Study may also result in new clinical laboratory tools for determining antimicrobial resistance and efficacy of existing antibiotics
Researchers find it increasingly difficult to develop antibiotics that are effective against strains of bacteria that display antibiotic resistance—a subset of antimicrobial resistance (AMR). However, a new study provides a glimmer of hope and may spur clinical laboratories to look at this research in novel ways.
Conducted at the University of California Santa Barbara, the study looked at more than 500 antibiotic-bacteria combinations. The researchers discovered that several widely used, FDA-approved, antibiotics may be more useful than previously thought against a large range of bacterial infections, said infectious disease specialist Judy Stone, MD, in an article she penned for Forbes titled, “Why Antibiotics Fail—and How We Can Do Better.”
The researchers also discovered a common culture medium that enables a better assessment of the properties of various strains of bacteria to resist different antibiotics.
Clinical laboratories and microbiologists are tasked with plating and growing bugs to identify a specific bug, what strain of bug, and whether that strain has resistance to specific antibiotics. Thus, this research touches on what they do daily. It is something that may provide microbiologists with new approaches to detect AMR more accurately.
“We know there are a variety of reasons why antibiotics don’t work as predicted, from wrongly prescribed doses to infrequent administration, but another less noticeable reason is that lab testing can show a bacteria is susceptible to antibiotics when it’s actually not. You know, the whole in vitro (culture plate) versus in vivo (life) balance,” wrote Judy Stone, MD, infectious disease expert, in her Forbes article. Clinical laboratories may soon have a better way of identifying antibiotic resistance in deadly bacteria. (Photo: LinkedIn profile.)
UCSB Antimicrobial Study Details
Antibiotic-resistant infections are responsible for more than 32,000 deaths in the US and 1.27 million globally every year, Forbes reported. A study like this can have a far-reaching impact.
To conduct their study, Michael Mahan, PhD, Professor of Molecular, Cellular, and Developmental Biology at UCSB, and his team at the Mahan Lab on the UCSB campus, used Fisher Scientific’s Gibco Dulbecco’s Modified Eagle Medium (DMEM), a basal medium for supporting the growth of many different mammalian cells.
The DMEM predicted antibiotic effectiveness better than Mueller Hinton Broth (MHB), another growth medium from Thermo Fisher Scientific that has been used in clinical laboratories by World Health Organization (WHO) decree since 1968, Forbes reported.
Assays were run against 13 isolates from nine species of bacteria to determine the efficacy of 15 different antibiotics. Using DMEM, the team found different sensitivities in 15% of the bacterial isolates tested in vitro compared to MHB.
In Mahan’s follow-up tests, which looked at mice infected with different bacteria, MHB was accurate in 54% of test predictions while DMEM was accurate 77% of the time. Part of the reason, Mahan believes, is because DMEM is more physiologic and closer in conditions to people (in vivo), Forbes reported.
“People are not Petri plates—that is why antibiotics fail. Testing under conditions that mimic the body improves the accuracy by which lab tests predict drug potency,” said Mahan in a UCSB press release.
The Mahan Lab researchers published their findings in the journal Cell Reports Medicine, titled, “Re-evaluation of FDA-Approved Antibiotics with Increased Diagnostic Accuracy for Assessment of Antimicrobial Resistance.”
Results Look Promising
“I think it has merit. I think this study has been very well-designed … and showed that this makes clinical sense … If it bears out in humans, it will be clinically very significant,” pulmonologist Ken Yomer Yoneda, MD, Professor Emeritus, Department of Internal Medicine at UC Davis Health, told Forbes.
Though the major limitation of the study is that it was conducted on mice and not humans, Yoneda said it gives an indication of potential success with humans. “If it bears out in humans it will be clinically very significant,” he told Stone for her Forbes article.
Rodney Rohde, PhD, Professor and Chair of Clinical Lab Science Program at Texas State University also shared enthusiasm on the findings. According to Stone, “[Rohde] was ‘intrigued’ by the finding that using a physiologic media predicted ‘a change in susceptibility’ thresholds used to categorize patient isolates as susceptible or resistant.
“He was also ‘excited about the results of increasing diagnostic accuracy’ with especially difficult-to-treat organisms,” she noted.
“Rohde added that the issue of these clinical breakpoints—setting the level at which an organism is defined as ‘sensitive’ or ‘resistant’ to an antibiotic is a hot topic, undergoing considerable discussion in lab circles. Multiple agencies need to reach agreement for the standards that are used globally, both in the US and Europe,” Stone wrote.
Old Drug, New Tricks
According to the UCSB press release, “Physicians are aware of the flaws in the gold-standard test [MHB]. When recommended antibiotics do not work, they must rely on their experience to decide on the appropriate antibiotic(s) for their patients. This study provides a potential solution to address the disparity between antibiotics indicated by standard testing and actual patient outcomes.”
Infectious disease physician Lynn Fitzgibbons, MD, remarked in the UCSB press release, “Re-evaluation of FDA-approved antibiotics may be of far greater benefit than the time and cost of developing new drugs to combat antimicrobial resistance, potentially leading to significant life-savings and cost-savings.”
In her Forbes article, Stone wrote, “Pharmaceutical companies are abandoning the acute infectious disease market and few new antibiotics are in sight. Pharma is profit driven and antibiotics are simply not as lucrative as life-style drugs (like Viagra/Cialis or Rogaine for hair loss) or those for chronic diseases. So, Mahan et al.’s findings are welcome news indeed.”
Once further studies validate the UCSB study findings and allow their use in clinical settings for patient care, clinical laboratories and microbiologists may have new tools for accurately determining a bacterium’s ability to resist existing antibiotics or its susceptibility to antibiotics not currently used to treat certain infections.
—Kristin Althea O’Connor