BOSTON – Infections with dangerous strains of Escherichia coli and Klebsiella pneumoniae are on the rise in some European hospitals and communities, with potentially serious implications for infection control efforts, warned researchers Sept. 13 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Investigators from the Netherlands mined data from a national laboratory–based surveillance system on changes in the drug susceptibility of E. coli and K. pneumoniae from 2008 through the first 6 months of 2010. They found “a strong increase in [extended-spectrum beta-lactamase-producing] E. coli in urine outside the hospital, and a strong increase in ESBL-positive K. pneumoniae in urine in hospitals,” said Dr. Maurine A. Leverstein-van Hall of the University Medical Center Utrecht, the Netherlands.
In a second study, French investigators examining the effect of bacteremias caused by ESBL-producing enterobacteria found that there was a significant increase in the prevalence of ESBL E. coli infections from 2005 to 2008.
Somewhat surprisingly, they did not see an increase in mortality rates associated with the infections, despite inadequate initial antimicrobial therapy in about half of all patients. However, that may have been due to study limitations, said Dr. Blandine Denis of St. Louis Hospital in Paris.
Dr. Leverstein-van Hall and her colleagues looked at the overall proportion of ESBL-positive isolates in the Netherlands from 2008 through 2010 in 19 labs covering one-third of all Dutch hospital beds. They found that during the study period, the proportion of ESBL-positive E. coli increased by 1.3%, and ESBL-positive K. pneumoniae rose by 1.5%.
Similarly, the proportion of ESBL-positive blood isolates increased by 1.5% and 1.7%, respectively, from 2008 through 2010. The increases in blood isolates were seen in both hospital inpatient and outpatient settings, and the increase in urine isolates were seen in general practices, long-term care facilities, and hospital inpatient and ambulatory settings.
The researchers also looked at the adequacy of empiric therapy for sepsis according to Dutch national guidelines. At least 30% of patients with sepsis received inadequate therapy, the researchers reported at the meeting, which was sponsored by the American Society for Microbiology.
The Dutch guidelines call for second- or third-generation cephalosporins or amoxicillin-clavulanic acid plus an aminoglycoside such as amikacin for sepsis of unknown origin, or an aminoglycoside combined with other agents for sepsis with a probable focus on the urogenital or digestive tracts. However, a substantial number of patients received only cephalosporins – despite the 100% resistance rate of ESBL-positive isolates to second- or third-generation agents in that class.
Empiric therapy for gram-negative sepsis should include beta-lactam/inhibitor combinations or cephalosporins, each in combination with amikacin. A switch to carbapenems could be made if culture results yield an ESBL-positive bacterial strain, Dr. Leverstein-van Hall said.
In the single-center French study, Dr. Denis and her colleagues performed a retrospective case-control analysis comparing patients with ESBL-positive bacteremia in their hospital with ESBL-negative controls matched by date. They found that slightly less than half of all ESBL-positive patients (48%) received adequate antimicrobial therapy based on the susceptibility of their respective isolates.
In an adjusted analysis of risk factors for ESBL-positive bacteremia, the French investigators found that the only statistically significant factor was previous ESBL colonization.
They also found that there were no significant differences in hospital length of stay or in 21-day mortality rates between cases and controls, although their failure to find an effect of ESBL positivity may be related to the relatively small sample size (45 cases from 2005 to 2008) and to the retrospective design, Dr. Denis acknowledged.
The Netherlands National Institute for Public Health and the Environment funded Dr. Leverstein-van Hall’s study. Dr. Denis’ study was internally funded. Neither physician had conflicts of interest to disclose.