouration in the area of cellulitis, “resolution” means pain, tenderness and other signs of acute inflammation have got better)
      Evidence level D
    • Immunocompromised patients and those with lymphoedema may need more prolonged antimicrobial therapy.2

    Justification/evidence review

    The duration of therapy required for cellulitis has not been well studied but antimicrobials can generally be stopped after 1-2 weeks treatment when symptoms of infection have resolved and there has been marked improvement in signs of inflammation.2 For example, a recent randomized open label study compared Vancomycin with Linezolid electronic Medicines Compendium information on Linezolid therapy for complicated skin and soft tissue infections: 91.5% of patients with cellulitis were cured in both treatment arms with a mean treatment duration of approximately 11 days.12

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    Switch to oral agent(s)

    Randomised trials and observational studies suggest that this can be done safely after 3-4 days, provided that fever, erythema and induration are resolving, white blood cell count and CRP are improving, systemic signs of infection are resolving and any co-morbidities are stabilised. Please see oral switch guidance.

    Empirical oral regimens (Table 3) can be used to guide choice or oral switch when the pathogen is not known; oral options are also given in Table 4.

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    Treatment Algorithm

    Appendix 1 Summary Treatment Algorithm

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    Appendix 2 CDU Treatment Algorithm







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    Treatment Failure

    Infections not responding to first or second choice therapy or these agents are contraindicated. Discuss with Infectious Diseases or Microbiology.

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    Referral Criteria
    • For cases of suspected Necrotising Fasciitis at the SJUH site initial referral should be to the General Surgical team
    • For cases of Suspected Necrotising Fasciitis at the LGI site initial referral should be to the Plastic Surgery Team.
    • Patients with relapsing/recurrent infection to Infectious Diseases
    • Patients with blistering (including haemorrhagic) and ulcers to Dermatology

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    Provenance

    Record: 1597
    Objective:

    Aims

    • To standardize and improve the diagnosis and management of cellulitis and necrotising fasciitis.

    Objectives

    • To provide evidence-based recommendations for appropriate investigation of cellulitis.
    • To provide evidence-based recommendations for appropriate antimicrobial therapy of cellulitis.
    • To provide objective tools to guide appropriate dose, route of administration of antimicrobial agents.
    • To advise in the event of antimicrobial allergy.
    • To set out criteria for referral for surgery or specialist input.
    Clinical condition: Cellulitis & necrotising fasciitis
    Target patient group: Adults
    Target professional group(s): Secondary Care Doctors
    Pharmacists
    Secondary Care Nurses
    Adapted from:

    Evidence base

    Evidence levels:
    A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
    B. Robust experimental or observational studies
    C. Expert consensus.
    D. Leeds consensus.

