Fatal Outcomes Following Family Transmission of M. pneumoniae
Abstract & Commentary
Fatal Outcomes Following Family Transmission of M. pneumoniae
By Dean L. Winslow, MD, FACP, FIDSA, Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.
Dr. Winslow is a consultant for Siemens Diagnostic.
Source: Kannan TR, et al. Fatal outcomes in family transmission of Mycoplasma pneumoniae. CID 2012;54:225-31.
A retrospective study was conducted on members of one family following the deaths of a 15 year old boy and his 13 year old sister. Airway, CSF and serum samples were collected from the two fatal cases. Serum was collected from the three remaining ill siblings and both parents. Autopsy evaluation of sibling 1 showed cerebral edema (consistent with out of hospital cardiorespiratory arrest and anoxic encephalopathy) and pulmonary findings consistent with bronchiolitis obliterans with organizing pneumonia (BOOP) in both. Postmortem examination of sibling 2 revealed lymphoplasmacytic bronchiolitis with intraluminal purulent exudate, BOOP, and pulmonary edema. Detailed examination of lung tissue from sibling 2 confirmed the presence of M.pneumoniae organisms by immunohistochemical and immunoelectron microscopic methods. Mycoplasma was also cultured directly from sibling 2 lung tissue. Autopsy tissue from sibling 2 was positive by immunohistochemical staining for the presence of community-acquired respiratory distress syndrome (CARDS) toxin.
Commentary
This report captured my attention for a number of reasons. The first was that at a human level, I was touched by the tragedy of the sudden deaths of two previously healthy teenagers from what I generally regarded as a seldom-fatal cause of atypical pneumonia. The second was that our Infectious Diseases consult service at our hospital was recently involved in the management of a previously healthy middle-aged woman who had multilobar pneumonia due to M. pneumoniae (confirmed by PCR of tracheal aspirate and serology) and despite initial treatment with a macrolide went on to rapidly develop an ARDS picture and respiratory failure requiring prolonged mechanical ventilation. Open lung biopsy in her case also revealed severe bronchiolitis obliterans. She did survive but required heroic levels of care in the ICU including high-frequency ventilation. As in the two fatal cases described in this case series, our patient had developed respiratory symptoms about 2 weeks before she developed respiratory failure, suggesting that the BOOP picture represented a reparative response to the initial infection.
While M. pneumoniae is usually thought of as producing a relatively mild community-acquired pneumonia ("walking pneumonia") the fact is that severe and fatal cases have been reported sporadically in the literature over the past 45 years. Since we do not regularly look for evidence of M. pneumoniae in cases of BOOP it is likely that many cases of this idiopathic condition may be due to antecedent infection with M.pneumoniae. As with all diseases, it is likely that both host factors and pathogenic characteristics of the infecting organism contribute to severe M. pneumoniae infections. The same group from San Antonio who reported this tragic case series previously described an adenosine diphosphate-ribosylating and vacuolating cytotoxin (CARDS toxin) which has been shown to be correlated with severe disease in experimentally-infected mice and shares similarities to the toxin of Bordetella pertussis.1 In fact, recombinant CARDS toxin alone elicits airway damage and perivascular cellular inflammation in baboons and mice after experimental inoculation.2
This case series is also concerning in light of the recent epidemic of M. pneumoniae infection which occurred in two waves in Denmark in 2010 and 2011.3 While primary macrolide resistance was unusual in the Denmark epidemic (1-3%), rates of macrolide resistance in the Midwestern U.S. were shown to be 8.2% in 2007-2010.4 Macrolide resistance rates as high as 90% have been reported in China.5
It is clear that M.pneumoniae should be considered in the differential diagnosis of severe pneumonia complicated by respiratory failure. Due to the significant amount of macrolide resistance now being seen, the use of fluoroquinolones or doxycycline (rather than macrolides) should be considered in patients with severe atypical pneumonia. However, it should be noted that it is unclear what the impact of macrolide resistance (or antibiotic therapy per se) is in patients who already have established bronchiolitis obliterans (with or without organizing pneumonia) since this particular manifestation is likely in part related to host response to the infection.
References
- Kannan TR, et al. ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinants among bacterial pathogens. Proc Natl Acad Sci USA 2006;103:6724-9.
- Hardy RD, et al. Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin. PLoS One 2009;4e:7652.
- Uldum SA, et al. Epidemic of Mycoplasma pneumoniae infection in Denmark, 2010 and 2011. Euro Surveill 2012;17(5): pii=20073.
- Yamada M, et al. Rising rates of macrolide-resistant Mycoplasma pneumoniae in the central United States. Ped Infect Dis Jrl 2012: 31: 409-11.
- Liu Y, et al. Characterization of macrolide resistance in Mycoplasma pneumoniae isolated from children in Shanghai, China. Diagn Microbiol Infect Dis 2010;67:355-8.
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