What is the dosage and administration of Flucloxacillin (Flucloxacillin) and Paracetamol (Acetaminophen) for bacterial infections?

Flucloxacillin and Paracetamol Dosing for Bacterial Infections

For staphylococcal skin and soft tissue infections in adults, flucloxacillin should be dosed at 500 mg orally four times daily or 50 mg/kg IV four times daily (up to 1-2 g every 4-6 hours for severe infections), while paracetamol can be used concurrently for fever/pain management but requires awareness of a rare but potentially fatal drug interaction causing pyroglutamic acidosis. 1, 2

Flucloxacillin Dosing by Indication

Skin and Soft Tissue Infections (Staphylococcal)

Adults:

• Oral: 500 mg four times daily for methicillin-susceptible Staphylococcus aureus (MSSA) 1
• Intravenous: 50 mg/kg every 6 hours (typical adult dose 1-2 g every 4 hours) for severe infections 1

Pediatric (beyond neonatal period):

• Oral: 25 mg/kg/day divided into 4 doses 1
• Intravenous: 50 mg/kg/dose every 6 hours 1

Specific Infections

Mastoiditis (Pediatric):

• Flucloxacillin IV 50 mg/kg four times daily for 10 days 1
• Second-line: ceftriaxone IV 1

Osteomyelitis (Children >3 years):

• Flucloxacillin IV 50 mg/kg four times daily for 10 days, then switch to oral (total 3 weeks therapy) 1
• Second-line: ceftriaxone IV or clindamycin IV 1

Sepsis with Suspected Staphylococcal Infection:

• Infants: Flucloxacillin IV 50 mg/kg four times daily plus gentamicin IV 5-7.5 mg/kg daily for 7-10 days (3 weeks for meningitis) 1
• Older children: Flucloxacillin IV 50 mg/kg four times daily plus gentamicin IV 7.5 mg/kg daily for 7-10 days 1

Pneumonia with Suspected Staphylococcal Infection:

• Cloxacillin IV 50 mg/kg four times daily for 7-10 days, then switch to oral (3 weeks total) plus gentamicin IV 7.5 mg/kg daily for at least 5 days 1

Paracetamol Dosing

While paracetamol dosing is not explicitly detailed in the provided bacterial infection guidelines, standard dosing applies:

• Adults: 500-1000 mg every 4-6 hours (maximum 4 g/day)
• Pediatric: 10-15 mg/kg/dose every 4-6 hours (maximum 75 mg/kg/day)

Critical Drug Interaction Warning

Concurrent use of flucloxacillin and paracetamol can cause pyroglutamic acidosis (5-oxoprolinaemia), a rare but potentially fatal complication presenting as high anion gap metabolic acidosis. 2 This occurs due to disruption of the γ-glutamyl cycle and is particularly dangerous in patients with:

• Multiple comorbidities
• Renal impairment
• Malnutrition
• Chronic paracetamol use

Clinical Pitfall

Most clinicians are unaware of this interaction despite both drugs being commonly prescribed together. 2 Monitor for unexplained metabolic acidosis in patients receiving both medications, especially those with risk factors.

Alternative Dosing Strategies for Severe Infections

Continuous infusion flucloxacillin may be superior for serious staphylococcal infections:

• 8-12 g/day by continuous infusion achieves serum concentrations of 8->40 mg/L, well above MIC for MSSA 3
• Provides better time above MIC (fT>MIC) compared to intermittent dosing 4
• Particularly effective for endocarditis, osteomyelitis, and deep abscesses 3
• Can be administered at home for completion of therapy 3

For near-maximal bacterial killing (fT>MIC ≥50%), continuous or prolonged infusion of 6 g/day achieves robust probability of target attainment up to MICs of 0.75-1 mg/L, compared to only 0.25-0.375 mg/L for short-term infusions. 4

Duration of Therapy

• Uncomplicated skin infections: 7-10 days 1
• Osteomyelitis: 3 weeks total (10 days IV, then oral) 1
• Sepsis/meningitis: 7-10 days (3 weeks for meningitis) 1
• Serious staphylococcal infections: Mean 29 days (range 4-60 days) with continuous infusion 3