Reducing drug resistance in the clinic

Over the past years, the injudicious use of antibiotics has led to a dramatic increase in the emergence of drug resistance. According to European health authorities, multi-drug resistant gram-negative bacteria (MDR-GNB) infections resulted in thousands of deaths and millions of hospitalisations. These statistics illustrate the urgent need of developing novel strategies for minimising the emergence and transmission of resistant microbial species.

The EU-funded R-GNOSIS (Resistance in gram-negative organisms: studying intervention strategies) project is assessing the efficacy and effectiveness of cutting-edge interventions in reducing MDR-GNB transmission through five international clinical intervention studies.

The first of these studies entail the development of a point-of-care-testing strategy for diagnosing uncomplicated urinary tract infection to improve the overall management of antibiotic prescription. The efficacy of another rapid diagnostic test is being assessed for the detection of MDR-GNB in faeces as a means of providing antibiotic prophylaxis in colorectal surgery.

In a trial with patients carrying intestinal MDR-GNB, R-GNOSIS proceeded with decolonisation using high concentrations of topical antibiotics and subsequent gut recolonisation with faecal microbiota. This procedure has already shown efficacy against recurrent infections with Clostridium difficile and this approach is now being pursued in patients carrying MDR-GNB.

During an international trial in 15 intensive care units R-GNOSIS is evaluating the effectiveness of decolonisation using topical antibiotics to prevent infections with and transmission of MDR-GNB.

An additional ongoing study includes the contact isolation of patients with ESBL-producing Enterobacteriaceae in general hospital wards using alcohol hand rub dispensers.

Collectively, these studies will provide the material for studying fundamental biological aspects of the MDR-GNB-host interaction in the presence and absence of antibiotic selection pressure. Researchers are also investigating the mechanisms associated with the emergence and persistence of drug resistance, and are combining modelling approaches to predict plasmid transmissibility.

R-GNOSIS will offer necessary evidence for using antibiotics as a preventive strategy in intensive care patients as well as for patients after abdominal operations. The decolonisation-recolonisation data will also provide innovative approaches for dealing with persistent potentially life-threatening infections.