Antibiotic stewardship is behind the sharp drop seen across the U.K. in Clostridium difficile infections over the past decade, according to new research.
The C. difficile epidemic in the U.K. "was overwhelming and best explained to be a consequence of the emergence of resistance to quinolone," Dr. Derrick Crook of Oxford University, one of the study's authors, told Reuters Health by phone. "The drug caused an outbreak, an epidemic, and we were able to control the epidemic by reducing the use of that drug by 50%."
In 2007, the U.K. issued national policies for controlling C. difficile infection, which included recommendations to avoid clindamycin and cephalosporins and minimize use of fluoroquinolone, carbapenem and aminopenicillin, along with improved infection prevention and control measures.
Fluoroquinolone use was reduced by 50%, while C. difficile infections fell by 80%, Dr. Crook and colleagues note in The Lancet Infectious Diseases, online January 25.
To investigate which measures were responsible for reducing C. difficile infection, the researchers looked at 1998-2014 data on antimicrobial prescribing and the incidence of C. difficile infection, and also performed phylogenetic analyses of more than 4,000 national and international C. difficile isolates.
National fluoroquinolone and cephalosporin prescribing correlated more strongly with C. difficile infection incidence (cross correlations > 0.88) than overall antibiotic prescribing (cross correlations < 0.59).
There was also an association between restriction of fluoroquinolone prescribing and regional declines in fluoroquinolone-resistant isolates. In Oxfordshire, 67% of infections were fluoroquinolone resistant in September 2006, compared to 3% in February 2013.
The number of inferred secondary cases of infection with fluoroquinolone-resistant isolates dropped significantly, although there was no change in cases caused by fluoroquinolone-susceptible isolates.
Phylogenetic analysis of the C. difficile isolates suggested heavy selection of quinolone-resistant isolates in four distinct lineages, which declined across all lineages during the course of the study.
Dr. Crook urged colleagues in North America to attempt to replicate the findings. He noted that Ireland has seen a similar decline in C. difficile infection after reducing quinolone use.
"Doctors like to see evidence, and this study provides some pretty strong evidence that we should at the very least be aggressively studying this approach to controlling C. diff," Dr. Curtis Donskey of the Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University School of Medicine in Cleveland told Reuters Health by phone.
"One of the major strengths of the study is that on a smaller scale other people have shown similar findings, that restricting of fluoroquinolones can not only reduce C. diff rates but provide a shift away from these epidemic C. diff strains," added Dr. Donskey, who wrote an editorial accompanying the study.
Restricting fluoroquinolone use would have other benefits, too, including reducing the development of other resistant pathogens, he noted.
"Physicians need to have a better understanding of the potential for adverse consequences of antibiotics," Dr. Donskey said. "We often tend to think of antibiotics as something that is potentially beneficial but with a low risk for adverse effects, and I think we need to change that mindset."
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