Streptococcus pyogenes Pneumonia in Adults: Clinical Presentation and Molecular Characterization of Isolates 2006-2015

Introduction In the preantibiotic era Streptococcus pyogenes was a common cause of severe pneumonia but currently, except for postinfluenza complications, it is not considered a common cause of community-acquired pneumonia in adults. Aim and Material and Methods This study aimed to identify current clinical episodes of S. pyogenes pneumonia, its relationship with influenza virus circulation and the genotypes of the involved isolates during a decade in a Southern European region (Gipuzkoa, northern Spain). Molecular analysis of isolates included emm, multilocus-sequence typing, and superantigen profile determination. Results Forty episodes were detected (annual incidence 1.1 x 100,000 inhabitants, range 0.29-2.29). Thirty-seven episodes were community-acquired, 21 involved an invasive infection and 10 developed STSS. The associated mortality rate was 20%, with half of the patients dying within 24 hours after admission. Influenza coinfection was confirmed in four patients and suspected in another. The 52.5% of episodes occurred outside the influenza seasonal epidemic. The 67.5% of affected persons were elderly individuals and adults with severe comorbidities, although 13 patients had no comorbidities, 2 of them had a fatal outcome. Eleven clones were identified, the most prevalent being emm1/ST28 (43.6%) causing the most severe cases. Conclusions S. pyogenes pneumonia had a continuous presence frequently unrelated to influenza infection, being rapidly fatal even in previously healthy individuals.

Pneumococcal etiology in hospitalised children with community-acquired penumonia in Belgium :evaluation by culture, RT-PCR and serotype-specific IgG and IgA serology.

info:eu-repo/semantics/nonPublished

Interobserver Reliability of Radiologists' Interpretations of Mobile Chest Radiographs for Nursing Home-Acquired Pneumonia

Objectives: To determine the interobserver reliability of radiologists' interpretations of mobile chest radiographs for nursing home-acquired pneumonia. Design: A cross-sectional reliability study. Setting: Nursing homes and an acute care hospital. Participants: Four radiologists reviewed 40 mobile chest radiographs obtained from residents of nursing homes who met a clinical definition of lower respiratory tract infections. Measurements: Radiologists were asked to interpret radiographs with respect to the film quality; presence, pattern, and extent of an infiltrate; and the presence of a pleural effusion or adenopathy. Interrater reliability was evaluated using the intraclass correlation coefficient derived from a 2-way random effects model. Results: On average the radiologists reported that 6 of the 40 films were of very good or excellent quality and 16 of the 40 were of fair or poor quality. When the finding of an infiltrate was dichotomized (0 = no; 1 = possible, probable, or definite) all 4 radiologists agreed on 21 of the 37 chest radiographs. The intraclass correlation coefficient for the presence or absence of infiltrates was 0.54 (95% confidence intervals [CI] 0.38 to 0.69). For the 14 radiographs where infiltrates were observed by all radiologists, intraclass correlation coefficients for the presence of pleural effusions was 0.08 (95% CI -0.10 to 0.41), hilar adenopathy 0.54 (95% CI 0.29 to 0.79), and mediastinal adenopathy 0.49 (95% CI 0.21 to 0.76). Conclusion: In conclusion, the interrater agreement among radiologists for mobile chest radiographs in establishing the presence or absence of an infiltrate can be judged to be "fair." Treatment decisions need to include clinical findings and should not be made based on radiographic findings alone. © 2006 American Medical Directors Association.

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Background: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.

Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. 

Methods: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10⁴ colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. 

Results: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). 

Conclusions: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

Effectiveness of a biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use: protocol for a randomised controlled trial (VAPrapid-2):Study protocol for a randomised controlled trial

Background Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence. Methods/Design This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at > 104 colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a ‘biomarker-guided recommendation on antibiotics’ in which BAL fluid is tested for IL-1β and IL-8 in addition to routine microbiology testing, or to ‘routine use of antibiotics’ in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD. Discussion This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP.

Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia

Background
Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function.
Methods and setting
159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >104 colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed.

Results
Mycoplasmataceaewerefoundin49%(95%CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide ( p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis ( p=0.005).

Discussion and conclusions
This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.