Question 15

Why do you think fluoroquinolone resistance among S. pneumoniae has remained relatively low and stable?

This may relate to the fluoroquinolones now available being more effective than the earliest ones. In addition, the administration regimens are more evidence-based, incorporating PK/PD data to ensure dosage schedules and duration of treatment are kept at an optimum in order to maintain efficacy while at the same time reducing the probability of resistance developing.

Another reason, and one not so clearly studied in patients, although it has been studied in vitro relates to the fitness cost of resistance (19). This means that when a pathogen develops resistance, the mutation associated with this usually results in a fitness cost to the bacterium, at least initially. This means that the resistant strain usually grows slower than the susceptible strain. While compensatory changes can lower this fitness cost, it is thought that in general resistance can’t initially increase without favorable selective conditions. Therefore, if there is a mixed population without selective pressure the susceptible isolate will win. This is another very important feature that has not been evaluated in terms of its impact on clinical use. There are obviously many factors involved in the development of resistance and not only the selective pressure of a single antibiotic.