Using Interrupted Time Series Analysis To Assess Associations of Fluoroquinolone Formulary Changes with Susceptibility of Gram-Negative Pathogens and Isolation Rates of Methicillin-Resistant Staphylococcus aureus

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Abstract
The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant Staphylococcus aureus (MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of Pseudomonas aeruginosa (P, 0.042) and Escherichia coli (P, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (P, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of Klebsiella pneumoniae or Proteus mirabilis to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism.

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