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Health

First cases of gonorrhea resistant to several classes of antibiotics identified in the U.S.

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CNN
 — 

Public health officials says they have found two cases of gonorrhea that appear to have reduced susceptibility to every kind of antibiotic available to treat them. It’s the first time strains of gonorrhea this resistant to antibiotics have been identified in the United States.

Increased sexual activity during the pandemic, coupled with fewer people getting routine health screenings, supercharged the spread of sexually transmitted infections around the world.

Those infections, including gonorrhea, are becoming increasingly resistant to antibiotics available to treat them, a problem that is becoming a dire threat to public health.

Globally, infections that are resistant to antibiotics kill approximately 700,000 people each year. That number is expected to rise to 10 million deaths per year by 2050 if steps aren’t taken to stop the spread of resistant organisms.

Experts say it was never a question of when this highly resistant gonorrhea strain would reach the US, but when.

“The concern is that this particular strain has been circulating around the world, so it was only a matter of time before it would hit the US,” says Dr. Jeffrey Klausner, a clinical professor of public health at the University of Southern California’s Keck School of Medicine in Los Angeles.

“It’s a reminder that gonorrhea is becoming increasingly resistant, increasingly hard to treat. We don’t have any new antibiotics. We haven’t had new antibiotics to treat gonorrhea for years and we really need a different treatment strategy,” said Klausner, who sits on the CDC workgroup for gonorrhea treatment.

Gonorrhea is sexually transmitted, and one of the most commonly diagnosed infections in the US. It is caused by the bacteria Niesseria gonorrhoeae, which can infect the mucous membranes in the genitals, rectum, throat and eyes.

People can be infected without having symptoms. Left untreated, the infection can cause pelvic pain and infertility in women and blindness in newborns.

In addition to reduced susceptibility to ceftriaxone, the strains of gonorrhea identified in Massachusetts also showed reduced susceptibility to cefixime and azithromycin; the strains were resistant to ciprofloxacin, penicillin and tetracycline, according to a clinical alert sent to physicians by the Massachusetts Department of Public Health.

The MDPH says it hasn’t yet found any connection between the two cases.

In 2021, the US Centers for Disease Control and Prevention recommended giving a double dose of the antibiotic ceftriaxone in an effort to overcome the bacteria’s building resistance to this antibiotic, and that seems to have worked in these cases, but that antibiotic is the last line of defense against this infection, and experts say a new approach is needed.

Klausner is hoping to win FDA approval for a test that would tailor antibiotic treatment to the genetic susceptibilities of the particular strain of gonorrhea that is infecting a person. This is called resistance-guided treatment, and Klausner says it works for HIV, TB and some other hospital acquired infections, but it’s never really been tried for gonorrhea.

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.

The first symptoms of gonorrhea are often painful urination, abdominal or pelvic pain, increased vaginal discharge, or bleeding between periods, but many infections are asymptomatic, according to the CDC, making routine screenings important for catching the infection.

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Health

Opinion | Drug-resistant bacteria are proliferating. We need new antibiotics.

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Antibiotics, drugs that kill bacteria or slow their growth, have been a mainstay of medicine since the 1940s. Yet bacteria can evolve to fight back. They can prevent antibiotics from entering their cells, for example, or pump out the drugs. The resulting antibiotic resistance has become a global public health crisis, a shadow pandemic, threatening the effectiveness of human medicine in areas such as joint replacements, Caesarean sections, organ transplants, chemotherapy, dialysis and more.

The relentless pace of antibiotic resistance is well-known. What to do about it is less clear. The inadequate pipeline of potential new drugs has been a subject of concern for years, prompting frequent debate about whether and how the government should help. With recent studies showing that antibiotic-resistant infections are on the rise and more lethal than previously thought, the new Congress should take on the issue, learning from the shortcomings of previous attempts to jump-start antibiotic development.

Antibiotics are used for a short, defined course and they are ideally prescribed sparingly to avoid overuse. The return on investment is often insufficient to cover research costs or satisfy shareholders. By the late 1990s and during the 2000s, the pipeline of new antibiotics under development had shrunk. Methicillin-resistant Staphylococcus aureus and drug-resistant tuberculosis raised alarms; additionally, so-called gram-negative bacteria were proving evermore resistant to antibiotics.

A period of renewed action followed. In 2012, Congress passed the Generating Antibiotic Incentives Now Act, which offered antibiotic developers a fast-track regulatory pathway for new antibiotics as well as five years of additional market exclusivity in which to sell their new drugs. Both “push” incentives, such as direct grants for research and development, and “pull” incentives, to reward those who succeed, were offered as well. In 2016 came the launch of CARB-X, a nonprofit public-private partnership at Boston University to help advance development of new antibiotics aimed at the most urgent public health threats. After passage in 2016 of the 21st Century Cures Act, the Food and Drug Administration eased clinical trial requirements for some antibiotics and antifungals. The result of these incentives was modest: There was an uptick in new antibiotics but they were often duplicative of existing ones and few addressed unmet needs.

