Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation in COPD at Stable State and Exacerbations


BACKGROUND:  Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear. Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.

METHODS:  Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, andStreptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform. Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR. Symptoms were quantified using the visual analog scale.

RESULTS:  At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae. Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis. Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α. H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β. In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzaecorrelated to changes in sputum TNF-α and IL-1β concentrations.

CONCLUSIONS:  At stable state, H influenzae is associated with increased airway inflammation in COPD. The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation.

Fluoroquinolone bested other antibiotics in Haemophilus influenzae-related pneumonia.


For adults with Haemophilus influenzae-related community acquired pneumonia, fluoroquinolones were significantly associated with early clinical response rates that were better than those seen with other antibiotics, based on the findings of a German study.

“Initial treatment with any fluoroquinolone was the only positive predictor of early clinical response, and use of macrolide monotherapy was the only negative predictor of early clinical response,” Dr. Christina Forstner, a researcher at the Medical University of Vienna in Austria, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Courtesy Dr. W.A. Clark/CDC

Initial treatment with any fluoroquinolone was the only positive predictor of early clinical response, Dr. Forstner said.

The multi-center, observational, prospective, cohort study was conducted between 2002 and 2012 in 171 adults who had community acquired pneumonia and tested positive forH.influenzae. In 124 patients, H.influenzae was the sole pathogen detected, whereas 47 patients had at least one other co-infection.

The primary end point of the study was an early clinical response ‑ clinical stability by day 4 of treatment. The secondary end point was clinical cure anywhere at day 14. The choice of antimicrobial treatment was left to the discretion of individual clinicians.

Early clinical response rates were seen for 46 of 47 patients (97.6%) given any fluoroquinolone, with 100% clinical cure by day 14. Fluoroquinolone monotherapy achieved a nearly 100% early clinical response rate (39 out of 40 patients), and complete clinical cure was seen in all patients by day 14. The rates were significantly different from those seen with other antibiotics (P = .01).

An early clinical response rate was seen in 92 of 108 patients (85.2%) given any beta-lactam. Beta-lactam monotherapy achieved an early clinical response rate in 63 out of 74 cases, with a clinical cure rate at day 14 in 68 out of 74 cases.

An early clinical response rate was seen in 29 of 36 patients (80.6%) who received any macrolide; an early clinical response rate was seen in 8 of 12 patients given monotherapy with a macrolide. Clinical cure rate at day 14 was 32 out of 36 patients given any macrolide, and 11 out of 12 given macrolide monotherapy.

The median duration of therapy was, according to Dr. Forstner, “quite long” at 10 days. Monotherapy was used in 78.4% of patients, and oral treatments in 63.7%.

The overall early clinical response rate was 88%, with an overall clinical cure of 93% on day 14, and of 95.9% on day 28.

A univariate analysis of age, body mass index, severity of disease, co-infection, and treatments used indicated the only factor associated with an early clinical response was the use of any fluoroquinolone (odds ration, 8.8). Macrolide monotherapy was associated with a negative clinical response (OR, 0.239).

The Long-Term Effects of Childhood Bacterial Meningitis.


Adult survivors of childhood bacterial meningitis have lower educational achievement and a lower likelihood of economic self-sufficiency than matched healthy controls.

 

The short-term sequelae of childhood bacterial meningitis can include hearing loss, motor deficits, seizures, and cognitive impairment. But what about functioning in adult life? In a recent cohort study, investigators used national patient registries in Denmark to compare the educational achievement and economic self-sufficiency of individuals with meningococcal, pneumococcal, or Haemophilus influenzae meningitis diagnosed between 1977 and 2007, before age 12 years, with those of age- and sex-matched controls who had not had meningitis. To assess for family-related cofactors, the researchers also evaluated the siblings and parents of these two cohorts.

Survivors of pneumococcal or H. influenzae meningitis were less likely than matched controls to complete high school or to obtain higher education by age 35. They also were less likely to attain these goals than their siblings, who performed similarly to the siblings of controls. In contrast, although meningococcal meningitis survivors were less likely than controls to complete high school or to obtain higher education by age 35, these survivors had educational achievement comparable to that of their siblings, who had lower achievement than the siblings of controls. Educational achievement was lower among parents of meningococcal meningitis survivors than among parents of controls; achievement among pneumococcal and H. influenzae meningitis survivor parents was comparable to that among controls. By 2010, fewer survivors than controls were economically self-sufficient (–3.8%, –10.6%, and –4.3%, respectively, for meningococcal, pneumococcal, and H. influenzae meningitis).

Comment: This large, well-designed study confirms sustained intellectual and economic sequelae of childhood bacterial meningitis but also suggests different routes to these long-term effects. Intellectual and economic impairments are likely direct consequences of the severity of pneumococcal and H. influenzae meningitis. However, family factors appear to predominate in the poorer intellectual and economic achievements of meningococcal meningitis survivors.

 

Source: Journal Watch Infectious Diseases

 

10-Valent Pneumococcal Vaccine Highly Effective in Infants and Toddlers.


A 10-valent pneumococcal conjugate vaccine is up to 100% effective in preventing vaccine-type invasive disease in young children, according to an industry-sponsored study in the Lancet. The PHiD-CV10 vaccine, marketed in Europe as Synflorix, contains 10 serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid carriers.

Researchers randomized nearly 46,000 Finnish children aged 6 weeks to 18 months to receive the pneumococcal vaccine or a control vaccine. Vaccination schedules depended on the patient’s age and included either two or three primary vaccinations at varying intervals, with or without a booster dose.

During over 2 years’ follow-up, there were 13 cases of vaccine-type invasive pneumococcal disease. The vaccine’s efficacy ranged from 92% to 100%, depending on the schedule followed. No safety concerns emerged.

A commentator says that the results “provide confirmatory, conclusive evidence about the vaccine’s benefits against invasive disease.”

Source: Lancet