Antibiotic resistance is perhaps the greatest public health threat we face today. Pathogens long thought to be conquered by medicine are back, and wreaking more havoc than ever in an increasingly defenseless society. Even the newest antibiotics are rapidly losing their effectiveness.
The situation is undoubtedly dire, but major efforts in clinical labs, hospitals, and other organizations could have a significant impact in addressing this crisis. In many countries, antibiotic use is now occurring more responsibly. Antimicrobial stewardship programs are helping to ensure that antibiotics are only used when truly warranted, and that time isn’t wasted on antibiotics to which an infection is already resistant.
One of the most important tools for dealing with this challenge is rapid molecular testing. Assays that quickly identify not only the cause of an infection, but also any relevant resistance markers, can inform treatment so patients do not spend extended periods on treatments that may be unnecessary or ineffective.
Health Crisis
Experts attribute 700,000 deaths each year to drug-resistant infections, and evidence suggests that number could swell to 10 million by 2050, according to a British health report. In its first report on the situation, the World Health Organization warned that medicine could be entering a post-antibiotic era. The report states that carbapenem-resistant Klebsiella pneumoniae, a strain resistant to the treatment used as a last resort, can be found throughout the world. In some countries, this type of K. pneumoniae is actually more common than the non-resistant pathogen.
Public health agencies and infectious disease experts have begun to issue warnings about the most urgent drug-resistant microbes. These microbes include C. difficile, N. gonorrhoeae, methicillin-resistant S. aureus (MRSA), carbapanem-resistant Enterobacteriaceae, and tuberculosis, among others. Just in the United States, MRSA is responsible for more deaths each year than the combined toll of Parkinson’s, homicide, emphysema, and HIV/AIDS.
Also of concern is that more pathogens are being found to have resistance to multiple treatments — and in some cases they are resistant to all medications. In 2011, the IDSA Emerging Infections Network polled infectious disease experts for a better sense of how widespread this problem is. In the survey, 63% of respondents reported having seen at least one patient in the prior year with an infection that was resistant to all available antibiotic therapies. Given how rapidly bacteria exchange the genetic mechanisms of drug resistance, it is safe to assume that the situation now has only gotten worse.
Diagnosing Resistance
Clinical labs are on the front lines of the antibiotic resistance epidemic. It is up to them to identify the pathogen causing an infection and its drug-resistance profile — and to do so quickly enough to make a difference for a patient in need of treatment.
Demand for these services leaves clinical lab teams with a number of challenges. Generating rapid results is no easy task, as traditional culture-based tests can take days to identify a bacterium and detect resistance markers. During that time, patients whose infection is not bacterial are likely being needlessly exposed to powerful antibiotics, while patients with bacterial infections may be receiving drugs that will be ineffective due to resistance.
Another challenge is accurately tracking resistance when the markers used to identify antibiotic resistance evolve beyond recognition. Bacterial genomes change quickly, and experts have seen that resistance markers do not always persist as reliable signals. The diagnostic community is working hard to understand how best to establish resistance profiles in the face of rapid genomic evolution.
Diagnostic assays must also overcome the complexity of detecting co-infections. Many single-analyte assays are unable to identify co-infections, but as these are becoming more common among patients, it is imperative that clinical labs get access to tools that can spot them. This information is essential for predicting how drug resistance might be passed from one organism to another within a patient — and for choosing the treatment that makes the most sense for the whole landscape of infection.
Antimicrobial Stewardship
Most healthcare institutions have launched antimicrobial stewardship programs to help rein in the spread of antibiotic resistance. These initiatives typically involve clinical labs for rapid testing to guide treatment selection.
In a number of studies, clinical lab experts involved in these programs have demonstrated that nucleic acid-based testing delivers more actionable results faster than traditional assays. For example, several studies of diagnostics for blood infections have found that turnaround times can be reduced from two days or more to as little as several hours. That speedup applies to both strain identification and detection of resistance markers, giving physicians useful information that can point the way to the treatment most likely to be successful.
Of course, one of the most important elements in confronting the antibiotic resistance epidemic is avoiding the use of these drugs in patients who would not benefit. To that end, ruling out a bacterial cause is just as important as identifying a bacterial strain when it does exist. Panel-based diagnostics that multiplex all of the usual suspects can be critical for this task, allowing lab professionals to quickly surmise when an infection is not bacterial and should not be treated with antibiotics.
In addition to faster, multiplexed testing, clinical labs also need the utmost flexibility to address antimicrobial stewardship needs. Being able to choose which targets to test for in specific situations, or to quickly introduce new tests as resistance markers evolve, is essential as labs adapt to shifting needs in their patient populations.
Looking Forward
Clinical labs will be instrumental in solving the antibiotic resistance crisis, but they will require continued advances in diagnostic assays to meet their needs. Increased flexibility and speed of testing will help lab teams provide medical professionals with the most reliable, useful results for optimal patient care and treatment choice. Together with other public health efforts to improve education about antibiotics and to reduce unnecessary use of these drugs, it may well be possible to stem the tide of resistance and significantly improve the outlook for global health.
