Mycoplasma pneumoniae may be suspected as a pathogen in pneumonia, because it is one of the most common pathogens of pneumonia in the community. The diagnosis may be made clinically, although blood counts, blood biochemistry, pulse oximetry, and chest x-ray are usually performed in patients with severe disease.
Diagnostic testing to confirm M pneumoniae as the infecting pathogen remains controversial. In general, microbiological investigations are not recommended unless disease is moderate or severe/the patient is hospitalized, as results do not usually change management.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
[31]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.doi.org/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Microbiological investigations may also be warranted in the setting of an outbreak or during epidemic mycoplasma years.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
According to Japanese Respiratory Society (JRS) guidelines, the following six factors increase the likelihood of atypical pneumonia such as that caused by M pneumoniae:[32]Miyashita N, Matsushima T, Oka M, et al. The JRS guidelines for the management of community-acquired pneumonia in adults: an update and new recommendations. Intern Med. 2006;45(7):419-28.
https://www.doi.org/10.2169/internalmedicine.45.1691
http://www.ncbi.nlm.nih.gov/pubmed/16679695?tool=bestpractice.com
<60 years of age
Absence of or only minor underlying disease
Paroxysmal cough
Abnormal findings on chest auscultation
Absence of sputum or presence of an identifiable etiologic agent by rapid diagnostic testing
Peripheral white blood cell count <10,0000/mm³.
A study that validated the JRS guidelines found that if four or more of these factors were present, M pneumoniae was easily discriminated from the other pathogens with high sensitivity (88.7%) and moderate specificity (77.5%).[33]Yin YD, Zhao F, Ren LL, et al. Evaluation of the Japanese Respiratory Society guidelines for the identification of Mycoplasma pneumoniae pneumonia. Respirology. 2012 Oct;17(7):1131-6.
http://www.ncbi.nlm.nih.gov/pubmed/22805282?tool=bestpractice.com
These findings have not yet been validated in populations outside of Japan.
Clinical evaluation
The first step in suspected pneumonia is usually to evaluate the patient based on a detailed history and a physical exam. In M pneumoniae infection, patients may present with symptoms including an unresolved persistent cough, low-grade fever, headache, hoarseness, rash, and, rarely (5%), bullous myringitis. Recent exposure to infected individuals and living in a close community may raise suspicion of M pneumoniae infection. Younger people and smokers may be at increased risk.
Laboratory evaluation
All patients admitted to hospital with suspected pneumonia should have the following investigations:[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
In M pneumoniae infection, a complete blood count may reveal leukocytosis and hemolytic anemia. Elevated liver enzymes and urea are associated with severe disease.
Imaging
Patients admitted to hospital with suspected pneumonia should have a chest x-ray to confirm the diagnosis. Chest x-ray is not required in nonhospitalized patients unless it will help with management of the acute illness.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
In M pneumoniae infection, infiltrates may be seen, which may provide a worse clinical picture than expected, given the patient's symptoms.
Results from small studies suggest that computed tomography (CT) lung scans may improve the diagnosis of pneumonia; however, evidence remains insufficient to routinely recommend CT scans for this purpose.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
[34]Miyashita N, Sugiu T, Kawai Y, et al. Radiographic features of Mycoplasma pneumoniae pneumonia: differential diagnosis and performance timing. BMC Med Imaging. 2009 Apr 29;9:7.
https://www.doi.org/10.1186/1471-2342-9-7
http://www.ncbi.nlm.nih.gov/pubmed/19400968?tool=bestpractice.com
[35]Saraya T, Ohkuma K, Tsukahara Y, et al. Correlation between clinical features, high-resolution computed tomography findings, and a visual scoring system in patients with pneumonia due to Mycoplasma pneumoniae. Respir Investig. 2018 Jul;56(4):320-5.
http://www.ncbi.nlm.nih.gov/pubmed/29764747?tool=bestpractice.com
Microbiological investigations
The decision to perform microbiological investigations should be based on clinical presentation, local etiological considerations, and local antimicrobial stewardship processes. In general, testing is limited to patients with moderate or severe disease, including those who are hospitalized.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
[31]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.doi.org/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[36]Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44(2 suppl):S27-72.
https://www.doi.org/10.1086/511159
http://www.ncbi.nlm.nih.gov/pubmed/17278083?tool=bestpractice.com
Microbiological investigations may also be warranted in the setting of an outbreak or during epidemic mycoplasma years.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
Please consult relevant local guidelines for further guidance on microbiological testing in your region.