This has led to a renewed search for policy models that might work. The traditional biotech route — backed by investors — is fraught. Small companies are still striving to create new antibiotics, but the field was shaken by the 2019 bankruptcy of Achaogen, a biotech company that had benefited from incentives and government support, developed an antibiotic drug against resistant pathogens that won FDA approval — and still could not make a sufficient profit to stay afloat.

A major new proposal that followed was the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance or Pasteur Act, first introduced by Sens. Michael F. Bennet (D-Colo.) and Todd C. Young (R-Ind.) in 2020. The legislation would create a “subscription model” in which the government would provide developers payments of $750 million to $3 billion each for antibiotics that target unmet needs. The government would pay only once, decoupled from the volume of medicine used, after the antibiotics are developed and approved. The proposal had bipartisan support in both houses but failed to clear the 117th Congress; it will be reintroduced this year.

The Pasteur Act is backed by Pharmaceutical Research and Manufacturers of America (PhRMA), the biopharmaceutical lobby, although it has never before supported such a large government purchase contract scheme. Jocelyn Ulrich, deputy vice president of policy and research at PhRMA, explained the reasoning: “Over a decade ago, I think 18 to 20 major pharmaceutical companies were still in this space, and now we’re down to just a handful. The market dynamics are just not there. It’s not viable. Everybody sort of agrees now that we have market failure in this particular area.”

The Pasteur Act might help drug developers get a predictable return on investment, but the $11 billion price tag drew criticism as excessive. Some see a parallel with the approximately $10 billion Operation Warp Speed, the crash coronavirus vaccine effort during the pandemic. But antibiotic resistance is not a one-time “moonshot” problem. Rather, it demands years of commitment to research, ultimately creating a steady pipeline of effective, new antibiotics.

Another interesting model would be to create a nonprofit, which is being tried with tuberculosis and malaria. Brad Spellberg, chief medical officer of the Los Angeles County and University of Southern California Medical Center, was one of the most vocal advocates of the incentives approach a decade ago, but now has proposed creating a nonprofit to nurture antibiotic discovery. Dr. Spellberg and others wrote in the New England Journal of Medicine in 2019, “A drug with annual sales in the tens of millions of dollars is a catastrophic failure for many for-profit companies but would be a lifeline for nonprofits …” A nonprofit would not have to worry about quarterly results or pesky shareholders, and it could use proceeds from selling its new antibiotics to fuel further research. It might still need to rely on for-profits in later drug development stages to license or sell the products. It also could require some seed money from the government, but that “might be a better long-term investment than perpetually offering multibillion-dollar prizes or other pull incentives for each new antibiotic,” Dr. Spellberg argued.

Congress should explore both approaches, and quickly. The end of the antibiotic era — when a doctor has nothing left to treat an infection — is too horrible to contemplate. Waiting is not a reasonable option.

The Post’s View | About the Editorial Board

Editorials represent the views of The Post as an institution, as determined through debate among members of the Editorial Board, based in the Opinions section and separate from the newsroom.

Members of the Editorial Board and areas of focus: Opinion Editor David Shipley; Deputy Opinion Editor Karen Tumulty; Associate Opinion Editor Stephen Stromberg (national politics and policy, legal affairs, energy, the environment, health care); Lee Hockstader (European affairs, based in Paris); David E. Hoffman (global public health); James Hohmann (domestic policy and electoral politics, including the White House, Congress and governors); Charles Lane (foreign affairs, national security, international economics); Heather Long (economics); Associate Editor Ruth Marcus; and Molly Roberts (technology and society).

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Health

Strep A antibiotics prices, shortages hit drugstores amid UK outbreak

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Drugstores are warning of major shortages of key antibiotics used to treat Strep A, as cases rise in the U.K.

Marko Geber | Digitalvision | Getty Images

LONDON — Drugstores in Britain are warning of shortages of key antibiotics used to treat Strep A, as cases rise and the number of child fatalities reaches 15.

A surge in Group A Streptococcus, especially among schoolchildren, has increased demand for amoxicillin and penicillin, the main antibiotic treatments, over the past week.

Where supplies do exist, they are “flying off the shelves,” according to drugstores, with some saying they are now dispensing medication at a loss due to soaring wholesale prices.

In some cases, pharmacists say wholesale prices for the drugs have spiked as much as 850%. These increased costs must be absorbed either by the U.K.’s National Health Service or drugstores, rather than parents, who typically receive children’s prescriptions for free.

At least 15 children have died in the U.K. from severe cases of Strep A this winter season, according to health agencies across England, Wales and Northern Ireland. A further death from suspected infection was reported Saturday but has not yet been confirmed.

While most cases of Strep A are mild and often go unnoticed, it can also lead to more serious illness and complications, such as scarlet fever. The bacteria can also get into the bloodstream and cause an illness called invasive Group A strep (iGAS). 

These severe infections can be deadly, and are thought to be the cause of the recent spate of deaths. It has led to an increase in clinicians prescribing antibiotics for children.

Cases have been on the rise in Britain this year, with the U.K. Health Security Agency reporting 6,602 cases of scarlet fever from Sept. 12 to Dec. 4, well above the 2,538 reported during the last peak in 2017-2018.

