PED- Antibiotic TIPS

An 18 yro boy with severe disability due to a metabolic disorder, with a tracheostomy and night home mechanical ventilation and artificial nutricion (PEG) is admitted with tachicardia, cyanosis, interstitial-alveolar involvement on X-ray, and high inflammatory markers.

An aspirate for the tracheal cannulae shows the following:

What antibiotic would you chose:

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As the future of this child will be characterized by a growing and growing number of hospitalization, I chose a carbapenem sparing regiment.

P. aeoroginosas has intermidiate sensitivity to Pip/Tazo, so this can be overcome by increasing the dosage and the duration of infusion.

In particular, studies suggest that similar to the recently adopted interpretative criteria for Enterobacterales, piperacillin/tazobactam doses of 3.375 g or 4.5 g q6h as 0.5-hour infusions are appropriate for a susceptible criteria up to an MIC of 8/4 mg/L, although their PTA was poor at an MIC of 16/4 mg/L. Conversely, doses of 4.5 g IV q6h (3-hour infusion) or 4.5 g IV q8h (4-hour infusion) provided adequate PTA up to an MIC of 16 mg/L.

Why this? Similar to other beta-lactam antibiotics, piperacillin-tazobactam exhibits time-dependent killing and the T > MIC appears to be the best outcome predictor. Beta-lactam antibiotics display time-dependent bactericidal activity, and in general, require fT>MIC for ∼50% of the dosing interval to achieve maximal effects. Time dependence of beta-lactam antibiotics has its origin in the acylation process of the serine active site of penicillin-binding proteins, which subsequently results in bacteriostatic and bactericidal effects during the dosing interval. To enhance the likelihood of target attainment, higher doses, and prolonged infusion strategies, with/or without loading doses, have been applied to compensate for subtherapeutic levels of antibiotics related to PK-PD changes, especially in the early phase of severe sepsis.

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