Recently during my pediatrics rotation, I encountered a large number of Mycoplasma pneumoniae pneumonia (MPP) cases. The general procedure is as follows:
- Patients present with respiratory symptoms such as cough and fever
- Blood test for Mycoplasma to confirm infection
- Start azithromycin treatment
During this process, I encountered several questions. Try to answer them yourself first; the following notes are my own answers to these questions:
- What are the differences between Mycoplasma pneumonia and ordinary pneumonia?
- Is blood testing for Mycoplasma pneumonia reliable? Are there risks of missed or incorrect diagnosis?
- Why is azithromycin used immediately once MPP is identified, given that there are so many types of antibiotics?
- What should be done if azithromycin is ineffective?
Differences Between Mycoplasma Pneumonia and Ordinary Pneumonia
First, let’s review the difference between Mycoplasma and bacteria. We only need to remember one point: Mycoplasma lack a cell wall, and their organelles only include ribosomes. This directly causes β-lactam antibiotics represented by penicillin to be ineffective since their mechanism is to inhibit cell wall synthesis.
Taking this opportunity, let’s review the main mechanisms of antibiotics:
- Inhibit bacterial cell wall synthesis (β-lactams, peptide antibiotics such as vancomycin, bacitracin)
- Increase bacterial cell membrane permeability (polymyxins, a subclass of peptides)
- Interfere with bacterial protein synthesis (aminoglycosides, macrolides, lincosamides)
- Inhibit nucleic acid and folate metabolism (tetracyclines, quinolones)
Polymyxins have relatively high nephrotoxicity[1], so they are rarely used in various situations. The antibiotics that can be used to treat Mycoplasma pneumonia are tetracyclines (e.g., doxycycline), quinolones (e.g., levofloxacin), aminoglycosides (e.g., streptomycin), and macrolides (e.g., azithromycin)[2].
Note:
- The above are common examples of various antibiotic classes to aid your recollection and do not represent clinical use of these specific drugs for Mycoplasma pneumonia treatment.
- This note will not deeply cover pharmacology; if you have forgotten the mechanisms of these major antibiotic classes, please review them in a timely manner, as they are crucial for your antibiotic decision-making!
Back to the difference between Mycoplasma pneumonia and ordinary pneumonia: without prior infection history or laboratory test results, it is personally difficult for me to distinguish based on clinical symptoms alone. The guidelines do not clearly state definitive distinguishing criteria[3].
Next, let’s address the question: Is blood testing for Mycoplasma pneumonia reliable?
Laboratory Tests for MPP
The gold standard for Mycoplasma pneumoniae (MP) diagnosis is culture, but it is very slow and difficult for clinical use. Recently, I have mainly seen MP antibody testing. A positive result suggests MP infection, and a negative result cannot completely exclude it. It is suitable for rapid screening of outpatients and emergency pediatric patients but can also produce false positives. Therefore, antibody test results must be interpreted in combination with clinical and imaging features[3:1].
In the past few days, I have indeed encountered several cases where patients had a history of Mycoplasma pneumonia; their respiratory symptoms recurred recently, but MP was negative in blood tests. However, considering history and symptoms, the attending physician strongly suspected MPP and prescribed azithromycin. Some patients were MP positive, but the physician did not believe it was MPP; to be safe, azithromycin was still administered (MP antibody positivity does not necessarily indicate infection; negativity does not necessarily exclude it. Thus, clinical judgment sometimes relies on guesswork. However, patients often evaluate a doctor’s skill based on whether Mycoplasma testing is ordered, so this test still needs to be done).
Treatment of MPP
Based on the above, the observed actual clinical path is: if pneumonia is suspected, order tests—complete blood count + CRP + Mycoplasma. If MP is positive or history strongly suggests infection, start azithromycin.
Wait, why azithromycin right away? Earlier, we said tetracyclines, quinolones, aminoglycosides, and macrolides can all be used. Why immediately choose macrolides? Also, among macrolides, why azithromycin first?
Let’s first answer why macrolides are used: it’s simple—other drugs have unacceptable side effects, each with an example below:
- Tetracyclines cause tetracycline teeth in children (during tooth crown calcification, tetracycline binds to calcium and deposits in dentin), so children before tooth replacement are contraindicated[4].