Fears of a national shortage

The government and wholesalers have insisted that the country is adequately equipped to deal with the outbreak. Prime Minister Rishi Sunak last week dismissed fears of a “national shortage” of antibiotics.

“There are no current shortages of drugs available to treat this and there are well-established procedures in place to ensure that that remains the case,” he told the House of Commons on Wednesday.

However, a letter to pharmacists from NHS England, seen by Sky News, acknowledged that local drugstores may be experiencing a “temporary interruption of supply of some relevant antibiotics due to increased demand.”

Dr. Leyla Hannbeck, chief executive of the Association of Independent Multiple Pharmacies (AIMP), which represents drugstore owners nationwide, told CNBC the reality on the ground was becoming desperate.

This just shows the incompetence of those in charge. This is not the first time this has happened.

Dr Leyla Hannbeck

CEO, Association of Independent Multiple Pharmacies

“Quite clearly there isn’t (enough supply), because it’s not finding its way to pharmacies,” she said. “And where there are patchy supplies, they are flying off the shelves.”

“This is very concerning for us, especially when we have parents coming into pharmacies, and unfortunately they haven’t got the stock,” she added.

Parents have been advised to call ahead to drugstores to check prescription availability after Hannbeck noted reports of families traveling for miles between stores.

She said the government shouldn’t be surprised by the shortages given similar shortfalls in medication for other outbreaks, such as monkeypox, earlier this year.

“This just shows the incompetence of those in charge,” she said. “This is not the first time this has happened. Since the beginning of this year, I have been discussing with community pharmacies that there is something the matter with the U.K.’s drug supply chains.”

The U.K. health department did not comment on allegations of incompetence when contacted by CNBC.

Drugstores ‘footing the bill’

Drug supply chains have been heavily disrupted this year due to a combination of factors including Russia’s invasion of Ukraine, inflation, Covid-19 and Brexit.

It has left drugstores spending more time — and money — sourcing medications.

Under the U.K.’s National Health Service (NHS) drug tariff scheme, drugstores receive set compensation for medication. There is also a concession list of medications for which higher prices can be paid.

Despite this, when wholesale prices jump, drugstores can end up making a loss.

The government’s Department of Health and Social Care has warned that, while prices may fluctuate, “no company should use this as an opportunity to exploit the NHS.”

Streptococcus A — or Group A Strep (GAS) — is a bacterial infection of the throat or skin, which typically arises during the winter months.

Halfpoint Images | Moment | Getty Images

However, over the past week, wholesale prices for amoxicillin and penicillin liquid solutions — which provide an alternative to tablets for children and are in particularly short supply — have risen in some places from around £2 to between £15 and £19, according to AIMP’s Hannbeck.

London-based drug wholesaler Sigma Pharmaceuticals reportedly hiked the price of its amoxicillin liquid solution by more than 10 times to £19 on Thursday, but later told CNBC the surge was due to an “IT glitch.”

Martin Sawer, executive director at the Healthcare Distribution Association, which represents drug wholesalers, said higher prices “directly reflect” the increased costs charged by manufacturers. He rejected claims of supply shortfalls, pointing instead to a “huge demand surge.”

“Right now there is too much demand for products and not enough competitive products being made available to buy from the manufacturers,” Sawer said.

If Government doesn’t intervene soon to protect pharmacies, patients can expect to see ever more problems with receiving their medicines.

Janet Morrison

chief executive, Pharmaceutical Services Negotiating Committee

Drugstore owners are now calling for the government to update its concessionary price for amoxicillin and penicillin, to ensure they are fairly reimbursed even if prices rise further.

Janet Morrison, chief executive of the Pharmaceutical Services Negotiating Committee, which negotiates the concessions list with the health department, said pricing assistance was “urgently” needed.

“Pharmacy teams are at breaking point,” she said. “They are helpless against market forces that are working against them, and urgently need Government assurance that all medicines will be available, and not at wildly inflated prices.”

A total of 158 drugs were on the NHS’s November concessions list, compared to 135 in October. Morrison said she expects to see a “record number” of medicines added to the list in December as supply constraints exacerbate shortages and push drug prices even higher.

“For months on end, pharmacies have been footing the bill for NHS medicines themselves when these should be covered by Government,” said Morrison.

“This can’t continue,” she added. “If Government doesn’t intervene soon to protect pharmacies, patients can expect to see ever more problems with receiving their medicines. Government and the NHS must fix this, and fast.”

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Health

Scientists Just Caught Bacteria Using a Never-Before-Seen Trick to Avoid Antibiotics : ScienceAlert

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Researchers have just caught bacteria sidestepping antibiotic treatment with a never-before-seen trick.

Bacteria’s troublesome talent for developing resistance against antibiotics is a rapidly growing health threat. This ability has ancient origins and allows drug-resistant bacterial infections like MRSA and gonorrhea to kill 1.3 million people globally each year.

These superbugs are even finding their way into wild animals, such as dolphins and bears.

The shifty microbes can steal genes from each other, quickly passing on antibiotic-resistant tactics: Strategies include directly inactivating the antibiotics, preventing antibiotics from accumulating in their systems, or changing the antibiotic’s targets so that the drugs are no longer effective.

