Avoiding the further spread of carbapenem-resistant Acinetobacter baumannii
Persistent and adaptable: The carbapenem-resistant pathogen Acinetobacter baumannii.
Researchers from the German Center for Infection Research (DZIF) at the University of Cologne have conducted a study on the carbapenem-resistant bacterium Acinetobacter baumannii. The pathogen was identified in 2017 by the World Health Organisation (WHO) as one of twelve multidrug-resistant pathogens for which new active agents are urgently needed. Among these twelve pathogens, three were classified as "critical", requiring the highest priority in antibiotic research—including carbapenem-resistant Acinetobacter baumannii. The scientists have analysed a worldwide collection of more than 300 samples of the bacterium to determine their molecular epidemiology, i.e. their relationships to each other. The results have now been published in the scientific journal mBio.
Acinetobacter baumannii is a gram-negative bacterium that is widespread throughout the world and repeatedly leads to outbreaks of infection in intensive care units, posing a serious risk especially for patients with a weakened immune system and severe underlying diseases. It causes ventilator-associated pneumonia, bloodstream infections, skin and soft tissue infections, meningitis and urinary tract infections.
The pathogens are persistent and adaptable
The bacterium can survive on hospital furniture or bed linen if hygiene measures are not carried out optimally and can thus be transmitted from patient to patient. In addition, the pathogen is capable of rapidly developing new antibiotic resistances, for example to the so-called carbapenems: broad-spectrum antibiotics from the group of beta-lactams that are effective against a large number of pathogenic bacteria. This increasingly poses a major public health problem, because carbapenems have long been considered reserve antibiotics against Acinetobacter baumannii; without these active agents, there are often few to no therapeutic options left. Already in 2017, the WHO issued a list of twelve multidrug-resistant pathogens for which new active agents are urgently needed. Among the three pathogens with the highest priority is the carbapenem-resistant bacterium Acinetobacter baumannii (CRAB). The majority of these pathogens are traced back to a few successful bacterial clones, i.e. lineages or families. This phenomenon is intensified by international patient transport and migration. In 2010, a worldwide collection of CRAB was already investigated at the University of Cologne with regard to their molecular epidemiology, i.e. their relationship to each other. Eight larger, globally distributed groups called "international high-risk clones" (ICs) were identified.
Worldwide distribution of carbapenem-resistant A. baumannii traces back to a few lineages
Researchers from the German Center for Infection Research (DZIF) at the University of Cologne have now provided an update of the former study results on the molecular epidemiology of CRAB. The scientists examined clinical samples of 313 isolates of the bacterium from 114 study sites in 47 countries and five world regions (Africa, Asia, Europe, Latin and North America), which were collected between 2012 and 2016 in frame of the global Tigecycline Evaluation and Surveillance Trial (TEST) study and made available by IHMA, USA. The number of isolates was proportional to the population size in each country.
First, the following question was investigated: Which carbapenem resistance-mediating genes are present in the isolates and how are they distributed within the collection? To this end, first the species Acinetobacter baumannii, the presence of resistance genes and subsequently the resistance to carbapenems were confirmed in all 313 isolates in the laboratory. The genome of the isolates qualified in this way was finally sequenced using Whole Genome Sequencing (WGS). Based on this, the scientists were able to assign the isolates to the different ICs using various typing methods.
Result: The study confirmed that CRABs worldwide can largely be assigned to the eight known relationship groups, the ICs. A ninth group (IC9) appeared for the first time. IC2 is the most widespread group and can be found on every continent; its frequency has increased significantly compared to 2010. CRAB isolates found in patients in initially completely unrelated regions, e.g. Brazil and Poland, could be assigned to the same family group. Regional characteristics have also emerged, for example IC5 is predominant in Latin and South America.
"Worldwide, the carbapenem-resistant bacterium Acinetobacter baumannii poses a major threat, especially to critically ill patients in intensive care units. In case of infection, the selection of a suitable drug is a challenge because of the existing resistances. In addition to the search for new active agents, we must do our utmost to maintain the necessary hygiene measures in the hospital to prevent further spread of the dangerous pathogens," says one of the study's two first authors, Carina Müller from the University of Cologne, whose laboratory work was funded by the DZIF as part of a doctoral scholarship.
