How biomarkers can improve pneumonia diagnosis and prognosis: procalcitonin and mid-regional-pro-adrenomedullin

Aim: The diagnostic and prognostic role of procalcitonin (PCT) and mid-regional-pro-adrenomedullin (MR-proADM) were investigated in patients with pneumonia. Material & methods: A total of 168 and 77 patients with pneumonia enrolled in two different hospital settings, an internal medicine unit and an emergency unit were included in the study. PCT and MR-proADM plasma concentrations and pneumonia severity index score were measured. Median values were compared by Mann–Whitney’s test. Receiver operating characteristic analysis and rank correlation were used to define the diagnostic and prognostic accuracy. Results: PCT confirmed the diagnostic role at values 0.08–0.10 ng/ml and MR-proADM the prognostic role for severe pneumonia. Significant correlation (p < 0.0001) between MR-proADM and pneumonia severity index score indicated expression of pneumonia severity. Conclusion: This combination of biomarkers presents a high positive predictive value in pneumonia diagnosis and prognosis.

Predictors of mortality in Middle East respiratory syndrome (MERS)

We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5–10, p<0.001) without adequate antibody titres (low antibody titre at hospital days 11–16, p=0.07) during the course of disease, were associated with mortality.

The value of signs and symptoms in differentiating between bacterial, viral and mixed aetiology in patients with community-acquired pneumonia

Current diagnostics for community-acquired pneumonia (CAP) include testing for a wide range of pathogens, which is costly and not always informative. We compared clinical and laboratory parameters of patients with CAP caused by different groups of pathogens to evaluate the potential for targeted diagnostics and directed treatment. In a prospective study, conducted between April 2008 and April 2009, adult patients with CAP were tested for the presence of a broad range of possible respiratory pathogens using bacterial cultures, PCR, urinary antigen testing and serology. Of 408 patients with CAP, pathogens were detected in 263 patients (64.5 %). Streptococcus pneumoniae and influenza A virus were the most frequently identified bacterial and viral pathogens, respectively. Age had a significant effect on the prediction of aetiology (P = 0.054), with an increase in the relative contribution of viruses with advancing age. Multivariate analyses further showed that the presence of cough increased the likelihood of detecting a viral pathogen [odds ratio (OR) 5.536, 95 % confidence interval (CI) 2.130–14.390], the presence of immunodeficiency decreased the likelihood of detecting a bacterial pathogen (OR 0.595, 95 % CI 0.246–1.437) and an increase in pneumonia severity index score increased the likelihood of detecting a pathogen in general. Although several variables were independently associated with the detection of a pathogen group, substantial overlap meant there were no reliable clinical predictors to distinguish aetiologies. Therefore, testing for common respiratory pathogens is still necessary to optimize treatment.

A Leukocyte Score to Improve Clinical Outcome Predictions in Bacteremic Pneumococcal Pneumonia in Adults

Background. Bacteremic pneumococcal pneumonia (BPP) is associated with high and early mortality. A simple procedure to predict mortality is crucial. Methods. All adult patients with BPP admitted from 2005 through 2013 to the University Hospital of Dijon, France, were enrolled to study 30-day mortality and associated factors, particularly leukocyte counts. A simple leukocyte score was created by adding 1 point each for neutropenia (&lt;1500 cells/mm3), lymphopenia (&lt;400), and monocytopenia (&lt;200). Results. One hundred and ninety-two adult patients (mean age, 69 years; standard deviation [SD], 19 years) who had developed and were hospitalized for BPP (58% community-acquired) were included. The 30-day crude mortality rate was 21%. The mean Pneumonia Severity Index score was high at 127.3 (SD = 41.3). Among the 182 patients who had a white blood cell count, 34 (19%) had a high leukocyte score (≥2). Multivariate analysis revealed that mortality was significantly associated with a high leukocyte score (odds ratio, 6.28; 95% confidence interval, 2.35–16.78), a high respiratory rate, a low serum bicarbonate level, and an altered mental status (all P &lt; .05). The leukocyte score was not significantly dependent on the previous state of immunosuppression, alcoholism, or viral coinfection, but it did correlate with an acute respiratory distress syndrome and a low serum bicarbonate level. Conclusions. This new leukocyte score, in combination with the well known predictive factors, seems of interest in predicting the risk of death in BPP. A high score correlated with organ dysfunction and probably reflects the level of immunoparalysis. Its predictive value has to be confirmed in other cohorts.

Macrolide Use in the Treatment of Critically Ill Patients with Pneumonia: Incidence, Correlates, Timing and Outcomes

BACKGROUND: Macrolide antibiotics are commonly used to treat pneumonia despite increasing antimicrobial resistance. Evidence suggests that macrolides may also decrease mortality in severe sepsis via immunomodulatory properties.OBJECTIVE: To evaluate the incidence, correlates, timing and mortality associated with macrolide-based treatment.METHODS: A population-based cohort of critically ill adults with pneumonia at five intensive care units in Edmonton, Alberta, was prospectively followed over two years. Data collected included disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score), pneumonia severity (Pneumonia Severity Index score), comorbidities, antibiotic treatments at presentation and time to effective antibiotic. The independent association between macrolide-based treatment and 30-day all-cause mortality was examined using multivariable Cox regression. A secondary exploratory analysis examined time to effective antimicrobial therapy.RESULTS: The cohort included 328 patients with a mean Pneumonia Severity Index score of 116 and a mean APACHE II score of 17; 84% required invasive mechanical ventilation. Ninety-one (28%) patients received macrolide-based treatments, with no significant correlates of treatment except nursing home residence (15% versus 30% for nonresidents [P=0.02]). Overall mortality was 54 of 328 (16%) at 30 days: 14 of 91 (15%) among patients treated with macrolides versus 40 of 237 (17%) for nonmacrolides (adjusted HR 0.93 [95% CI 0.50 to 1.74]; P=0.8). Patients who received effective antibiotics within 4 h of presentation were less likely to die than those whose treatment was delayed (14% versus 17%; adjusted HR 0.50 [95% CI 0.27 to 0.94]; P=0.03).CONCLUSIONS: Macrolide-based treatment was not associated with lower 30-day mortality among critically ill patients with pneumonia, although receipt of effective antibiotic within 4 h was strongly predictive of survival. Based on these results, timely effective treatment may be more important than choice of antibiotics.