Study Highlights Impact of CREs on Mortality and Hospital Stays in Lower-Income Countries

A study conducted by an international team of investigators highlights the burden of antibiotic resistance on low-income and middle-income countries (LMICs), which have been underrepresented in researching carbapenem resistance and its health outcomes.

The new study, published in The Lancet Infectious Diseases, details findings of the PANORAMA study, a multinational prospective cohort study at 16 tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, where microbiology laboratories were able to detect carbapenem-resistant Enterobacteriaceae (CRE). Among bacteria with resistance to last-line antibiotics such as carbapenems, species in the Enterobacteriaceae family, including Klebsiella pneumoniae, Klebsiella oxytoca, and Providencia alcalifaciens have become an emerging health threat impacting rates of in-hospital mortality and length of hospital stays.

In an interview with Contagion^®, study co-author Andrew J. Stewardson, MBBS, noted that there have been few studies on the impact of carbapenem resistance on health outcomes, particularly outside of high-income settings. “There are clearly many important health priorities to address in low- and middle-income countries. It's challenging to prioritize interventions for problems such an antimicrobial resistance when there's very little information about its impact on patient outcomes,” he explained. “Our study fills a gap in the literature by quantifying the impact of carbapenem resistance on outcomes of patients with invasive infections in low- and middle-income countries. Most previous studies have been performed in high income countries.”

The study recruited 297 patients from August 1, 2014, to June 30, 2015, 123 with CRE bloodstream infections and 174 with carbapenem-susceptible Enterobacteriaceae (CSE). Investigators founds that the crude mortality for CRE patients was 35% compared with 20% for CSE patients. In addition, carbapenem resistance was associated with an increased length of hospital stay of 3.7 days, higher probability of in-hospital mortality, and a decreased probability of being discharged alive. The study team also found that patients with CRE bloodstream infections were more likely than those with CSE infections to have had health care exposure, intensive care, exposure to antibiotics, and surgery within the month prior to infection, highlighting the problem of health care-associated infections.

The rate of septic shock was similar between the 2 patient groups. Among patients with CSE bloodstream infections and CRE bloodstream infection, those in the latter group were more likely to experience persistent bacteremia as well as recurrent bacteremia.

The investigators note that, although their findings were not surprising, the new study provides data on a well-known problem on which there has been little research. “Carbapenem resistance is associated with increased mortality and morbidity among patients with bloodstream infections due to Enterobacteriaceae in LMICs,” said Stewardson. “There is a need to improve surveillance of antimicrobial resistance in LMICs, but this must this be accompanied by coordinated strategies to limit the impact of resistance on patients.”

With the new findings comes justification for allocating additional resources to improving laboratories, infection control, antibiotic stewardship programs, and other efforts to address antibiotic resistance in LMICs, say the authors. In addition, the research team emphasized the need for including data from LMICs in estimates of the global clinical burden of antibiotic resistance, rather than extrapolating such estimates from high-income countries.