Where has the Flucloxacillin gone?

📋 Executive Summary

Recent updates to the Royal Children's Hospital Melbourne (RMCH) Antimicrobial Guidelines now endorse cefazolin as the primary intravenous therapy for pediatric skin, soft tissue, bone, and invasive staphylococcal infections, notably replacing flucloxacillin in all indications except for endocarditis.

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🔍 Why the Change? Evidence and Rationale

Clinical Equivalence

Clinical trials and meta-analyses have shown equivalent efficacy between cefazolin and flucloxacillin for methicillin-susceptible Staphylococcus aureus (MSSA) and Group A streptococcal infections with respect to:

• Mortality rates

• Recurrence rates

• Resolution rates

✅ Tolerability: A Key Advantage

Cefazolin presents a LOWER RISK of adverse events compared to flucloxacillin:

• Reduced phlebitis

• Fewer GI symptoms

• Fewer premature discontinuations

This is crucial in children, where tolerability and IV line complications significantly impact care delivery.

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💊 RMCH Approved Dosing for Cefazolin

Standard Pediatric Dose:

Cefazolin 50 mg/kg (maximum 2 grams) IV every 8 hours

Indications:

✓ Moderate and severe infections

✓ Cellulitis

✓ Osteomyelitis

✓ Septic arthritis

✓ Sepsis (meningitis excluded)

✓ Other invasive staph/strep infections

Duration:

• Tailored to clinical response

• Typically 7 days+ for uncomplicated infections

• 3 weeks for bone/joint infections

Oral Switch:

Switch to oral cephalexin (usually 45 mg/kg/dose, max 1.5 g three times daily) when afebrile and inflammatory markers improve.

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💊 Oral Cephalexin (Cefalexin) Therapy - RMCH Guidelines

Standard Oral Dose:

Cefalexin 45 mg/kg (maximum 1.5 g) oral three times daily (tds)

Used for step-down therapy from IV cefazolin once the patient is afebrile and clinical improvement with decreasing inflammatory markers.

Alternative Oral Doses from Guidelines:

• UTI/Pyelonephritis: 45 mg/kg (max 1.5 g) oral tds

• Cellulitis (mild/moderate): 20 mg/kg (750 mg) oral tds

• Preseptal cellulitis: 20 mg/kg (750 mg) oral tds

• Lymphadenitis: 20 mg/kg (750 mg) oral tds

• Impetigo: 20 mg/kg (750 mg) oral tds

Conditions Treated with Oral Cephalexin:

• Step-down from IV therapy for osteomyelitis, septic arthritis, cellulitis

• Urinary tract infections and pyelonephritis

• Skin and soft tissue infections (cellulitis, impetigo)

• Preseptal (periorbital) cellulitis

• Cervical lymphadenitis

• Endocarditis prophylaxis (penicillin hypersensitivity): 50 mg/kg (max 2 g) oral

Duration: Varies by condition—typicallyQueso 5-10 days for skin infections, 3 weeks total for bone/joint infections

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📖 Practical Prescribing Guidance from RMCH, Victoria, Australia

Cellulitis/Skin/Soft Tissue/Bone

→ Cefazolin is now the SOLE IV agent, with ceftriaxone reserved for hospital-in-the-home

Sepsis (Meningitis Excluded)

→ Cefazolin plus gentamicin is first-line in non-high-risk patients over 2 months old

Facial Cellulitis in Under 5s (non-Hib immunised)

→ Add third-generation cephalosporin for coverage

Endocarditis

→ Flucloxacillin is still indicated here, alongside benzylpenicillin and gentamicin

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⚠️ Special Considerations and Exceptions

Flucloxacillin

→ Now LIMITED to indications for suspected or proven ENDOCARDITIS only

→ All other prior uses (including skin, bone, sepsis) have been transitioned to cefazolin

Penicillin/Cephalosporin Hypersensitivity

→ Use clindamycin or vancomycin as indicated by severity and risk profile

Maximum Doses Apply

→ No more than 2 g per dose for IV cefazolin

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Clinical Scenario Table: New Approach (2025)

Infection Type	First-Line IV Agent	Previous Practice	Changes (2025)	Oral Step-down Agent
Cellulitis / Soft Tissue / Bone	Cefazolin 50 mg/kg IV 8H	Flucloxacillin	Now exclusively cefazolin	Cefalexin 20 mg/kg (750 mg) oral tds
Sepsis (meningitis excluded)	Cefazolin + Gentamicin	Flucloxacillin	Transitioned	Cefalexin 45 mg/kg (max 1.5 g) oral tds
Osteomyelitis / Arthritis	Cefazolin 50 mg/kg IV 8H	Flucloxacillin	Transitioned	Cefalexin 45 mg/kg (max 1.5 g) oral tds
Endocarditis	Flucloxacillin + others	Flucloxacillin	No change	No oral step-down (continue IV)
Oral step-down	Cephalexin	Cephalexin	No change	Already oral therapy

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📝 Selected Protocol Excerpts (2025) – Direct from RMCH Guidelines

▶ Moderate/severe skin infections:

"Cefazolin 50 mg/kg (2 g) IV 8H (max 2 g/dose) … switch to oral cephalexin when improving."

▶ Sepsis (over 2 months, meningitis excluded):

"Cefazolin 50 mg/kg (2 g) IV 8H and gentamicin (as per age-specific dosing)."

▶ Endocarditis:

"Flucloxacillin 50 mg/kg (2 g) IV 6H (in combination with benzylpenicillin and gentamicin)."

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🎯 Implications for Practice

❌ CEASE ROUTINE USE

Cease routine use of flucloxacillin in pediatric IV staphylococcal and streptococcal infections except for endocarditis.

✅ NEW STANDARD

All moderate-to-severe admissions for skin, bone, and systemic staph/strep infections should be started on cefazolin IV.

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📚 References & Further Reading

• RMCH Clinical Practice Guidelines: Antimicrobial guidelines—October 2025 update

• Key Publications: [PMC11142999], [PubMed 38296936], [PCH WA Monograph], [Charles Darwin University]