Why are many antibiotics ineffective against mycoplasma? ——Eight questions about "walking pneumonia"

Due to drug resistance, the treatment of mycoplasma infection in young children in China faces an embarrassing situation.

Written by Wang Chenguang (popular science writer, former professor of Peking Union Medical College)

Following continued reports of high incidences of respiratory diseases such as mycoplasma in mainland China, on November 22, the WHO requested China to provide more epidemiological data and clinical information, as well as further information on the current burden on the medical system in accordance with the International Health Regulations.

Since the SARS outbreak 20 years ago, when mycoplasma was initially mistaken as a pathogen, people seem to have never paid as much attention to mycoplasma, a pathogen that is not uncommon. However, the public's understanding of this pathogen is still vague, and even some clinicians may not fully understand it - for example, Asian mycoplasma pneumonia has generally been resistant to azithromycin, but most doctors still use this antibiotic as the first choice for treating mycoplasma pneumonia.

The following questions and their answers can help you understand mycoplasma in general.

Why are many antibiotics ineffective against mycoplasmas?

Mycoplasma is a type of bacteria that can infect different parts of the body. Which part of the body is affected (lungs, skin, or urinary tract, etc.) depends on the type of Mycoplasma bacteria causing the infection.

Unlike other bacteria we often talk about (such as Escherichia coli, Streptococcus pneumoniae, etc.), mycoplasma is smaller in size and cannot be removed by conventional sterile filtration; and it has no cell wall. Many antibiotics kill bacteria by destroying the cell wall, and these antibiotics (such as penicillin) are ineffective against mycoplasma.

There are about 200 species of mycoplasma bacteria, but most are harmless to humans. Those that are potentially harmful to human health include Mycoplasma pneumoniae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum.

What symptoms does Mycoplasma pneumoniae cause?

Most people do not show symptoms after being infected with mycoplasma, and the incubation period for symptomatic patients is 1-4 weeks (mostly around 3 weeks). If symptoms occur, typical symptoms include fever, cough, bronchitis, sore throat, headache, fatigue and discomfort. Symptoms generally subside after a few days, but symptoms such as cough may last for more than a month.

About one-third of infected people will develop mild pneumonia, but it is usually mild and few patients need hospitalization. This pneumonia is atypical pneumonia (abbreviated as "SARS". In 2003, due to the initial misjudgment that the pathogen of SARS was mycoplasma, the term "SARS" was mistakenly used as a synonym for SARS among the public). The main type of infection that causes SARS symptoms clinically is Mycoplasma pneumoniae. In addition, it also includes pneumonia symptoms caused by Chlamydia pneumoniae or Legionella. It is also often used to refer to pneumonia symptoms caused by atypical pneumonia bacteria, such as respiratory virus-related pneumonia.

Why is Mycoplasma pneumonia called "walking pneumonia"?

"Walking pneumonia" is not a strict medical term. The medical term is atypical pneumonia. The term "walking" is mainly used to describe a very mild type of pneumonia that usually does not require bed rest or hospitalization and does not affect daily activities, so it is called "walking pneumonia." Because this type of pneumonia is mainly caused by Mycoplasma pneumoniae infection, "walking pneumonia" has become a special term for pneumonia infected with Mycoplasma pneumoniae.

Most people start to get better within three to five days after symptoms appear, but the cough caused by pneumonia may last for weeks or even months. Just like other respiratory infections such as COVID-19, Mycoplasma pneumoniae infection has similar high-risk groups. The severity and recovery time after infection vary from person to person. For example, patients with impaired immune function, asthma or chronic obstructive pulmonary disease often show more severe symptoms than those without these problems.

How is Mycoplasma pneumoniae spread?

Mycoplasma is transmitted through contact with droplets produced when an infected person coughs or sneezes. Prolonged, close contact with an infected person is required for transmission. Some studies have speculated that the basic reproduction number (R0) of Mycoplasma pneumoniae is 1.7, which is less contagious. Even in densely populated places such as schools and workplaces, the transmission speed is much slower than respiratory viruses such as influenza and COVID-19.

Anyone can be infected with Mycoplasma pneumoniae, but the main susceptible groups are school-age children and adolescents.

Mycoplasma infections occur sporadically throughout the year. Widespread community outbreaks occur every 4-8 years. Mycoplasma pneumoniae infections are most common in the fall and winter.

