Dorkina Myrick, MD, PhD

“Some experts say we are moving back to the pre-antibiotic era. No. This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry. A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s cough could once again kill.”

–   Dr. Margaret Chan, World Health Organization

Fever. Heart palpitations. Difficult, rapid, shallow breathing. Confusion. Abdominal pain. Inability to urinate. Kidney failure. Multiple organ failure. Death. These symptoms are typically associated with septic shock, an often fatal condition for patients infected with antibiotic-resistant bacteria. Media outlets worldwide stunned the world with recent news of a woman’s death from septic shock after she unsuccessfully battled an infection from an antibiotic-resistant strain of Klebsiella pneumoniae bacteria. The woman had recently traveled from India to the United States, where her condition rapidly deteriorated after her arrival. Although the patient was aggressively treated, she was resistant to 26 different antibiotics.

Unfortunately, these deaths are no longer isolated incidents as antibiotic-resistant infections cause illnesses in approximately 2 million people and kill 23,000 annually in the United States, alone. According to a recent United Kingdom Department of Health report, antimicrobial resistant (AMR) organisms (which include bacteria, viruses, fungi, and parasites) kill at least 10,000 annually. This rate is predicted to increase to 10 million by the year 2050 without steps for effective health intervention such as education, improved hygiene, reducing antibiotic abuse and overuse, new medications, better surveillance, and more accurate and precise diagnostics.

The post-antibiotic era is here.

Developing nations such as India are impacted harshly by AMR, where a number of factors including poverty, high rates of antibiotic use and abuse, and poor AMR surveillance converge to make fighting this scourge an extreme challenge. As such, India could greatly benefit from a low-cost diagnostic system that could aid in quickly identifying and documenting AMR cases.

Scientific Reports, a subsidiary of the journal Nature, cited a low-cost system that can be used to test strains of bacteria to evaluate the effectiveness of several different antibiotics. This process is known as antibiotic susceptibility testing (AST). Traditionally, samples of bacteria placed in 96 well microtiter testing plates in the presence and absence of varying concentrations of antibiotics. The plates are then incubated so that the bacteria can grow and the added antibiotics have time to work optimally. The paper references this as a broth microdilution method of AST. Samples are later assessed to determine the Minimum Inhibitory Concentration (MIC) – or, the least concentrated amount of antibiotic deemed necessary to inhibit bacterial growth. Trained scientists then examine the plates. The presence of turbidity – or cloudiness – within the wells represents the growth of bacteria that is resistant or not hindered by the presence of antibiotics. Increasing levels of well clarity demonstrate that antibiotics are working to kill bacteria in those wells.

The problem with this method is that properly trained experts may not always be available to set up the test and evaluate the results of the broth microdilution test. Additionally, the system is vulnerable to variability in assessment and reporting of results among observers. Furthermore, data collection is poor or non-existent. Finally, there is no guarantee that data is consistently stored in a uniform manner that might yield opportunities for useful long-term surveillance and epidemiological tracking.

The solution? A more accurate, precise, and user-friendly AST method (provided that some training is needed to set up the test) in which data can be preserved for further scientific study. The paper describes a system in which microtiter plates are illuminated by light-emitting diodes (LEDs). A smartphone is mounted above the microtiter plate containing bacterial and antibiotic samples. Images of the microtiter plates are captured and transmitted to a computer server that calculates the MIC of the samples in less than one minute. Data is then stored and maintained for future surveillance and epidemiologic tracking. This study showed that the drug susceptibility of Klebsiella pneumonaie to 17 different antibiotics could be interpreted with greater than 99% accuracy.

In hindsight, this method would not likely have saved the life of the unfortunate woman whose antibiotic-resistant infection originated in India. However, the use of rapid, user-friendly, low-cost AMR diagnostics in poor and developing nations at high AMR risk may very well have utility for streamlining and targeting the development of new antimicrobials in the future on a global scale.

Categories: MSP3