What are the guidelines for using plazomycin (antibiotic) in treating bacterial infections?

Guidelines for Using Plazomicin in Treating Bacterial Infections

Plazomicin is primarily recommended for complicated urinary tract infections (cUTI) caused by carbapenem-resistant Enterobacterales (CRE) at a dose of 15 mg/kg IV every 12 hours. 1

Indications and Dosing

Complicated Urinary Tract Infections (cUTI)

• Plazomicin is FDA-approved for the treatment of cUTI in adults, particularly those caused by multidrug-resistant gram-negative bacteria 2
• Recommended dose: 15 mg/kg IV every 12 hours for 5-7 days 1
• Plazomicin demonstrated non-inferiority to meropenem in the treatment of cUTI in the EPIC trial 3
• Particularly effective against infections caused by:
  • Extended-spectrum β-lactamase (ESBL) producing Enterobacterales 2
  • Carbapenem-resistant Enterobacterales (CRE) 1
  • Organisms with aminoglycoside-modifying enzymes 4

Bloodstream Infections

• Limited evidence supports plazomicin-based combination regimens for serious CRE infections 1
• In the CARE trial, plazomicin-based combinations showed numerically lower mortality compared to colistin-based regimens (24% vs 50%) 1
• However, this trial was stopped prematurely due to slow enrollment 1

Antimicrobial Activity

• Active against most KPC and OXA-48 producing CRE 1
• Variable activity against MBL-producing strains 1
• Effective against many bacteria producing carbapenemases or other specific hydrolases 5
• Stable against aminoglycoside-modifying enzymes that compromise traditional aminoglycosides 1, 2
• Shows synergistic effects when combined with:
  • Piperacillin/tazobactam 4
  • Ceftazidime 4

Treatment Considerations

Renal Function Monitoring

• Monitor renal function during therapy 2
• Increases in serum creatinine levels of ≥0.5 mg/dL above baseline occurred in 7.0% of patients in clinical trials 3
• Dosage adjustments required for patients with moderate to severe renal impairment 2

Alternative Treatment Options for CRE Infections

• For cUTI due to CRE, alternative options include:
  • Ceftazidime-avibactam 2.5 g IV q8h 1
  • Meropenem-vaborbactam 4 g IV q8h 1
  • Imipenem-cilastatin-relebactam 1.25 g IV q6h 1
  • Single-dose aminoglycosides for simple cystitis due to CRE 1

Special Populations

• Not recommended in patients with severe renal impairment, including those receiving renal replacement therapy 2
• May cause fetal harm in pregnant women 2
• Therapeutic drug monitoring warranted in patients with moderate or severe renal impairment 2

Common Adverse Effects

• Decreased renal function 2
• Diarrhea 2
• Hypertension 2
• Headache 2
• Nausea and vomiting 2
• Hypotension 2
• Potential for neuromuscular blockade and ototoxicity (as with other aminoglycosides) 2

Clinical Pearls

• Plazomicin showed higher microbiological eradication rates compared to meropenem at test-of-cure visits (78.8% vs 68.6%) for non-susceptible Enterobacteriaceae 3
• Lower rates of microbiological recurrence (3.7% vs 8.1%) and clinical relapse (1.6% vs 7.1%) compared to meropenem at late follow-up 3
• Consider plazomicin as a carbapenem or β-lactam/β-lactamase inhibitor-sparing alternative for MDR infections 6
• European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines note insufficient evidence comparing plazomicin to colistin for CRE infections 1