| disease | Mycoplasma Pneumonia in Children |
| alias | Cold Agglutination Positive Pneumonia, Primary Atypical Pneumonia |
Mycoplasmal pneumonia, formerly known as primary atypical pneumonia or cold agglutinin-positive pneumonia, is a pulmonary inflammation caused by Mycoplasma (MP) infection. It primarily manifests as interstitial pneumonia and bronchiolitis-like changes during the basic disease course, with clinical symptoms including persistent severe cough. MP is one of the major pathogens responsible for pneumonia and other respiratory infections in children.
bubble_chart Epidemiology
The disease is mainly transmitted through respiratory droplets. Sporadic cases are common throughout the year, with a higher incidence in winter. Regional epidemics occur approximately every 3 to 7 years, characterized by prolonged durations that can last up to a year. For example, the 1990 epidemic in Beijing lasted from January 1990 to March 1991, spanning over a year and two months. In addition to pneumonia, it can also manifest as bronchitis, tracheitis, and pharyngitis. Many outpatients exhibit mild symptoms, making it easy to misdiagnose without serological testing. School-aged children are more frequently affected, though preschool children can also contract the disease. During the 1990 epidemic, for instance, infants under 3 years old accounted for 15% of cases at Beijing Children's Hospital, with the youngest patient being only 1.5 years old. Some individuals may carry the pathogen even after recovery.
The main pathogen of this disease is Mycoplasma pneumoniae, an "interstitial pneumonia-like microorganism" that lies between bacteria and viruses. It is the smallest known independently living pathogenic microorganism, capable of passing through bacterial filters. It requires a special cholesterol-containing culture medium and forms colonies only after 10 days of inoculation. The colonies are very small, rarely exceeding 0.5 mm. The pathogen has a diameter of 125–150 nm, similar in size to paramyxoviruses. Lacking a cell wall, it exhibits various forms such as spherical, rod-shaped, and filamentous, and is Gram-negative. It can withstand freezing but survives only a few hours at 37°C.
1. Incubation period: Approximately 2 to 3 weeks (8 to 35 days).
2. Symptoms: Vary in severity. Most cases have an insidious onset, with symptoms such as fever, anorexia, cough, fear of cold, headache, sore throat, and substernal pain. Body temperature ranges from 37 to 41°C, mostly around 39°C, and may be persistent, remittent, or merely low-grade, or even absent. Cough is often severe, starting as a dry cough in the initial stage [first stage], followed by sputum production (occasionally containing small amounts of blood streaks), sometimes with paroxysmal coughing resembling whooping cough. Nausea, vomiting, and transient maculopapular or urticarial rashes may occasionally occur. Dyspnea is generally absent, but infant patients may exhibit wheezing and respiratory distress. Signs vary with age: older children often lack significant chest signs, while infants may show grade I dullness on percussion, diminished breath sounds, and moist rales, sometimes with signs of obstructive lung qi swelling. Symptoms often worsen in children with sickle cell anemia complicated by this pneumonia, manifesting as dyspnea, chest pain, and pleural effusion. Mycoplasma pneumonia may occasionally be complicated by exudative pleuritis and lung abscess. There is a certain relationship between chronic lung disease and Mycoplasma pneumoniae. Berkwick (1970) reported a fourfold increase in recurrence among 27 asthmatic children. Mycoplasma pneumonia can involve multiple systems and organs, with extrapulmonary manifestations affecting the skin and mucous membranes, presenting as measles-like or scarlet fever-like rashes, Stevens-Johnson syndrome, etc. Nonspecific myalgia and migratory arthralgia are occasionally seen. Gastrointestinal involvement may include vomiting, diarrhea, and liver dysfunction. Hemolytic anemia is relatively common in the hematologic system; we have observed two cases where hemolytic anemia was the initial and primary complaint. Other complications include polyradiculitis, meningoencephalitis, and cerebellar injury. Cardiovascular involvement may occasionally present as myocarditis or pericarditis. Bacterial co-infections are rare. White blood cell counts vary, mostly normal or slightly elevated. ESR shows moderate acceleration.
