Acute otitis media (AOM), acute bacterial rhinosinusitis (ABRS) and the lower respiratory tract infection, community-acquired pneumonia (CAP), are common childhood infections that are often treated with antibiotics. This paper evaluates the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the preferred agents, amoxicillin and amoxicillin + clavulanic acid, compared with oral cephalosporins also prescribed in AOM, ABRS, and CAP.
Interpreting susceptibility breakpoints
Antibiotic susceptibility is interpreted from the minimum inhibitory concentration (MIC), which is the lowest concentration of antibiotic that prevents visible in vitro growth after a given incubation period. However, even an antibiotic with a low MIC will not be useful if adequate concentrations cannot be achieved at the site of infection. Prescribers must, therefore, understand both the PD relationships that define goal exposure and the PK profiles of each antibiotic to predict the likelihood of reaching that goal.
- Minimum inhibitory concentration (MIC) is the lowest concentration of antibiotic that prevents visible in vitro growth after a given incubation period; MIC90 is the MIC at which 90% of bacteria in a given population are inhibited.
- The Clinical Laboratory Standards Institute (CLSI) susceptibility breakpoint is the MIC below which a given organism is deemed susceptible to a given antibiotic.
- The PK-PD susceptibility breakpoint is the MIC at which the antibiotic is expected to remain above the MIC90 for ≥50% of the dosing interval.
- A PK-PD susceptible breakpoint higher than the CLSI susceptible breakpoint indicates superior PK behaviour in vivo that may attain PD targets against pathogens reported as non-susceptible.
- A PK-PD susceptible breakpoint lower than the CLSI susceptible breakpoint suggests that in vivo drug exposure may not be adequate, even in the pathogens reported as susceptible.
Pharmacokinetic characteristics and projected pharmacodynamic exposures of selected oral beta-lactams
Oral cephalosporins: Role in therapy
Oral cephalosporins should be used with caution and reserved only as alternatives for patients who have failed or are intolerant of first-line amoxicillin-based therapy, and often in combination with other antibiotics. In addition to suboptimal exposure against the pathogens of concern, oral cephalosporins provide unnecessarily broad spectra of activity, including pathogens not associated with these infections. Preferential use of narrow-spectrum antibiotics to limit antibiotic resistance is a key component of antibiotic stewardship.
- Amoxicillin remains the oral beta-lactam with good activity against S. pneumoniae.
- Due to the evolving bacteriology of AOM and ABRS with H. influenzae becoming predominant, amoxicillin + clavulanic acid will likely emerge as a preferred therapy to provide broadened activity against H. influenzae while maintaining optimal treatment of S. pneumoniae, though this may be at a reduced dose as penicillin resistance declines.
- Oral cephalosporins should be used with caution and reserved as alternatives for patients who have failed or are intolerant of first-line amoxicillin-based therapy.
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