A brand-new class of aminoglycoside antibiotic with an elimination half-life of four hours is designed for intravenous administration. A clinical experiment compares two distinct dosage schedules: a lower dose administered three times per day and a greater dose administered once per day. In both regimens, the total daily dose per kilogram of body weight (mg/kg/day) is the same. The graph below shows the monitoring of serum medication levels in both groups: (extended interval) dosing, Green: multiple-daily dosing, MIC: minimum inhibitory concentration] It is found that both regimens are effective against gram-negative pathogens, with clinical improvement occurring slightly earlier on average with once-daily dosing. Which of the following best explains the efficacy of once-daily dosing despite the short half-life of this antibiotic?

Question

A brand-new class of aminoglycoside antibiotic with an elimination half-life of four hours is designed for intravenous administration. A clinical experiment compares two distinct dosage schedules: a lower dose administered three times per day and a greater dose administered once per day. In both regimens, the total daily dose per kilogram of body weight (mg/kg/day) is the same. The graph below shows the monitoring of serum medication levels in both groups: (extended interval) dosing, Green: multiple-daily dosing, MIC: minimum inhibitory concentration]  It is found that both regimens are effective against gram-negative pathogens, with clinical improvement occurring slightly earlier on average with once-daily dosing.  Which of the following best explains the efficacy of once-daily dosing despite the short half-life of this antibiotic?

Quizplus · Accepted Answer

Eductional Objective: The concentration of the medicine at the target location and the duration of the microorganisms' exposure to the drug are the two main parameters affecting how effective antimicrobial drugs are. Depending on the specific agent, these characteristics may or may not contribute equally to medication effectiveness. Generally speaking, antibiotics may be divided into two groups based on which aspect is more significant: 
Concentration-dependent killing: Antibiotics with this pattern of activity (such as aminoglycosides and fluoroquinolones) have a long-lasting, suppressive impact on bacterial growth after a brief exposure, which increases killing power when drug levels are maximum at the site of infection. The antibacterial activity increases with the peak medication level in relation to the minimum inhibitory concentration (MIC). In order to maximize bacterial killing, higher-dose, extended-interval (i.e., once-daily) regimens are routinely utilized.
Time-dependent killing: Antibiotics with this pattern of activity, such as beta-lactams (penicillins, cephalosporins, and clindamycin), have few long-lasting side effects and rely on prolonged exposure times to be effective. When serum concentrations are higher than the MIC for an extended length of time, they are more efficient. Therefore, more frequent, multiple-daily dosing regimens are used to maintain plasma concentrations greater than the MIC for as long as possible.

A Brand-New Class of Aminoglycoside Antibiotic with an Elimination Half-Life