Variation in Target Attainment of Beta‐Lactam Antibiotic Dosing Between International Pediatric Formularies

Abstract

As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. Beta‐lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dosing recommendations from the major pediatric reference sources and tries to answer the questions: Does beta‐lactam dose heterogeneity matter? Does it impact pharmacodynamic target attainment? For three important severe clinical infections—pneumonia, sepsis, and meningitis—pharmacokinetic models were identified for common for beta‐lactam antibiotics. Real‐world demographics were derived from three multicenter point prevalence surveys. Simulation results were compared with minimum inhibitory concentration distributions to inform appropriateness of recommended doses in targeted and empiric treatment. While cephalosporin dosing regimens are largely adequate for target attainment, they also pose the most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin, and meropenem doses as potentially requiring review/optimization in order to preserve the use of these agents in future.

Simultaneous pharmacokinetic/pharmacodynamic (PKPD) assessment of ampicillin and gentamicin in the treatment of neonatal sepsis

“…Both drugs were simulated to be infused over 5 min. As ampicillin dose recommendations vary across formularies 23 and severity of infection, additional simulations were also carried out with the highest proposed dose (100 mg/kg) using infusion rates of 5 min and, to explore prolonged infusion, also with infusion rates of 1 h, 2 h and continuous infusion.…”

“…Ampicillin dosing recommendations vary across guidelines and depend on the severity of the infection. 23 Figure S2 shows the difference in target attainment of the upper and lower end of dose recommendations (50 and 100 mg/kg dosing) when given by 5 min short infusion. Figure S3 shows the scenario of extending the infusion time from 5 min to 1 h and 2 h along with a continuous infusion.…”

A Train-the-Trainer Simulation Program Implemented Between Two International Partners

“…There is wide variation in both brand and generic medications on a country-by-country basis, an essential component for ensuring the fidelity of scenario design and implementation. Beyond this, even when there are commonalities, there remain differences in dosing regimens that must be accounted for, especially as it relates to pediatric dosing ( 24 ).…”

Antibiotic Therapy, Antibiotic Resistance, Drug-Induced Pathomorphosis, and Evolutionary Medicine

“…Of course, some attempts to introduce systemic solutions to control antibiotic resistance have been made. We can also mention the principle of division into nosocomial and community-onset infections [22,23,24,25], the principles of the formulary system [26,27,28,29,30,31,32], and the creation of an infection control team, with a special role for clinical pharmacologists and epidemiologists. Moreover, it is not just an epidemiologist, it is a hospital epidemiologist, because we realize that the out-of-hospital and in-hospital environment are completely different ecosystems, and the infection progression in these cases has its own peculiarities.…”