Thanks in part to antibiotic overuse, superbugs have been accumulating multiple resistant tactics, making them extremely difficult to treat.

“This new form of resistance is undetectable under conditions routinely used in pathology laboratories, making it very hard for clinicians to prescribe antibiotics that will effectively treat the infection, potentially leading to very poor outcomes and even premature death,” explains Telethon Kids Institute infectious disease researcher Timothy Barnett.

Telethon Kids Institute microbiologist Kalindu Rodrigo and colleagues discovered this new mechanism while investigating how Group A Streptococcus responds to antibiotics.

This bacteria commonly cause sore throats and skin infections, but it can also lead to systemic infections like scarlet fever and toxic shock syndrome.

“Bacteria need to make their own folates to grow and, in turn, cause disease. Some antibiotics work by blocking this folate production to stop bacteria growing and treat the infection,” explains Barnett.

“When looking at an antibiotic commonly prescribed to treat Group A Strep skin infections, we found a mechanism of resistance where, for the first time ever, the bacteria demonstrated the ability to take folates directly from its human host when blocked from producing their own.”

So Streptococcus has been acquiring already processed folate from outside its own cells; these molecules are abundant in our bodies.

The process completely bypasses the action of sulfamethoxazole, an antibiotic that inhibits folate synthesis within the bacteria, thus rendering the drug ineffective.

Rodrigo and the team identified at least one gene involved: thfT. It encodes part of the folate harvesting system, not unlike our own, as we also can’t produce folate and must get it from our food.

Streptococcus bacteria with this gene, therefore, have found a way to suck up folate and subvert sulfamethoxazole.

In the lab, Group A Streptococcus does succumb to sulfamethoxazole antibiotics because it doesn’t have another accessible source of folate.

In this case, the bacteria are only resistant to the antibiotics when they’re causing an actual infection inside our bodies. This means there’s no easy way of detecting this antibiotic resistance in pathology labs yet.

This mechanism suggests antibiotic resistance is far more varied than researchers previously realized and emphasizes the need to establish more diverse treatments against bacteria.

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“Unfortunately, we suspect this is just the tip of the iceberg – we have identified this mechanism in Group A Strep, but it’s likely it will be a broader issue across other bacterial pathogens,” says Barnett.

Understanding these mechanisms is the first step towards being able to test for them and counter them by prescribing other classes of antibiotics instead.

“It is vital we stay one step ahead of the challenges of antimicrobial resistance and, as researchers, we should continue to explore how resistance develops in pathogens and design rapid accurate diagnostic methods and therapeutics,” urges Rodrigo.

This research was published in Nature Communications.

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Business

Gepotidacin: New antibiotic appears to be effective against UTIs, company says

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CNN
 — 

The first new type of antibiotic developed in more than 20 years to treat urinary tract infections (UTIs) appears to be so effective that the pharmaceutical company stopped testing and will soon submit its data to the US Food and Drug Administration for approval.

Drug company GSK said Thursday the new antibiotic, called gepotidacin, works at least as well as nitrofurantoin, a current front-line medication used to treat UTIs.

The company said it would follow a recommendation from its independent data monitoring committee to stop the study early because the drug had already proven to be effective.

GSK said it would prepare its findings for publication in a medical journal and submit its data to the FDA for approval next year. That’s about a year ahead of the study’s anticipated completion date on the website clinicaltrials.gov.

“Stopping studies in such circumstances is a pretty rare occurrence in the industry. So it’s something I’m absolutely delighted about, both from public health and from a company perspective,” said GSK Chief Scientific Officer Tony Wood, on a call with reporters, Thursday.

Gepotidacin works by blocking enzymes that bacteria need to unzip their DNA – their operating instructions – so they can multiply in the body.

It was developed in partnership with the US government, as one of 19 projects currently funded by the Biomedical Advanced Research and Development Authority, or BARDA, to combat antimicrobial resistance. Government investment was needed because new drugs are expensive to develop, and antibiotics tend not to turn large profits.

New antibiotics are desperately needed because over time, many kinds of bacteria have become resistant to the agents used to treat them. A 2021 report from the World Health Organization warned there are not enough new antibiotics in development to overcome the looming threat of antibiotic resistance. Antibiotic resistant infections kill more than a million people globally each year.

“It’s definitely a big deal,” said Dr. Cindy Liu, chief medical officer at the Antibiotic Resistance Action Center at George Washington University.

“The antibiotic pipeline is what we would call pretty leaky, because, you know, you end up with antibiotics dropping out,” Liu said, meaning many of the drugs don’t make it from the first to second phase of human trials. Another round will drop out between the second and third phase, typically because companies run out of funds to develop them. ” And so this is something that we’ve been dealing with, at the same time when there are increasing numbers of infections that are harder and harder to treat with the drugs that we do have.”

Liu said getting marketing approval for gepotidacin was just the first hurdle. She said she’s seen drugs win approval, only to be abandoned by their manufacturers when they don’t turn a profit.

