Grant W. Waterer

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panels recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects

Background: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70–79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 (adjusted regression coefficients (β) = −5.3 (95% CI −9.1 to−1.5) and −3.1 (95% CI −4.3 to −1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (β = −6.4 (95% CI −12.8 to −0.03) and −3.4 (95% CI −5.4 to −1.3), respectively, for IL-6 and β = −10.1 (95% CI −18.7 to −1.5) and −3.8 (95% CI −7 to −0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.

Severity of Pneumococcal Pneumonia Associated with Genomic Bacterial Load

BACKGROUND There is a clinical need for more objective methods of identifying patients at risk for septic shock and poorer outcomes among those with community-acquired pneumonia (CAP). As viral load is useful in viral infections, we hypothesized that bacterial load may be associated with outcomes in patients with pneumococcal pneumonia. METHODS Quantification of Streptococcus pneumoniae DNA level by real-time polymerase chain reaction (rt-PCR) was prospectively conducted on whole-blood samples from a cohort of 353 patients who were displaying CAP symptoms upon their admission to the ED. RESULTS CAP caused by S pneumoniae was documented in 93 patients (36.5% with positive blood culture findings). A positive S pneumoniae rt-PCR assay finding was associated with a statistically significant higher mortality (odds ratio [OR], 7.08), risk for shock (OR, 6.29), and the need for mechanical ventilation (MV) [OR, 7.96]. Logistic regression, adjusted for age, sex, comorbidities, and pneumonia severity index class, revealed bacterial load as independently associated with septic shock (adjusted odds ratio [aOR], 2.42; 95% CI, 1.10 to 5.80) and the need for MV (aOR, 2.71; 95% CI, 1.17 to 6.27). An S pneumoniae bacterial load of >or= 10(3) copies per milliliter occurred in 29.0% of patients (27 of 93 patients; 95% CI, 20.8 to 38.9%) being associated with a statistically significant higher risk for septic shock (OR, 8.00), the need for MV (OR, 10.50), and hospital mortality (OR, 5.43). CONCLUSION In patients with pneumococcal pneumonia, bacterial load is associated with the likelihood of death, the risk of septic shock, and the need for MV. High genomic bacterial load for S pneumoniae may be a useful tool for severity assessment.

Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia.

Recent studies suggest that macrolides may have beneficial effects for patients at risk for certain infections. The current authors examined the effect of macrolide therapy on 30- and 90-day mortality for patients with severe sepsis caused by pneumonia. A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had chest radiography consistent with, and had a discharge diagnosis of pneumonia and clinical criteria of severe sepsis. Subjects were considered to be on macrolides if they received at least one dose within 48 h of admission. Severe sepsis was present in 237 (30.1%) subjects, out of whom 104 (43.9%) received macrolides. Mortality was 20.3% at 30 days and 24.5% at 90 days. In the multivariable analysis, the use of macrolide was associated with decreased mortality at 30 days (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.2–0.7) and at 90 days (HR 0.3, 95% CI 0.2–0.6) in patients with severe sepsis and in patients with macrolide-resistant pathogens (HR 0.1, 95% CI 0.02–0.5). Macrolide use was associated with decreased mortality in patients with severe sepsis due to pneumonia and macrolide-resistant pathogens. Confirmatory studies are needed to determine whether macrolide therapy may be protective for patients with sepsis.

The impact of estrogen and progesterone on asthma.

OBJECTIVE This paper describes evidence of a positive effect of both endogenous and exogenous estrogen and progesterone on lung function across the life span in women. DATA SOURCES Articles were identified using the keywords asthma, pulmonary function, menarche, menopause, estrogen, progesterone, hormone replacement therapy, oral contraceptives, and menstrual cycle from years 1966 to 2001 in MEDLINE. Additional studies were identified from article reference lists. STUDY SELECTION Relevant, peer-reviewed original research articles in the English language were selected. RESULTS Estrogen and/or progesterone may alter pulmonary function and asthma. Premenopausal women experience decreases in pulmonary function and increases in asthma exacerbations and hospitalizations during the premenstrual and menstrual phases. Oral contraceptives and hormone replacement therapy are associated with improved pulmonary function and decrease in asthma exacerbation. Some asthmatic patients experience improved pulmonary function and reduced asthma medication requirement during pregnancy. CONCLUSIONS Estrogen and progesterone modify airway responsiveness. Further research is needed to elucidate the clinical relevance of estrogen and progesterone in the pathophysiology and therapy of asthma.

Legionella and community-acquired pneumonia: a review of current diagnostic tests from a clinician’s viewpoint

Many physicians are unaware of the limitations of the available tests for diagnosing infections with Legionella organisms. Geographic differences in the importance of nonpneumophila Legionella species as pathogens are underrecognized, in part because available diagnostic tests are biased toward the detection of pneumophila serogroup 1. Routine laboratory practices reduce the likelihood of culturing Legionella species from clinical isolates. Failure of seroconversion is common, particularly with nonpneumophila species; even when seroconversion occurs, it may take much longer than 4 weeks. Urinary antigen testing has insufficient sensitivity to affect clinical management in most regions of the United States, as it can reliably detect only L. pneumophila serogroup 1 infections. Polymerase chain reaction-based techniques offer hope of providing highly sensitive, rapid diagnostic tests for all Legionella species, but limitations in the current tests will make validating them difficult.

Association between surfactant protein B + 1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia.

