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

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.

Impact of a Change in Antibiotic Prophylaxis on Total Antibiotic Use in a Surgical Intensive Care Unit

“…Some groups of antibiotics seem to have a higher risk of causing collateral damage than others. Quinolones, for example, are linked with isolation and infection with MRSA and Gram-negative bacilli [12][13][14]. Thirdly, confounding factors could act in both directions and also mask a positive effect of antibiotic restriction even in an unadjusted before-after comparison.…”

Impact of a Reduction in the Use of High-Risk Antibiotics on the Course of an Epidemic of Clostridium difficile-Associated Disease Caused by the Hypervirulent NAP1/027 Strain

“…Segmented regression analysis for interrupted time series was used to determine the significance of the differences in levels and slopes over time due to (1) infection control strengthening and (2) antibiotic optimization. This type of analysis provides a methodologically acceptable alternative for the assessment of long-term effects on an outcome attributable to a specific intervention [17,18]. The level and trend of the preintervention segment serve as controls for the postintervention segment.…”

Impact of an Antimicrobial Stewardship Program on Antimicrobial Utilization, Bacterial Susceptibilities, and Financial Expenditures at an Academic Medical Center

“…While we did not evaluate this relationship in our study, statistical correlations between fluoroquinolone use and MRSA rates in our institution have been established previously. 22,23 This phenomenon has also been described in a study by Madras-Kelly and colleagues with levofloxacin restriction leading to 50% reduction in MRSA. 24 These reports suggest that the decrease in MRSA rates is correlated with decrease in fluoroquinolone use.…”