antibiotic

china-has-a-big-problem-with-super-gonorrhea,-study-finds

China has a big problem with super gonorrhea, study finds

antibiotic, antibiotic resistance, bacterial infection, CDC, ceftriaxone, china, drug resistance, gonorrhea, health, Science, sexually transmitted infection, sti / /

Alarming —

Drug-resistant gonorrhea is a growing problem—one that doesn’t heed borders.

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A billboard from the AIDS Healthcare Foundation is seen on Sunset Boulevard in Hollywood, California, on May 29, 2018, warning of a drug-resistant gonorrhea.

Enlarge / A billboard from the AIDS Healthcare Foundation is seen on Sunset Boulevard in Hollywood, California, on May 29, 2018, warning of a drug-resistant gonorrhea.

Health officials have long warned that gonorrhea is becoming more and more resistant to all the antibiotic drugs we have to fight it. Last year, the US reached a grim landmark: For the first time, two unrelated people in Massachusetts were found to have gonorrhea infections with complete or reduced susceptibility to every drug in our arsenal, including the frontline drug ceftriaxone. Luckily, they were still able to be cured with high-dose injections of ceftriaxone. But, as the US Centers for Disease Control and Prevention bluntly notes: “Little now stands between us and untreatable gonorrhea.”

If public health alarm bells could somehow hit a higher pitch, a study published Thursday from researchers in China would certainly accomplish it. The study surveyed gonorrhea bacterial isolates—Neisseria gonorrhoeae—from around the country and found that the prevalence of ceftriaxone-resistant isolates nearly tripled between 2017 and 2021. Ceftriaxone-resistant strains made up roughly 8 percent of the nearly 3,000 bacterial isolates collected from gonorrhea infections in 2022. That’s up from just under 3 percent in 2017. The study appears in the CDC’s Morbidity and Mortality Weekly Report.

While those single-digit percentages may seem low, compared to other countries they’re extremely high. In the US, for instance, the prevalence of ceftriaxone-resistant strains never went above 0.2 percent between 2017 and 2021, according to the CDC. In Canada, ceftriaxone-resistance was stable at 0.6 percent between 2017 and 2021. The United Kingdom had a prevalence of 0.21 percent in 2022.

Ceftriaxone is currently the first-line treatment for gonorrhea because Neisseria gonorrhoeae has spent the past several decades building up resistance to pretty much everything else. As the CDC notes, in the 1980s, the drugs of choice for gonorrhea infections were penicillin and tetracycline. But the bacteria developed resistance. By the 1990s, the CDC was forced to switch to a class of antibiotics called fluoroquinolones, including ciprofloxacin (Cipro). But fluoroquinolone-resistance developed, too, and resistance to Cipro is now widespread. In the early 2000s, the CDC began having to tweak the recommendations as resistance spread to new places and populations.

Resistance rising

By 2007, the agency switched to cephalosporins, including cefixime. In 2010, the CDC updated the treatment again, recommending that doctors combine cephalosporins with one of two other types of antibiotics—azithromycin or doxycycline—to try to thwart the development of resistance. But, it also was no use. Two years later, in 2012, the CDC updated recommendations when cefixime resistance developed. In 2020, azithromycin was also abandoned. The cephalosporin ceftriaxone is the last drug standing in the US to treat gonorrhea infections.

Resistance of gonococcal isolates to ciprofloxacin, penicillin, tetracycline, azithromycin, cefixime, ceftriaxone, and spectinomycin—13 Gonococcal Resistance Surveillance Program sentinel sites, China, 2022.

Enlarge / Resistance of gonococcal isolates to ciprofloxacin, penicillin, tetracycline, azithromycin, cefixime, ceftriaxone, and spectinomycin—13 Gonococcal Resistance Surveillance Program sentinel sites, China, 2022.

In China, the swift spread of ceftriaxone-resistance isolates is alarming. The data stems from 2,804 isolates, representing 2.9 percent of all cases reported in China during 2022. Those figures come from 13 of the country’s 19 provinces. While the overall prevalence of ceftriaxone-resistance isolates was 8.1 percent among the 2,804 isolates, five of those 13 provinces had prevalence rates above 10 percent. Three provinces had prevalence rates above 25 percent. In all, 18 isolates were resistant to all the antibiotics tested except for a bygone antibiotic called spectinomycin, which is discontinued in the US and elsewhere.

The study has limitations. For one, the reported number of gonorrhea cases are very likely an undercount of actual cases. Beyond gaps in reporting, many people with gonorrhea have no symptoms and, as such, don’t seek treatment. Additionally, the isolates the researchers did have represented less than 3 percent of reported cases, so it’s possible the prevalence rates don’t represent the isolates of the entire country. Also, the researchers didn’t have detailed case data that might help identify specific risk factors for resistance development, such as the antibiotic treatments patients had. The authors did note that antibiotics are only given by prescription in China.

