Bacteria that cause diseases and infections in humans are becoming increasingly resistant to drugs that were effective in the past. The day when doctors could do nothing to cure patients’ infections might not be too far on the horizon.

Recognising the emerging threat of these extensively drug-resistant bacteria, a team of researchers led by the Departments of Pharmacy, Infectious Diseases, and Microbiology at Singapore General Hospital (SGH) has developed and studied the outcomes of a novel test and treatment approach. It combines Polymyxins, a potent antibiotic, with other antibiotics against infections caused by extensively drug-resistant Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae, that can cause death in a matter of days if not treated promptly and appropriately. Such combinations may also prevent the likelihood of bacteria becoming more resistant.

“Extensively drug-resistant infections often lead to higher medical costs, longer hospital stays and more deaths, simply because there are very limited options left to treat such infections. We are fast running out of ammunition to fight the war, especially when there is a lack of new antibiotics. A possible solution is to combine existing antibiotics which work well together for better efficacy. These antibiotics are otherwise ineffective for such infections when used alone,” said Associate Professor (Dr) Andrea Kwa, Pharmacy Clinician-Scientist, SGH, and senior author of the study.

The data of 300 SGH inpatients who received polymyxins from 2009 to 2014 for extensively drug-resistant infections were analysed for the retrospective study. Patients were divided into three treatment groups - polymyxin-only; non-guided polymyxin-based combination; and guided polymyxin-based combination. They had an average age of 60 and had existing medical conditions such as diabetes and heart diseases, which made treatment even more challenging.

Bacteria samples obtained from patients in the guided polymyxin-based combination treatment group were sent to the SGH Pharmacy Anti-infective Laboratory. The team used a Multiple Combinations Bactericidal Test (MCBT) developed by SGH in 2009 to identify different combinations of antibiotics that are synergistic and kill the bacterial, in varying concentrations. They worked with a list of 12 antibiotics that produced over 100 possible combinations. The most effective combination, was then given to the patient, and relevant information on the outcome is stored in a database, serving as a future guide for doctors when they need to prescribe antibiotics combinations for such difficult-to-treat infections.

The study showed that the overall infection-related death rate in the entire cohort of patients was more than 20 percent. However, patients who received MCBT-guided polymyxin-based combination had significantly lower infection-related death at over 10 percent compared to 25 percent and 23 percent in the non-guided polymyxin-based combination and polymyxin-only treatment groups respectively.

To shorten the current turnaround time of identifying the most effective antibiotics combination from 48 hours to less than 30 hours, Dr Lim Tze Peng, Senior Principal Pharmacist Researcher, SGH, is leading a follow-up study that leverages on an enhanced version of this newly SGH-developed test to do so.

The findings of the study supported in part by the National Medical Research Council (NMRC) Exploratory and Developmental Grant, NMRC Center Grant and the SGH Research Grants were presented at the SGH 22nd Annual Scientific Meeting in April 2017.