Nucleic acid amplification tests (NAATs)
Use of NAATs, specifically polymerase chain reaction (PCR)-based assays, have become increasingly widespread for the detection of M pneumoniae owing to their high sensitivity and quick turnaround times compared to culture and serology-based methods.[9]Beeton ML, Zhang XS, Uldum SA, et al. Mycoplasma pneumoniae infections, 11 countries in Europe and Israel, 2011 to 2016. Euro Surveill. 2020 Jan;25(2):1900112.
https://www.doi.org/10.2807/1560-7917.ES.2020.25.2.1900112
http://www.ncbi.nlm.nih.gov/pubmed/31964459?tool=bestpractice.com
[37]Leal SM Jr, Totten AH, Xiao L, et al. Evaluation of commercial molecular diagnostic methods for detection and determination of macrolide resistance in Mycoplasma pneumoniae. J Clin Microbiol. 2020 May 26;58(6):e00242-20.
https://www.doi.org/10.1128/JCM.00242-20
http://www.ncbi.nlm.nih.gov/pubmed/32269102?tool=bestpractice.com
If an atypical pathogen such as M pneumoniae is suspected, it is best to confirm the diagnosis using PCR of a sputum or other respiratory sample (e.g., nose and throat swabs) because it may have implications for duration of therapy.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
[31]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.doi.org/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[38]Lim WS, Baudouin SV, George RC, et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(3 suppl):iii1-55.
http://thorax.bmj.com/content/64/Suppl_3/iii1.full.pdf+html
http://www.ncbi.nlm.nih.gov/pubmed/19783532?tool=bestpractice.com
[39]Loens K, Ieven M. Mycoplasma pneumoniae: current knowledge on nucleic acid amplification techniques and serological diagnostics. Front Microbiol. 2016;7:448.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814781
http://www.ncbi.nlm.nih.gov/pubmed/27064893?tool=bestpractice.com
[40]Diaz MH, Winchell JM. The evolution of advanced molecular diagnostics for the detection and characterization of Mycoplasma pneumoniae. Front Microbiol. 2016;7:232.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781879
http://www.ncbi.nlm.nih.gov/pubmed/27014191?tool=bestpractice.com
In the US, five different commercial assays are approved for this purpose: four of these detect multiple respiratory pathogens (M pneumoniae, Chlamydia pneumoniae, and Legionella species), with one assay specific to M pneumoniae.[37]Leal SM Jr, Totten AH, Xiao L, et al. Evaluation of commercial molecular diagnostic methods for detection and determination of macrolide resistance in Mycoplasma pneumoniae. J Clin Microbiol. 2020 May 26;58(6):e00242-20.
https://www.doi.org/10.1128/JCM.00242-20
http://www.ncbi.nlm.nih.gov/pubmed/32269102?tool=bestpractice.com
Culture with or without Gram stain
Blood and sputum culture is recommended in all patients with severe pneumonia by the Infectious Diseases Society of America and the American Thoracic Society, and in all patients with moderate- and high-severity pneumonia by the British Thoracic Society.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
[31]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.doi.org/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Nasopharyngeal viral diagnostics can be used for differential diagnosis of viral pneumonia.[3]Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring hospitalization among US children. N Engl J Med. 2015;372:835-45.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697461
http://www.ncbi.nlm.nih.gov/pubmed/25714161?tool=bestpractice.com
Specific cultures for M pneumoniae are relatively insensitive compared to NAATs. The growth rate of M pneumoniae is also slow, and there is a requirement for specialized media.[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
[31]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.doi.org/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
Sputum Gram stain may be available in some regions; however, it will not detect M pneumoniae due to lack of a cell wall.
Serology
Serology to detect antibodies against M pneumoniae (specifically IgM, IgG, and IgA) may be useful as an adjunctive test to help support the diagnosis. However, caution is needed when interpreting findings due to risk of false-positive results.[9]Beeton ML, Zhang XS, Uldum SA, et al. Mycoplasma pneumoniae infections, 11 countries in Europe and Israel, 2011 to 2016. Euro Surveill. 2020 Jan;25(2):1900112.
https://www.doi.org/10.2807/1560-7917.ES.2020.25.2.1900112
http://www.ncbi.nlm.nih.gov/pubmed/31964459?tool=bestpractice.com
[30]British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Jan 2015 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/pneumonia-adults
Convalescent serum takes 2-4 weeks after the infection to show an increase in specific antibody levels, and so serology cannot be used to influence treatment.
Serology lacks sensitivity and specificity for reasons including high prevalence of background antibodies in healthy individuals and lack of an IgM response in older adults.[37]Leal SM Jr, Totten AH, Xiao L, et al. Evaluation of commercial molecular diagnostic methods for detection and determination of macrolide resistance in Mycoplasma pneumoniae. J Clin Microbiol. 2020 May 26;58(6):e00242-20.
https://www.doi.org/10.1128/JCM.00242-20
http://www.ncbi.nlm.nih.gov/pubmed/32269102?tool=bestpractice.com
Available assay types include the complement fixation test and enzyme immunoassays; performance of these assays varies significantly between laboratories.[41]Nir-Paz R, Michael-Gayego A, Ron M, et al. Evaluation of eight commercial tests for Mycoplasma pneumoniae antibodies in the absence of acute infection. Clin Microbiol Infect. 2006 Jul;12(7):685-8.
https://www.doi.org/10.1111/j.1469-0691.2006.01469.x
http://www.ncbi.nlm.nih.gov/pubmed/16774570?tool=bestpractice.com
Antigen testing
In some regions (e.g., Japan) antigen testing is available for diagnosis; however, comparative data on sensitivity and specificity is not yet widely available.[42]Saraya T. Mycoplasma pneumoniae infection: basics. J Gen Fam Med. 2017 Jun;18(3):118-25.
https://www.doi.org/10.1002/jgf2.15
http://www.ncbi.nlm.nih.gov/pubmed/29264006?tool=bestpractice.com