Friday, January 20, 2023

Massachusetts DPH: First Detection Of Gonorrhea Strain With Resistance To 5 Classes of Antibiotics



In the 80-year history of antibiotics, one truth has been apparent from almost the start; given enough time - and particularly with repeated exposure - bacteria can evolve to become resistant to antimicrobials.

Even before penicillin could be rolled out for clinical use in 1941, a β-lactamase (Penicillinase) was identified by researchers Abraham and Chain in a sample of Gram-negative E. coli in 1940 (cite).

Over the next couple of decades penicillinase resistance spread to other bacteria, which required the creation of newer generations of the drug (such as Methicillin in 1959), that were resistant to these enzymes.

Methicillin resistance emerged in the UK only 2 years later, and while it is no longer used, we retain its name in the term MRSA (Methicillin-resistant Staphylococcus aureus) (cite).

One of the earliest, and most important uses for penicillin was in curing gonorrhea. But by the 1970s penicillin/tetracycline resistant forms of Neisseria gonorrhoeae began to appear in the United States, and eventually cephalosporins  replaced them as the first-line treatment for gonorrhea.

In 1993, the CDC also recommended the use of fluoroquinolones (i.e., ciprofloxacin, ofloxacin, or levofloxacin) to treat gonorrhea, as they were relatively cheap, effective, and allowed for a 1 dose treatment.

But in less than a decade, fluoroquinolone-resistant N. gonorrhoeae (QRNG) emerged out of Asia and began showing up in Hawaii and then California (see MMWR Increases in Fluoroquinolone-Resistant Neisseria gonorrhoeae --- Hawaii and California, 2001).
In 2007, the CDC announced Fluoroquinolones No Longer Recommended for Treatment of Gonococcal Infections, leaving just one class of antibiotics - the cephalosporins - still recommended and available for the treatment of gonorrhea.

As of 2020, the CDC recommends a single 500 mg intramuscular dose of ceftriaxone for uncomplicated gonorrhea, but the incidence of antibiotic resistant gonorrhea continues to rise around the world.

Yesterday the Massachusetts Department of Public Health announced the nation's first (2) detections of highly resistant gonorrhea, which showed some degree of resistance to 5 classes of antibiotics, including ceftriaxone

While both cases were ultimately cured, we've seen warnings for years (see 2011's The Path Of Increased Resistance and Going, Going, Gonorrhea) that our armamentarium against this all-too-common STD was eroding. 

First the press release from the MDPH (clinicians will want to follow the link to the alert), after which I'll have a brief postscript. 

Department of Public Health announces first cases of concerning gonorrhea strain

1/19/2023 Department of Public Health

BOSTON — The Department of Public Health (DPH) today announced it has detected a novel strain of gonorrhea in a Massachusetts resident that showed reduced response to multiple antibiotics and another case with genetic markers that indicate a similar drug response.
This is the first time that resistance or reduced response to five classes of antibiotics has been identified in gonorrhea in the United States.

Both cases in Massachusetts were successfully cured with ceftriaxone, the antibiotic currently recommended to treat gonorrhea. To date, no direct connection between the two individuals has been identified.

Gonorrhea is a bacterial sexually transmitted infection. It may present without symptoms, and if left untreated, can result in pelvic inflammatory disease, infertility, and other health problems.

This strain of gonorrhea has been previously seen in Asia-Pacific countries and in the United Kingdom, but not in the US. A genetic marker common to these two Massachusetts residents was also previously seen in a case in Nevada, though that strain retained sensitivity to at least one class of antibiotics. Overall, these cases are an important reminder that strains of gonorrhea in the US are becoming less responsive to a limited arsenal of antibiotics.

The Massachusetts cases were detected by DPH’s State Public Health Laboratory as part of disease surveillance activities. Field epidemiologists in DPH’s Division of Sexually Transmitted Disease Prevention are conducting contact tracing to determine if other individuals have acquired this infection. Working with the US Centers for Disease Control and Prevention (CDC) and local hospitals and health centers, DPH is expanding its testing of gonorrhea specimens for evidence of this strain in other patients.

DPH has issued an alert to clinicians and laboratories to raise awareness of this new strain. The alert recommends increased use of laboratory culture testing for individuals with symptoms of gonorrhea to detect antibiotic resistance and reminds providers of the process for submission of gonorrhea specimens to the State Public Health Laboratory to support DPH’s and CDC’s surveillance of further resistance in this organism. This alert also reinforces the CDC’s recommendation to use high doses of the antibiotic ceftriaxone for the treatment of all gonorrhea cases and to perform follow-up tests to ensure all patients with gonorrhea are successfully treated.

“The discovery of this strain of gonorrhea is a serious public health concern which DPH, the CDC, and other health departments have been vigilant about detecting in the US,” said Public Health Commissioner Margret Cooke. “We urge all sexually active people to be regularly tested for sexually transmitted infections and to consider reducing the number of their sexual partners and increasing their use of condoms when having sex. Clinicians are advised to review the clinical alert and assist with our expanded surveillance efforts.”

Gonorrhea has been increasing in Massachusetts and nationally, adding to concerns about the potential spread of this strain which is more difficult to treat. In Massachusetts, laboratory-confirmed cases of gonorrhea have increased 312% since a low point of 1,976 cases in 2009 to 8,133 in 2021. Nationally, confirmed cases have risen by 131% between 2009 and 2021, with 696,764 cases reported in the US in 2021 according to preliminary data released by the CDC.

Each year we draw a little closer to a dreaded, but highly plausible `post-antibiotic era', where even common infections become resistant to most antibiotics, and something as simple as a scraped knee, or elective surgery, could be deadly.

And while antibiotics still work today for most infections, for tens of thousands of people every year, that `post-antibiotic era' is already here. According to a recent report from the CDC:

In the 2019 report, the last year comprehensive healthcare and community data were available to calculate, CDC estimated that more than 2.8 million antimicrobial-resistant infections occur in the U.S. each year, with more than 35,000 people dying as a result. 

While I cover AMR topics occasionally in this blog, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about the growing global threat of AMR.

You'll also want to check out the CIDRAP-ASP Youtube Channel, which has more than 24 hours of lectures and webinars on Antimicrobial stewardship.