Antibiotics don’t generate large profits for pharmaceutical companies because patients only take them for a short time. They aren’t maintenance medications like drugs for cholesterol or depression. Eventually, if they are used enough, the bacteria they were developed to kill will develop resistance to them, and the drugs will stop working. So they have a limited lifespan.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Liu said.

Urinary tract infections can happen to both men and women of any age, but are more common in women and girls, who have shorter urethras that are closer to the rectum, making it easier for bacteria to infect the urinary tract.

UTIs are one of the most common infections. Studies show they afflict 1 in 8 women each year and 1 in 5 women over age 65. Somewhere between 30% to 44% of UTIs are recurrent, meaning they come back after treatment. Most are caused by E. coli bacteria, which are becoming more resistant to the drugs used to treat them.

Symptoms of UTIs include frequent urination that is painful or burns, bloody urine, low stomach cramps and the need to urinate even after having just gone.

In clinical trials of 3,000 women, GSK said gepotidacin met its goals of both resolving the symptoms of a UTI as well as clearing the bacteria causing it. The study compared gepotidacin to nitrofurantoin, which is currently recommended as a first-line therapy.

Gepotidacin is taken as a pill. GSK is also testing it to treat the sexually transmitted infection gonorrhea. On Thursday, GSK said the study testing gepotidacin for gonorrhea was ongoing and had not yet progressed to the same stage as the UTI trial.

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US

Some forms of popular antibiotic amoxicillin in short supply due to increased demand

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CNN
 — 

Amoxicillin, a common antibiotic used to treat a broad range of conditions, is in short supply, according to the US Food and Drug Administration.

The agency lists amoxicillin oral solution in its drug shortage database, which relies on reports from manufacturers. The oral solution is an anti-infective used with pediatric patients.

The FDA told CNN on Friday that it was aware of “some intermittent supply interruptions” in the US and is working with manufacturers to evaluate the supply chain to help prevent or reduce the effects of drug shortages.

The American Society of Health-System Pharmacists, which gets reports about drug shortages from health-care practitioners, patients and caregivers, said Friday that it started hearing about a shortage of amoxicillin tablets and oral solution in some areas about three weeks ago.

Erin Fox, whose team creates the content for the group’s drug shortage website, said it is getting reports that the antibiotic may be available in some areas, but not in some of the more commonly prescribed strengths.

“I think it’s going to be challenging for doctors and prescribers to give their patients a prescription that they’ll then be able to get filled, because pharmacies are going to have a variety of different strengths in stock, and you hate to have that delay of the back and forth, especially for an antibiotic they usually want to get started pretty quick. So I think it’s going to be a frustrating shortage,” said Fox, a senior pharmacy director at University of Utah Health.

Government databases in Ireland, Australia, Malaysia and Romania also reported a lack of availability of the drug due to some manufacturing issues and unexpected demand.

Drugmakers Aurobindo, Rising, Sandoz, Teva and US Antibiotics did not respond to requests for comment.

Some companies say there has been little demand for the drug during the pandemic, when Covid-19 mitigation measures also lowered rates of other infections. Companies make the antibiotic when there is a demand for it, but they need time to catch up when demand increases.

A spokesperson for Hikma said that company is delivering to its customers in full and has adequate supplies to meet its commitments.

“Our number one priority is to honor the commitments we have to our current customers, and allocation allows us to achieve this,” said Steve Weiss, Hikma’s head of communications and corporate affairs. “We understand the importance of this medication and are looking at ways to increase production. “

In the US, the amoxicillin shortage does not seem to follow the usual pattern, according to Michael Ganio, the American Society of Health-System Pharmacists’ senior director for pharmacy practice and quality.

“Generally, what we see in the drug shortages is on the production side. In this case, we don’t have any indication from the manufacturers that they’re having any sort of difficulty with production,” he said. “This one seems to be driven by demand, which is a little unusual. We see increased demand as a cause of a shortage fairly infrequently.”

The US is struggling with an early surge in RSV cases, and although doctors would not use amoxicillin to treat the viral infection, some children can develop secondary bacterial infections that may require antibiotics. It’s also possible that if a doctor can’t narrow down the cause of an infection, they may opt to prescribe an antibiotic.

“It seems like that may be what’s happening right now,” Ganio said.

With a shortage driven by demand, it is possible that one pharmacy will have the drug in stock while others won’t.

Walgreens told CNN it was not experiencing any shortages. CVS and Walmart did not respond to requests for comment.

Fox suggests that someone who gets a prescription for amoxicillin check with the pharmacy first to see if they have the drug in stock at the strength that was prescribed. The health-care provider could also write a prescription for a couple of options. Amoxicillin-clavulante and cefuroxime are also good alternatives, particularly for pediatric bacterial infections.

“My first advice would be, don’t panic,” Fox said. “There is still some amoxicillin. It just might need a quick change of prescription.”

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Health

An Ancient Killer Is Rapidly Becoming Resistant to Antibiotics, Scientists Warn

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Typhoid fever might be rare in developed countries, but this ancient threat, thought to have been around for millennia, is still very much a danger in our modern world.

According to new research, the bacterium that causes typhoid fever is evolving extensive drug resistance, and it’s rapidly replacing strains that aren’t resistant.

