Tuberculosis (TB): Practice Essentials, Background, Pathophysiology

Antibiotics Do Not Provide Relief From Lower Respiratory Tract Infections, Study Finds

Cross section of the lower organs of the respiratory system, This image shows the lower organs of ... [+] the respiratory system, which are the trachea, the lungs and the diaphragm. (Photo by: QAI Publishing/Universal Images Group via Getty Images)

Universal Images Group via Getty Images

A new study of 718 patients who sought treatment in U.S.-based primary and emergency care settings found that antibiotics were ineffective in providing symptomatic relief from lower respiratory tract infections. Out of the 718 patients included in the study, 29% had been prescribed common antibiotics like amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin.

"Provision of an antibiotic had no effect on the duration or overall severity of cough, including in patients with viral, bacterial, and mixed infections," the researchers wrote in the study that was published in the Journal of General Internal Medicine on April 15, 2024.

In a press release, lead author Dan Merenstein, a professor of family medicine at Georgetown University School of Medicine said: "Lower respiratory tract infections tend to have the potential to be more dangerous, since about 3% to 5% of these patients have pneumonia. But not everyone has easy access at an initial visit to an X-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection. Plus, patients have come to expect antibiotics for a cough, even if it doesn't help. Basic symptom-relieving medications plus time brings a resolution to most people's infections."

"We know that cough can be an indicator of a serious problem. It is the most common illness-related reason for an ambulatory care visit, accounting for nearly 3 million outpatient visits and more than 4 million emergency department visits annually," added Merenstein. "Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial as this study was observational and there haven't been any randomized trials looking at this issue since about 2012."

Another study author, Mark H. Ebell, a professor in the College of Public Health at the University of Georgia, highlighted in a press release that physicians tend to "overestimate the percentage of lower tract infections that are bacterial."

"They also likely overestimate their ability to distinguish viral from bacterial infections," added Ebell. "In our analysis, 29% of people were prescribed an antibiotic while only 7% were given an antiviral. But most patients do not need antivirals as there exist only two respiratory viruses where we have medications to treat them: influenza and SARS-COV-2. There are none for all of the other viruses."

Antibiotic overuse and the over-prescribing of antibiotics has led to drug-resistant bacteria that are much harder to treat. In fact, within the last two decades, antibiotic resistance has become a global public health threat which caused more than one million deaths worldwide in 2019, according to the Lancet.

Other than the growing threat of antibiotic resistance, one in 300 patients can also experience severe side-effects from frequently using antibiotics. A 2023 study reported that one of the rare adverse events could be a potentially fatal diarrheal infection called Clostridium difficile. Researchers estimate that in the U.S. Alone, doctors give out 34 million unnecessary antibiotic prescriptions every year.

At present, antibiotic resistance is far more prevalent in low-income and middle-income countries — thanks to the financial incentives that doctors get from over-prescribing antibiotics.

Common Antibiotic May Be Helpful In Fighting Respiratory Viral Infections

A new, Yale-led study suggests that a range of respiratory viral infections — including COVID-19 and influenza — may be preventable or treatable with a generic antibiotic that is delivered to the nasal passageway.

A team led by Yale's Akiko Iwasaki and former Yale researcher Charles Dela Cruz successfully tested the effectiveness of neomycin, a common antibiotic, to prevent or treat respiratory viral infections in animal models when given to the animals via the nose. The team then found that the same nasal approach — this time applying the over-the-counter ointment Neosporin — also triggers a swift immune response by interferon-stimulated genes (ISGs) in the noses of healthy humans.

The findings were published in the journal Proceedings of the National Academy of Sciences.

"This is an exciting finding, that a cheap over-the-counter antibiotic ointment can stimulate the human body to activate an antiviral response," said Iwasaki, the Sterling Professor of Immunobiology and professor of dermatology at Yale School of Medicine and co-senior author of the new study.

"Our work supports both preventative and therapeutic actions of neomycin against viral diseases in animal models, and shows effective blocking of infection and transmission," said Iwasaki, who is also professor of molecular, cellular, and developmental biology in Yale's Faculty of Arts and Sciences, professor of epidemiology at Yale School of Public Health, and an investigator at the Howard Hughes Medical Institute.

