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Antibiotic restriction, not deep cleaning, appears to have halted C. difficile epidemic
Widespread overuse of fluoroquinolone antibiotics like ciprofloxacin appears to have been the primary driver of the Clostridium difficile epidemic in the U.K., according to new research.
Investigators concluded that restriction of fluoroquinolone antibiotics, rather than deep cleaning and other infection control measures, led to significant reductions in the incidence of C. difficile infections.
“Alarming increases in U.K. hospital infections and fatalities caused by C. difficile made headline news during the mid-2000s and led to accusations of serious failings in infection control,” Derrick W. Crook, MD, professor of microbiology at the University of Oxford, said in a press release. “Emergency measures such as ‘deep cleaning’ and careful antibiotic prescribing were introduced and numbers of C. difficile infections gradually fell by 80% but no one was sure precisely why. Our study shows that the C. difficile epidemic was an unintended consequence of intensive use of an antibiotic class, fluoroquinolones, and control was achieved by specifically reducing use of this antibiotic class, because only the C. difficile bugs that were resistant to fluoroquinolones went away.”
To determine whether it was antibiotic restriction or hospital infection control measures that achieved the significant decline in C. difficile infections (CDIs) after 2006, Crook and colleagues evaluated regional and national data on CDI incidence and antimicrobial prescriptions from 1998 to 2014. They also evaluated whole genome sequences from 4,045 national and international C. difficile isolates to estimate the incidence of CDIs caused by strains resistant or susceptible to fluoroquinolone.
They hypothesized that CDIs caused by fluoroquinolone-resistant strains would have declined faster if the outbreak was stopped by antibiotic restriction, and that secondary transmitted infections of both resistant and susceptible strains would decline at the same rate if the outbreak was stopped by infection control measures.
First, they determined that prescribing of fluoroquinolone and cephalosporin strongly correlated with CDI incidence compared with overall antibiotic prescribing.
Additionally, they found that the reduction of regional CDIs was largely driven by reductions of CDI strains that were resistant to fluoroquinolone. About 67% of CDIs in Oxfordshire were fluoroquinolone-resistant in September 2006, which fell to about 3% by February 2013 (annual incidence risk ratio [IRR] = 0.52; 95% CI, 0.48-0.56 vs. susceptible strains, annual IRR = 1.02; 95% CI, 0.97-1.08). Four distinct genotypes of fluoroquinolone-resistant CDIs declined.
Furthermore, secondary transmitted CDIs caused by fluoroquinolone-resistant strains declined significantly regardless of hospital contact (P < .0001), while secondary transmitted CDIs caused by fluoroquinolone-susceptible strains showed no change regardless of hospital contact (P > .2).
“Reducing the type of antibiotics like ciprofloxacin was, therefore, the best way of stopping this national epidemic of C. difficile and routine, expensive deep cleaning was unnecessary,” Crook said in the press release. “However it is important that good hand hygiene continues to be practiced to control the spread of other infections. These findings are of international importance because other regions such as North America, where fluoroquinolone prescribing remains unrestricted, still suffer from epidemic numbers of C. difficile infections.”
Mark H. Wilcox
“Our results mean that we now understand much more about what really drove the U.K. epidemic of C. diff infection in the mid-2000s,” Mark H. Wilcox, MD, FRCPath, professor of medical microbiology at the University of Leeds, said in the press release. “Crucially, part of the reason why some C. diff strains cause so many infections is because they find a way to exploit modern medical practice. Similar C. diff bugs that affected the U.K. have spread around the world, and so it is plausible that targeted antibiotic control could help achieve large reductions in C. diff infections in other countries.”
The evidence provided in this report that restriction of fluoroquinolone antibiotics was the most important factor in reducing CDIs is “compelling,” but caution should be exercised in interpreting the results “given the retrospective, quasi-experimental nature of the study,” Curtis J. Donskey, MD, professor of medicine at Case Western Reserve University School of Medicine, and staff physician at the Geriatric Research, Education and Clinical Center at Louis Stokes Veterans Affairs Medical Center in Cleveland, Ohio, wrote in a related editorial. “Epidemic C. difficile strains sometimes decline in the absence of antibiotic restriction,” and randomized trials of fluoroquinolone restriction for CDI control are therefore still needed, he wrote.
However, the findings “might herald a new era in which antimicrobial stewardship interventions for C. difficile infection outbreaks are informed by data on antimicrobial susceptibility of epidemic strains,” he concluded. – by Adam Leitenberger
Disclosures: Wilcox reports he has received grants and personal fees from Actelion, Cubist, Astellas, Merck, Sanofi-Pasteur, Summit, Biomerieux and Qiagen; personal fees from Optimer and Synthetic Biologics; and grants, personal fees and other funding from Alere. Donskey reports grants from Clorox, Merck, GOJO, EcoLab and Altapure. Please see the full study for a list of all other researchers’ relevant financial disclosures.