Mobile multidrug-resistance: A new dimension in hospital-acquired infections
More and more dangerous: multidrug-resistant Enterobacteriaceae
Researchers from the German Center for Infection Research (DZIF) have confirmed the spread of a “multidrug-resistant plasmid” in a hospital. This plasmid is a mobile genetic element which can transfer resistance against certain antibiotics to different bacteria. This mechanism can increase the risk of infectious outbreaks in hospitals, which are difficult to control.
More and more frequently, doctors and health authorities are faced with almost insurmountable challenges concerning multidrug-resistant bacteria, because different antibiotics are powerless against them. Besides Staphylococcus aureus strains, which are already known as hospital superbugs, multidrug-resistant gram-negative bacteria—Enterobacteriaceae—are playing an increasingly important role in hospital-acquired infections. In a current outbreak in a hospital in Hessen, DZIF researchers have identified clusters of different gram-negative bacteria which are resistant to carbapenem. Carbapenems are antibiotics with a broad antimicrobial spectrum, which are often used as a last resort in emergencies. The researchers identified a mobile genetic element in these strains, a plasmid, which is responsible for the multidrug-resistance. This newly discovered multidrug-resistant plasmid is transferable to different pathogens, which constitutes a completely new dimension in outbreaks. An infection with the emerging carbapenem resistant pathogens can develop into a dead-end situation with no more treatment options.
The DZIF Bioinformatics Platform, which is located in Giessen, analyses data from genome sequencing and is able to rapidly and specifically identify the genes responsible for resistance, the possible mechanisms of transfer, and the bacterial strains in an outbreak. Its central focus is to investigate mobile genetic elements, for example, in plasmids.
In the current 2014 outbreak in Hessen, researchers have been able to identify clusters of different gram-negative bacteria (Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella oxytoca, among others), which have been classified as so-called 4MRGN pathogens due to their resistance to carbapenems (KPC-2). These include multidrug-resistant gram-negative bacteria resistant to acylureido pencillins, 3rd and 4th generation cephalosporins and fluorquinolones.
An extremely mobile genetic element is likely to exist in this case, because there is an unusually broad species distribution with the same resistance pattern. To test this, 21 representative KPC-2 positive strains were sequenced in the Department of Medical Microbiology at the Justus-Liebig-University Giessen. Subsequent bioinformatic data analysis localised a blaKPC-2 gene on a certain plasmid, which was present in all of the isolates. This proves that the clusters of bacteria expressing carbapenemase were no coincidence, and were caused by a rapid spread of a specific resistance plasmid. This investigation is the first in the world to describe a nosocomial, i.e. hospital-acquired, outbreak of a mobile genetic element carrying carbapenemase. Carbapenemase is an enzyme that makes carbapenems ineffective, and hence generates resistance to this antibiotic. A multidrug-resistant plasmid which is transferable to different pathogens has superseded the classic multidrug-resistant hospital superbugs.
The situation could get particularly dangerous when a plasmid like this is transferred to pathogens such as Escherichia coli or Klebsiella pneumonia. An infection with a disease-causing pathogen which at the same time is resistant to antibiotics may possibly become untreatable. A second risk, which is difficult to assess, is the event of a cured patient taking the multidrug-resistant pathogen home. The risk for his/her environment, family and colleagues is difficult to estimate.
For the first time in the world, epidemiological connections could be ascertained within a few days during the outbreak, owing to the infrastructure of the Institute for Medical Microbiology in Giessen and the successful collaboration between federal and national authorities, the German National Reference Center (NRZ) for gram-negative hospital pathogens and the Robert Koch Institut. In this way, the outbreak source could be identified rapidly and the outbreak was stopped. Additionally, a specific diagnostic PCR method was developed and validated in collaboration with the NRZ, in order to rapidly and effectively identify and fight further outbreaks. “This example impressively illustrates the possibilities of molecular epidemiology at the DZIF,” Chakraborty underlines.
According to DZIF Spokesperson Prof Martin Krönke, the insidious spread of multidrug-resistant pathogens in Germany has become a threat of unknown scale. Public health authorities will face big problems in future due to this development.