 

Currently, antibiotics are the only way to effectively treat typhoid, which is caused by the bacterium Salmonella enterica serovar Typhi (S Typhi). Yet over the past three decades, the bacterium’s resistance to oral antibiotics has been growing and spreading.

Sequencing the genomes of 3,489 S Typhi strains contracted from 2014 to 2019 in Nepal, Bangladesh, Pakistan, and India, researchers found a recent rise in extensively drug-resistant (XDR) Typhi. 

XDR Typhi is not only impervious to frontline antibiotics, like ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, but it is also growing resistant to newer antibiotics, like fluoroquinolones and third-generation cephalosporins.

Even worse, these strains are spreading globally at a rapid rate.

While most XDR Typhi cases stem from south Asia, researchers have identified nearly 200 instances of international spread since 1990. 

Most strains have been exported to Southeast Asia, as well as East and Southern Africa, but typhoid superbugs have also been found in the United Kingdom, the United States, and Canada.

“The speed at which highly-resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk,” says infectious disease specialist Jason Andrews from Stanford University.

 

Scientists have been warning about drug-resistant typhoid for years now, but the new research is the largest genome analysis on the bacterium to date.

In 2016, the first XDR typhoid strain was identified in Pakistan. By 2019, it had become the dominant genotype in the nation.

Historically, most XDR typhoid strains have been fought with third-generation antimicrobials, like quinolones, cephalosporins, and macrolides.

But by the early 2000s, mutations that confer resistance to quinolones accounted for more than 85 percent of all cases in Bangladesh, India, Pakistan, Nepal, and Singapore. At the same time, cephalosporin resistance was also taking over.

Today, only one oral antibiotic is left: the macrolide, azithromycin. And this medicine might not work for much longer.

The new study found mutations that confer resistance to azithromycin are now also spreading, “threatening the efficacy of all oral antimicrobials for typhoid treatment”. While these mutations have not yet been adopted by XDR S Typhi, if they are, we are in serious trouble.

If untreated, up to 20 percent of typhoid cases can be fatal, and today, there are 11 million cases of typhoid a year.

 

Future outbreaks can be prevented to some extent with typhoid conjugate vaccines, but if access to these shots is not expanded globally, the world could soon have another health crisis on its hands.

“The recent emergence of XDR and azithromycin-resistant S Typhi creates greater urgency for rapidly expanding prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries,” the authors write.

“Such measures are needed in countries where antimicrobial resistance prevalence among S Typhi isolates is currently high, but given the propensity for international spread, should not be restricted to such settings.”

South Asia might be the main hub for typhoid fever, accounting for 70 percent of all cases, but if COVID-19 has taught us anything, it is that disease variants in our modern, globalized world are easily spread.

To prevent that from happening, health experts argue nations must expand access to typhoid vaccines and invest in new antibiotic research. One recent study in India, for instance, estimates that if children are vaccinated against typhoid in urban areas, it could prevent up to 36 percent of typhoid cases and deaths.

 

Pakistan is currently leading the way on this front. It is the first nation in the world to offer routine immunization for typhoid. Last year, millions of children were administered the vaccine, and health experts argue more nations need to follow suit.

Antibiotic resistance is one of the world’s leading causes of death, claiming the lives of more people than HIV/AIDS or malaria. Where available, vaccines are some of the best tools we have to prevent future catastrophe.

We don’t have time to waste.

The study was published in The Lancet Microbe.

 

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Health

Antibiotics Can Lead to Life-Threatening Fungal Infection Because of Disruption to the Gut’s Immune System

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Hospital patients that are prescribed antibiotics are more likely to get fungal infections because of disruption to the immune system in the gut. Immune-boosting drugs could reduce the health risks from complex infections.

Patients prescribed antibiotics in the hospital are more likely to get fungal infections because of disruption to the immune system in the gut.

Using immune-boosting drugs alongside the antibiotics could reduce the health risks from these complex infections, according to a new study from the

Candidiasis is a fungal infection caused by a yeast (a type of fungus) called Candida. Some species of Candida can cause infection in people; the most common is Candida albicans. Candida normally lives on the skin and in places on the body, such as the mouth, throat, gut, and vagina, without causing any problems. Candida can cause infections if it grows out of control or if it enters deep into the body (for example, the bloodstream or internal organs like the kidney, heart, or brain).

A team in the University’s Institute of Immunology and Immunotherapy, in conjunction with researchers at the National Institutes of Health, discovered that antibiotics disrupt the immune system in the intestines, meaning that fungal infections were poorly controlled in that area. Unexpectedly, the team also found that where fungal infections developed, gut bacteria were also able to escape, leading to the additional risk of bacterial infection.

The study, published in Cell Host and Microbe, demonstrates the potential for immune-boosting drugs, but the researchers also say their work also highlights how antibiotics can have additional effects on our bodies that affect how we fight infection and disease. This in turn underscores the importance of careful stewardship of available antibiotics.

Lead author Dr. Rebecca Drummond said: “We knew that antibiotics make fungal infections worse, but the discovery that bacterial co-infections can also develop through these interactions in the gut was surprising. These factors can add up to a complicated clinical situation – and by understanding these underlying causes, doctors will be better able to treat these patients effectively.”