4. Course: The natural course varies from a few days to 2–4 weeks, with most cases defervescing within 8–12 days. The convalescent stage lasts 1–2 weeks. Complete resolution of X-ray shadows lags behind symptom relief by 2–3 weeks. Recurrence is occasionally seen.
The diagnostic points are: ① Persistent severe cough, with X-ray findings significantly more pronounced than clinical signs. If multiple cases occur simultaneously in older children, an epidemic may be suspected, allowing for early confirmation. ② White blood cell counts are mostly normal or slightly elevated, with increased erythrocyte sedimentation rate (ESR) and positive Coombs test. ③ Penicillin, streptomycin, and sulfonamides are ineffective. ④ Serum agglutinins (IgM type) often show titers rising to 1:32 or higher, with a positive rate of 50–75%. The more severe the illness, the higher the positive rate. Cold agglutinins typically appear by the end of the first week of illness, peak at weeks 3–4, then decline and disappear within 2–4 months. This is a nonspecific reaction and may also occur in liver disease, hemolytic anemia, infectious mononucleosis, etc., but titers generally do not exceed 1:32. In older children with adenovirus pneumonia, cold agglutinins are usually negative. ⑤ Measurement of serum-specific antibodies has diagnostic value. Commonly used clinical tests include complement fixation, indirect hemagglutination, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Additionally, ELISA can detect antigens. Recent reports describe monoclonal antibodies targeting Mycoplasma pneumoniae membrane proteins for antigen detection. In recent years, DNA probes and PCR for detecting Mycoplasma pneumoniae DNA have been applied domestically and internationally, offering rapid and highly specific diagnostic advantages. ⑥ Culturing Mycoplasma from patient sputum or throat swab washings takes too long, often 2–3 weeks, providing limited clinical utility.
bubble_chart Treatment Measures
The treatment of pediatric MP pneumonia is fundamentally similar to that of general pneumonia, adopting comprehensive therapeutic measures. It includes five aspects: general treatment, symptomatic treatment, antibiotic application, adrenal corticosteroids, and treatment of extrapulmonary complications.
1. General Treatment
⑴ Respiratory Isolation: Since Mycoplasma infection can cause small outbreaks and the duration of Mycoplasma shedding in children after illness is relatively long, lasting up to 1–2 months, infants may initially present only with upper respiratory tract infection symptoms, developing pneumonia only after reinfection. Additionally, during MP infection, children are prone to co-infection with other viruses, leading to worsening and prolonged illness. Therefore, respiratory isolation should be implemented as much as possible for affected children or those with close contact history to prevent reinfection and cross-infection.
⑵ Nursing Care: Maintain fresh indoor air, provide easily digestible, nutritious food, and sufficient fluids. Ensure oral hygiene and respiratory tract patency. Frequently turn the child, pat their back, and change their position to promote secretion drainage. If necessary, suction may be performed to remove viscous secretions.
⑶ Oxygen Therapy: For severe cases with signs of hypoxia or significant airway obstruction, oxygen should be administered promptly. The goal is to improve arterial oxygen partial pressure and alleviate tissue hypoxia caused by hypoxemia. The method of oxygen administration is the same as for general pneumonia.
2. Symptomatic Management
⑴ Expectoration: The aim is to thin the sputum for easier expulsion, as failure to do so may increase the risk of bacterial infection. However, effective expectorants are limited. In addition to measures like turning, back patting, nebulization, and suction, expectorants such as bromhexine or acetylcysteine may be used. Since cough is the most prominent clinical manifestation of Mycoplasma pneumonia, frequent and severe coughing may disrupt the child’s sleep and rest. Sedatives like chloral hydrate or phenobarbital can be administered appropriately, and small doses of codeine may be used for cough suppression as needed, though excessive use should be avoided.
⑵ Antiasthmatic Treatment: For severe wheezing, bronchodilators such as oral aminophylline (4–6 mg/kg per dose, every 6 hours) or salbutamol inhalation may be employed.
