Clinical Outcomes and Trends of Patients with Carbapenem-Resistant Infections

Antimicrobial resistance is becoming an increasingly difficult problem on a global level; the statistics are startling and the complexity of the issue makes response measures that much more critical. As we search for new medications and try to strengthen surveillance, the burden on health care providers can easily be forgotten.

A new study sought to address the clinical outcomes and risk factors of patients who were unfortunately infected with a carbapenem-resistant infection. The study was conducted in a single-center tertiary-care hospital in St. Louis, Missouri, at which researchers reviewed differences between patients with carbapenem-resistant Enterobacteriaceae (CRE) or carbapenem-resistant non-Enterobacteriaceae (CRNE). Patients with positive CRE or CRNE cultures found from January 2012 to December 2015 were analyzed. However, researchers sought to avoid inclusion of those with colonization instead of true infection, so patients without sepsis and cystic fibrosis were excluded, as were those who were discharged without having received targeted antimicrobial therapy.

The researchers noted that “the primary outcome was hospital survival. We hypothesized that survival would be lower for patients with CRNE sepsis compared to CRE sepsis due to the virulence of this group of organisms and known differences in mechanisms of resistance.”

A total of 448 of the 84,955 patients who met inclusion criteria were ultimately included in the final analysis. The investigators found that CRNE infections were more common but that there were some distinguishable characteristics between the groups. Investigators noted that there were significantly more genitourinary infections in patients with CRE sepsis, while there were significantly more respiratory tract infections in patients with CRNE sepsis. Those with CRE sepsis also tended to have longer delays in the start of their antimicrobial treatment while those with CRNE sepsis were more likely to be medically ventilated and in the intensive care unit (ICU), while also having been recently hospitalized. Furthermore, patients with CRNE sepsis had a median length of stay of 20 days, while those with CRE sepsis were hospitalized for roughly 17 days. Additionally, there were several factors which contributed to poor survival (overall hospital mortality was 21.7% though), which included increased age, ICU admission, and health care-associated infection. The median age between the groups was the same (58) and a majority of the CRNE cases were admitted to the ICU (33%) versus about 12% in CRE patients.

Ultimately, the researchers noted epidemiologically relevant changes in carbapenem-resistant gram-negative sepsis between the observed years.

“Infections caused by carbapenem-resistant Enterobacter spp. are rising, whereas infections caused by carbapenem-resistant K. pneumoniae are decreasing. These changes appear to be occurring in the absence of appreciable increases in the incidence of infections caused by carbapenemase-producing organisms. Dramatic increases in the incidence of CRE infection appear to be causing a shift in the burden of clinically significant carbapenem-resistant gram-negative disease," the authors write.

Such findings are not only relevant for medical intervention and management of patients with carbapenem-resistant gram-negative sepsis, but also infection control efforts to prevent the spread of resistant organisms. Surveillance data reported to the Centers for Disease Control and Prevention (CDC) in 2013 found that 4.6% of acute care hospitals reported at least one CRE health care-associated infection, and that the proportion of Enterobacteriaceae that were CRE actually increased from 1.2% to 4.2% between 2001 and 2011. The growing burden of CRE and CRNE underscores the importance of understanding epidemiological characteristics and patient outcomes to strengthen medical response measures.

Antimicrobial resistance is a unique and complex burden upon society, which means that our understanding of such infections must be holistic and tireless.