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Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid, Spain

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Abstract

The objective of our study was to evaluate by pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the antimicrobials used for the treatment of invasive pneumococcal disease (IPD) in adults, including meningitis, are adequate considering the susceptibility profile of S. pneumoniae in Spain after the implantation of PVC13 vaccine. Pharmacokinetic parameters of benzylpenicillin and cefotaxime were obtained from the literature, and susceptibility data of invasive S. pneumoniae strains recovered in 2017 (post-PCV13 vaccination period) were provided by the Public Health Regional Laboratory of Madrid. We have also studied levofloxacin because it is used to treat pneumococcal pneumonia previously to be diagnosed as bacteremic pneumonia. Monte Carlo simulation was used to estimate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). All doses of benzylpenicillin except 2 mU q6h provide a high probability of treatment success for MIC values ≤ 1 mg/L; 4 mU q4h is even useful for MIC values up to 4 mg/L. This high dose, used for the treatment of meningitis, also provides high probability of treatment success for MIC ≤ 0.5 mg/L. At the susceptibility EUCAST breakpoint (≤ 0.5 mg/L), cefotaxime provides a high rate of PD target achievement, even at the lowest dose (1 g q8h). For meningitis, 2 g q6h ensures probabilities of target attainment ≥90% for MIC up to 1 mg/L. Our study confirms that after the implementation of PCV13 vaccine, the treatment with benzylpenicillin and cefotaxime provides high probability of the therapy success of IPD, including meningitis.

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Funding

This work was supported by the University of the Basque Country UPV/EHU (GIU17/32).

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Authors and Affiliations

  1. Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy; Lascaray Research Centre, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain

    Maitane Ibar-Bariain, Arantxazu Isla, María Ángeles Solinís & Alicia Rodríguez-Gascón

  2. Bioaraba Health Research Institute, Vitoria-Gasteiz, Spain

    Arantxazu Isla, María Ángeles Solinís, Andrés Canut & Alicia Rodríguez-Gascón

  3. Public Health Regional Laboratory of the Community of Madrid, General Directorate of Public Health, Community of Madrid, Madrid, Spain

    Juan Carlos Sanz-Moreno

  4. Microbiology Service, Osakidetza Basque Health Service, Araba University Hospital, Vitoria-Gasteiz, Spain

    Andrés Canut

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  1. Maitane Ibar-Bariain
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  2. Arantxazu Isla
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  3. María Ángeles Solinís
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Correspondence to Alicia Rodríguez-Gascón.

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Ibar-Bariain, M., Isla, A., Solinís, M.Á. et al. Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid, Spain. Eur J Clin Microbiol Infect Dis 40, 2145–2152 (2021). https://doi.org/10.1007/s10096-021-04255-w

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