Is Resistance Brewing Among Streptococcus Pyogenes Isolates?

Antimicrobial resistance (AMR) is a burden to public health and health care on an international level. As an estimated 2 million Americans are infected with resistant infections and 23,000 die each year as a result, AMR is a wicked problem. Even more startling is that the costs of care and treatment for patients with resistant infections are only increasing.

A particular challenge with antimicrobial resistance and response though is the surveillance. How can we combat a problem if we’re still struggling to understand it?

American surveillance of AMR has been limited and efforts have been made to change this vulnerability to ensure several things. First, in order to respond to resistant microbes, we have to understand the scope of the problem. Second, how can we know if existing antimicrobials are working if we don’t keep an eye out for molecular shifts in microbes? In many ways, it seems that when a new resistance is identified, it’s by accident rather than through intentional and proactive surveillance.

Streptococcus pyogenes (group A Streptococcus or GAS) is one such infection that we worry will become resistant to available treatments. It is estimated that GAS causes 1.8 million severe infections and over 500,000 deaths per year globally. Currently, the recommended treatment for GAS infections is β-lactam penicillin and amoxicillin. That being said, it’s not surprising that there might be concern for the organism to develop a resistance to β-lactam antibiotics. There haven’t been any reports of such infections, but there have been instances of treatment failures, meaning that it’s likely something that’s brewing but we haven’t been able to quite catch it yet.

Unfortunately, a new study stumbled across a GAS mutation that revealed reduced susceptibility to β-lactam antibiotics—something we’ve all worried about. In June 2017, Public Health Seattle & King County (PHSKC) investigated an outbreak of GAS infections within a hospital. Working with the US Centers for Disease Control and Prevention (CDC), they stumbled across 2 identical GAS isolates that had the same deeply concerning mutation: an elevated β-lactam minimum inhibitory concentration (MICs). MIC is the lowest concentration of an antibiotic that will prevent the growth of a microorganism.

Of all the isolates taken (282 total during the outbreak, including 44 blood, 6 other sterile fluid, and 232 wound), isolates from 5 patients were assessed for further analysis. Among those patients, 80% were experiencing homelessness and also reported using injection drugs. Of the 5 isolates, 2 were particularly unique and indicated a potential mutation.

Upon a deeper analysis of these 2 identical Streptococcus pyogenes isolates (emm subtype emm43.4) was a pbp2x missense mutation (T553K), which led to a higher MIC for ampicillin and amoxicillin—8 times higher in fact. The MIC for cefotaxime was 3-fold higher.

In short, this means that what they stumbled upon was the first documented step in the GAS mutation towards β-lactam resistance. Thanks to the efforts of the CDC and the strong collaboration with PHSKC, the isolates had the whole-genome sequencing-based characterization performed and further analysis to establish this finding.

These findings and the review the patients’ comorbidities (including infections) are deeply relevant to the future of antimicrobial resistance and surveillance at even the health care-level to more rapidly identify patients at risk for extremely resistant infections.