“These findings underscore the urgent need for a comprehensive approach to address antibiotic-resistant N. gonorrhoeae in China, including identifying factors contributing to this high resistance rate, especially in provinces where the percentage of gonococcal isolates resistant to ceftriaxone is >10 percent,” the authors write.

But they also note that this is not just an alarming finding for China but also a “pressing public health concern” for the entire world. “These resistant clones have spread internationally, and collaborative cross-border efforts will be essential to monitoring and mitigating its further spread,” they write.

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Experimental antibiotic kills deadly superbug, opens whole new class of drugs

Acinetobacter baumannii, antibiotic, antibiotic resistance, bacteria, carbapenem-resistant Acinetobacter baumannii, CRAB, drug development, Gram-negative bacteria, health, LPS, roche, Science / /

fingers crossed —

The relatively large molecule clogs a transport system, leading to lethal toxicity.

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This Scanning Electron Microscope image depicts several clusters of aerobic Gram-negative, non-motile <i>Acinetobacter baumannii</i> bacteria under a magnification of 24,730x.” src=”https://cdn.arstechnica.net/wp-content/uploads/2024/01/10096-800×544.jpg”></img><figcaption> <p><a data-height=Enlarge / This Scanning Electron Microscope image depicts several clusters of aerobic Gram-negative, non-motile Acinetobacter baumannii bacteria under a magnification of 24,730x.

A new experimental antibiotic can handily knock off one of the world’s most notoriously drug-resistant and deadly bacteria —in lab dishes and mice, at least. It does so with a never-before-seen method, cracking open an entirely new class of drugs that could yield more desperately needed new therapies for fighting drug-resistant infections.

The findings appeared this week in a pair of papers published in Nature, which lay out the extensive drug development work conducted by researchers at Harvard University and the Swiss-based pharmaceutical company Roche.

In an accompanying commentary, chemists Morgan Gugger and Paul Hergenrother of the University of Illinois at Urbana-Champaign discussed the findings with optimism, noting that it has been more than 50 years since the Food and Drug Administration has approved a new class of antibiotics against the category of bacteria the drug targets: Gram-negative bacteria. This category—which includes gut pathogens such as E. coli, Salmonella, Shigella, and the bacteria that cause chlamydia, the bubonic plague, gonorrhea, whooping cough, cholera, and typhoid, to name a few—is extraordinarily challenging to kill because it’s defined by having a complex membrane structure that blocks most drugs, and it’s good at accumulating other drug-resistance strategies

Weighty finding

In this case, the new drug—dubbed zosurabalpin—fights off the Gram-negative bacterium carbapenem-resistant Acinetobacter baumannii, aka CRAB. Though it may sound obscure, it’s an opportunistic, invasive bacteria that often strikes hospitalized and critically ill patients, causing deadly infections worldwide. It is extensively drug-resistant, with ongoing emergence of pan-resistant strains around the world—in other words, strains that are resistant to every current antibiotic available. Mortality rates of invasive CRAB infections range from 40 to 60 percent. In 2017, the World Health Organization listed it as a priority 1: critical pathogen, for which new antibiotics are needed most urgently.

Zosurabalpin may just end up being that urgently needed drug, as Gugger and Hergenrother write in their commentary: “Given that zosurabalpin is already being tested in clinical trials, the future looks promising, with the possibility of a new antibiotic class being finally on the horizon for invasive CRAB infections.”

An international team of researchers, led by Michael Lobritz and Kenneth Bradley at Roche, first identified a precursor of zosurabalpin through an unusual screen. Most new antibiotics are small molecules—those that have molecular weights of less than 600 daltons. But in this case, researchers searched through a collection of 45,000 bigger, heavier compounds, called tethered macrocyclic peptides (MCPs), which have weights around 800 daltons. The molecules were screened against a collection of Gram-negative strains, including an A. baumannii strain. A group of compounds knocked back the bacteria, and the researchers selected the top one—with the handy handle of RO7036668. The molecule was then optimized and fine-tuned, including charge balancing, to make it more effective, soluble, and safe. This resulted in zosurabalpin.

Deadly drug

In further experiments, zosurabalpin proved effective at killing a collection of 129 clinical CRAB isolates, many of which were difficult-to-treat isolates. The experimental drug was also effective at ridding mice of infections with a pan-resistant A. baumannii isolate, meaning however the drug worked, it could circumvent existing resistance mechanisms.

Next, the researchers worked to figure out how zosurabalpin was killing off these pan-resistant, deadly bacteria. They did this using a standard method of subjecting the bacteria to varying concentrations of the antibiotic to induce spontaneous mutations. For bacteria that developed tolerance to zosurabalpin, the researchers used whole genome sequencing to identify where the mutations were. They found 43 distinct mutations, and most were in genes encoding LPS transport and biosynthesis machinery.

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