Infectious Diseases in Clinical Practice:
Community-Onset Staphylococcus aureus Lower Respiratory Tract Infections: A Young Man’s Foe?
Oosterheert, Jan Jelrik MD, PhD; Hoepelman, Andy I.M. MD, PhD; Written as an editorial commentary regarding Tosh et al. Characterization of Hospitalized Community-Onset Staphylococcus aureus Lower Respiratory Tract Infections Among Generally Healthy Persons 50 Years of Age or Younger on pages (359–365) of the Journal.
From the Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, The Netherlands.
Correspondence to: Andy I.M. Hoepelman, MD, PhD, Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Room F02-126; PO Box 85500; 3508 GA Utrecht, The Netherlands. E-mail: firstname.lastname@example.org.
The authors have no funding or conflicts of interest to disclose.
In this issue, Tosh et al1 describe the demographic and clinical characteristics of patients younger than 50 years needing hospitalization because of community-acquired lower respiratory tract infections caused by Staphylococcus aureus. In addition, they explore potential associations of such infections with influenza by evaluating data from a large structured surveillance.1
The authors bring up some interesting points, which are partially addressed in this study, but also give rise to additional questions that may guide future research. For example, the incidence and mortality of community-acquired pneumonia caused by S aureus, especially during influenza epidemics, has been questioned for years.2 In the present study, the authors identified 94 cases of community-acquired S aureus lower respiratory tract infection (CA-SA-LRTI) in a 2-year period in 5 metropolitan areas in the United States. Although this sketches the contours of the incidence, a more precise estimate can only be made when the total number of persons in the catchment area is clear. This may be important to know to advice on empirical treatment strategies for community-acquired pneumonia, especially in influenza seasons. Now, empirical treatment for (methicillin resistant) CA-SA-LRTI is only considered in severely ill patients needing ICU admission, in patients with classical risk factors such as those presenting with cavitary lesions or after proven influenza infection, in those who have bronchiectasis or pulmonary obstructions, or in patients who use intravenous drugs.3 From the present study, we learn that S aureus occurred in patients without any comorbid condition and across all age groups, albeit more prevalent in the higher age groups (60% occurred in the highest age group). This gives direction in our thoughts on risk factors for CA-SA-LRTI, but some questions remain. Whether CA-SA-LRTI is really a young man’s foe and whether S aureus is overrepresented in the younger age group can only be determined if data are also available for the elderly. As the elderly seemed to be relatively protected from H1N1, the role of influenza is especially interesting. In their exploration of the possible role of influenza in CA-SA-LRTI in the younger age group, the authors found no seasonality and only a quarter of patients tested for influenza when influenza was circulating had evidence of influenza infection. The authors conclude that influenza may facilitate the development of CA-SA-LRTI, but is no “condition sine qua non” for CA-SA-LRTI. This finding raises the question on how influenza facilitates bacterial superinfection, in what patients, and how it can be prevented. As this was not the primary research question, the authors do not further elaborate on the potential pathophysiological mechanism of bacterial superinfection after influenza, but the interplay between influenza and S aureus is interesting at least. Influenza viral neuraminidase cleaves respiratory epithelial cell sialic acids, facilitating bacterial adhesion and dissemination.4 The other way around, proteases secreted by certain strains of S aureus can cleave influenza hemagglutinin, an essential step required for influenza replication.5 This may guide future research in specific treatment options for bacterial coinfection of influenza. In a recent study, treatment with antibiotics for pneumococcal pneumonia in influenza-recovered mice led to lysis of the superinfecting bacteria and extensive influx of neutrophils causing severe lung damage, mediated through Toll-like receptor 2. Anti-inflammatory treatment with azithromycin prevented death in these mice.6 Whether treatment with additional macrolides has also clinical benefit in humans remains to be determined. It would therefore be interesting to evaluate treatment data of patients included in the current study to see what treatment was associated with beneficial outcome in these patients. Especially because despite 40% being admitted to the ICU and 36% being bacteremic in the Tosh study, the inhospital mortality was “only” 6%. This is comparable to community-acquired pneumonia cohorts with higher median ages and much lower than previous reports on CA-SA-LRTI.1,7,8 This might be explained by the absence of comorbidities in the current cohort; but also, these patients may have had more exposure to immunomodulatory macrolide treatment, as atypical pneumonia is more often considered in the young. Strikingly, only 55% of admitted patients with CA-SA-LRTI were tested for influenza during the influenza season. The cost-effectiveness of a strategy of influenza vaccination, especially with newer, cheaper influenza vaccines being expected, compared to a strategy that includes early case finding by means of influenza polymerase chain reaction and subsequent early treatment in younger patients without apparent comorbidities can be a future directive for study.9 In conclusion, community-onset lower respiratory tract infections caused by S aureus, especially in patients infected with influenza, have been a challenging condition for years. Many questions have been answered, but the relative contribution of younger patients without comorbidities, the potential role of anti-inflammatory treatment, and the cost-effectiveness of vaccination strategies for this patient group remain to be determined.
1. Tosh PK, Bulens SN, Nadle J, et al. Characterization of hospitalized, community-onset Staphylococcus aureus
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© 2013 by Lippincott Williams & Wilkins.