6.7: Infectious Disease Therapeutics & Antimicrobial Stewardship

6.7 Infectious Disease Therapeutics & Antimicrobial Stewardship

Infectious disease management in Australia is heavily guided by the Therapeutic Guidelines: Anti-infective (eTG). For the OPRA exam, candidates must demonstrate a deep understanding of empirical antibiotic selections, clinical decision-making, and the application of Antimicrobial Stewardship (AMS) principles. AMS aims to optimize patient outcomes, minimize drug toxicity, and curb the emergence of antimicrobial resistance by restricting broad-spectrum agents.

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1. Principles of Antimicrobial Stewardship (AMS)

AMS is a systematic approach to optimizing antimicrobial use. In Australian healthcare settings, this involves multidisciplinary teams implementing several key strategies:

• Formulary Restriction and Approval Systems: Antibiotics are often categorized using a traffic light system to restrict broad-spectrum or "last-resort" agents:
  • Green (Unrestricted): Narrow-spectrum agents with low resistance potential (e.g., benzylpenicillin, amoxicillin).
  • Orange (Restricted): Requires clinical indication or local approval (e.g., ceftriaxone, ciprofloxacin).
  • Red (Highly Restricted): Requires infectious disease (ID) or clinical microbiologist approval (e.g., meropenem, linezolid, piperacillin-tazobactam).
• Intravenous-to-Oral Switch (IVOS): Transitioning from IV to oral therapy as soon as clinical criteria are met to reduce catheter-related infections, hospital length of stay, and costs.
  • IVOS Criteria: Clinical improvement, afebrile for >24 hours, functioning gastrointestinal tract, no vomiting/diarrhoea, and no high-risk conditions requiring prolonged IV therapy (e.g., endocarditis, meningitis, osteomyelitis, undrained abscesses, or severe sepsis).
• Therapeutic Drug Monitoring (TDM): Essential for aminoglycosides (gentamicin) and glycopeptides (vancomycin) to ensure efficacy and prevent nephrotoxicity/ototoxicity.

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2. Respiratory Tract Infections (RTIs)

Empirical therapy for respiratory infections depends on severity assessment. In Australia, the CORB (Confusion, Oxygenation, Respiratory rate, Blood pressure) score or SMART-COP tool is used to assess Community-Acquired Pneumonia (CAP) severity.

Community-Acquired Pneumonia (CAP)

Acute Bronchitis and Pharyngitis

• Acute Bronchitis: Typically viral. Antibiotics are not recommended routinely unless the patient is systemically unwell or at high risk of complications (e.g., severe chronic lung disease).
• Acute Pharyngitis/Tonsillitis: Mostly viral. Antibiotic treatment is reserved for patients at high risk of acute rheumatic fever (e.g., Aboriginal and Torres Strait Islander peoples living in rural/remote areas) or those meeting $\ge$ 3 Centor criteria. First-line is phenoxymethylpenicillin (Penicillin V) 500 mg orally, 12-hourly for 10 days (crucial for eradicating Group A Streptococcus and preventing rheumatic fever).

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3. Urinary Tract Infections (UTIs)

Urinary tract infections require differentiation between cystitis (lower UTI) and pyelonephritis (upper UTI), as well as special patient groups (pregnancy, renal impairment).

Uncomplicated Cystitis (Non-pregnant Females)

• First-Line Options:
  1. Trimethoprim 300 mg orally, daily at night for 3 days.
  2. Nitrofurantoin 100 mg orally, 6-hourly (or 50 mg 6-hourly) for 5 days.
  3. Cefalexin 500 mg orally, 12-hourly for 5 days.
• Renal Impairment Warning: Nitrofurantoin requires an eGFR $\ge$ 30 mL/min to achieve therapeutic concentrations in the urine. Below this level, it is ineffective and carries an increased risk of peripheral neuropathy and pulmonary toxicity. Trimethoprim should be avoided if eGFR < 15 mL/min.
• Pregnancy Cystitis: First-line is cefalexin 500 mg orally, 12-hourly for 5 days or nitrofurantoin 100 mg orally, 6-hourly for 5 days.
  • Contraindications in Pregnancy: Trimethoprim is a folate antagonist and is contraindicated in the first trimester due to neural tube defect risks. Nitrofurantoin must be avoided at term (36+ weeks) due to the risk of neonatal haemolytic anaemia (immature glutathione system).

Acute Pyelonephritis (Mild-to-Moderate)

• Managed orally if tolerated: Cefalexin 1 g orally, 6-hourly for 10–14 days or amoxicillin/clavulanate 500/125 mg orally, 8-hourly for 10–14 days.
• Severe pyelonephritis requires IV therapy: Gentamicin IV (single daily dose adjusted for renal function) + ampicillin 2 g IV, 6-hourly.

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4. Skin and Soft Tissue Infections (SSTIs)

Empirical therapy must cover Staphylococcus aureus (including MRSA) and Streptococcus pyogenes (Group A Streptococcus).

• Cellulitis (Mild/Moderate, Non-purulent):
  • First-line: Flucloxacillin 500 mg to 1 g orally, 6-hourly for 5 to 10 days. Flucloxacillin requires empty stomach administration (1 hour before or 2 hours after food) for optimal absorption.
  • Penicillin hypersensitivity (mild): Cefalexin 500 mg to 1 g orally, 6-hourly.
  • Penicillin hypersensitivity (severe/anaphylaxis): Clindamycin 300 mg to 450 mg orally, 8-hourly.
• Impetigo:
  • Localized (few lesions): Topical mupirocin 2% ointment, 8-hourly for 5 days.
  • Widespread or multiple lesions: Oral flucloxacillin or cefalexin for 5 days.

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5. Surgical Prophylaxis

The goal of surgical prophylaxis is to reduce the risk of surgical site infections (SSIs) by establishing bactericidal drug levels in tissue at the time of surgical incision.

• Drug Choice: Cephazolin IV (first-generation cephalosporin) is the standard agent for most surgeries (cardiac, orthopaedic, gastrointestinal) because of its Gram-positive efficacy, long half-life, and safety.
  • Anaerobic coverage: In colorectal surgery, metronidazole IV is added.
• Dosing and Timing:
  • Standard dose is cephazolin 2 g IV (or 3 g IV for patients weighing > 120 kg).
  • Must be administered within 60 minutes prior to surgical incision (ideally during induction of anaesthesia). If administered too early (>120 minutes) or after incision, SSI rates rise.
• Intraoperative Redosing: Required if the procedure exceeds 4 hours from the first dose (due to cephazolin's half-life of 2 hours) or if there is major blood loss (> 1.5 litres).
• Post-operative Duration: Single pre-operative doses are usually sufficient. Prophylaxis should never exceed 24 hours post-operatively; prolonged use increases resistance and Clostridioides difficile risk without reducing infections.