Kate Johnson

May 20, 2014

BARCELONA, Spain — Bloodstream infections caused by Enterobacteriaceae are more common than those caused by Staphylococcus aureus, but hospital stays are longer and mortality rates are higher with S aureus infection, new research shows.

Around the world, Enterobacteriaceae resistance to cephalosporins is currently increasing, whereas methicillin resistance is in decline, said investigator Andrew Stewardson, MD, from the infection control program at the University of Geneva.

"We hope these results will help inform analyses of the health-economic burden of antimicrobial resistance," he told Medscape Medical News.

Dr. Stewardson presented study results here at the 24th European Congress of Clinical Microbiology and Infectious Diseases.

In the multicenter retrospective cohort study, the researchers assessed 606,649 acute-care admissions at 10 European hospitals that lasted more than 2 days.

Of the 1048 bloodstream infections caused by S aureus they identified, 163 were resistant to methicillin (MRSA) and 885 were susceptible. Of the 2460 infections caused by Enterobacteriaceae, 360 were resistant to third-generation cephalosporins and 2100 were susceptible.

Third-generation cephalosporin resistance was defined as nonsusceptibility to ceftazidime or to cefotaxime, ceftriaxone, or cefpodoxime.

The primary outcomes of length of hospital stay and in-hospital mortality rate were calculated for the resistant and susceptible strains of S aureus and Enterobacteriaceae bloodstream infections, after adjustment for patient age and sex, emergent or elective admission, hospitalization in the previous year, comorbidities, admission to the intensive care unit, and surgical procedures.

Overall, mortality rates were higher with S aureus infection than with Enterobacteriaceae infection for resistant strains (22.1% vs 16.1%) and susceptible strains (16.8% vs 10.1%).

Likewise, hospital stays were longer with S aureus infection than with Enterobacteriaceae infection for resistant strains (13.33 vs 9.28 days) and susceptible strains (11.54 vs 5.87 days).

For patients infected with S aureus, mortality risk was not significantly greater with resistant strains than with susceptible strains (adjusted hazard ratio [aHR], 2.38 vs 1.82).

However, for patients infected with Enterobacteriaceae, mortality risk was significantly greater with resistant strains (aHR, 1.79 vs 1.16).

This last point should be interpreted be with caution, given the small numbers of Gram-positive bacteria, said session chair Susan Huang, MD, associate professor and medical director of epidemiology and infection prevention at the University of California, Irvine in Orange.

"More work is needed to confirm if this is true, given that other equally well-adjusted studies have found a difference," she told Medscape Medical News.

However, overall, the study "is striking, in that they found that the frequency of resistant Gram-negatives, for which treatment is increasingly scarce, has surpassed MRSA," she said. "Given the seriousness of these infections and the likelihood that initial antibiotics will not work against these bacteria, it is not surprising that patients require prolonged medical therapy and have worse outcomes. Learning how best to prevent these infections will require us to be increasingly better stewards of our antibiotics."

The differences between S aureus and Enterobacteriaceae in terms of mortality and hospitalization are also striking, said David Melnick, MD, vice president of clinical development at AstraZeneca.

An important variable that was not accounted for in this analysis is the time to initiation of "adequate therapy," defined as an antibiotic with activity against the isolated pathogen, said Dr. Melnick, who did not attend the presentation.

"We know that a delay in therapy increases mortality," he told Medscape Medical News. "The incidence of MRSA is so high that it is likely that patients who presented with Gram-positive cocci in blood cultures were immediately treated with an anti-MRSA antibiotic. In contrast, because it is less common, the initiation of therapy with an anti-extended-spectrum beta-lactamase antibiotic may have been delayed."

Dr. Stewardson agrees. The most important reason for the difference in outcomes between susceptible and resistant strains is that the initiation of appropriate antibiotics for resistant strains is often delayed until antibiotic susceptibility results are known, he explained. "And it is fair to say that we have a more difficult time predicting which patients have resistant Enterobacteriaceae than which have methicillin-resistant S aureus."

The study was funded by Pfizer. Dr. Stewardson and Dr. Huang have disclosed no relevant financial relationships. Dr. Melnick is an employee of AstraZeneca.

24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID): Abstract O192. Presented May 13, 2014.


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