• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)
• Treatment Failure

These guidelines apply to children (>1 month and ≤16 years old) with suspected acute joint infection (septic arthritis).

Diagnosis is made by aspiration / washout of the joint, ideally before antibiotics. Suspicion of Diagnosis (and so need for aspiration / washout) is clinically based:
History: Usually rapid onset and progressive pain in affected region. The hip and knee are the most commonly affected joints. Fever and systemic upset is common but variable. In infants and younger children the parent may report reduced use of limb or limping. Multifocal septic arthritis is very uncommon in children who are not immunosuppressed and raises the possibility of a non-infectious ‘rheumatological’ cause.
Ask about: penicillint [and other] allergies and information on previous MRSA carriage/infection.

Examination: Look for joint swelling, inflammation and tenderness to palpation. Movement will be restricted.  Assess systemic signs of infection. In infancy the only sign may be “pseudoparalysis”. EXAMINE ALL JOINTS, as presence of arthritis in more than one joint may help prompt consideration of a non-infectious patient.

Irritable hip (also known as transient synovitis, reactive arthritis) is common in walking children and needs to be differentiated from hip sepsis. Irritable hip is a generally milder non-infective inflammatory and non-progressive condition without systemic features. It can mimic early sepsis.
http://lthweb/sites/emibank/guidelines-folder/pages/copy_of_management-of-the-atraumatic-limping-child

In addition many children with Juvenile idiopathic arthritis / reactive arthritis affecting joints other than a hip can be apyrexial, systemically well and have normal inflammatory markers. Blood tests such as Rheumatoid factor or ANA are rarely of use to discriminate infectious vs. non-infectious arthritis and are not offered acutely by the laboratory. If in doubt senior orthopaedic assessment is required. Consider a Consultant Paediatric Rheumatological opinion - details of on-call consultant through LGI switchboard.

Investigations

• Routine blood tests: Blood cultures [before antimicrobials] FBC (including considering possibility of leukaemia) and CRP.
• A plain x-ray of affected joint(s) and adjacent bones.
• Ultrasound scan (MRI is an alternative if available)
• Joint aspiration (see below)

Non-antimicrobial treatment

• Fluid resuscitation as necessary.
• Pain relief
• Splintage of peripheral joint in a ‘back-slab’ cast as recommended by orthopaedic surgeon.

Aspiration/Surgery
When clinical suspicion of infection within a joint, the joint should be evacuated urgently.
In the large majority turbid fluid or frank pus will be aspirated which is presumptive evidence of infection. Fluid is sent for microscopy in sterile container and culture/sensitivity in blood culture bottles. In this case proceed to mini arthrotomy or washout using wide bore arthroscopic cannulae.

IN THE CASE OF HIP SEPSIS UNDERTREATMENT RESULTS IN RAPID JOINT DESTRUCTION SO FORMAL SURGICAL EXPOSURE AND WASHOUT IS REQUIRED.

Awake aspiration is possible in older mature children with parental support. Entonox sedation helps. Awake aspiration helps in doubtful/borderline cases. Using the criteria listed above the majority of cases will proceed to general anaesthetic and theatre so a selective approach should be adopted. Where there is doubt seek a senior orthopaedic opinion. Keep the child starved.

Consider discussing with the on-call Consultant Paediatric Rheumatological, if you think the child may have a non-infectious cause of arthritis.

Adjuvant antimicrobial treatment is also required (see below).

Empirical antimicrobial treatment
UNLESS THE CHILD HAS SEPTICAEMIA, DO NOT START ANTIMICROBIALS UNTIL BLOOD CULTURES & JOINT FLUID SAMPLES HAVE BEEN TAKEN (AS SOON AS POSSIBLE).
N.B. Dose reductions may be required in patients with hepatic or renal impairment, consult product literature or pharmacy for further information.

Children and infants age 1 month to 5 years:

• No penicillin or cephalosporin allergy or MRSA colonisation:
  Intravenous Cefuroxime (50–60 mg/kg (max. 1.5 grams) every 6–8 hours)
• True immediate-type penicillin or cephalosporin allergy:
  Intravenous Vancomycin (15 mg/kg every 6 hours (do not exceed an initial maximum of 2 grams/day).  Adjust dose according to plasma concentrations, aim for ‘trough’ levels of 10-20mg/L). PLEASE NOTE: this dose is DIFFERENT to BNF-C PLUS
  Intravenous Ciprofloxacin : Child 1 month–18 years 10 mg/kg (max. 400 mg) every 12 hours increased to 10 mg/kg every 8 hours in severe infection (max. 400 mg every 8 hours)
• Previous MRSA infection or colonisation:
  Intravenous Cefuroxime (dose as above) PLUS intravenous Vancomycin (dose as above)

Children age 5 years to 16 years:

• No penicillin or cephalosporin allergy or MRSA colonisation:
  Intravenous Flucloxacillin (50 mg/kg (max. 2 grams) every 6 hours.)
• True immediate-type penicillin or cephalosporin allergy and/or previous MRSA infection or colonisation:
  Intravenous Vancomycin monotherapy (dose as above)

Duration
see full guideline.

