What alternative treatment options are available for a patient resistant to initial tx (treatment) but susceptible to amikacin?

Alternative Treatment Options for Patients with Amikacin Susceptibility

For patients resistant to initial treatment but susceptible to amikacin, adding amikacin liposome inhalation suspension (ALIS) to the treatment regimen is strongly recommended, particularly for MAC pulmonary disease that has failed standard therapy for at least 6 months. 1

Treatment Approach for Mycobacterial Infections

For MAC Pulmonary Disease

1. For treatment-resistant MAC pulmonary disease:

   • Add ALIS to the existing guideline-based therapy (GBT)
   • Culture conversion rates: 29% with ALIS+GBT vs. 8.9% with GBT alone 1
   • Where ALIS is not available, inhaled parenteral amikacin is a reasonable alternative 1

2. Important considerations:

   • Monitor for development of amikacin resistance (occurs in approximately 10.3% of patients on ALIS) 1
   • Consider adding another companion drug to prevent resistance development 1
   • Ensure the isolate retains in vitro susceptibility to amikacin before initiating therapy

For M. abscessus Pulmonary Disease

1. Initial phase treatment:

   • Minimum 4-week course of:
     • Intravenous amikacin (10-15 mg/kg daily) 1, 2
     • Intravenous tigecycline
     • Intravenous imipenem (where tolerated)
     • Oral macrolide (if not constitutively resistant) 1

2. Continuation phase treatment:

   • Nebulized amikacin in combination with 2-4 oral antibiotics:
     • Clofazimine
     • Linezolid
     • Minocycline or doxycycline
     • Moxifloxacin or ciprofloxacin
     • Co-trimoxazole 1

Dosing and Administration

Intravenous Amikacin

• Standard dosing: 15 mg/kg/day (maximum 1.0 g/day) 2, 3
• For M. abscessus infections: 10-15 mg/kg daily to achieve peak serum levels in the low 20 μg/mL range 2
• Long-term therapy: Consider three-times-weekly dosing at 25 mg/kg for therapy >3 months 2
• Administration: Infuse over 30-60 minutes 3

Nebulized Amikacin

• Consider when intravenous administration is impractical, contraindicated, or longer-term treatment is required 1
• Particularly useful as part of a salvage regimen for treatment-resistant cases 1

Monitoring and Safety

1. Potential adverse effects:

   • Respiratory events (most common with ALIS): dysphonia, cough, hemoptysis, dyspnea 1
   • Ototoxicity: tinnitus, vestibular effects (dizziness, balance disorder, vertigo) 1, 2
   • Nephrotoxicity: monitor renal function regularly 2, 3

2. Monitoring recommendations:

   • Baseline audiogram and vestibular testing 2
   • Regular assessment of serum creatinine and creatinine clearance 2
   • Target peak serum levels: 25-35 mg/L for daily dosing 2
   • Target trough serum levels: <5 mg/L to minimize toxicity 2

Special Considerations

1. Dosage adjustments:

   • For renal impairment: Reduce dose or extend interval based on creatinine clearance 3
   • For elderly patients (>59 years): Consider reduced dose of 10 mg/kg/day 2
   • For obese patients: Calculate using ideal body weight plus 40% of excess weight 2

2. Contraindications:

   • Known hypersensitivity to aminoglycosides 2
   • Pregnancy (risk of fetal nephrotoxicity and congenital hearing loss) 2
   • Amikacin-resistant isolates (MIC >64 mg/L or presence of 16S rRNA gene mutation) 1

Treatment Duration

• Continue treatment for a minimum of 12 months after culture conversion 1
• For patients who fail to culture-convert, consider long-term suppressive antibiotic regimen 1
• For M. abscessus infections, the duration of intravenous treatment should be influenced by severity of infection, treatment response, and tolerance 1

Clinical Efficacy

Once-daily dosing regimen of amikacin 15 mg/kg has shown 83.1% primary success and 83.9% definitive cure in severely infected patients 4, with bacteriological eradication achieved in 67.3% of cases. This regimen may also decrease the risk of nephrotoxicity compared to multiple daily doses.

Remember that amikacin should be part of a multi-drug regimen, as it has impressive in vitro synergy against aminoglycoside-sensitive and resistant organisms when used in combination with other antibiotics 5.