De novo development of antibiotic resistance in patients forms a serious threat to our health. PhD student Yanfang Feng of the Swammerdam Institute for Life Sciences studied this phenomenon together with the Department of Medical Microbiology of the AMC. She found that the risk of developing resistance can be reduced by using the highest possible dose for a short amount of time or combining two types of antibiotics. This month, Yanfang Feng will defend her thesis.
‘Can a first course of unsuccessful antibiotics treatment cause resistance, leading to a persistent infection in the patient? Does the resistance that often develops in intensive care patients arise from the treatment, or from transfer of resistance genes from other microorganisms?’ This month, Yanfang Feng will defend her thesis answering above questions.
To begin with, Feng studied whether treatment with antibiotics by a primary care physician that is not successful can cause resistance, leading to problems when the patient subsequently needs to be hospitalised with a persistent infection. Yanfang used chemostat cultures of P. aeruginosa to simulate infections and treatment regimens and managed to show convincingly that at the end of the initial cure, the pathogen was able to survive and grow at concentrations of antibiotics high enough to make a follow-up treatment fail.
Next, she studied the resistance that is observed often in P. aeruginosa in intensive care patients at the end of a standard one week treatment. Can this be explained as a consequence of the treatment itself, or by the transfer of resistance genes present in the microbiota of the patient or in bacteria in the intensive care? In the latter case the IC units would have to be disinfected even better than already is standard practice or the patient would have to be screened for resistant bacteria. By again simulating usual treatment protocols in chemostats applying antibiotic concentrations that are measured in patients’ blood, she showed that de novo resistance induced in the small fraction of cells that survives can explain the resistance encountered at the end of the treatment. Treatment with a standard or low dose of antibiotics was therefore shown to be detrimental to the patient’s health.
Finally, she explored experimentally alternative strategies to achieve the treatment goal while causing as little development of resistance as possible. If a single antibiotic is to be used, the optimal strategy is using the highest dose that the patient can handle for the shortest time needed to cure the infection. Two antibiotics used in alternation or in combination clear the infection even more effectively and result in less resistance.
On 31 October, 14:00 Yanfang Feng will defend her Ph.D. thesis on ‘Optimization of treatment protocols to prevent de novo development of antibiotic resistance in Pseudomonas aeruginosa’ (promotores Brul & ter Kuile). Her daily supervisor prof. Benno ter Kuile will deliver his inaugural lecture on 23 November 2016, 16:00 in the Aula.