Oral switch
IV initially and completed orally.  See full guideline

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Pathogenesis
Septic arthritis is usually the result of haematogenous seeding. It can also occur by direct spread from an adjacent focus of osteomyelitis where the metaphysis is intra-articular e.g. femoral neck/hip, distal femur/knee and distal fibula/ankle. Rarely does it result from open or penetrating injury (or surgery).

In haematogenous joint sepsis with the exception of skin rashes e.g. chickenpox a primary focus is seldom identified.

Reactive arthritides, rheumatological diseases including juvenile idiopathic arthritis and transient synovitis of the hip/irritable hip http://lthweb/sites/emibank/guidelines-folder/pages/copy_of_management-of-the-atraumatic-limping-child can confuse particularly in the early stages but these are generally milder illnesses compared to joint sepsis. They can be associated with raised CRP, neutrophilia and fevers, but in the presence of these findings it is usually appropriate to initially assume the possibility of septic arthritis, unless there are other features specific to an autoimmune disease. Consider a Consultant Paediatric Rheumatological opinion - details of on-call consultant through LGI switchboard.

Microbiology
The causative organism of joint infection varies with the age of the child and this difference in epidemiology influences the choice of empirical antimicrobial therapy.

The most common causes of septic arthritis in children in England and Wales during the early 1990s were: Staphylococcus aureus, Streptococcus pneumoniae, beta-haemolytic streptococci [mostly A and B] and Haemophilus influenzae, which caused 44% of cases in the under 10 year olds (Ryan et al., 1997).  While most of the pathogens have not changed in more recent studies (Peltola et al., 2009), two significant developments have occurred:

1. Invasive H. influenzae infections have decreased markedly, following widespread introduction of introduction of the Hib vaccine.
2. Kingella kingae has been identified as an important cause of osteoarticular infections in younger children including septic arthritis (Yagupsky et al., 1992)(Rasmont et al., 2008).  Most invasive Kingella infections have occurred in the 6 month to 3 year age range in a recent survey. 

The most common causes of septic arthritis in children >5 to 16 years are Staphylococcus aureus and streptococci (Yagupsky et al., 1992) but Gram negatives continue to cause a small proportion of cases.  Neisseria meningitidis, Haemophilus influenzae, Enterobacteriacaea [“coliforms”], and other streptococci are uncommon causes of septic arthritis in children (Yagupsky et al., 1992).

In some parts of the world community-acquired MRSA is more prevalent and a cause of septic arthritis in children (Yamagishi et al., 2009).

Culture negative septic arthritis

PCR on bone biopsy is required to make a diagnosis.  Tuberculosis should be considered in more insidious infections with epidemiological risk factors or typical radiological findings.

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The typical history is of a previously well child who develops a febrile illness and malaise with localized pain in an extremity. In infants the history is necessarily sketchy but systemic features as above and “pseudo paralysis” of the affected limb draws the parents’ attention.  Older children will provide an account of increasing localized pain and demonstrate a limp if the leg is affected. It is important to ask about: penicillin [and other] allergies, Haemophilus influenzae vaccination status and information on previous MRSA carriage/infection because these will influence empirical therapy.  Any relevant history of recent trauma should be elicited.

Examination reveals swelling and periarticular tenderness to palpation especially in subcutaneous bones [e.g. around the knee and ankle]. The hip joint is more deeply located and palpation is usually unhelpful. A fever is usual [>90%] but not universal and especially in infants.  On occasion the child will present with septic shock reflecting delayed diagnosis or an unusually aggressive organism. These are medical and surgical emergencies.

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1. Blood tests
Recommendation: Blood cultures should be sent prior to starting antimicrobials in all patients.
[Evidence level C ]
Blood cultures provide a microbiological diagnosis in up to 60% of cases.