Respiratory viruses affect millions of people each year. The global COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has led to 774.5 million cases worldwide as of February 2024, with global mortality of 6.9 million people. Influenza viruses account for up to 5 million cases of severe illness and 500,000 deaths annually worldwide.

Currently, most therapies used to fight respiratory viral infections — including antivirals, monoclonal antibodies, and convalescent plasma therapy — are delivered intravenously or orally. They focus on stopping the progression of existing infections.

A nasal-centered therapy has a much better chance of stopping infections before they can spread to the lower respiratory tract and cause severe diseases, the researchers said.

"This collaborative multi-disciplinary work combined important insights from animal pulmonary infection modeling experiments with human study evaluation of this intranasal approach to stimulate antiviral immunity," said Dela Cruz, former associate professor of pulmonary, critical care, and sleep medicine, and of microbial pathogenesis at Yale School of Medicine and former director of the Center for Pulmonary Infection Research and Treatment. Dela Cruz is currently at the University of Pittsburgh.

In their study, the researchers found that mice treated intranasally with neomycin showed a robust ISG line of defense against both SARS-CoV- 2 and a highly virulent strain of influenza A virus. The researchers also found that an intranasal treatment of neomycin strongly mitigated contact transmission of SARS-CoV-2 in hamsters.

In healthy humans, intranasal application of Neosporin (containing neomycin) also initiated a strong expression of ISGs in a subset of volunteers, the researchers said.

"Our findings suggest that we might be able to optimize this cheap and generic antibiotic to prevent viral diseases and their spread in human populations, especially in global communities with limited resources," Iwasaki said. "This approach, because it is host-directed, should work no matter what the virus is."

The co-first authors of the new study, all from Yale, are Tianyang Mao, Jooyoung Kim, and Mario Peña-Hernández.

WHO Overturns Dogma On Airborne Disease Spread. The CDC Might Not Act On It.

The World Health Organization (WHO) has issued a report that transforms how the world understands respiratory infections like COVID-19, influenza, and measles.

Motivated by grave missteps in the pandemic, the WHO convened about 50 experts in virology, epidemiology, aerosol science, and bioengineering, among other specialties, who spent 2 years poring through the evidence on how airborne viruses and bacteria spread.

However, the WHO report stops short of prescribing actions that governments, hospitals, and the public should take in response. It remains to be seen how the CDC will act on this information in its own guidance for infection control in healthcare settings.

The WHO concluded that airborne transmission occurs as sick people exhale pathogens that remain suspended in the air, contained in tiny particles of saliva and mucus that are inhaled by others.

While it may seem obvious, and some researchers have pushed for this acknowledgment for more than a decade, an alternative dogma persisted -- which kept health authorities from saying that COVID was airborne for many months into the pandemic.

Specifically, they relied on a traditional notion that respiratory viruses spread mainly through droplets spewed out of an infected person's nose or mouth. These droplets infect others by landing directly in their mouth, nose, or eyes -- or they get carried into these orifices on droplet-contaminated fingers. Although these routes of transmission still happen, particularly among young children, experts have concluded that many respiratory infections spread as people simply breathe in virus-laden air.

"This is a complete U-turn," said Julian Tang, MBBS, PhD, a clinical virologist at the University of Leicester in England, who advised the WHO on the report. He also helped the agency create an online tool to assess the risk of airborne transmission indoors.

Peg Seminario, an occupational health and safety specialist in Bethesda, Maryland, welcomed the shift after years of resistance from health authorities. "The dogma that droplets are a major mode of transmission is the 'flat Earth' position now," she said. "Hurray! We are finally recognizing that the world is round."

The change puts fresh emphasis on the need to improve ventilation indoors and stockpile quality face masks before the next airborne disease explodes. Far from a remote possibility, measles is on the rise this year and the H5N1 bird flu is spreading among cattle in several states. Scientists worry that as the H5N1 virus spends more time in mammals, it could evolve to more easily infect people and spread among them through the air.