- Quinolones can damage joint cartilage, affect bone development, and cause arthritis; contraindicated in minors (mechanism not well studied)[5].
- Aminoglycosides have ototoxicity and nephrotoxicity and are strictly prohibited for children under 6 years old (see references for detailed mechanisms)[6].
Therefore, only macrolides remain. Among them, erythromycin and roxithromycin with 14-membered lactone rings are first-generation; azithromycin has a 15-membered lactone ring and belongs to the second generation. The larger the ring, the newer, more advanced, and better the effect. A 16-membered ring macrolide like midecamycin also exists.
These drugs can treat MPP, but the third generation is not widely used due to higher toxicity[7]. The second generation is better than the first, especially azithromycin among the second generation, which has better efficacy, longer half-life, and fewer side effects. In summary, azithromycin is the best choice, so it is usually the first-line treatment upon mention of MPP.
In fact, I also encountered an MPP case where the family had erythromycin at home. The attending physician said it was also okay to give erythromycin (a first-generation macrolide with extensive clinical experience and proven safety), not necessarily azithromycin.
Now, the last question: What if azithromycin does not work for MPP?
Drug Resistance in Mycoplasma Pneumonia
With widespread azithromycin use in MPP, resistance problems have gradually emerged. However, resistance is a very clinical, complex, and experiential issue; I have not looked into it in detail.
Generally speaking, when macrolides like azithromycin show poor efficacy, less preferred antibiotics must be used as a last resort—choosing the lesser evil. (Clinicians’ experience shows quinolones rarely cause bone and cartilage developmental disorders; the incidence is low, but I have not checked the exact side effect probabilities.) Currently, tetracyclines like minocycline are commonly used.
Of course, Chinese medicine has shown good efficacy in this area. Clinicians have recognized over years of practice that integrating traditional Chinese and Western medicine yields better efficacy and fewer side effects[8].
Acknowledgments
Thanks to Teacher Fan Yanping and student Ruan Zechen for their corrections to this article.
References
Chinese Society of Critical Care Medicine and Chinese Society of Infectious Diseases, Expert Consensus on Polymyxin Clinical Application[J]. Chinese Journal of Emergency Medicine, 2019, 28(10): 1218-1222. DOI:10.3760/cma.j.issn.1671-0282.2019.10.007 ↩︎
Sindeli, Shi Dawei. Advances in the antibiotic treatment of drug-resistant Mycoplasma pneumoniae infections[J]. Chinese Journal of Practical Pediatrics, 2013, 28(22): 1695-1697. DOI:10.3760/cma.j.issn.2095-428X.2013.22.005 ↩︎
National Health Commission of the People’s Republic of China. Guidelines for Diagnosis and Treatment of Pediatric Mycoplasma pneumoniae Pneumonia (2023 Edition)[J]. International Journal of Epidemiology and Infectious Diseases, 2023, 50(02): 79-85. DOI:10.3760/cma.j.cn331340-20230217-00023 ↩︎ ↩︎
Tetracycline in chickens, oxytetracycline in pigs, penicillin in milk: Have you ever eaten these “delicacies”? 【The story of antibiotics ④ - Tetracyclines】 ↩︎
Gene violence demolition team: Why is levofloxacin so brutal? 【The story of antibiotics ⑫ - Quinolones】 ↩︎
Han Hezhou, Dong Yaodong, Wei Wei, et al. Progress in Research on Ototoxicity of Aminoglycoside Antibiotics[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2020, 55(10): 985-989. DOI:10.3760/cma.j.cn115330-20191126-00725 ↩︎
Hao Tianyi, He Weiqing. Research Progress on Metabolic Engineering of Macrolide Antibiotics. Journal of Bioengineering, 2021, 37(5): 1737-1747 ↩︎
Gao Hengmiao, Qian Suyun. Treatment of refractory, epidemic, and macrolide-resistant Mycoplasma pneumoniae pneumonia[J]. Chinese Journal of Pediatric Emergency Medicine, 2021, 28(01): 1-6. DOI:10.3760/cma.j.issn.1673-4912.2021.01.001 ↩︎