Objective:Pulmonary surfactant protein (SP)-B plays a vital role in the formation and function of surfactant in the lung. A genetic polymorphism (SP-B + 1580) is postulated to result in diminished activity of SP-B. The objective was to determine whether the SP-B + 1580 CC genotype is associated with an increased risk of respiratory failure and ARDS in adults with community-acquired pneumonia. Design:Prospective cohort of adults diagnosed with community-acquired pneumonia. Setting:Hospital system. Patients:We enrolled 402 adults ≥18 yrs of age with community-acquired pneumonia; 158 were white, 243 were African American, and one was Asian. Interventions:Genotypic analysis was performed on DNA isolated from whole blood using polymerase chain reaction amplification and DdeI restriction enzyme digestion. Measurements and Main Results:We recorded the requirement for mechanical ventilation, the presence of acute respiratory distress syndrome (ARDS) or septic shock, and mortality. Sixty-three patients required mechanical ventilation, 12 patients developed ARDS, and 35 patients developed septic shock. Genotypic frequencies at the SP-B+1580 site were T/T 183 of 402 (0.45), T/C 160 of 402 (0.40), and C/C 59 of 402 (0.15). Of the 59 patients who were C/C at the SP-B + 1580 site, 21 (0.356) required mechanical ventilation, compared with 26 of 160 patients (0.163) who were T/C and 16 of 183 (0.087) patients who were T/T (p < .001). ARDS developed in five of 59 (0.085) patients with the C/C genotype, compared with six of 160 (.038) patients with T/C and one of 183 patients with T/T (0.005, p < .009). Septic shock occurred in 12 of 59 (0.203) patients with the C/C genotype, compared with 13 of 160 (0.081) patients with T/C and ten of 183 (0.055) patients with T/T (p < .001). Mortality rate was not different between the three genotypes. Conclusion:Carriage of the C allele at the SP-B + 1580 site is associated with ARDS, septic shock, and the need for mechanical ventilation in adults with community-acquired pneumonia.

Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion

BACKGROUND Patients with malignant pleural effusion (MPE) have limited prognoses. They require long-lasting symptom relief with minimal hospitalization. Indwelling pleural catheters (IPCs) and talc pleurodesis are approved treatments for MPE. Establishing the implications of IPC and talc pleurodesis on subsequent hospital stay will influence patient choice of treatment. Therefore, our objective was to compare patients with MPE treated with IPC vs pleurodesis in terms of hospital bed days (from procedure to death or end of follow-up) and safety. METHODS In this prospective, 12-month, multicenter study, patients with MPE were treated with IPC or talc pleurodesis, based on patient choice. Key end points were hospital bed days from procedure to death (total and effusion-related). Complications, including infection and protein depletion, were monitored longitudinally. RESULTS One hundred sixty patients with MPE were recruited, and 65 required definitive fluid control; 34 chose IPCs and 31 pleurodesis. Total hospital bed days (from any causes) were significantly fewer in patients with IPCs (median, 6.5 days; interquartile range [IQR] = 3.75-13.0 vs pleurodesis, mean, 18.0; IQR, 8.0-26.0; P = .002). Effusion-related hospital bed days were significantly fewer with IPCs (median, 3.0 days; IQR, 1.8-8.3 vs pleurodesis, median, 10.0 days; IQR, 6.0-18.0; P < .001). Patients with IPCs spent significantly fewer of their remaining days of life in hospital (8.0% vs 11.2%, P < .001, χ(2) = 28.25). Fewer patients with IPCs required further pleural procedures (13.5% vs 32.3% in pleurodesis group). There was no difference in rates of pleural infection (P = .68) and protein (P = .65) or albumin loss (P = .22). More patients treated with IPC reported immediate (within 7 days) improvements in quality of life and dyspnea. CONCLUSIONS Patients treated with IPCs required significantly fewer days in hospital and fewer additional pleural procedures than those who received pleurodesis. Safety profiles and symptom control were comparable.

Heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia

ObjectiveHeat shock protein (HSP)70-2 is an important immunomodulatory protein induced in response to inflammatory stimuli. We assessed whether HSP70-2+1267 genotype influenced the risk of septic shock in a prospective cohort study of community-acquired pneumonia and whether HSP70-2+1267 genotype is a better predictor of septic shock than the genotype at lymphotoxin-&agr; +250. DesignProspective cohort study. SettingA large, nonprofit, private hospital system in Memphis, TN. PatientsAdults admitted with community-acquired pneumonia between 1998 and 2001. Septic shock was defined according to consensus criteria (American College of Chest Physicians/Society of Critical Care Medicine, 1992). InterventionsBlood sampling. Measurements and Main ResultsA total of 343 subjects were enrolled; 30 had septic shock. HSP70-2+1267 and lymphotoxin-&agr; +250 genotype was determined using polymerase chain reaction and restriction enzyme digestion. HSP70-2+1267 AA genotype was the strongest predictor of septic shock (p = .0005; relative risk, 3.5). Lymphotoxin-&agr; +250 AA genotype was also associated with an increased risk of septic shock (p = .002; relative risk, 2.7). Logistic regression analysis found only age (p = .04) and HSP70-2+1267 genotype (p = .006) were predictors of septic shock. The greatest risk of septic shock was associated with carriage of the HSP70-2+1267 A/lymphotoxin-&agr; +250 A haplotype (p < .0001). ConclusionsHSP70-2+1267 genotype is a stronger predictor of septic shock in patients with community-acquired pneumonia than lymphotoxin-&agr; +250 genotype.

Influenza vaccine effectiveness against hospitalisation with confirmed influenza in the 2010-11 seasons: a test-negative observational study.

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.