In the study, the team used mice treated with a broad-spectrum antibiotic cocktail and then infected these animals with Candida albicans, the most common fungus that causes invasive candidiasis in humans. They found that although infected mice had increased mortality, this was caused by infection in the intestine, rather than in the kidneys or other organs.

“These factors can add up to a complicated clinical situation – and by understanding these underlying causes, doctors will be better able to treat these patients effectively.”

— Dr. Rebecca Drummond, Institute of Immunology and Immunotherapy

In a further step, the team pinpointed what parts of the immune system were missing from the gut after antibiotic treatment, and then added these back into the mice using immune-boosting drugs similar to those used in humans. They found this approach helped reduce the severity of the fungal infection.

The researchers followed up the experiment by studying hospital records, where they were able to show that similar co-infections might occur in humans after they have been treated with antibiotics.

“These findings demonstrate the possible consequences of using antibiotics in patients who are at risk of developing fungal infections,” added Dr Drummond. “If we limit or change how we prescribe antibiotics we can help reduce the number of people who become very ill from these additional infections – as well as tackling the huge and growing problem of antibiotic resistance.”

Reference: “Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria” by Rebecca A. Drummond, Jigar V. Desai, Emily E. Ricotta, Muthulekha Swamydas, Clay Deming, Sean Conlan, Mariam Quinones, Veronika Matei-Rascu, Lozan Sherif, David Lecky, Chyi-Chia R. Lee, Nathaniel M. Green, Nicholas Collins, Adrian M. Zelazny, D. Rebecca Prevots, David Bending, David Withers, Yasmine Belkaid, Julia A. Segre and Michail S. Lionakis, 13 May 2022, Cell Host & Microbe.
DOI: 10.1016/j.chom.2022.04.013



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Health

Doctors, patients warn of side effects with popular antibiotic

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DENVER — Some of the most popular drugs prescribed to treat bacterial infections can cause serious side effects and are overprescribed, according to studies and reports.

The Food and Drug Administration has said that Cipro (ciprofloxacin), Ofloxacin and Levaquin (levofloxacin) — prescription drugs known as fluoroquinolones — can have rare but serious side effects. Those side effects include tendon rupture, neuropathy, impacts to the central nervous system and suicide.

“It destroyed my life,” said Jon Horne, who was prescribed Ofloxacin.

Horne lives in Aurora and says his doctor prescribed him Ofloxacin to treat a stomach infection while on vacation with his family.

“I took the pills and I just don’t know, I went full psychotic,” he said.

Horne has been diagnosed with neuropathy, which leaves him in chronic pain.

“I’m being burned alive and getting stung by bees and have constant Charlie horses,” he said.

Horne says he does not believe he was properly warned of the risks by the doctors who prescribed him the drugs.

Dr. Tim Jenkins, an infectious disease physician at Denver Health, was part of an expert Center for Disease Control and Prevention panel investigating the overuse of antibiotics like fluoroquinolones. The study found 47% of fluroquinolones given to patients in the hospital should have never been prescribed.

“It’s been very easy for clinicians to prescribe fluroquinolones because it treats so many of these infections so effectively,” Jenkins said. “(The) fluroquinolone drug class should really only be used when there are no equally effective alternative antibiotics that are available to treat infections.”

In response to growing reports of disabling reactions, in 2018, the FDA issued its strongest black box warning for these drugs. The warning is designed to call attention to serious, even life-threatening side effects.

Jenkins says more than a warning, doctors need to be better educated.

“Getting the message out to both providers and patients that there are real risks associated with these medications, but there is a lot of work left to be done,” he said.

“Life can turn on a dime, and it did”

Mike Mendoza says his wife Dawn was a happy, healthy 49-year-old until she started taking Cipro.

“I saw her at the bottom of the pool, and that’s how I found my wife that day,” he said. “Life can turn on a dime, and it did.”

Mendoza says a doctor prescribed his wife the antibiotic after she was diagnosed with pneumonia. Seven days later, he says he found his wife at the bottom of their pool in Florida.

“She had latched herself to a chase lounge and rolled herself into the pool,” he said. “I know this drug put her in a state of mine where it was over. She lost hope.”

Mendoza says in the 27 years they were together, his wife never suffered from depression.

“And she gets on this drug in seven days and takes her life,” he said.

Reports filed with the FDA tie 221 suicides to Cipro and Levaquin as of Dec. 31, 2021.

A last resort

Denver Attorney Seth Katz has filed multiple lawsuits involving this class of drug. He stressed it’s important patients ask lots of questions before taking these antibiotics.

“It’s a very strong drug, and it should be used carefully,” Katz said. “Ask your doctor hard questions. Do some research. Are they getting their information solely from a drug manufacturer or are they doing their own independent research?”

Katz insists fluroquinolones should always be the last resort, not the first choice.

Bayer, the drug company that makes Cipro, said in a statement, “Fluroquinolones are an important class of medications that treat a wide range of bacterial infections… All medications have potential side effects, but those risks are communicated with doctors and patients through FDA-approved labeling.”

