Vancomycin resistance rates vary throughout Europe

November 2006

SAN FRANCISCO — Resistance rates have escalated during the last 10 to 15 years; however, institutional and even national differences in prevalence remain.

“Clearly there is a worldwide emergence of glycopeptide resistant enterococci [GRE], which is still limited in certain countries,” said Roland Leclercq, MD, PhD, microbiology professor at CHU Cote de Nacre, France. “Multidrug resistance is still increasing in [Enterococcus] faecium the problem is the transmission of van plasmid to other species through E. faecalis.”

In countries with high rates of methicillin-resistant Staphylococcus aureus and high rates of GRE, the problem is the emergence of vancomycin–MRSA, he explained at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, held here. Although the prevalence of vancomycin resistant enterococci remains minimal in France, and some other European countries, Leclercq remains hopeful that adapted measures will help to prevent a large spread like that seen in the United States.

“I think we have to take lessons learned from the United States’ experience, both the positive and negative,” he said. “We have a lot of countries in Europe with few cases of resistance and the thoughts in these countries should be put on these few cases to prevent the emergence of resistance.”

Global emergence of resistance

In the 1980s, vancomycin use increased about 50% each year and by 1986 GRE emerged in Europe. Researchers did not see cases in Europe until the use of avoparcin in routine breeding in food animals became more common. Avoparcin is a glycopeptide antibiotic with a gram-positive spectrum of activity. Researchers detected GRE in frozen meat and animal carcasses, which lead them to suspect the transmission of GRE in the food chain to humans, according to Leclercq. It was then that VRE spread among the European community. Specifically, in France GRE occurred in patients treated with oral vancomycin.

“The association between the use of glycopeptide avoparcin as a growth promoter for animals and the occurrence of GRE in food animals was demonstrated in several studies and formally translated in retrospective cohort studies,” he said. “Rapidly, it appeared there was a high prevalence of fecal carriage of GRE in the community in healthy people.”

Research showed that the United Kingdom had 2% to 5% of carriers, Germany had 11% in a rural area where vancomycin was not used, Belgium had a high rate of 28% and France 2% to 9%, according to Leclercq. Between 1995 and 1996, health officials in Europe began banning use of avoparcin.

Enterococci have reigned in the United States for about 15 years, with a high rate of colonization among patients in intensive care, hematology and/or dialysis. In the 1990s, GRE emerged in U.S. hospitals, starting in New York.

GRE epidemiology was different between Europe and the United States. Researchers found a decreased prevalence, with infrequent outbreaks among community and food animal reservoirs in Europe and a higher prevalence in the United States, more commonly seen in hospitals.

Furthermore, there was an inconstant emergence of multidrug resistance in Europe, and resistant and co-resistant cases were more frequent in the United States.

Researchers noticed that resistance in European countries varied from region to region and despite the ban of avoparcin, resistance is still emerging.

Danish study

Danish researchers followed resistance patterns since 1995 and found that the percentage of resistant isolates in feed animals decreased progressively, with fecal carriage in humans being nearly zero. The same was seen in France; in 1999, studies showed 5.4% of GRE in samples of chicken caeca collected in 10 slaughterhouses, which decreased progressively after the implementation of the avoparcin ban. According to Leclercq, there is a proportion of E. faecium resistant to vancomycin in Europe. In 2002 and 2003, while most countries like Spain and the Netherlands account for less than 1% to 5% of E. faecium resistance rates in blood isolates, some like Italy, Greece, England and Ireland have 10% to 25% of resistance. Likewise, rates are increasing in Germany and Belgium.

Generally, France experiences very low resistance rates, only 2% or 3%; however, indications remain that resistance is still at hand, according to Leclercq. From 2001 through 2003 French health officials declared only a few cases of VRE. Then, in 2004 and 2005, three hospitals experienced large and unusual outbreaks; hospital A had 133 cases and 49 infections in 24 departments, hospital B experienced 126 cases and three infections in 15 departments and hospital C experienced 57 cases and 11 infections in two departments.

“These outbreaks were controlled, although the strains are still present,” he said. “Researchers often experience difficulties in control of outbreaks in part due to the late implementation of control measures and rapid dissemination of GRE.”

Leclercq highlighted additional data, presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, by R. N. Jones et al., which showed the evolution of resistance in bacteremic E. faecium from 1997 through 2005. This study, called SENTRY, showed that the number of bacteremia between 1997 and 1999 and 2003 and 2005 multiplied by 2 in Asia, 3.1 in Europe and 1.6 in the United States. In Asia, 5.4% of enterococci are VRE, in Europe 11.5% (with an increasing rate between 1997 and 2005), in Latin America 12% and in the United States 69.4% are resistant, according to the abstract.

Leclercq hypothesized that some of the reasons for the later emergence of GRE in some European countries may be in part due to the replacement of E. faecalis and old E. faecium by E. faecium clones better adapted to hospitals and changes in antibiotic treatment regimens that contribute to resistance because of increased use of vancomycin for MRSA and/or Clostridium difficile treatment.

“Cases have been increasing over the years, even though there are some countries where rates of resistance are low, and in others rates are high,” he said. “This is only for E. faecium, which represents 10% to 25% of enterococci ... There is also resistance to E. faecalis.”

For more information:

• Leclercq R. Is Europe finally following the path of the U.S.? An update on recent trends in worldwide, nosocomial VRE epidemiology. Symposium 142 (K) Vancomycin-resistant enterococci: current status in Europe, U.S. and elsewhere.
• Jones RN, Turnidge J, Sader HS, et al. Evolutionary trends in antimicrobial resistances (R) in E. faecium (EFM) bacteremia: report from the SENTRY antimicrobial surveillance program (1997-2005). Abstract C2-208.
• Both presented at: 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept. 27-30, 2006; San Francisco.