Viktorija Tomič
University Clinic of Respiratory and Allergic Diseases Golnik
Abstract
Microorganisms causing community-acquired pneumonia can be cathegorised into typical bacterial, atypical and viral. Identification of microbial pathogen causing CAP is an important issue for quality management of patients with CAP and is a big challenge for conventional methods. Development and implementation of molecular techniques for CAP has been a major advance in the microbiological diagnosis of respiratory pathogens and a step closer to optimal antimicrobial treatment of CAP.
Izvleček
Povzročitelje zunajbolnišničnih pljučnic lahko razvrstimo v tipične bakterijske, atipične in virusne patogene. Identifikacija povzročiteljev ZBP je pomembna za kakovostno obravnavo bolnikov s pljučnico in je velik izziv za konvencionalne mikrobiološke metode. Razvoj in uporaba molekularnih diagnostičnih metod pomeni velik napredek v mikrobiološki diagnostiki respiratornih okužb in predstavlja pomemben korak v smeri optimalnega protimikrobnega zdravljenja.
Introduction
Community-acquired pneumonia (CAP) is a global disease with substantial morbidity and mortality as well as significant economic cost. Estimates of annual incidence of CAP in various countries differ according to how the data was captured, the age of population, comorbidities, etc. Resent estimates of CAP incidence in the USA are 24.8 cases per 10.000 adults and 164.3 cases per 10.000 in adults aged over 80, in the Netherlands 172.4 cases per 10.000 adults aged 85 and over, in Germany 76.5 cases per 10.000 adults aged 65 and over, in United Kingdom 31.2 cases per 10.000 adults (1). Initial antimicrobial treatment of CAP is empiric and based on etiological studies which are used to determine the recommended treatment choices in national CAP management guidelines.
Etiology of pneumonia
For decades Streptococcus pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila spp., some viruses with influenza being the most important, were considered the major pathogens in CAP. In resent years molecular diagnostic tests have improved and became more widely used. As a consequence many recent etiologic studies demonstrated that a large portion of patients with pneumonia have viral pathogens and that multiple pathogens are frequently isolated from the same patient, typically the combination of one or more viruses and bacteria (2, 3). From a global perspective, etiology of CAP is not uniform and there are many differences in the most prevalent pathogens between different countries (1).
Therefore for the management of patients with CAP we should apply national guidelines based on local epidemiological data to avoid adverse outcome through inappropriate choices of empiric antimicrobial treatment.
The lung microbiome
Until recently we thought that the lungs are sterile but studies using novel molecular techniques have shown that the lungs are populated by diversity of microbial communities (4). These communities exist in the absence of infection and they are modified in the event of acute or chronic infection. The composition of the lung microbiome is determined by the balance of three factors: microbial immigration into the airways, elimination of microbes from the airways, and the relative reproduction rates of its community members, as determined by regional growth conditions. Of the dozens of studies that have compared the microbiota of diseased lungs with those of healthy subjects, virtually all have found significant differences in community composition (4). In the coming years with the better knowledge and understanding of the lung microbiome we will most probably change our view of the pathophysiology, treatment and prevention of pneumonia.
Microbiological diagnosis of etiology of CAP
In patients with CAP, microbiological testing should consist of at least a sputum culture, a urinary antigen test for S. pneumoniae and L. pneumophila, and a blood culture. When intensive microbiological investigation in studies with patients with CAP was performed the etiology was determined in 53 – 75% of cases (5). The most common pathogens detected in these studies were S. pneumoniae, M. pneumoniae and Haemophilus influenzae.
Sputum and blood cultures are not helpful for the decision on initial antimicrobial treatment but are very important for the choice of targeted treatment once specific pathogen has been isolated. In addition, isolating pathogens causing CAP from blood and/or sputum allows susceptibility testing which is important for monitoring trends in antimicrobial susceptibilities and subsequent empiric treatment recommendations.
Legionella urinary antigen is now generally available. The sensitivity of this test is 70-80% and specificity is 95 – 100% (5). In patients with severe CAP sensitivity increases to 88 – 100%. The test is easy to perform and the results are available in 15 minutes. Antigen tests are not affected by previous antimicrobial treatment (5).
Pneumococcal urinary antigen compared to sputum cultivation and blood cultures has the highest diagnostic yield and addition of this test to the diagnostic work-up may increase the number of patients with documented pneumococcal infection (5, 6).
Reported sensitivities for this test have ranged from 65 – 92% in adult patients with definite pneumococcal CAP (6). In most studies specificities have ranged between 80 – 100%. Positive test results may occur in children and in patients with exacerbation of COPD (5, 6).
Viral and atypical pathogens represent 10 – 22% and 11 – 28% of all CAP cases, respectively (5). Molecular techniques are better than microbiological cultures, are much less labour intensive, have rapid turnaround times but are still relatively expansive. Where available PCR is now considered the test of choice due to its high sensitivity and specificity. Recently, multiplex PCR platforms that detect a range of
respiratory viruses and atypical bacterial pathogens are increasingly being used in the clinical setting.
Advantages and disadvantages of different diagnostic methods
All methods used to determine the etiology of CAP have advantages as well as disadvantages. Advantages of bacterial cultivation are: they are easy to perform and cheap, they allow susceptibility testing. Disadvantages are long turnaround time (1 – 4 days), low sensitivity especially if samples are collected after starting antimicrobial treatment, sometimes difficult differentiation between pathogen and colonizing bacteria. Advantages of molecular assays are: rapid turnaround time (1 – 6 hours), high sensitivity and specificity, allows diagnosis early when bacterial load/viral load is low, lower influence of antibiotic pretreatment compared to cultivation, detection of some resistance markers. Disadvantages are cost, not all pathogens causing respiratory tract infections are included in the multiplex panel, doesn’t determine susceptibility to all antibiotics thus conventional antibiogram remains the “gold standard”.
Conclusions
Combination of conventional and molecular techniques will improve our ability to determine the causative agent of CAP more rapidly and precisely. This will ensure that patients receive the most appropriate antimicrobial treatment and subsequently may reduce the overuse of broad-spectrum antibiotics. National guidelines should incorporate algorithms of recommended microbiologic diagnostic testing to establish the etiology of CAP in majority of patients. Finally, the concept of lung microbiome will definitely influence and change our understanding of pulmonary infection, how to prevent it and how to improve its treatment.
Reference:
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