For victims like Horne, they want more done to protect patients.

“It’s a growing issue and it’s not getting addressed,” he said.

Bayer also stated it closely monitors these antibiotics on an ongoing basis and the safety of fluroquinolones has been well documented in clinical trials. But for those who suffer side effects, it can have devastating impacts.

“That drug, it killed my wife,” Mendoza said. “It took her down a rabbit hole that she couldn’t get out of.”

Bayer’s full statement:

“The health and safety of patients who use Bayer products is our top priority.

Fluoroquinolone antibiotics are an important class of medications that treat a wide range of bacterial infections, many of which are serious and can be life-threatening. Cipro® (ciprofloxacin) is one such medication in this class and is widely available as a generic medication that is manufactured and supplied widely throughout the United States by several companies.

All medicines have potential side effects, and the risks are communicated to physicians and patients in FDA-approved product labeling. The Cipro label already contains FDA-approved language advising physicians and their patients about the potential side effects associated with the use of this therapy, including specific warnings about the risks of central nervous system and other psychiatric effects to help physicians and patients make informed decisions.

The safety and efficacy of Bayer’s fluoroquinolones have been demonstrated in clinical trials involving more than 90,000 patients and extensive clinical experience in more than 800 million patients. Cipro was originally approved by the FDA in 1987.

Bayer closely monitors the safety and efficacy of its fluoroquinolones on an ongoing basis, as we do with all of our products. As with any prescription medication, Bayer encourages patients to discuss the risks and benefits of these medications with their healthcare provider.

We recommend visiting fda.gov for more information on the FDA’s position of adverse event reporting.”

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Health

Women who use antibiotics for at least two months during their 50s suffer increased Alzheimer’s risk

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Women who use antibiotics for at least two months during their 50s suffer an increased risk of developing Alzheimer’s, study finds

  • Using antibiotics at the age of 50 or older could increase a woman’s risk of developing Alzheimer’s, a new study finds
  • Women who took the drugs had a brain that was on average three to four years older than their peers
  • There was also a noticeable degradation effect, as women who had taken the drugs further back scored worse of cognitive tests
  • Experts believe this is due to how the gut microbiome, and the bacteria in it, is affected by the drugs 
  • If you or someone you know suffered cognitive decline, Alzheimer’s or a similar condition after taking antibiotics contact us at Mansur.Shaheen@mailonline.com

By Mansur Shaheen U.S. Deputy Health Editor For Dailymail.Com

Published: | Updated:

Using antibiotics for extended periods of time can harm a middle-aged woman’s brain, and even increase their risk of developing Alzheimer’s a new study finds.

Researchers from Harvard University, in Cambridge, Massachusetts, and Rush University, in Chicago, Illinois, found that women who took antibiotics for at least two consecutive months during their 50s consistently scored worse on cognitive tests.

Scoring included measures of processing speed, brain functioning, attention and memory capacity.

The researchers write that the use of antibiotics aged women by around three to four years compared to their peers, and even raised their risk of developing devastating cognitive conditions down the line.

Women in their 50s who use antibiotics for at least two months are at an increased risk of developing Alzheimer’s and also score worse off on cognitive tests (file photo)

Researchers, who published their findings last week in PLOS, gathered data from over 14,000 women who took part in the biennial Nurses’ Health Study II.

As part of the study, the women would report if they had used medication over the past two year period, and if they were suffering any health related issues – along with other questions.

In 2009, when many of the participants had reached their 50s, a question on antibiotics was included in the survey.

In 2016, seven years later, the women were given a cognitive exam to determine a variety of cognitive factors.

Women who reported at least two consecutive months of antibiotic usage universally performed worse than their peers.

There was also a clear sign of cognitive degradation over time, as women who were further away from their middle-age antibiotic usage tested even more poorly.

The exact mechanism causing antibiotics to have such a terrifying effect on the brain can not be pin-pointed, but experts have one potential hunch.

Researchers point to the gut-brain axis for the cognitive decline experienced by women.

A person’s gut has more control over their body and brain than they may believe, and previous studies have even found that the gut microbiome could determine a person’s personality.

Past studies have also found that gut health is tied to cognitive conditions like Alzheimer’s and others in both humans and animals.

Experts have long known that antibiotics can affect cognitive process as the body’s gut microbiome has large control over processes across the body, and the bacteria in the microbiome is hurt by the drugs

The gut microbiome is affected by antibiotics, that can kill and change the population of the body’s stomach.

As far back as Hippocrates in 400 BC have humans known that there was some link between internal body processes and outward displays of personality and other cognitive functioning.

In 2016, researchers at Johns Hopkins University found that antibiotic treatments could alter a person’s gut microbiome, and as a result harm people suffering from psychiatric disorders.

‘More research is needed, but ours suggests that if we can prevent infections and minimize antibiotic treatment in people with mental illness, then we might be able to prevent the occurrence of manic episodes,’ Dr Robert Yolken, a researcher at the Baltimore, Maryland, school, wrote.

Why the microbiome has so much control over the body has not yet been determined, but it has been under investigation from experts for decades. 

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