3. Antibiotic Application
Based on the microbiological characteristics of MP, antibiotics that inhibit microbial cell wall synthesis, such as penicillin, are ineffective against Mycoplasma. Therefore, antibiotics that inhibit protein synthesis should be selected for MP infection treatment, including macrolides, tetracyclines, and chloramphenicols. Other options include lincomycin, clindamycin, vancomycin, and sulfonamides such as SMZ-TMP.
⑴Macrolide antibiotics Among the various options, macrolide antibiotics such as erythromycin, spiramycin, midecamycin, and leucomycin are commonly selected. Erythromycin is the preferred choice due to its widespread use and proven efficacy. It is effective in alleviating the symptoms and signs of Mycoplasma pneumoniae pneumonia, although it does not eliminate Mycoplasma pneumoniae (MP) effectively and cannot eradicate its colonization. The usual dosage is 50mg/(kg·d). Mild cases can be treated with oral administration in divided doses, while severe cases may require intravenous administration. The treatment course is generally recommended to be no less than 2–3 weeks, as premature discontinuation may lead to relapse. Common oral formulations include tasteless erythromycin and erythromycin enteric-coated tablets. Oral erythromycin is absorbed through the intestines; a 250mg dose taken on an empty stomach reaches a peak blood concentration of 0.3–0.7μg/ml 2–3 hours after administration. Doubling the dose results in a peak blood concentration of 0.3–1.9μg/ml. Intravenous injection of 300mg erythromycin lactobionate yields an average blood concentration of 40.9μg/ml after 4 minutes, 2.6μg/ml after 2 hours, and 0.32μg/ml after 6 hours. Continuous intravenous infusion of 1g erythromycin lactobionate every 12 hours maintains a blood concentration of 4–6μg/ml after 8 hours. The average concentration in sputum is 2.6 (0.9–8.4)μg/ml. Erythromycin is primarily excreted through the gallbladder, with partial reabsorption from the intestines. A significant amount is metabolized and inactivated in the liver. About 2.5% of the oral dose and 15% of the injected dose are excreted in urine as active substances. Neither hemodialysis nor peritoneal dialysis can remove erythromycin from the body. When using erythromycin preparations, attention should be paid to their toxic side effects. Various oral formulations can cause gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea. Intravenous infusion may lead to thrombophlebitis, and occasional allergic reactions may manifest as drug fever or urticaria. Notably, erythromycin-induced jaundice often occurs 14–21 days after administration, presenting with epigastric pain, nausea, and vomiting, followed by fever, jaundice, leukocytosis, eosinophilia, elevated serum bilirubin, and transaminase levels. These symptoms typically resolve 2–3 days after discontinuation but may recur upon re-administration. Additionally, high-dose erythromycin may occasionally cause tinnitus and temporary hearing impairment, particularly in patients receiving intravenous administration or those with impaired renal and/or liver function. Infants and young children may develop hypertrophic pyloric stenosis after taking tasteless erythromycin, and pseudomembranous colitis has been reported following oral erythromycin use. During erythromycin therapy, urinary catecholamines, 17-hydroxycorticosteroids, and serum transaminase levels may increase, while serum folate and urinary estradiol levels may decrease. Concurrent use with theophylline derivatives may increase theophylline blood concentrations, necessitating dose reduction or avoidance of combined use.
Given that erythromycin causes significant gastrointestinal irritation, may elevate serum bilirubin and transaminase levels, and has reports of resistant strains emerging, people have begun opting for newer macrolide products such as roxithromycin, clarithromycin, and azithromycin. These are well-tolerated orally, exhibit strong tissue penetration, can infiltrate cells, have a long half-life, and an MIC of 0.002–0.03 mg/L. In recent years, leucomycin has shown good efficacy in treating this condition in Japan. This drug has no significant toxic side effects and is relatively safe. The oral dosage is 20–40 mg/(kg·d), divided into four doses; the intravenous drip dosage is 10–20 mg/(kg·d).
