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PYRAZINAMIDE PAEDIATRIC FORMULATION AS A SUBSTRATE FOR A MULTIRESISTANT ENTEROCOCCUS FAECALIS
  1. A N Silva1,2,
  2. J Marto3,
  3. A Salgado1,3,
  4. A Almeida1,3,
  5. A Duarte1,2
  1. 1Imed, Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, Lisbon, Portugal
  2. 2Microbiological Control Laboratory, Faculty of Pharmacy, Lisbon, Portugal
  3. 3Pharmaceutical Technology Laboratory, Faculty of Pharmacy, Lisbon, Portugal

Abstract

Pyrazinamide is an important antituberculosis drug, currently unavailable in dosage forms for paediatric use, and thus it is necessary to compound extemporaneous medicines. However, manipulation may cause problems due to the risk in dispensing contaminated compounded oral liquid forms.

In a previous study, pyrazinamide oral suspension in simple syrup had no activity against vancomycin resistant Enterococcus faecalis.1 The aim of this study is to confirm the mechanism of E faecalis survival in the pyrazinamide suspension.

Pyrazinamide suspensions 50mgml in simple syrup were contaminated with E faecalis CIP 106996 and the antimicrobial activity was evaluated during 21days. MuellerHinton broth and simple syrup placebo were used as controls. Drug content was assessed using HPLC. As a control, an identical set of experiments were carried out with methicillin resistant Staphylococcus aureus.

At day 21, E faecalis showed 3104cfumL in suspension and in placebo 14cfumL, whereas pyrazinamide concentration decreased 30 in the same period. Unpredictably, no pyrazinoic acid could be detected in the suspension. Despite a 6 log reduction of S aureus in suspension and placebo, by day 21 the pyrazinamide content remained unchanged. Regardless, both microorganisms survived in MuellerHinton without affecting drug content.

Results suggest that the E faecalis may use pyrazinamide as a substrate and further investigations are being performed to elucidate these findings. Nevertheless, the need for GMP application during compounding and a thorough microbiological control of oral liquid forms must be emphasized.

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