A. Torres

Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults

Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW® immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone

A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to β-lactam empirical treatment decreases mortality rates. Patients admitted to the intensive care unit were excluded. Severity was assessed using the PORT score. An etiological diagnosis was achieved in 498 (35.8%) patients (292 infections due to Streptococcus pneumoniae). Treatment was chosen by the attending physician according to his/her own criteria: β-lactam agent in 270 and β-lactam agent plus a macrolide in 918 cases. The mortality rate was 13.3% in the group treated with a β-lactam agent alone and 6.9% in the group treated with a β-lactam agent plus a macrolide (p=0.001). The percentage of PORT-group V patients was 32.6% in the group treated with a beta-lactam agent alone compared to 25.7% in the group who received a β-lactam agent plus a macrolide (p=0.02). After controlling for PORT score, the odds of fatal outcome was two times higher in patients treated with a beta-lactam agent alone than in those treated with a β-lactam agent plus a macrolide (adjusted OR = 2, 95%CI 1.24–3.23). The results suggest that the addition of a macrolide to an initial β-lactam-based antibiotic regimen is associated with lower mortality in patients with community-acquired pneumonia, independent of severity of infection, thus supporting the recommendation of a β-lactam-agent plus a macrolide as empirical therapy.

C-reactive protein levels in community-acquired pneumonia

The diagnostic value of C-reactive protein (CRP) admission serum levels as an indicator of the aetiology of community-acquired pneumonia (CAP) was evaluated. A cohort of 1,222 patients with CAP was assessed. CRP levels were analysed in 258 patients with a single aetiological diagnosis. The mean CRP values in patients with pyogenic, atypical, viral and Legionella pneumophila pneumonia were: 16 mg·dL−1, 13 mg·dL−1, 14 mg·dL−1 and 25 mg·dL−1, respectively. CRP levels were not significantly different among patients outcome research team (PORT) groups (19 mg·dL−1 in groups I–II, 16 mg·dL−1 in group III and 16 mg·dL−1 in groups IV–V. A cut-off point of 25 mg·dL−1 had a sensibility, specificity, positive predictive value and negative predictive value of 0.6, 0.83, 0.3, and 0.94, respectively. After controlling for age and PORT score, the odds of having a CRP level >25 mg·dL−1 was 6.9 times higher in patients with L. pneumophila pneumonia than in those with non-L. pneumophila pneumonia. Patients with Legionella pneumophila pneumonia had higher C-reactive protein levels than those with pneumonia of any other aetiology, independently of severity of infection. Being a cheap and readily available test, C-reactive protein may be a useful adjunctive procedure in the diagnosis of community-acquired pneumonia.

Virological diagnosis in community-acquired pneumonia in immunocompromised patients

Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality in immunocompromised patients. The present study evaluated the clinical spectrum of CAP in immunocompromised hosts and the role of respiratory viruses, as well as the yield of viral diagnostic methods. Conventional microbiological tests were routinely performed in immunocompromised patients with CAP. Nasopharyngeal swabs were processed for respiratory viruses by indirect immunofluorescence assay, cell culture and PCR. Four groups were defined according to aetiology of CAP, as follows: group 1 (nonviral), group 2 (mixed, nonviral and viral), group 3 (only viral) and group 4 (unknown aetiology). Over a 1-yr period, 92 patients were included. An aetiological diagnosis was achieved in 61 (66%) patients: 38 (41%), group 1; 12 (13%), group 2; and 11 (12%), group 3. The most frequent pathogen detected was Streptococcus pneumoniae (n = 29, 48%), followed by rhinovirus (n = 11, 18%). PCR identified 95% of respiratory viruses. Clinical characteristics could not reliably distinguish among the different aetiological groups. Respiratory viruses represent a substantial part of the aetiologies of community-acquired pneumonia in immunocompromised patients and its routine assessment through PCR in nasopharyngeal swabs should be considered in the clinical care of these patients.

An experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated piglets

The objectives of the study were to validate a model of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in ventilated piglets and to study the time-course of biological markers and histopathological changes. 12 piglets were intubated and inoculated with 15 mL of a suspension of 106 colony forming units of MRSA in every lobe through the bronchoscope channel. The piglets were ventilated for 12 h (n = 6) and 24 h (n = 6). Clinical parameters were assessed every 6 h and pro-inflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL) at baseline and sacrifice. Histopathology of each lobe and cultures from blood, lungs and BAL were performed. Animals developed histopathological evidence of pneumonia at necropsy. At 12 h, pneumonia was present in all animals and was severe pneumonia at 24 h. Microbiological studies confirmed the presence of MRSA. A significant increase in interleukin (IL)-6, IL-8 and tumour necrosis factor-&agr; values was seen in BAL at 24 h and IL-6 at 12 h. In serum, only IL-6 levels had increased significantly at 24 h. In ventilated piglets, bronchoscopic inoculation of MRSA induces pneumonia at 12 h and severe pneumonia at 24 h. This severity was associated with a corresponding increase in systemic and local inflammatory response.

What lessons have been learnt from animal models of MRSA in the lung

Staphylococcus aureus is one of the most common causes of nosocomial pneumonia contributing to significant morbidity and mortality. Therapeutic options for patients with methicillin-resistant S. aureus (MRSA) infection are limited. In addition, little is known about the S. aureus virulence factors that may influence the presentation and prognosis of severe lower respiratory tract infections. Animal models of severe pneumonia allow investigators to control and exclude potential confounders and to examine the influence of comorbid conditions. Therefore, these models may improve our knowledge of the intimate pathophysiological mechanisms affecting pharmacodynamics, pharmacokinetics and efficacy of therapy. So far, animal research studies on MRSA and vancomycin-resistant S. aureus, performed both in small and large animal models, have improved knowledge of the mechanisms of disease, which may lead to a better treatment for this severe and complex infection in humans.