Study Finds Enterobacteriaceae Mortality Lower Than Expected

CHICAGO – The prognosis for infections caused by Enterobacteriaceae that harbor Klebsiella pneumoniae carbapenemase (KPC) may not be as poor as some statistics have suggested, according to a small study of patients with bloodstream infections due to these resistant pathogens.

The 30-day mortality rate in the study of 39 patients was 13% – or roughly half to a third of that seen in previous studies – researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Moreover, 41% of the patients did not even receive an antibiotic active against KPC-positive pathogens.

"Maybe in other studies reporting such high mortality rates, it’s just that patients at baseline are very sick, and it’s not necessarily attributed to having the KPC."

"There has been a really high mortality associated with this type of infection," lead investigator Elizabeth B. Hirsch, Pharm.D., of Northeastern University in Boston, commented in an interview. "Some people are reporting from 30% to 50% mortality with this type of infection, so we were a little bit surprised at that [13% rate]."

The study also found that a greater severity of illness, as assessed by Acute Physiology and Chronic Health Evaluation (APACHE) II scores, independently predicted death in this population, which may in part explain the disparate findings, she speculated. "Maybe in other studies reporting such high mortality rates, it’s just that patients at baseline are very sick, and it’s not necessarily attributed to having the KPC."

The investigators studied 39 patients with bloodstream infections due to KPC-harboring Enterobacteriaceae treated between May 2009 and December 2010. Study results were reported in a poster session at the meeting, which was sponsored by the American Society for Microbiology.

The patients were 62 years old, on average; 54% were male and 36% were white. They had been hospitalized for a mean of 27 days, and their mean APACHE II score was 12.4.

The most common source of the bacteremia was abdominal (39%), followed by urinary (26%) and pulmonary (15%). In terms of the specific pathogen, 61.5% of patients had Klebsiella species, 36% had Escherichia coli, and 2.5% had Enterobacter aerogenes.

Overall, 13% of the patients died in the 30 days after diagnosis. In a multivariate analysis, patients with an APACHE II score of 17 or higher were more likely to die (odds ratio, 45.4; P = .013), whereas the risk of death fell with advancing age (OR, 0.9; P = .038).

"Surprisingly, a lot of these patients didn’t even receive any therapy that was active against the KPC, but they cleared their bloodstream infection [anyway]," noted Dr. Hirsch.

Specifically, 16 patients did not receive any KPC-active therapy. In this subset, the most common source of bacteremia was urinary (44%) and the 30-day mortality rate was the same as that in the cohort overall (13%).

Given the high prevalence of a urinary source of infection in this group, "if they are receiving carbapenems, which we know the KPC can hydrolyze, maybe they are getting high enough concentrations of the drug in the urine, which I guess is sort of clearing the main source of infection," she said.

Molecular analyses in the overall cohort identified 14 unique clones among the Klebsiella isolates and 7 unique clones among the E. coli isolates.

"Since we found a lower rate of mortality [than previously reported], we are kind of wondering what the virulence is associated with these isolates," Dr. Hirsch concluded. "So that’s the next step – we are going to do some analyses of the isolates to see really how virulent they are."

Dr. Hirsch reported having no conflicts of interest related to the study.

CHICAGO – The prognosis for infections caused by Enterobacteriaceae that harbor Klebsiella pneumoniae carbapenemase (KPC) may not be as poor as some statistics have suggested, according to a small study of patients with bloodstream infections due to these resistant pathogens.

The 30-day mortality rate in the study of 39 patients was 13% – or roughly half to a third of that seen in previous studies – researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Moreover, 41% of the patients did not even receive an antibiotic active against KPC-positive pathogens.

"Maybe in other studies reporting such high mortality rates, it’s just that patients at baseline are very sick, and it’s not necessarily attributed to having the KPC."

"There has been a really high mortality associated with this type of infection," lead investigator Elizabeth B. Hirsch, Pharm.D., of Northeastern University in Boston, commented in an interview. "Some people are reporting from 30% to 50% mortality with this type of infection, so we were a little bit surprised at that [13% rate]."

The study also found that a greater severity of illness, as assessed by Acute Physiology and Chronic Health Evaluation (APACHE) II scores, independently predicted death in this population, which may in part explain the disparate findings, she speculated. "Maybe in other studies reporting such high mortality rates, it’s just that patients at baseline are very sick, and it’s not necessarily attributed to having the KPC."

The investigators studied 39 patients with bloodstream infections due to KPC-harboring Enterobacteriaceae treated between May 2009 and December 2010. Study results were reported in a poster session at the meeting, which was sponsored by the American Society for Microbiology.

The patients were 62 years old, on average; 54% were male and 36% were white. They had been hospitalized for a mean of 27 days, and their mean APACHE II score was 12.4.

