Streck manufactures products for clinical laboratories. Together with Dr Nancy Hanson, director of the Center for Research, Anti-Infectives and Biotechnology at Creighton University, it is studying how molecular tests can complement current susceptibility test methods in hospitals, and why plasmid-mediated transmission of resistance genes is important in research.
Dr Nancy Hanson: It dates back to around five or six years ago, when I was asked by the business school at Creighton University to develop a course for business people who wanted to oversee scientists. An employee from Streck on the course couldn't believe that there was no diagnostics for these resistant superbugs. So he went back to the company and we did a couple of pilots, and they liked that. We started from there.
A conventional susceptibility test will tell the lab in most cases what antibiotics the organism is resistant to, but not what is causing the resistant phenotype. Some resistances genes, like the carbapenemase KPC, are present in an organism but are not always detected with conventional susceptibly testing.
It is important in our era of very few antibiotic choices that the lab is able to report to the physician the cause of the resistance phenotype observed, not just the phenotypic susceptibility pattern. This can only be done with a molecular test identifying the mechanism.
In addition, many resistant organisms carry multiple resistance mechanisms. In the case of resistance to beta-lactam antibiotics, an organism can carry multiple genes, leading to a multidrug-resistant phenotype. Infection control efforts can also benefit from knowing the resistance mechanisms used by the organism, as this will help determine the selective pressure in the hospital allowing the spread of the organism.
The definition of a high-risk patient varies among healthcare providers but whatever the definition, selection of the most therapeutic antibiotic for high-risk patients is essential. Molecular-screening patients prior to hospital admittance can help determine if a patient is colonised with a resistant organism and what classes of antibiotic may be most applicable in case treatment of an infection is warranted.
Surveillance is a key component for decreasing the prevalence of resistant organisms in a hospital setting - or any setting, for that matter. Emergence of resistance can be acquired through chromosomal or plasmid-encoded resistance.
If resistance is acquired through changes in the chromosomal expression of certain genes associated with resistance, or a plasmid-mediated resistance, the emergence or maintenance of resistance may be due in part to the formularies used by the hospital or physicians. Knowing those resistance mechanisms may help modify formularies used by the hospital.
Antibiotic stewardship programmes, therefore, can gain immense benefit from knowing the mechanism of resistance that a molecular test can provide.
It is imperative that phenotypic and molecular testing be used together. As mentioned before, phenotypic susceptibility testing can tell the lab what antibiotics the organism is resistant to, but not the mechanism. Molecular tests are designed by knowing what genes are associated with a resistant pattern; molecular tests can only test for what we know.
A phenotypic test can let the lab know that, if a specific molecular test is negative, either emergence of a new resistance gene is occurring or other genes not identified in the molecular test are causing the resistance.
There are two reasons why we need to know whether a resistance gene is transported via a plasmid.
First, when an organism is resistant due to a chromosomal mechanism and the organism is killed, the resistance is killed. When the organism carries the resistance gene on a plasmid, the organism can be killed but the plasmid can move to another host, thus keeping the resistance gene in bacterial populations.
Second, resistance genes on the plasmids can move among different types of bacteria, such as different genera of Gram-negative organisms. Resistance genes not normally a part of an organism's genome can now become part of their genome with the acquisition of the plasmid that carries the gene.