Plasma protein binding of fluoroquinolones affects antimicrobial activity.
OBJECTIVE
In contrast to most antimicrobial classes, there is a doubt about the impact of protein binding (PB) on the antimicrobial activity of fluoroquinolones. We set out to evaluate the suitability of previously used models for investigating the influence of PB on bacterial killing by fluoroquinolones.


METHODS
PB of moxifloxacin and trovafloxacin was determined in Mueller-Hinton broth (MHB) containing different concentrations of human serum or albumin. Bacterial growth curves of Staphylococcus aureus and Pseudomonas aeruginosa were determined in pure serum, pure MHB and MHB containing different amounts of serum or albumin. Killing of both strains at concentrations equal to the MIC was investigated for moxifloxacin and trovafloxacin in MHB and also in medium that showed PB values identical to those of pure serum.


RESULTS
Frequently used media for investigating the impact of PB, i.e. MHB containing 20% to 70% serum or 4% albumin, did not reach the level of PB achieved in pure serum or significantly hampered bacterial growth compared with pure MHB. PB in MHB containing 12% albumin was identical to that in pure serum but did not impair bacterial growth. Addition of 12% albumin significantly reduced bacterial killing by both fluoroquinolones compared with that found in pure MHB.


CONCLUSIONS
For fluoroquinolones, standard media might be insufficient to investigate the impact of PB on bacterial killing. MHB containing 12% albumin seems to be a promising medium in this context. For moxifloxacin and trovafloxacin, PB leads to significant reduction of antimicrobial activity.
Zeitlinger
Markus
M
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Austria. markus.zeitlinger@meduniwien.ac.at
Sauermann
Robert
R
Fille
Manfred
M
Hausdorfer
Johann
J
Leitner
Irmgard
I
Müller
Markus
M
D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D024841:Fluoroquinolones / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
D000890:Anti-Infective Agents; D001798:Blood Proteins; D024841:Fluoroquinolones