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Rev Esp Quimioter 2019; February 5

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine

MAITANE IBAR-BARIAIN, ALICIA RODRÍGUEZ-GASCÓN, ARANTXA ISLA, MARÍA ÁNGELES SOLINÍS, ANDRÉS CANUT-BLASCO

Objectives. To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumo-coccal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM).
Material and methods. PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful.
Results. When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study.
Conclusions. We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Rev Esp Quimioter 2019; February 5  [Full-text PDF]