Rapid investigation of New Delhi metallo-beta-lactamase (NDM)-1-producing Providencia stuartii in hospitals in Romania
This report describes the results of an epidemiological and genomic study carried out in six hospitals in Romania to determine the extent of the spread of Providencia stuartii carrying blaNDM-1.
Most of the 74 submitted P. stuartii isolates were resistant to penicillins, cephalosporins, carbapenems, amikacin and ciprofloxacin. Almost all the isolates were associated with infections (with decreasing frequency) lower respiratory tract infection, urinary tract infection, multiple sites/systemic infection, bloodstream infection, skin and soft tissue infection, thus showing the clinical relevance of the detected multidrug-resistant P. stuartii isolates for hospitalised patients.
We identified four multi-hospital clusters including isolates from December 2021 to September 2023, which were detected over more than a year pointing to ongoing and sustained spread of P. stuartii carrying blaNDM-1 within the healthcare system in Romania. Clusters included isolates from up to four hospitals and three different regions indicating interregional spread. The phylogenetic tree revealed that several clusters were part of distinct clades. This indicates that P. stuartii carrying blaNDM-1 had already been circulating and diversifying in hospitals in Romania over a longer period which is in line with previous reports.
Three of the multi-hospital clusters were caused by a specific P. stuartii sequence type (ST)46 clone carrying metallo-beta-lactamase (MBL) genes. Investigating this clone in an international context showed that it had already been detected in nine countries, i.e. Bulgaria, France, Germany, Ireland, the Netherlands, Romania, Switzerland, the United Kingdom and the United States. Isolates belonging to this clone carry a large set of resistance determinants and show sustained healthcare-associated and interregional transmission in Romania for more than a year. This suggests that this clone can colonise and effectively transmit between hosts and, in this study, most isolates were associated with infections. All these features are part of the criteria proposed for the definition of international high-risk clones.
Although, in European Union (EU)/European Economic Area (EEA) countries, P. stuartii carrying blaNDM-1 initially received attention when detected in relation with patient transfers from Ukraine, there is evidence of wider dissemination in Eastern Europe and the Balkan region including Bulgaria (published genomic analysis), Greece (published study), Hungary (reported epidemiological links), North Macedonia (reported epidemiological link), Romania (this report) and Serbia (described epidemiological link). Nevertheless, evidence is still limited at this stage and further studies are required to determine the extent of spread of P. stuartii in Eastern Europe and the Balkan region, and the emergence and persistence of P. stuartii high-risk clones. From a public health perspective, however, current evidence regarding the spread of P. stuartii, including sustained transmission in hospitals in Romania, is sufficient for a warning regarding the potential of P. stuartii carrying MBL genes to further disseminate throughout healthcare systems in the EU/EEA and the related adverse consequences for patients.