The most common source of the bacteremia was abdominal (39%), followed by urinary (26%) and pulmonary (15%). In terms of the specific pathogen, 61.5% of patients had Klebsiella species, 36% had Escherichia coli, and 2.5% had Enterobacter aerogenes.

Overall, 13% of the patients died in the 30 days after diagnosis. In a multivariate analysis, patients with an APACHE II score of 17 or higher were more likely to die (odds ratio, 45.4; P = .013), whereas the risk of death fell with advancing age (OR, 0.9; P = .038).

"Surprisingly, a lot of these patients didn’t even receive any therapy that was active against the KPC, but they cleared their bloodstream infection [anyway]," noted Dr. Hirsch.

Specifically, 16 patients did not receive any KPC-active therapy. In this subset, the most common source of bacteremia was urinary (44%) and the 30-day mortality rate was the same as that in the cohort overall (13%).

Given the high prevalence of a urinary source of infection in this group, "if they are receiving carbapenems, which we know the KPC can hydrolyze, maybe they are getting high enough concentrations of the drug in the urine, which I guess is sort of clearing the main source of infection," she said.

Molecular analyses in the overall cohort identified 14 unique clones among the Klebsiella isolates and 7 unique clones among the E. coli isolates.

"Since we found a lower rate of mortality [than previously reported], we are kind of wondering what the virulence is associated with these isolates," Dr. Hirsch concluded. "So that’s the next step – we are going to do some analyses of the isolates to see really how virulent they are."

Dr. Hirsch reported having no conflicts of interest related to the study.

CHICAGO – The prognosis for infections caused by Enterobacteriaceae that harbor Klebsiella pneumoniae carbapenemase (KPC) may not be as poor as some statistics have suggested, according to a small study of patients with bloodstream infections due to these resistant pathogens.

The 30-day mortality rate in the study of 39 patients was 13% – or roughly half to a third of that seen in previous studies – researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Moreover, 41% of the patients did not even receive an antibiotic active against KPC-positive pathogens.

"Maybe in other studies reporting such high mortality rates, it’s just that patients at baseline are very sick, and it’s not necessarily attributed to having the KPC."

"There has been a really high mortality associated with this type of infection," lead investigator Elizabeth B. Hirsch, Pharm.D., of Northeastern University in Boston, commented in an interview. "Some people are reporting from 30% to 50% mortality with this type of infection, so we were a little bit surprised at that [13% rate]."

The study also found that a greater severity of illness, as assessed by Acute Physiology and Chronic Health Evaluation (APACHE) II scores, independently predicted death in this population, which may in part explain the disparate findings, she speculated. "Maybe in other studies reporting such high mortality rates, it’s just that patients at baseline are very sick, and it’s not necessarily attributed to having the KPC."

The investigators studied 39 patients with bloodstream infections due to KPC-harboring Enterobacteriaceae treated between May 2009 and December 2010. Study results were reported in a poster session at the meeting, which was sponsored by the American Society for Microbiology.

The patients were 62 years old, on average; 54% were male and 36% were white. They had been hospitalized for a mean of 27 days, and their mean APACHE II score was 12.4.

The most common source of the bacteremia was abdominal (39%), followed by urinary (26%) and pulmonary (15%). In terms of the specific pathogen, 61.5% of patients had Klebsiella species, 36% had Escherichia coli, and 2.5% had Enterobacter aerogenes.

Overall, 13% of the patients died in the 30 days after diagnosis. In a multivariate analysis, patients with an APACHE II score of 17 or higher were more likely to die (odds ratio, 45.4; P = .013), whereas the risk of death fell with advancing age (OR, 0.9; P = .038).

"Surprisingly, a lot of these patients didn’t even receive any therapy that was active against the KPC, but they cleared their bloodstream infection [anyway]," noted Dr. Hirsch.

Specifically, 16 patients did not receive any KPC-active therapy. In this subset, the most common source of bacteremia was urinary (44%) and the 30-day mortality rate was the same as that in the cohort overall (13%).

Given the high prevalence of a urinary source of infection in this group, "if they are receiving carbapenems, which we know the KPC can hydrolyze, maybe they are getting high enough concentrations of the drug in the urine, which I guess is sort of clearing the main source of infection," she said.

Molecular analyses in the overall cohort identified 14 unique clones among the Klebsiella isolates and 7 unique clones among the E. coli isolates.

"Since we found a lower rate of mortality [than previously reported], we are kind of wondering what the virulence is associated with these isolates," Dr. Hirsch concluded. "So that’s the next step – we are going to do some analyses of the isolates to see really how virulent they are."

Dr. Hirsch reported having no conflicts of interest related to the study.