Plazomicin

Plazomicin is a newer aminoglycoside designed to resist most aminoglycoside-modifying enzymes. It is given intravenously for complicated urinary tract infection, including pyelonephritis, caused by resistant Enterobacterales. It is a reserve drug with little availability in East Africa.

Classification. Aminoglycoside.

Mechanism. Binds the 30S ribosomal subunit; bactericidal, concentration-dependent.

Spectrum. Enterobacterales, including ESBL-producing strains, many carbapenem-resistant strains and strains resistant to gentamicin and amikacin through enzyme modification. Not active against strains that carry 16S rRNA methyltransferases. Weak against Pseudomonas and Acinetobacter and not active against anaerobes.

Pharmacokinetics. IV only. Half-life 3.5 to 4 hours. Over 90% excreted unchanged in urine by glomerular filtration. Low protein binding.

Reserve agent; infectious diseases consultation advised.

Adults. - Complicated urinary tract infection including pyelonephritis: 15 mg/kg IV over 30 minutes once every 24 hours for 4 to 7 days. - Creatinine clearance 30 to under 60 mL/min: 10 mg/kg once every 24 hours. - Creatinine clearance 15 to under 30 mL/min: 10 mg/kg once every 48 hours. - Creatinine clearance under 15 mL/min or on dialysis: no dose established. - Dose by actual body weight, using adjusted weight in obesity.

Children. Not established.

Alternatives. Meropenem, ertapenem, ceftazidime avibactam, amikacin, fosfomycin IV, colistin-based regimens.

Boxed-warning level risks. Nephrotoxicity, ototoxicity, neuromuscular blockade and foetal harm.

Contraindications. Aminoglycoside hypersensitivity; pregnancy unless the benefit clearly outweighs the risk; myasthenia gravis; known mitochondrial 12S rRNA mutation (m.1555A>G).

Adverse effects. Raised creatinine (most common), hypotension, nausea, vomiting, headache, diarrhoea. Serious: acute kidney injury, hearing loss, tinnitus, vestibular dysfunction, neuromuscular blockade, anaphylaxis, Clostridioides difficile infection.

Interactions. Loop diuretics, vancomycin, amphotericin B, ciclosporin, cisplatin, contrast agents and NSAIDs; neuromuscular blockers; other aminoglycosides.

Common prescribing errors. No dose reduction in renal impairment, no drug level in patients with creatinine clearance under 90 mL/min, and use in bacteraemia of non-urinary source without data.

Special groups. - Pregnancy: avoid (foetal eighth nerve damage). Breastfeeding: compatible (poor oral absorption), with caution. - Older adults: dose by creatinine clearance; closer hearing and kidney review. - Kidney impairment: creatinine clearance 30 to under 60 mL/min 10 mg/kg every 24 hours; 15 to under 30 mL/min 10 mg/kg every 48 hours; levels are needed when creatinine clearance is under 90 mL/min. - Liver impairment: no adjustment.

Preparation. Dilute the dose in 0.9% sodium chloride or Hartmann solution to a final volume of 50 mL and infuse over 30 minutes. Do not mix with other drugs in the same line.

Baseline and monitoring. - Baseline: creatinine and creatinine clearance, weight, hearing history, medication review, pregnancy test. - Trough levels before the second dose and as clinically needed in creatinine clearance under 90 mL/min, aiming for a trough under 3 mg/L. - Creatinine at least twice weekly; hearing and balance review if symptoms arise.

Stop rules. Stop for new hearing loss, tinnitus, vertigo, creatinine rising by 0.3 mg/dL (26 micromol/L) or more, or neuromuscular weakness.

Referral and escalation. Infectious diseases consultation before use; nephrology for acute kidney injury.