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Serum Bactericidal Activity of Levofloxacin and Moxifloxacin Against Strains of Streptococcus pneumoniae With First-Step Mutations

Stein, Gary E. PharmD*; Smith, Curtis PharmD†; Kim, Grace MD*; Dybas, Leslie MD*; Chung, Won MD*; Nicolau, David P. PharmD‡

Infectious Diseases in Clinical Practice:
doi: 10.1097/IPC.0b013e3181f6990f
Original Articles
Abstract

Background: The increase in minimal inhibitory concentrations (MICs) to fluoroquinolones (FQ) among Streptococcus pneumoniae is of global concern. Strains with first-step mutations have a higher likelihood of subsequent mutations that can lead to complete resistance and clinical failure.

Methods: Patients admitted to the hospital with a diagnosis of community-acquired bacterial pneumonia were equally randomized to receive levofloxacin (Levo; 750 mg intravenously for 60 minutes) or moxifloxacin (Moxi; 400 mg intravenously for 60 minutes) once daily for treatment of their infection. After the third dose, blood samples were obtained at the end of the infusion (peak), at 12 hours (midpoint), and before the next dose (trough). The bactericidal activities of Levo and Moxi at each time point were determined by time-kill methodology against S. pneumoniae isolates including those with first-step mutations.

Results: Peak concentrations of both Levo and Moxi produced bactericidal activity by 6 hours against a wild-type strain of S. pneumoniae. Against a parC mutation, both FQs exhibited bactericidal activity with the peak and midpoint concentrations. Only Moxi exhibited antibacterial activity with the trough serum concentrations. Against the parE mutant, similar kill curves were observed by the peak and midpoint concentrations for Levo and Moxi. With the trough concentration, Moxi continued to produce bactericidal activity, whereas no inhibition was observed with Levo. Against the gyrA mutants, neither FQ exhibited bactericidal activity. Moxi exhibited greater inhibitory activity than Levo against one of these strains, although regrowth occurred by 24 hours with the midpoint and trough concentrations. We did not detect any changes in the MICs of these study isolates to either of these FQs during our time-kill experiments.

Conclusions: Using concentrations achieved in serum with 750 mg of Levo and 400 mg of Moxi, we would expect comparable treatment outcomes for these 2 respiratory FQs against susceptible isolates of S. pneumoniae including those with first-step mutations. Alternative antimicrobial agents should be used to treat S. pneumoniae strains with intermediate susceptibility (Levo MICs > 2 mg/L and Moxi MICs > 0.5 mg/L) to fluoroquinolones.

Author Information

From the *Michigan State University, East Lansing; †Ferris State University, Lansing, MI and ‡Center for Anti-infective Research, Hartford Hospital, Hartford, CT.

Correspondence to: Gary E. Stein, PharmD, Michigan State University, B323 Life Science Bldg, East Lansing, MI 48824. E-mail: steing@msu.edu.

This study was supported by the Sparrow Hospital/Michigan State University Internal Medicine Residency Program (GK and WC). Additional funding was provided by Ortho-McNeil Pharmaceuticals and Schering-Plough.

The authors have no conflicts of interest to disclose.

© 2011 Lippincott Williams & Wilkins, Inc.