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Sunday, July 27, 2025

Flucloxacillin


Flucloxacillin is a narrow-spectrum, beta-lactamase-resistant penicillin antibiotic that belongs to the isoxazolyl penicillin subclass. It is commonly used to treat infections caused by Gram-positive bacteria, particularly Staphylococcus aureus strains that produce beta-lactamase enzymes. Flucloxacillin is widely used in both community and hospital settings for skin, soft tissue, bone, and joint infections, as well as for prophylaxis in certain surgical procedures.

Pharmacological Classification

  • Therapeutic class: Antibacterial agent

  • Pharmacologic class: Beta-lactam antibiotic – Penicillinase-resistant penicillin

  • ATC code: J01CF05

  • Formulations: Capsules, oral suspension, powder for reconstitution (intravenous or intramuscular injection)

Mechanism of Action

Flucloxacillin exerts its bactericidal activity by inhibiting the synthesis of the bacterial cell wall. It binds to penicillin-binding proteins (PBPs), particularly PBP-1, -2, and -3, and prevents the final transpeptidation step in peptidoglycan cross-linking. This leads to weakening of the cell wall, resulting in cell lysis and death.

Unlike other penicillins, flucloxacillin is resistant to beta-lactamases produced by most Staphylococcus aureus strains due to its bulky side chain, which protects the beta-lactam ring from enzymatic degradation. However, it is not active against methicillin-resistant Staphylococcus aureus (MRSA).

Spectrum of Activity

Sensitive Organisms

  • Staphylococcus aureus (methicillin-sensitive, MSSA)

  • Streptococcus pyogenes

  • Streptococcus pneumoniae

  • Streptococcus agalactiae

  • Listeria monocytogenes (less commonly)

Not Effective Against

  • MRSA (methicillin-resistant strains)

  • Most Gram-negative bacteria

  • Anaerobes

  • Enterococcus species

  • Atypical pathogens (Chlamydia, Mycoplasma, Legionella)

Therapeutic Indications

Flucloxacillin is indicated for the treatment of infections caused by beta-lactamase-producing Gram-positive organisms, particularly:

  • Skin and soft tissue infections: impetigo, cellulitis, folliculitis, abscesses, infected eczema, infected wounds

  • Osteomyelitis and septic arthritis

  • Respiratory tract infections: pneumonia, empyema, lung abscess (when MSSA is suspected)

  • Endocarditis: in combination therapy

  • Bacteremia and septicemia due to susceptible organisms

  • Surgical prophylaxis in cardiac, orthopedic, or breast surgery

  • Infected burns and diabetic foot infections

  • Otitis externa and media (occasionally)

Dosage and Administration

Adults

Oral (capsules or suspension)

  • Typical dose: 250 mg to 500 mg four times daily (QID)

  • Taken on an empty stomach, 1 hour before or 2 hours after meals for optimal absorption

  • Duration: typically 5 to 14 days depending on infection severity

Intravenous (IV)

  • Dose: 1–2 g every 6 hours

  • Max: up to 8 g/day in severe infections

  • May be administered as bolus (3–4 minutes) or infusion (20–60 minutes)

Intramuscular (IM)

  • For mild/moderate infections: 250–500 mg every 6 hours

Children

  • Oral: 12.5–25 mg/kg every 6 hours

  • IV: 50–100 mg/kg/day in divided doses

  • Neonates may require adjusted intervals

Renal Impairment

  • No dose adjustment usually required unless renal function is severely compromised

Hepatic Impairment

  • Use with caution due to risk of cholestatic hepatitis

  • Monitor liver function with prolonged use

Pharmacokinetics

  • Absorption: Incomplete (~50%) but adequate when fasting

  • Peak plasma concentration: 1–2 hours post-dose (oral)

  • Protein binding: ~95%

  • Distribution: Widely distributed; penetrates bone, synovial fluid, and skin

  • Half-life: ~0.75 to 1 hour

  • Metabolism: Hepatic metabolism to inactive metabolites

  • Excretion: Primarily renal (unchanged drug); some biliary excretion

Contraindications

  • Known hypersensitivity to flucloxacillin or other beta-lactam antibiotics (penicillins or cephalosporins)

  • History of flucloxacillin-induced jaundice or hepatic dysfunction

  • Caution in patients with renal or hepatic dysfunction, prolonged treatment, or elderly patients

Warnings and Precautions

  • Cholestatic jaundice and hepatitis: Rare but serious; may occur several weeks after therapy

  • Monitor liver function with treatment >2 weeks

  • Use with caution in patients with liver disease, elderly, or existing hepatobiliary conditions

  • Superinfection risk: Prolonged use may promote overgrowth of non-susceptible organisms

  • Sodium content: High sodium load in IV formulation; consider in heart failure and renal impairment

Adverse Effects

Common (1–10%)

  • Gastrointestinal: nausea, diarrhea, abdominal discomfort

  • Skin reactions: rash, urticaria

  • Injection site reactions: phlebitis (IV), pain (IM)

Uncommon (0.1–1%)

  • Elevated liver enzymes

  • Pruritus

  • Eosinophilia

Rare but Serious (<0.1%)

  • Cholestatic hepatitis: often delayed onset, may persist after discontinuation

  • Anaphylaxis: immediate hypersensitivity reaction

  • Interstitial nephritis

  • Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)

  • Neutropenia, thrombocytopenia

Drug Interactions

  • Methotrexate: Flucloxacillin may reduce renal excretion of methotrexate → increased toxicity

  • Probenecid: Decreases renal clearance of flucloxacillin → increased plasma levels

  • Oral contraceptives: Efficacy may be reduced by antibiotic-induced GI flora disruption (minimal with flucloxacillin, but caution advised)

  • Warfarin: Antibiotic use may enhance anticoagulant effect → increased INR

  • Live vaccines: May reduce vaccine efficacy during acute infection

Pregnancy and Lactation

Pregnancy

  • Category B (Australia)

  • No evidence of teratogenicity

  • Safe in all trimesters when clearly needed

Breastfeeding

  • Excreted in small amounts into breast milk

  • Generally considered safe

  • Monitor infant for GI upset or allergic reactions

Use in Special Populations

Elderly

  • Increased risk of hepatic adverse effects

  • Monitor liver function periodically during treatment

Renal Impairment

  • Use cautiously in severe impairment

  • May require reduced frequency if renal clearance significantly compromised

Hepatic Impairment

  • Baseline and periodic LFTs required

  • Avoid if previous flucloxacillin-related jaundice

Clinical Pearls

  • Take on an empty stomach to maximize absorption

  • Monitor liver function with courses >14 days or in at-risk patients

  • Choice agent for penicillinase-producing Staphylococcus infections

  • Not effective for MRSA

  • IV form contains significant sodium – assess sodium balance in cardiac/renal disease

  • In osteomyelitis or endocarditis, treatment may continue for 4–6 weeks or longer

  • May be used in combination with rifampicin for bone/joint infections




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