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Acute respiratory tract infections (RTIs), both upper (URTIs) and lower respiratory tract infections (LRTIs), are the most common reason for consultation with a general prac- titioner. RTIs result in about 180 million antibiotic prescrip- tions per year in the EU-27 member states (ESAC website, 2008; www.esac.ua.ac.be), and 6.4 million antibiotic prescrip- tions were prescribed for acute bronchitis and cough in 2003 in adults between 16 and 64 years old in the United States (65). The number of pathogens involved in LRTI, with various susceptibilities to antimicrobials, is large constituting an enor- mous challenge for diagnostic microbiology. In general, in only 50% of cases is an etiologic agent detected. Documented in- fection is uncommon in community-managed infection and is usually only defined in 25 to 50% of hospital-managed infec- tions. The upper end of the respiratory tract, the rhinopharynx, is widely open to the introduction of airborne microorganisms. It is, however, also a very efficient barrier for invading bacteria. The barrier function of the rhinopharynx results from the local lymphoid tissue producing phagocytic cells and secretory im- munoglobulin (Ig) and from the rich commensal flora of aerobic and anaerobic microbes establishing an interfering col- onization resistance. The number of these organisms varies from 2.6 104 to 4 108 CFU of cultivable bacteria per cm2 (95). Aerobes tend to decrease and anaerobes tend to increase with age (98). Colonization starts during the first year of life and is com- posed not only of commensal organisms but also of potential pathogens: group A -hemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrha- lis. These are present permanently or intermittently, with rates varying with age (decreasing in adults), exposure to other chil- dren, geographic location, socioeconomic status, and vaccina- tion status (39). In most cases, these organisms cause disease in only a small percentage of persons colonized. Viruses do not normally colonize the rhinopharynx. However, most bacterial respiratory infections start with or are accompanied by their proliferation in the nasopharynx. Thus, the URT with its commensal flora acts both as a defense mechanism and as a primary site for LRTI, which creates tremen- dous diagnostic challenges. Any bacteriological examination of nonsterile respiratory specimens must indeed distinguish between organisms infect- ing the LRT and organisms colonizing the rhinopharynx. Nor- mally sterile samples therefore are considered the "gold stan- dard." Different specimens commonly collected to detect patho- gens causing LRTI have been compared, but the results were not consistent (12, 43, 49, 58, 103) (Table 1; and see Table S1 in the supplemental material). This minireview presents an overview of the optimal detection of Streptococcus pneu- moniae, Haemophilus influenzae, Moraxella catarrhalis, Myco- plasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, and respiratory viruses from specimens in pa- tients with community-associated (CA)-LRTI (Table 2).

Optimal Sampling Sites and Methods for Detection of Pathogens Possibly Causing Community-Acquired Lower Respiratory Tract Infections