Antibiotic Resistance Predicted to Take Big Toll in Surgery

Lara C. Pullen, PhD

October 19, 2015

The safety and efficacy of surgical procedures and immunosuppressive chemotherapy may be threatened by increasing antibiotic resistance, according to a new analysis. In both settings, patients commonly receive antibiotic prophylaxis, but the drugs are losing efficacy.

Aude Teillant, MS, from the Department of Ecology and Evolutionary Biology, Princeton University, New Jersey, and colleagues published the results of their literature review and modeling study online October 15 in the Lancet Infectious Diseases. The meta-analyses included randomized controlled trials performed in clinical settings from 1968 to 2011.

The researchers studied the ability of antibiotic prophylaxis to prevent infections and deaths from infections for the 10 most common surgeries and blood cancer chemotherapy regimens in the United States. They then calculated the additional number of infections and deaths related to infections that would occur under different scenarios of reduced efficacy of antibiotic prophylaxis.

The investigators also used National Health Safety Network data and existing studies to estimate the proportion of infections caused by bacteria that are resistant to standard antibiotics currently in use for prophylaxis.

"Teillant and colleagues describe a future in which patients who need surgery or chemotherapy can no longer be protected from life-threatening infections by antibiotic prophylaxis. All clinicians have a responsibility to prevent this situation from becoming our patients' reality by supporting efforts to combat antimicrobial resistance worldwide and by supporting antimicrobial stewardship at home," writes Joshua Wolf, MBBS, from St Jude Children's Research Hospital in Memphis, Tennessee, in an accompanying editorial.

Dr Teillant and colleagues found that in the United States, from 38.7% to 50.9% of pathogens causing surgical site infections and 26.8% of pathogens causing infection after chemotherapy are resistant to standard prophylactic antibiotics.

"Our estimates suggest that currently recommended antibiotic prophylactic regimens might have insufficient activity against the most commonly reported pathogens that cause infections after surgeries and cancer chemotherapy. This very high proportion of resistant pathogens might be partly explained by the disproportionate effect of prophylactic antibiotics on susceptible pathogens, leaving a residual subset of resistant pathogens, or by the emergence of resistant pathogens replacing a proportion of susceptible pathogens. For example, a substantially higher prevalence of fluoroquinolone resistance has been reported in rectal cultures obtained after fluoroquinolone-based prophylaxis (20.4%) than in those obtained before prophylaxis (12.8%)," the authors write.

Future Grim

The researchers estimate that an additional 30% reduction in the efficacy of antibiotic prophylaxis would likely result in an additional 120,000 infections and 6300 infection-related deaths per year. A 10% reduction in efficacy would likely result in 40,000 additional infections and 2100 additional deaths, and a 70% reduction in efficacy would result in an estimated 280,000 additional infections and 15,000 additional deaths each year.

The increasing prevalence of multidrug-resistant bacterial strains is even more concerning, given the lack of development of new antibiotics targeting these organisms.

Moreover, the effect of the increasing rate of antibiotic resistance on surgical site infection has not been well investigated. As a consequence, there are insufficient data to support or discourage the use of broader-spectrum regimens for surgical procedures or cancer chemotherapy.

"We also acknowledge that antibiotic prophylaxis might not be 100% effective, since organisms endogenously resistant to prophylactic antibiotics could cause infections and are included in these estimates. Furthermore, the proportion of resistant organisms does not account for all patients receiving prophylaxis; therefore, the resistance percentage in those who developed infections could be high," the authors explain.

They suggest that future studies should focus on optimizing antibiotic prophylaxis recommendations within the context of increasing rates of resistance. Such studies may become especially important if physicians use alternative or last-resort prophylaxis regimens to combat increasing rates of infection.

Study Limitations

The investigators acknowledge that the historical nature of the meta-analyses means that the results of some of the older studies may not be applicable to hospital settings with improved infection control procedures.

Moreover, although infection rates vary greatly between low-risk and high-risk patients, the meta-analyses did not distinguish between such patient groups. In addition, the researchers assumed that the proportion of organisms resistant to standard surgical prophylaxis was the same for various surgical procedures.

One coauthor has been a research consultant for Welch Allyn and 3M; has received personal fees from Welch Allyn; grants from VA Health Services Research and Development Service and the Agency for Healthcare Research and Quality; and expenses from the Infectious Diseases Society of America, the American Society for Microbiology, and the Society for Healthcare Epidemiology of America to organize or present at national meetings outside the submitted work. Another coauthor was supported by the Science and Technology Directorate, Department of Homeland Security, to Princeton University. Two other coauthors were supported by the Global Antibiotic Resistance Partnership, which is supported by the Bill & Melinda Gates Foundation. The other authors and Dr Wolf have disclosed no relevant financial relationships.

Lancet Infect Dis. Published online October 15, 2015. Abstract

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