(2) Tetracycline antibiotics Although tetracyclines have confirmed efficacy against MP infections, they carry numerous toxic side effects. Notably, tetracycline affects bone and tooth growth—even short-term use can lead to tetracycline pigments binding with calcium in newly formed bones and teeth, causing yellowing of deciduous teeth. Therefore, it should not be used in children under 7 years of age.
(3) Chloramphenicol and sulfonamides Because the treatment course for MP infections is prolonged, and chloramphenicol and sulfonamide antibiotics have significant toxic side effects, they are not suitable for long-term use. Thus, they are less commonly employed clinically for MP infections.
(4) Fluoroquinolones In recent years, there have been reports of using fluoroquinolone drugs to treat MP infections. Fluoroquinolones are synthetic antibacterial agents that exert their effects by inhibiting DNA gyrase and blocking DNA replication. Drugs such as ciprofloxacin and ofloxacin achieve high concentrations in lung and bronchial secretions, penetrate cell walls, and have a long half-life of 6.7–7.4 hours. With a broad antibacterial spectrum, they are highly effective against MP. The former is administered at 10–15 mg/(kg·d), divided into 2–3 oral doses or intravenous drips; the latter is given at 10–15 mg/(kg·d), divided into 2–3 oral doses, with a treatment course of 2–3 weeks.
4. Application of adrenal glucocorticoids
Because MP pneumonia is currently believed to result from the immune system's reaction to MP, adrenal corticosteroids may be used for severe, rapidly progressing MP pneumonia during the acute phase, or for cases with prolonged pulmonary lesions leading to atelectasis, pulmonary interstitial fibrosis, bronchiectasis, or extrapulmonary complications. Examples include hydrocortisone or hydrocortisone succinate at 5–10 mg/kg per dose via intravenous drip; dexamethasone at 0.1–0.25 mg/(kg·dose) via intravenous drip; or prednisone at 1–2 mg/(kg·d), divided into oral doses. The typical treatment course is 3–5 days. When using corticosteroids, care should be taken to rule out infections such as subcutaneous nodules.
5. Treatment of extrapulmonary complications
Current understanding suggests that complications arise due to immune mechanisms. Therefore, in addition to actively treating pneumonia and controlling MP infection, corticosteroids may be administered based on the condition, with symptomatic management tailored to different complications.
Rest, care, and diet should be emphasized. Small doses of antipyretics may be taken if necessary, along with Chinese medicinals. Other symptomatic treatments are the same as those described in the bronchitis section. Mycoplasma is sensitive to tetracyclines and macrolide antibiotics, with erythromycin being the drug of choice. A dose of 30mg/(kg·d), taken orally three times a day, can improve clinical symptoms, reduce lung shadows, and shorten the course of the disease. The treatment course for erythromycin is 2–3 weeks. Additionally, miocamycin, rifampicin, and acetylspiramycin are also effective. Severe cases may require the addition of adrenal corticosteroids. The prognosis is good; although the course of the disease may sometimes be prolonged, complete recovery is ultimately achieved. Complications are rare, with only occasional occurrences of otitis media, pleural effusion, hemolytic anemia, myocarditis, pericarditis, meningoencephalitis, and mucocutaneous syndrome. However, relapses may occasionally occur, and sometimes lung lesions and pulmonary function recover slowly.
In recent years, there has been considerable research abroad on Mycoplasma pneumoniae vaccines, leading to the development of both inactivated and live attenuated vaccines. Wenzel (1977) observed that formalin-inactivated Mycoplasma pneumoniae vaccines showed some effectiveness.
This disease sometimes needs to be differentiated from the following conditions: ① pulmonary subcutaneous nodules; ② bacterial pneumonia; ③ whooping cough; ④ cold-damage disease; ⑤ infectious mononucleosis; ⑥ wind-dampness pneumonia. Differentiation can be made based on medical history, subcutaneous nodule tuberculin test, X-ray follow-up observations, bacteriological examinations, and serological reactions.