Traditional beliefs on droplet transmission help explain why the WHO and the CDC focused so acutely on hand-washing and surface-cleaning at the beginning of the pandemic. Such advice overwhelmed recommendations for N95 masks that filter out most virus-laden particles suspended in the air. Employers denied many healthcare workers access to N95s, insisting that only those routinely working within feet of COVID patients needed them. More than 3,600 healthcare workers died in the first year of the pandemic, many due to a lack of protection.

However, a committee advising the CDC appears poised to brush aside the updated science when it comes to its pending guidance on healthcare facilities.

Lisa Brosseau, ScD, an aerosol expert and a consultant at the Center for Infectious Disease Research and Policy in Minnesota, warns of a repeat of 2020 if that happens.

"The rubber hits the road when you make decisions on how to protect people," Brosseau said. "Aerosol scientists may see this report as a big win because they think everything will now follow from the science. But that's not how this works and there are still major barriers."

Money is one. If a respiratory disease spreads through inhalation, it means that people can lower their risk of infection indoors through sometimes costly methods to clean the air, such as mechanical ventilation and using air purifiers, and wearing an N95 mask. The CDC has so far been reluctant to press for such measures, as it updates foundational guidelines on curbing airborne infections in hospitals, nursing homes, prisons, and other facilities that provide healthcare. This year, a committee advising the CDC released a draft guidance that differs significantly from the WHO report.

Whereas the WHO report doesn't characterize airborne viruses and bacteria as traveling short distances or long, the CDC draft maintains those traditional categories. It prescribes looser-fitting surgical masks rather than N95s for pathogens that "spread predominantly over short distances." Surgical masks block far fewer airborne virus particles than N95s, which cost roughly 10 times as much.

Researchers and healthcare workers have been outraged about the committee's draft, filing letters and petitions to the CDC. They say it gets the science wrong and endangers health. "A separation between short- and long-range distance is totally artificial," Tang said.

Airborne viruses travel much like cigarette smoke, he explained. The scent will be strongest beside a smoker, but those farther away will inhale more and more smoke if they remain in the room, especially when there's no ventilation.

Likewise, people open windows when they burn toast so that smoke dissipates before filling the kitchen and setting off an alarm. "You think viruses stop after 3 feet and drop to the ground?" Tang said of the classical notion of distance. "That is absurd."

The CDC's advisory committee is comprised primarily of infection control researchers at large hospital systems, while the WHO consulted a diverse group of scientists looking at many different types of studies. For example, one analysis examined the puff clouds expelled by singers and musicians playing clarinets, French horns, saxophones, and trumpets. Another reviewed 16 investigations into COVID outbreaks at restaurants, a gym, a food processing factory, and other venues, finding that insufficient ventilation probably made them worse than they would otherwise be.

In response to the outcry, the CDC returned the draft to its committee for review, asking it to reconsider its advice. Meetings from an expanded working group have since been held privately. But the National Nurses United union obtained notes of the conversations through a public records request to the agency. The records suggest a push for more lax protection. "It may be difficult as far as compliance is concerned to not have surgical masks as an option," said one unidentified member, according to notes from the committee's March 14 discussion. Another warned that "supply and compliance would be difficult."

The nurses' union, far from echoing such concerns, wrote on its website, "The Work Group has prioritized employer costs and profits (often under the umbrella of 'feasibility' and 'flexibility') over robust protections." Jane Thomason, MSPH, the union's lead industrial hygienist, said the meeting records suggest the CDC group is working backward, molding its definitions of airborne transmission to fit the outcome it prefers.

Tang expects resistance to the WHO report. "Infection control people who have built their careers on this will object," he said. "It takes a long time to change people's way of thinking."

The CDC declined to comment on how the WHO's shift might influence its final policies on infection control in health facilities, which might not be completed this year. Creating policies to protect people from inhaling airborne viruses is complicated by the number of factors that influence how they spread indoors, such as ventilation, temperature, and the size of the space.

Adding to the complexity, policymakers must weigh the toll of various ailments, ranging from COVID to colds to tuberculosis, against the burden of protection. And tolls often depend on context, such as whether an outbreak happens in a school or a cancer ward.

"What is the level of mortality that people will accept without precautions?" Tang said. "That's another question."

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF -- an independent source of health policy research, polling, and journalism. Learn more about KFF.

Please enable JavaScript to view the comments

---