(Vienna, 10 January 2019) The Staphylococcus aureus bacterium is one of the commonest pathogens and can even cause sepsis. The new antibiotic dalbavancin is very effective against many bacterial pathogens. However, resistance to the antibiotic was seen to develop during the long-term treatment of a patient with an infection caused by an implanted cardiac device. A team of researchers led by infectiologists from the Division of Infectious Diseases and Tropical Medicine within the Department of Medicine I at MedUni Vienna, Manuel Kussmann and Heimo Lagler, have now described the phenotypical and genotypical mechanism of this development of resistance for the first time. The study was published in leading journal "Emerging Microbes & Infections".
Staphylococci are bacteria and are part of the normal flora on the skin of humans and animals. Approximately 20% of the Austrian population permanently carry the germ, which is often located in the nasal cavity. There are harmless variants, which only cause mild symptoms, if any at all. In serious cases, the pathogen can find its way into the bloodstream and cause endocarditis and sepsis.
A problematic strain is Staphylococcus aureus, which can be acquired outside hospital but also in hospital as a so-called "hospital-acquired infection". There are multi-resistant forms of it, which do not necessarily cause serious illness in healthy people. However, in weakened hospital patients or where the natural skin barrier is damaged, infection can result in complications. Nowadays dalbavancin, a latest generation antibiotic, is one of the drugs successfully used to treat multi-resistant bacteria. One of the advantages of this drug is its very long half-life of approximately nine days, so that intravenous treatment can be given on an outpatient basis. However, clinical experience has shown that, sooner or later, resistance develops to any therapeutic use of new antibiotics, so it was just a matter of time with this one.
A "prosthesis infection" with Staphylococcus aureus was diagnosed in the blood of a patient with complex heart disease, who had been fitted with a cardiac pacemaker. Such infections can occur following the surgical implantation of this kind of medical device but it is also possible for bacteria to find their way into the blood for whatever reason and settle on a prosthesis. The incidence of such an infection is approximately 0.5 – 2.2%. Following in-patient treatment, this patient was treated with dalbavancin on an outpatient basis to bridge the time until the pacemaker probe could be removed. However, following an initial improvement, his clinical condition worsened. Staphylococcus aureus was once again detected in his blood using a blood culture but it was now found to be resistant to the drug.
Infectiologists Manuel Kussmann and Heimo Lagler from the Division of Infectious Diseases and Tropical Medicine at the Department of Medicine I then conducted a complex microbiological study in collaboration with other departments, primarily MedUni Vienna's Division of Clinical Microbiology, investigating both the phenotypical and genotypical mechanism of development of resistance in the laboratory. Using the very latest techniques on an interdisciplinary basis, it was possible to detect a significant increase in bacterial cell wall-thickness and a change in bacterial cell division by means of electron microscopy. The genetic analysis of the whole genome of Staphylococci showed that mutations had occurred in specific gene segments.
The course of development of a potential resistance to the new antibiotic dalbavancin was thus described for the first time. The function of the specific modified genes is now being investigated in a follow-up study.
Service:
"Emergence of a dalbavancin induced glycopeptide/lipoglycopeptide non-susceptible Staphylococcus aureus during treatment of a cardiac device-related endocarditis"
Manuel Kussmann, Matthias Karer, Markus Obermueller, Katy Schmid, Wolfgang Barousch, Doris Moser, Marion Nehr, Michael Ramharter, Wolfgang Poeppl, Athanasios Makristhatis, Stefan Winkler, Florian Thalhammer, Heinz Burgmann and Heimo Lagler.
Doi.org/10.1038/s41426-018-0205-z