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Medicines Update
What do I need to know about fluoroquinolones for children?
  1. Kevin Meesters1,2,
  2. Ann M Raes1,
  3. Johan G Vande Walle1
  1. 1 Department of Paediatrics and Medical Genetics, Ghent University Hospital, Gent, Belgium
  2. 2 Department of Paediatrics, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium
  1. Correspondence to Dr Kevin Meesters, Department of Paediatrics and Medical Genetics, Ghent University Hospital, Gent 9000, Belgium; Kevin.Meesters{at}uzgent.be

https://doi.org/10.1136/archdischild-2017-313513

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    Introduction

    Fluoroquinolones are potent antibiotics that are derivatives of nalidixic acid. This first quinolone molecule was discovered as a by-product of chloroquine synthesis in the 1960s. Its clinical use was hampered by a limited antimicrobial spectrum, low bioavailability and adverse effects. In the 1980s, a fluorine atom was added to the molecule of nalidixic acid, resulting in the second generation of fluoroquinolones with improved antimicrobial activity and pharmacokinetic characteristics (see table 1). Further molecular modifications resulted in the third and fourth generations of fluoroquinolones. Shortly after the marketing of ciprofloxacin in the 1990s, studies on juvenile animals found irreversible joint cartilage erosions, skeletal deformities and reduced growth following administration of ciprofloxacin. This led to class label warnings against the use of fluoroquinolones for children. Currently, probably due to the emergence of pathogens that are resistant to other antibiotics, and to treat infections for which there are only intravenous antibiotics as alternative available, fluoroquinolones are being increasingly prescribed to children. Concurrently, rising fluoroquinolone resistance is reported for different pathogens. In this article, we review essential pharmacologic considerations when prescribing systemic fluoroquinolones to children.

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    Table 1

    Overview of different fluoroquinolones

    Mode of action

    Fluoroquinolones owe their bactericidic action to inhibition of the bacterial enzymes gyrase (also called topoisomerase II) and topoisomerase IV, which are essential in cell replication of bacteria.1 For transcription, the process in which DNA is copied into RNA, the two DNA strands that are squeezed in the cell nucleus need to be separated. The point where the two strands separate is called the replication fork. Superhelical twists arise ahead of the replication fork, meaning that DNA there is increasingly twisted. The bacterial enzyme gyrase is essential in unwinding these superhelical twists during DNA replication. At the end of the cell cycle, the two interlinked strands should be separated in two daughter cells. Topoisomerase IV …

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    Footnotes

    • Funding This study was funded by Agentschap voor Innovatie door Wetenschap en Technologie (Grant No IWT/SBO 130033).

    • Competing interests None declared.

    • Provenance and peer review Commissioned; externally peer reviewed.