Community-Acquired Pneumonia: Etiology, Epidemiology, and Treatment

Dynamic host–pathogen relationships take place at the mucosal epithelia of the respiratory and gastrointestinal tracts. The nasal mucosa harbors a rich microbial community that transitions to a relatively sparse microbiome in the lung; in contrast, pathogenic interactions in the gut must override an abundant commensal flora. In all these sites, pathogens exploit normal host cell processes to their advantage. Co-opting the host's machinery implies that diverse pathogens target similar receptors and that common themes of pathogenesis can be elucidated. This is especially true of the respiratory tract and may form the basis of medical interventions. Virtually all mucosal pathogens adhere to and then invade the epithelial cells of their target organ. The details of these interactions are discussed in the framework of not only cell biology, but also the host response. The innate and adaptive immune responses are as critical to eliminating the pathogens as to causing symptoms secondary to inflammation.

Respiratory infections are a major cause of morbidity and mortality worldwide. A high percentage of all respiratory tract infections are caused by RNA viruses. Real-time PCR is a highly sensitive method for the detection of respiratory viruses in clinical samples. A good RNA isolation protocol is of high importance, since RNA is more unstable than DNA and many clinical samples contain RNAses.

To evaluate the performance of three different RNA extraction protocols for the extraction of respiratory viral RNA from sputum samples obtained from patients with the suspicion of a viral respiratory tract infection.

A total of 50 sputum samples, PCR positive for a respiratory RNA virus, were used for viral RNA isolation with the phenol/chloroform method, RTP^® DNA/RNA virus mini kit and the automated MagNa Pure LC (MPLC) extraction system. After isolation, real-time PCR was performed for the detection of viral RNA in the sputum samples.

The MPLC extraction increased the detection probability from 82% (phenol/chloroform) and 86% (RTP^® DNA/RNA virus mini kit) to 94%. In 16% the RTP^® DNA/RNA virus mini kit resulted in lower C_t values compared to the phenol/chloroform method, while in 32% the phenol/chloroform resulted in lower C_t values.

The extraction of viral RNA performed with the MPLC extraction method was superior to the extraction with the RTP^® DNA/RNA virus mini kit and to the extraction with phenol/chloroform. In general, there was no difference in the detection of viral RNA between the phenol/chloroform extraction method and the RTP^® DNA/RNA virus mini kit.

This study presents the results of a survey of the in-vitro susceptibility to antimicrobial agents of major pathogens responsible for community-acquired respiratory tract infections in Poland during 2002–2004. The collection of 1184 bacterial isolates comprised 398 Streptococcus pneumoniae, 344 Haemophilus influenzae, 302 Streptococcus pyogenes and 140 Moraxella catarrhalis. Among the pneumococcal isolates, 16.8% were penicillin-non-susceptible (PNSP), of which 80.6% were identified as multidrug-resistant. Overall, 9.0% of H. influenzae isolates were β-lactamase-positive, although this percentage increased noticeably in the third year of the study. Based on PCR results, 12.8% of H. influenzae isolates were identified as low-level β-lactamase-negative, ampicillin-resistant (BLNAR), and one isolate as low-level β-lactamase-positive, amoxycillin–clavulanic acid-resistant (BLPACR). Pulsed-field gel electrophoresis (PFGE) classified 45 H. influenzae isolates with altered penicillin-binding proteins into 15 PFGE types, including two predominant types (with four and six sub-types) containing 15 and ten isolates, respectively. Resistance to tetracycline, erythromycin and clindamycin was found in 20.9%, 8.9% and 4.6% of S. pyogenes isolates, respectively. The production of β-lactamase characterised 91.4% of M. catarrhalis isolates. In summary, the overall occurrence of PNSP in Poland remains stable, although there was a noticeable increase in the proportion of fully-resistant isolates. A rising trend in the prevalence of β-lactamase producers and low-level BLNAR isolates was observed among Polish isolates of H. influenzae.

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. The inability or failure of many subjects to adhere to standard antibiotic regimens, which may last up to 10 days, results in suboptimal antibiotic treatment. Treatment with a single-dose antibiotic regimen may improve compliance with prescribed therapy. A novel microsphere formulation of azithromycin provides a single-dose regimen while maintaining tolerability.

To compare the efficacy and safety of a single 2.0-g dose of azithromycin microspheres to that of an extended-release formulation of clarithromycin (1.0 g/d for 7 days) for the treatment of adults with mild-to-moderate CAP.

A phase III, multinational, multicenter, randomized, double-blind, double-dummy study, comparing single-dose azithromycin microspheres to extended-release clarithromycin, both administered orally.

Subjects with mild-to-moderate CAP (Fine class I and II) were included. The primary end point was clinical response at the test-of-cure (TOC) visit (days 14 to 21) in the clinical per protocol (CPP) population. The bacteriologic response at the TOC visit was assessed in subjects with a baseline pathogen.

A total of 501 subjects were randomized, and 499 were treated. Clinical cure rates at the TOC visit in the CPP population were 92.6% (187 of 202 subjects) for azithromycin microspheres and 94.7% (198 of 209 subjects) for extended-release clarithromycin. Overall pathogen eradication rates were 91.8% (123 of 134 subjects) for azithromycin microspheres and 90.5% (153 of 169 subjects) for extended-release clarithromycin. Both agents were well tolerated. The incidence of treatment-related adverse events was 26.3% with azithromycin microspheres and 24.6% with extended-release clarithromycin. Most adverse events were mild to moderate in severity.

A single 2.0-g dose of azithromycin microspheres was as effective and well tolerated as a 7-day course of extended-release clarithromycin in the treatment of adults with mild-to-moderate CAP.