In the quest for solutions to modern antibiotic resistance, researchers at Goethe University Hospital in Frankfurt, together with their colleagues from European Synchrotron, the ESRF (Grenoble, France) and the EMBL Heidelberg are turning back to the past—and finding hope in an old, often-overlooked drug. Using X-ray nanofluorescence at the ESRF, they have uncovered how the rarely used antibiotic nitroxoline can fight back against drug-resistant bacteria. Their findings, published in Nature Communications, could spark renewed medical interest in the forgotten drug as a potential weapon against hard-to-treat infections.
Five years ago at Goethe University Hospital in Frankfurt, a patient in the intensive care unit was battling with a stubborn urinary tract infection. Despite multiple rounds of antibiotics, nothing seemed to make a difference. Then, as a last resort, doctors turned to an old drug from the 1960s—nitroxoline, typically reserved for uncomplicated urinary tract infections (UTIs). To their surprise, it worked.
Doctor and researcher Stephan Göttig was investigating this drug. “I realised that the potential of nitroxoline is huge towards multidrug-resistant Gram-negative bacteria, so we started studying its spectrum and mechanism”, he explains.
Targeting hospital pathogens
Nitroxoline is only used in a handful of countries today, after the rise of newer antibiotics and lack of clinical research. In Germany, where Göttig and the first author of the paper, Elisabetta Cacace were based (Cacace has now moved to ETH Zurich), it is an approved drug and it is still commonly prescribed for uncomplicated UTIs. However, it is not included in the WHO’s essential medicines list nor is it FDA approved in the US. “New pharmaceutical compounds are difficult to market, so it is useful to repurpose existing antibiotics”, explains Cacace.
Göttig and Cacace investigated more than a thousand isolates of different Gram-negative bacteria that nitroxoline could potentially fight against. Gram-negative bacteria have an outer membrane that can block many antibiotics and even some immune system components. They focused on Enterobacteriaceae, a group of bacteria that includes notorious hospital pathogens such as Klebsiella pneumoniae and Escherichia coli.
Read more on ESRF website