Question 2

How do clinicians use PK/PD data to ensure optimal dosage regimens?

We now know that in order to optimise the use of fluoroquinolones we should use administration schedules based on PK/PD features. Due to their concentration-dependent killing action, fluoroquinolones are more effective at eradicating pathogens when given in higher doses as these achieve greater AUC_0-24/MIC values (3). We can use the PK/PD values to individualise dosage regimens according to the type of infection being treated as well as for specific patient subgroups and the type of pathogen. For example, in respiratory tract infections (RTI) it is clear that we should use the higher dose of 750 mg once daily if we suspect or demonstrate that the infection is caused by Pseudomonas aeruginosa (P. aeruginosa ). In Spain, high-dose recommended regimens include 750 mg once daily or 500 mg twice daily depending on the infection. However the PK/ PD data are similar for both regimens, therefore the 750 mg once daily schedule is easier for patients and nurses.

There is also emerging evidence suggesting that the fluoroquinolone dose should be modified when treating bloodstream infections that are caused by less susceptible pathogens. Recent results have shown that patients with infections caused by Gram-negative pathogens with MICs indicating susceptibility but at the high end of the scale, have worse outcomes than similar patients infected with pathogens with lower MICs. Those with high, but still susceptible MICs, had a longer length of stay in hospital and a longer duration of infection. Therefore, using MIC susceptibility data in patients with bloodstream infection can help to define the optimal dose to be administered in order to reduce morbidity, and potentially lower overall treatment costs (4).