How is Mycoplasma pneumoniae infection diagnosed and treated?

Mycoplasma pneumoniae infection is usually diagnosed based on typical symptoms. Nonspecific blood tests (cold agglutinins) can help with diagnosis, but there are cases of misdiagnosis and missed diagnosis. More specific nucleic acid tests are usually not used as a routine method for clinical diagnosis of mycoplasma and are limited to special epidemic investigations.

Mycoplasma infections usually get better on their own, so for patients with mild symptoms, there is no need to use antibiotics to treat them, let alone use them preventively.

How to use antibiotics for treatment when necessary?

In the treatment of mycoplasma pneumonia, tetracycline and erythromycin are generally effective, especially second-generation tetracyclines (such as doxycycline) and macrolides (such as azithromycin) are the first choice. However, in Asia, including China, almost all prevalent Mycoplasma pneumoniae strains have developed resistance to macrolides, so drugs such as azithromycin need to be excluded. If adults need to use antibiotics after infection (such as those with immunodeficiency or systemic infection), fluoroquinolones (such as levofloxacin) can be used. As mentioned earlier, penicillin and cephalosporin antibiotics are ineffective because mycoplasmas lack the cell wall structure unique to other bacteria.

If we assume that the recent rumors of mycoplasma infection are true, from the photos of patients who went to the hospital for treatment released by the media, many of them are young children. The treatment of mycoplasma infection in young children in China faces an awkward situation. Because tetracycline drugs are usually for older children and adults, and fluoroquinolones are not recommended for children. Macrolide drugs (such as azithromycin) are generally considered to be the first choice for children, especially young children, but almost all mycoplasma pneumoniae in China are resistant to this type of antibiotics. For young children with severe symptoms, doctors need to use medications based on experience (such as tetracycline antibiotics).

How to prevent Mycoplasma pneumoniae infection?

There is currently no vaccine to prevent mycoplasma infection, nor are there effective control measures. As with other respiratory infections, the most basic preventive measure is to reduce going out and avoid crowded places as much as possible. If you must go out to a place with a higher risk of infection (such as medical treatment), it is recommended to wear a mask. Cover your mouth and nose when coughing or sneezing (this is to protect others).

The body can acquire immunity after infection with mycoplasma, but the protection is not lifelong. Secondary infection is known to occur, although the symptoms are milder. At present, there is a lack of systematic research in the medical community on the duration of mycoplasma immunity protection.

What other mycoplasmas are potential health hazards?

Mycoplasma infection mainly refers to Mycoplasma pneumoniae, so many people ignore other mycoplasmas that infect humans and may cause diseases.

Mycoplasma genitalium infection mainly occurs in the genital area and is transmitted through sexual intercourse. Symptoms that women may experience after infection include pain during intercourse, vaginal bleeding after intercourse, and abnormal vaginal discharge; men may experience urethritis, stinging sensation when urinating, and discharge from the penis.

Mycoplasma hominis infections are common and can be detected in the urethra and genitals of half of women and some men. Because they rarely cause symptoms, many people carry the bacteria without knowing it, so most people don't need to worry. Women with impaired immune function are at greatest risk for this type of mycoplasma, which is associated with some pelvic inflammatory diseases. In addition, this type of mycoplasma can be passed from mother to child, causing infection and fever in newborns.

Ureaplasma urealyticum and Ureaplasma parvum are also found in the cervix or vagina of most healthy women and in the urethra of a few men. They usually do not cause any problems. Women with compromised immune systems may experience pain when urinating, abdominal pain, vaginal pain, an odor, or an unusual discharge.

References

[1] Waites KB, Xiao L, Liu Y, Balish MF, Atkinson TP. Mycoplasma pneumoniae from the Respiratory Tract and Beyond. Clin Microbiol Rev. 2017 Jul. 30 (3):747-809.

[2] https://www.cdc.gov/pneumonia/atypical/mycoplasma/hcp/antibiotic-treatment-resistance.html

The author of this article is a PhD in biology. He has served as a researcher at the Sidney Kimmel Cancer Center of Thomas Jefferson University, an associate professor in the Department of Cancer Biology, a researcher at the Institute of Radiation Medicine, Chinese Academy of Medical Sciences/director of the Radiation Damage Protection and Drug Research Laboratory, and a professor/doctoral supervisor at Peking Union Medical College. He is currently engaged in the research and development of anti-tumor drugs.

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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