Tracking Susceptibility and Reducing Resistance - Fluoroquinolones at the Forefront in the Fight Against Bacterial Pathogens

29 March, 2018

Question 16

Could you discuss the use of levofloxacin against ciprofloxacin-resistant S. pneumoniae?

First, it is necessary to define fluoroquinolone-resistance among S. pneumoniae. Such resistance develops following mutations in gyrA and/or parC regions, resulting in increased MIC levels among these isolates. Ciprofloxacin, one of the first fluoroquinolones, has now been shown to be associated with a greater probability of developing pneumococcal resistance than levofloxacin. In fact, levofloxacin has been demonstrated to maintain some activity against ciprofloxacin-resistant pathogens (20). This is of interest due to the cross-resistance usually shown among the fluoroquinolones and potential avoidance of selective action. PK/PD data might support that levofloxacin can still be used to treat part of these pathogens, particularly if the 750 mg dose is used or 500 mg scheduled twice a day. Further analysis has shown that ciprofloxacin possesses very little antibacterial activity against ciprofloxacin-resistant strains while levofloxacin 750 mg rapidly killed parC mutant strains, and parC/parE mutant strains. However, PD of levofloxacin against strains with double mutations in both parC and gyrA/B and thus higher ciprofloxacin and levofloxacin MIC were also diminished highlighting the importance of preventing the development and spread of double mutants (Table5) (20,21).

Table 5. MICs and pharmacodynamic parameters of levofloxacin against ciprofloxacin-resistant Streptococcus pneumoniae

S. pneumoniae Strain Number	Ciprofloxacin MIC (μg/ml)^a	Levofloxacin MIC (μg/ml)^b	AUC/MIC Levofloxacin 500 mg dose	AUC/MIC Levofloxacin 750 mg dose
212	4	1.4	33	49
331	4	1.8	29	43
256	16	3.2	14	22
257	16	2.6	18	27

^a	Minimum inhibitory concentrations were measured by agar dilution.
^b	Minimum inhibitory concentrations were measured by macrobroth dilution in THB using 0.2 μg/ml increments.

Abbreviations:

MIC = minimum inhibitory concentration, AUC = area under the plasma concentration-time curve.

Adapted from reference (20).