    1. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014; 59(2): e10-52.
    2. Eron LJ, Lipsky BA, Low DE, Nathwani D, Tice AD, Volturo GA. Managing skin and soft tissue infections: expert panel recommendations on key decision points. J Antimicrob Chemother 2003; 52 Suppl 1: i3-17.
    3. Moran GJ, Talan DA. Cellulitis: Commonly Misdiagnosed or Just Misunderstood? JAMA 2017; 317(7): 760-1.
    4. Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med 2004; 32(7): 1535-41.
    5. Holland MJ. Application of the Laboratory Risk Indicator in Necrotising Fasciitis (LRINEC) score to patients in a tropical tertiary referral centre. Anaesth Intensive Care 2009; 37(4): 588-92.
    6. Al-Hindawi A, McGhee J, Lockey J, Vizcaychipi M. Validation of the laboratory risk indicator for necrotising fasciitis scoring system (LRINEC) in a Northern European population. J Plast Reconstr Aesthet Surg 2017; 70(1): 141-3.
    7. Bechar J, Sepehripour S, Hardwicke J, Filobbos G. Laboratory risk indicator for necrotising fasciitis (LRINEC) score for the assessment of early necrotising fasciitis: a systematic review of the literature. Annals of the Royal College of Surgeons of England 2017; 99(5): 341-6.
    8. Jorup-Ronstrom C. Epidemiological, bacteriological and complicating features of erysipelas. Scand J Infect Dis 1986; 18(6): 519-24.
    9. Perl B, Gottehrer NP, Raveh D, Schlesinger Y, Rudensky B, Yinnon AM. Cost-effectiveness of blood cultures for adult patients with cellulitis. Clin Infect Dis 1999; 29(6): 1483-8.
    10. Hook EW, 3rd, Hooton TM, Horton CA, Coyle MB, Ramsey PG, Turck M. Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med 1986; 146(2): 295-7.
    11. Newell PM, Norden CW. Value of needle aspiration in bacteriologic diagnosis of cellulitis in adults. J Clin Microbiol 1988; 26(3): 401-4.
    12. Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2005; 49(6): 2260-6.
    13. Lewis P, Garaud JJ, Parenti F. A multicentre open clinical trial of teicoplanin in infections caused by gram-positive bacteria. J Antimicrob Chemother 1988; 21 Suppl A: 61-7.
    14. Lang E, Foldes M, Marghescu S. Teicoplanin in the treatment of skin and soft tissue infections: results of a multicentre study. Infection 1991; 19(3): 190-4.
    15. Ferreira A, Bolland MJ, Thomas MG. Meta-analysis of randomised trials comparing a penicillin or cephalosporin with a macrolide or lincosamide in the treatment of cellulitis or erysipelas. Infection 2016; 44(5): 607-15.
    16. Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J 1999; 18(12): 1096-100.
    17. Fahimi J, Singh A, Frazee BW. The role of adjunctive antibiotics in the treatment of skin and soft tissue abscesses: a systematic review and meta-analysis. CJEM 2015; 17(4): 420-32.
    18. Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. The New England journal of medicine 2017; 376(26): 2545-55.
    19. Ferreira A, Bolland MJ, Thomas MG. Meta-analysis of randomised trials comparing a penicillin or cephalosporin with a macrolide or lincosamide in the treatment of cellulitis or erysipelas. Infection 2016; 44(5): 607-15.
    20. Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2013; 56(12): 1754-62.
    21. Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. The New England journal of medicine 2015; 372(12): 1093-103.
    22. Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. The Lancet Infectious diseases 2014; 14(8): 696-705.
    23. McCool R, Gould IM, Eales J, et al. Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA. BMC infectious diseases 2017; 17(1): 39.
    24. Thom H, Thompson JC, Scott DA, Halfpenny N, Sulham K, Corey GR. Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis. Current medical research and opinion 2015; 31(8): 1539-51.
    25. Gurusamy KS, Koti R, Toon CD, Wilson P, Davidson BR. Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds. The Cochrane database of systematic reviews 2013; (8): CD009726.
    26. Yue J, Dong BR, Yang M, Chen X, Wu T, Liu GJ. Linezolid versus vancomycin for skin and soft tissue infections. The Cochrane database of systematic reviews 2016; (1): CD008056.
    27. Wang SZ, Hu JT, Zhang C, et al. The safety and efficacy of daptomycin versus other antibiotics for skin and soft-tissue infections: a meta-analysis of randomised controlled trials. BMJ open 2014; 4(6): e004744.
    28. Corey GR, Good S, Jiang H, et al. Single-dose oritavancin versus 7-10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2015; 60(2): 254-62.
    29. Corey GR, Kabler H, Mehra P, et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. The New England journal of medicine 2014; 370(23): 2180-90.
    30. Dunne MW, Puttagunta S, Giordano P, Krievins D, Zelasky M, Baldassarre J. A Randomized Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin and Skin Structure Infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016; 62(5): 545-51.

    Approved By

    Improving Antimicrobial Prescribing Group

    Document history

    LHP version 1.0

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