Mycoplasma pneumoniae infections – Does treatment help?
Introduction
Respiratory tract infections (RTI's) form a major burden of disease worldwide in children. The World Health Organization estimates that there are 150.7 million cases of pneumonia each year in children younger than 5 years of age, with as many as 20 million cases severe enough to warrant hospital admission.1 A wide range of pathogens may cause respiratory tract infections. One of the most common bacterial causes of both upper and lower RTI is Mycoplasma pneumoniae. This bacterium is of particular importance in children, in which it is the second most common bacterial cause of pneumonia after Streptococcus pneumoniae.2 In this review, we will focus on the treatment of RTI's caused by M. pneumoniae in children.
M. pneumoniae is a human pathogen from the bacterial class of Mollicutes (lat. soft skin). The common features shared by the bacteria in this class are1: the permanent lack of a rigid cell wall,2 relatively small cellular dimensions, and 3 a relatively small genome.3, 4, 5 As a consequence of the limited genomic size, M. pneumoniae has a limited metabolic capacity; the bacterium is thus dependent on its host for the production of crucial biomolecules, such as purines and pyrimidines.3 It is therefore imperative that M. pneumoniae be in close contact with its host to scavenge for nutrients. To establish a close association with the host respiratory epithelium, M. pneumoniae contains a specialized attachment organelle. This organelle consists of a number of adhesion proteins and accessory proteins that are essential for attachment.6, 7, 8 Loss of function of one of these proteins results in a non-virulent bacterium that is unable to attach to the human respiratory epithelium.9, 10
The clinical signs and symptoms of a M. pneumoniae RTI and available diagnostic assays have recently been reviewed elsewhere.11 In short, there are no clinical, biochemical or radiological findings that are pathognomonic or specific for an M. pneumoniae RTI. Although a clinical syndrome has previously been described that was considered to be characteristic for M. pneumoniae infections (i.e. ‘walking pneumonia’), a recent Cochrane review did not reveal any M. pneumoniae-specific clinical symptoms and signs.12 The diagnosis of an M. pneumoniae RTI therefore has to be supported by microbiological findings. At present, different diagnostic techniques are available, but all of these have drawbacks that should be taken into consideration before starting treatment for a presumed M. pneumoniae RTI.
Although culture media have been optimized over the years, bacterial culture is still an insensitive tool to detect M. pneumoniae in clinical samples. In addition, it has a long turnaround time and is both laborious and expensive. The culturing of M. pneumoniae is therefore rarely used as a diagnostic method for clinical purposes. The current diagnosis of M. pneumoniae RTI relies either on the detection of serum antibodies against M. pneumoniae (serology) or on the detection of bacterial DNA in samples from the upper respiratory tract, as recommended in the guidelines published by the British Thoracic Society and the Infectious Disease Society of America.13, 14
From a clinical point of view, serology is an inconvenient diagnostic tool since it requires a serum sample in the acute phase of the disease and a convalescent serum sample taken 2–4 weeks later to provide reliable results. This inherent retrospective aspect of serology is not helpful for clinicians to make a therapeutic management decision in the acute phase of the infection. As a consequence, clinicians often rely on single-sample IgM and IgG antibody titers in order to diagnose acute M. pneumoniae infections. Such a procedure, however, lacks predictive power. This was recently demonstrated in a study performed in the Netherlands, in which a similar range of single-sample M. pneumoniae IgM and IgG antibody titers was found in children with and without symptoms of an RTI.15
In the past two decades, a solution to the drawbacks of culture and serology has seemingly been provided by molecular diagnostic methods (based on nucleic acid amplification techniques, such as PCR), which can provide fast, sensitive, and specific results in the acute phase of an infection. Consequently, molecular methods are increasingly used in clinical practice, as well as in clinical studies for the detection of M. pneumoniae DNA. However, the above mentioned observational study on a population of children with and without signs of an RTI detected a similar prevalence of M. pneumoniae by real-time PCR in asymptomatic children and symptomatic children with 21.2% [95% CI 17.2%–25.2%] versus 16.2% [95% CI 12.2%–20.2%], respectively.15 A difference in M. pneumoniae genomic copy load in respiratory tract samples was not detected between the symptomatic and asymptomatic group. Real-time PCR therefore does not represent an unambiguous method for the diagnosis of symptomatic M. pneumoniae infections. The diagnostic accuracy did not improve when the PCR results were combined with serological data.15 Thus, at this moment, it appears that there is no definitive procedure that allows the reliable diagnosis of acute (symptomatic) infections with M. pneumoniae. Clearly, this notion has major consequences for the management of children with a symptomatic RTI and calls for novel procedures that allow discrimination between (harmless) carriage of M. pneumoniae and symptomatic infections caused by this bacterium.
Section snippets
Choice of antibiotics based on biological characteristics
M. pneumoniae lacks a rigid bacterial cell wall, but is instead protected by a sterol-containing membrane. As a direct result, M. pneumoniae has an innate resistance to any antibiotic that is directed at the destruction or disruption of a bacterial cell wall, such as beta-lactams and glycopeptides. In contrast, antibiotics that are directed at the inhibition of DNA metabolism and protein synthesis do have appropriate inhibitory activity against M. pneumoniae. The antibiotics with the best
Conclusion
At present, there is no clear evidence that antibiotic treatment of presumed M. pneumoniae RTI is effective. This lack of evidence, however, may be caused by1 the lack of appropriate diagnostic tools to diagnose symptomatic M. pneumoniae infections, and2 the lack of well-designed randomized controlled trials on antibiotic treatment for M. pneumoniae RTI. Studies on treatment results in children infected with MRMP demonstrate a significant reduction of duration of disease when treated with
Conflict of interest
The authors declare that there is no conflict of interest.
Acknowledgments
P.M.M.S. is funded by a Swiss National Science Foundation grant (PBZHP3_147290).
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