Recommendation: Full blood count and CRP should be sent from all patients being treated with intravenous antimicrobials at baseline.
[Evidence level ]
CRP is more sensitive than ESR, increases and responds to treatment earlier.  NB CRP is occasionally normal, at least initially, and particularly in infants. Baseline white cell count [WCC] can be helpful, but, again, the WCC may be normal at least initially.

2. Joint aspiration
Hip aspiration with U/S guidance but without sedation/anaesthesia in radiology department. Recommendation: refer to protocol http://lthweb/sites/emibank/guidelines-folder/pages/copy_of_management-of-the-atraumatic-limping-child. This should be regarded as a procedure to exclude sepsis (fluid appearance and urgent microscopy) in the low risk case and allow early discharge. Currently this is seldom done in this hospital.
Awake aspiration has a place in older co-operative children where there is SIGNIFICANT doubt about the diagnosis. Refer to Summary section above.

Recommendation : Joint aspirate should be sent in a sterile container for Gram stain and cultures and inoculated directly in BACTEC™ Peds Plus™ blood culture bottle.

Inoculation of synovial fluid directly into blood culture bottles improves bacteriologic diagnosis of paediatric septic arthritis and facilitates better detection of fastidious organisms e.g. Kingella kingae

3. Imaging
Recommendation: plain x-rays of the affected joint/adjacent bones should be undertaken in all cases.
[Evidence level B]

Bone lysis and periosteal elevation indicate associated adjacent osteomyelitis but X-ray changes are usually absent during the initial 10 days or so of the evolution of bone infection. X-rays may occasionally demonstrate the painful limb is in fact broken or has some other pathological lesion. Established hip sepsis can cause hip subluxation and even dislocation.

Recommendation: Ultrasound scanning (U/S) of the affected joint should be undertaken in children with a suspicion of joint sepsis. The false negative rate is low (<5%). In young children where the history is poor and clinical findings inconclusive U/S of adjacent joints is helpful e.g. image both hips and knees.[Evidence level B ]
Because the conversion rate to theatre/washout is high it is prudent to be certain the affected joint does contain fluid.

Recommendation: Magnetic resonance imaging [MRI] is useful in cases where diagnostic uncertainty remains.  [Evidence level B]
Most sepsis occurs in appendicular joints which can be readily examined clinically and imaged by X-ray and U/S which are simple and easily available investigations. MRI is very specific but only needed in the minority where diagnostic doubt remains. MRI is especially useful in axial disease affecting the pelvis and spine. MRI is also useful in refractory cases or slow responders. General anaesthesia is often required to obtain diagnostic quality MRI in younger children. This is a senior orthopaedic/radiological decision.

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Resuscitation
Fluid resuscitation as necessary

Analgesia
Pain relief and splintage of adjacent joint in a cast as necessary, according to existing protocols.

Surgery
When turbid fluid or frank pus is aspirated this is presumptive evidence of infection.
Mini-arthrotomy and washout is performed immediately.
Because undertreated hip infection causes rapid joint destruction SUSPICION OF HIP SEPSIS REQUIRES PROMPT FORMAL SURGICAL EXPLORATION AND WASHOUT.

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DO NOT START ANTIMICROBIALS UNTIL Blood Cultures & JOINT FLUID SAMPLES HAVE BEEN TAKEN.
Children and infants age 1 month to 5 years:

• No penicillin or cephalosporin allergy or MRSA colonisation:
  Intravenous Cefuroxime (50–60 mg/kg (max. 1.5 grams) every 6–8 hours)
• True immediate-type penicillin or cephalosporin allergy:
  Intravenous Vancomycin (15 mg/kg every 6 hours (do not exceed an initial maximum of 2 grams/day).  Adjust dose according to plasma concentrations, aim for ‘trough’ levels of 10-20mg/L) PLEASE NOTE: dose is DIFFERENT to BNF-C PLUS
  Intravenous Ciprofloxacin : Child 1 month–18 years 10 mg/kg (max. 400 mg) every 12 hours increased to 10 mg/kg every 8 hours in severe infection (max. 400 mg every 8 hours)
• Previous MRSA infection or colonisation:
  Intravenous Cefuroxime (dose as above) PLUS intravenous Vancomycin (dose as above)
  [Evidence level C/D]

Children age 5 years to 16 years:

• No penicillin or cephalosporin allergy or MRSA colonisation:
  Intravenous Flucloxacillin (50 mg/kg (max. 2 grams) every 6 hours.)
• True immediate-type penicillin or cephalosporin allergy and/or previous MRSA infection or colonisation:
• Intravenous Vancomycin monotherapy (dose as above)
• In the sick child [> 5 years to 16 years] with concurrent features of meningococcal meningitis or meningococcal bloodstream infection it is wise to extend the spectrum initially by adding ceftriaxone as per the meningitis guidelines pending Blood Cultures and PCR.

