Antibiotics

Empiric antibiotics for abdominal infections (from eTG 15/5/25)

• Surgical triple antibiotics
  • Amoxicillin 1g QID
  • Metronidazole 500mg BD
  • Gentamicin 4-5mg/kg daily
• If aminoglycosides are contraindicated, use piperacillin/tazobactam 4.5g QID
• Non-severe hypersensitivity reaction to penicillin: ceftriaxone 2g daily/metronidazole 500mg BD
• Severe immediate or severe delayed (days after) reaction to penicillin: (for immediate hypersensitivity, also appropriate to give ceftriaxone/metronidazole in hospitalised patients if it is felt to be a better regimen than the below; however in delayed hypersensitivity must avoid cephalosporins)
  • Gentamicin
  • Clindamycin 600mg TDS
  • Consider adding metronidazole if gram-negative anaerobes are expected
• Oral step-down therapy: Augmentin DF or Bactrim DS/metronidazole

Relevant pharmacology

• Pharmacokinetics - what the body does to the drug
• PharmacoDynamics - what the Drug does to the body
  • MIC - lowest concentration that inhibits bacterial growth
  • Concentration-dependent e.g. aminoglycosides
  • Time-dependent e.g. beta-lactams
  • Some agents have both types - e.g. fluoroquinolones

Beta-lactam antibiotics

• Interfere with peptidoglycan synthesis, which is required for bacterial cell walls - bactericidal
• Drugs
  • Penicillins
    • Allergy is HUGELY overstated by patients - 5-20% will report it
    • It also settles with time, if it ever even truly existed
    • Risk of cross-reactivity with cephalosporins is about 5% and highest for first-gen, so if the penicillin allergy is only a rash or something, definitely worth giving cephalosporins still
    • The main benefit to tazocin over iv augmentin is that tazocin also covers pseudomonas and some extra anaerobes. Of note, those species all grow quite quickly in the lab, if they’re ever going to grow.
  • Cephalosporins
    • First and second generations are useful only for prophylaxis, de-escalation, or uncomplicated infections
    • Third gen has enhanced gram negative activity, but ineffective against anaerobes
    • Fourth-gen has pseudomonal activity
    • No cephalosporin is active against enterococcus
  • Monobactams
  • Carbapenems
    • Good activity against aerobic and anaerobics, MRSA, and almost all gram negative bacilli, and pseudomonas

Lipoglycopeptides

• Inhibit cell wall synthesis - bactericidal
  • Vancomycin
    • Poor tissue penetration
    • Starting dose of 15mg/kg for patients with normal renal function
    • Minimum trough concentration of 15-20 microg/mL
    • Look out for 'red man syndrome' if it's given too quickly - not a true allergic reaction
    • Nephrotoxicity, ototoxicity
    • Not actually as good at MSSA coverage as cefazolin/fluclox
  • Serious indications caused by MRSA or MRSE, gram positive infections in patients with penicillin allergies, and oral therapy for C diff

Cyclic lipopeptides

• Daptomycin

Polymyxins

• Colistimethate

Aminoglycosides

• Bind to bacterial 30S ribosomal subunit, inhibiting protein synthesis
• Gentamicin
  • 5mg/kg/day
  • Reduce dose in renal insufficiency
  • Can give 3 doses without serum monitoring
  • Typically wouldn't continue empiric gent beyond 3 doses (72 hours) unless discussed with ID
• Risk of nephrotoxicity relates to ischaemia of proximal tubular cells - decreased GFR but usually reversible
  • Risk factors are older age, frequent dosing, sodium and volume depletion, acidaemia, hypokalaemia, hypomagnesaemia, coexistent liver disease
  • Pretty low risk if you just give one dose a day
• Ototoxicity is usually irreversible and may develop later - may occur in 5-15% of patients

Tetracyclines

• Broad spectrum - inhibit protein synthesis - bacteriostatic
  • Doxycycline
  • Tigecycline

Lincosamide

• Clindamycin
  • Good anti-anaerobic activity and most gram positive cocci, but not MRSA
  • Effective against Bacteroides
  • PO bioavailability is essentially 100%
  • Theoretically suppresses toxin production by streptococcus

Macrolide

• Azithromycin
• Erythromycin
• Clarithromycin

Fluoroquinolones

• Ciprofloxacin, levofloxacin, norfloxacin, moxifloxacin
  • Inhibit bacterial DNA synthesis
  • Broad-spectrum
  • Good oral bioavailability (IV ciprofloxacin is rarely needed)

Metronidazole

• Active against almost all anaerobes and many protozoa
• Excellent oral bioavailability

Sulfonamides

• Competitive folate antagonist, which prevents DNA/RNA synthesis
• Doesn't work well when pus or necrosis is present, because bacteria can take up and use thymidine/purine directly
• Unwanted effects: hepatitis, hypersensitivity, bone marrow suppression, acute renal failure
• Trimethoprim-sulfamethoxazole
  • Complete oral bioavailability
  • Affects bacterial nucleotide synthesis at two points in the pathway

Oxazolidinones

• Linezolid
  • Active against a wide variety of gram-positives - MRSA, VRE, C diff too

Fusidic acid

• Narrow spectrum steroidal, effective against gram-positives

Fidaxomicin

• Inhibits bacterial RNA polymerase
• Poorly absorbed from gut
• Works well against C diff