Should I give a catch‑up dose of liposomal amphotericin B (AmBisome) now for a patient with a central nervous system infection who missed today's dose and the next scheduled dose is 12 hours away?

Should You Give a Catch-Up Dose Now?

Yes, administer the missed dose of liposomal amphotericin B immediately, even though the next scheduled dose is 12 hours away. In CNS fungal infections, maintaining consistent antifungal drug exposure is critical for treatment success and survival.

Rationale for Immediate Administration

Critical Nature of CNS Fungal Infections

• CNS cryptococcal and candidal infections carry mortality rates exceeding 20-24% even with optimal therapy, making any delay in treatment potentially life-threatening 1.

• Liposomal amphotericin B achieves therapeutic concentrations in CNS tissue primarily through focal disruption of the blood-brain barrier at sites of infection, with concentrations in infected brain tissue reaching 4.35-times higher than normal tissue 2.

• The antifungal efficacy of amphotericin B formulations is both concentration-dependent and time-dependent, meaning both peak levels and duration of exposure above the minimum inhibitory concentration directly correlate with fungal clearance from brain tissue 3.

Pharmacodynamic Considerations

• Research demonstrates a strong correlation between pharmacodynamic parameters (C_max, AUC_0-24, and time above MIC) and successful clearance of Candida from brain tissue (P ≤ 0.0002) 3.

• Liposomal amphotericin B at 3-4 mg/kg per day is the recommended first-line therapy for CNS cryptococcal disease in transplant recipients and non-HIV infected patients, emphasizing the importance of maintaining daily dosing 1.

• A 12-hour gap without drug exposure represents a significant interruption in the time above MIC, potentially compromising treatment efficacy in a life-threatening infection 3.

Practical Implementation

Dosing Strategy

• Administer the full missed dose immediately upon recognition of the error.

• Continue with the regularly scheduled dose 12 hours from now as planned—this will result in doses closer together than usual for one cycle only.

• This approach is safer than skipping the dose entirely, as the risk of treatment failure in CNS fungal infections far outweighs the minimal increased toxicity risk from temporarily closer dosing 1.

Safety Monitoring

• Monitor renal function closely, as nephrotoxicity is the primary concern with amphotericin B formulations, though liposomal formulations have significantly lower nephrotoxicity than conventional amphotericin B deoxycholate 4.

• Infuse the catch-up dose over the standard 3-6 hours to minimize infusion-related reactions 5.

• Consider administering 1 L of normal saline 30 minutes before the infusion to reduce nephrotoxicity risk 5.

Critical Pitfall to Avoid

Do not wait until the next scheduled dose in an attempt to maintain the regular dosing interval. The consequences of subtherapeutic drug exposure in CNS fungal infections—including treatment failure, progressive infection, and death—far exceed the minimal risk of administering two doses within a 12-hour period. The mortality benefit of maintaining adequate antifungal therapy is well-established, with survival rates dramatically improved when appropriate therapy is given without delay 1, 6.