Evidence review
Empirical therapy should cover the most likely pathogens, which vary with age (see above).  For this reason, empirical recommendations vary with age. There is little high level evidence to direct the choice of appropriate antimicrobial therapy and some data is extrapolated from treatment of adults. Ampicillin-sulbactam has been compared with Ceftriaxone in a randomised study of treatment for skin, joint and bone infections in children (Kulhanjian et al., 1989)  Ceftriaxone had a satisfactory clinical and microbiological response in 93% compared to 100% with Ampicillin-sulbactam but ceftriaxone failed in two cases of Staphylococcus aureus infection and is not therefore recommended as a routine empirical agent.  A recent randomized, multicenter prospective trial of children aged 3 months to 15 years who had culture-positive septic arthritis included Clindamycin or a first-generation cephalosporin as therapy (Peltola et al., 2009).  The primary aim was to evaluate duration of therapy but both agents had high cure rates.  While Clindamycin may be an appropriate agent for directed therapy we have concerns about its empirical use because of resistance.

Recommendation:  Initial antimicrobial therapy for septic arthritis should be intravenous.
[Evidence level D]

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In culture negative cases directed therapy is not possible but empirically in >90%+ cases monotherapy with Flucloxacillin is appropriate.  In a child commenced on Flucloxacillin and Ceftriaxone for severe sepsis and suspected meningococcal infection, Ceftriaxone can usually be stopped if Blood Cultures do not grow meningococci and meningococcal PCR on blood samples is negative.

Directed antimicrobial regimens, when a pathogen is identified from Blood Cultures or bone samples are given in Table 1.

Table 1 Directed antimicrobial regimens for osteomyelitis in children and infants. *Provided isolate is susceptible.
Note: The recommended antibiotics doses are generally in agreement with BNFC March 2018.  Dose reductions may be required in patients with hepatic or renal impairment, consult product literature or pharmacy for further information. When prescribing high dose oral antibiotics (e.g. Amoxicillin , Flucloxacillin ) patients may experience an increase in gastrointestinal upset (nausea and diarrhoea).

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Recommendation: 14 day course of antimicrobial therapy, if the clinical response is good and the C-reactive protein level normalizes (<20mg/L) shortly after initiation of treatment.
[Evidence level A]

Recommendation: Slow responders (e.g. CRP remaining elevated (>20mg/L) or persistent fever or systemic signs of infection at 96 hours) require 3-4 weeks antimicrobial therapy.
[Evidence level D]

Various regimes have been described from one week IV therapy to six weeks IV then step-down oral therapy.  Until recently there was no RCT evidence to guide this issue.  A randomized, multicentre prospective trial of children aged 3 months to 15 years with culture-positive septic arthritis has now concluded that large doses of well-absorbed antimicrobials for <2 weeks (initially administered intravenously) are sufficient for treatment of most cases of childhood septic arthritis (Peltola et al., 2009).  Patients were randomized to receive Clindamycin or a first-generation cephalosporin for 10 days (short term) or 30 days (long term).  Intravenous therapy was given for the first 2-4 days. Of the total 130 cases, 63 patients were in the short-term treatment group, and 67 were in the long-term treatment group. The median durations of antimicrobial treatment were 10 days and 30 days, respectively.  All patients recovered without sequelae (Peltola et al., 2009)

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Recommendation: Initial IV treatment is mandatory and should continue for at least 3 days.
[Evidence level C]

Recommendation:  If the clinical response is good [usual case] as indicated by the child’s general well-being [feeding etc.], rapidly resolving temperature and rapidly falling CRP [preferably < 20mg/L] then oral antibiotics can be substituted.
[Evidence level A]

Recommendation: Hospital discharge should be at least 24 hrs. after switch to oral antimicrobials to confirm continuing improvement.
[Evidence level D]

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Slow/non-responders: In patients that fail to respond by 96 hours, the causative pathogen may not be sensitive to empirical regimens or abscess formation/recurrent joint sepsis or underlying osteomyelitis may be compromising antimicrobial activity.  Repeat aspiration or surgical drainage may be required.
Recommendation: Discuss with senior orthopaedic surgeon and microbiology and consider paediatric rheumatological opinion.
[Evidence level D]

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