Constant Vt Ventilation and Surfactant Dysfunction: An Overlooked Cause of Ventilator-induced Lung Injury.

Ventilator-induced lung injury (VILI) is currently ascribed to volutrauma and/or atelectrauma, but the effect of constant Vt ventilation (CVtV) has received little attention. This Perspective summarizes the literature documenting that CVtV causes VILI and reviews the mechanisms by which it occurs. Surfactant is continuously inactivated, depleted, displaced, or desorbed as a function of the duration of ventilation, the Vt, the level of positive end-expiratory pressure (PEEP), and possibly the respiratory rate. Accordingly, surfactant must be continuously replenished, and secretion primarily depends on intermittent delivery of large ventilatory excursions. The surfactant abnormalities resulting from CVtV result in atelectasis and VILI. Although surfactant secretion is reduced by the absence of intermittent deep breaths, continuous administration of large Vts depletes surfactant and impairs subsequent secretion. Low or normal lung volumes result in desorption of surfactant. PEEP can be protective by reducing surface film collapse and subsequent film rupture on reexpansion, and/or by reducing surfactant displacement into the airways, but PEEP can also downregulate surfactant release. The effect of CVtV on surfactant is complex. If attention is not paid to facilitating surfactant secretion and limiting its inactivation, depletion, desorption, or displacement, surface tension will increase and atelectasis and VILI will occur.

Sigh Ventilation in Patients With Trauma: The SiVent Randomized Clinical Trial.

Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown. Objective: To determine whether adding sigh breaths improves clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours. Interventions: Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished. Main Outcomes and Measures: The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality. Results: Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]). Conclusions and Relevance: In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02582957.

Effectiveness of Alberta Family Integrated Care on infant length of stay in level II neonatal intensive care units: a cluster randomized controlled trial.

BACKGROUND: Parents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits. METHODS: In this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge. RESULTS: We enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups. CONCLUSIONS: Alberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016.

A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.

BACKGROUND: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. METHODS: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked. RESULTS: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes. CONCLUSIONS: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .).

Bosea psychrotolerans sp. nov., a psychrotrophic alphaproteobacterium isolated from Lake Michigan water.

Three strains of a Gram-stain negative bacterium were isolated from Lake Michigan water. 16S rRNA gene sequence analysis revealed that strain 1131 had sequence similarities to Bosea vaviloviae LMG 28367T, Bosea lathyri LMG 26379T, Bosea lupini LMG 26383T, Bosea eneae CCUG 43111T, Bosea vestrisii CCUG 43114T and Boseamassiliensis CCUG 43117T of 99.8, 99.1, 98.4, 98.4, 98.4 and 98.2 %, respectively. The average nucleotide identity value between strain 1131T and Bosea vaviloviae Vaf-18T was 93.4 % and the DNA relatedness was 38 %. The primary cellular fatty acids of strain 1131T were C16 : 1ω7c and C18 : 1ω7c. The primary polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. The major compound in the quinone system was ubiquinone Q-10 and in the polyamine pattern sym-homospermidine was predominant. Additional phenotypic characteristics included growth at 5-35 °C, pH values of pH 5.5-8.0, a salt tolerance range of 0.0-1.2 % (w/v), and production of an unknown water soluble brown pigment. After phenotypic, chemotaxonomic and genomic analyses, this isolate was identified as a novel species for which the name Bosea psychrotolerans is proposed. The type strain is 1131T (NRRL B-65405=LMG 30034).

Imaging in Acute Pyelonephritis: Utilization, Findings, and Effect on Management.

OBJECTIVES: To determine the frequency, timing, and types of imaging obtained in patients with a discharge diagnosis of acute pyelonephritis, and how often imaging findings affect therapy. METHODS: This was a retrospective chart review of 1062 adults with a diagnosis of acute pyelonephritis discharged from an urban, safety-net hospital between January 1, 2008 and December 31, 2012. From the 739 patients selected after exclusions, we determined the number and proportion of patients imaged within the first 24 hours of admission, stratified by risk factors for pyelonephritis complications, and the frequency of positive findings leading to invasive interventions. RESULTS: Of 739 patients, 468 (63%) were imaged within 24 hours of admission, 262/414 (63%) of whom had risk factors for complications and 206/325 of whom (63%) did not. Among these, studies were positive in 117/468 (25%), 78/262 (30%) in those with risk factors, and 39/206 (19%) of those without risk factors. Of the 117 patients with positive imaging findings within 24 hours of admission, 58 (50%) underwent invasive procedures, 47 (60%) with risk factors and 11 (28%) without. Among all of the patients, interventions were directed at relieving obstructions much more commonly than treating abscess (51 patients vs 8). CONCLUSIONS: Among this population, imaging is frequently done earlier than recommended. Because the majority of interventions targeted stone disease, ultrasound may be the preferred initial modality rather than contrasted tomography when obtaining imaging early. Current guidelines may need to be revisited.

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.

BACKGROUND: The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. METHODS: We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. RESULTS: One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. CONCLUSIONS: Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts. TRIAL REGISTRATION: This study used serum samples from participants of the MACRO ( NCT00325897 ) and STATCOPE ( NCT01061671 ) trials.

Simvastatin for the prevention of exacerbations in moderate-to-severe COPD.

BACKGROUND: Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial. METHODS: We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second [FEV1] of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers. RESULTS: A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (±SD) age of 62.2±8.4 years, an FEV1 that was 41.6±17.7% of the predicted value, and a smoking history of 50.6±27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36±1.61 exacerbations and 1.39±1.73 exacerbations, respectively (P=0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval [CI], 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P=0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P=0.89). CONCLUSIONS: Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.).

Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline.

This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.

Prevention of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline.

This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent versus a long-acting ß2-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.

Azithromycin and risk of COPD exacerbations in patients with and without Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP) infection is associated with reduced lung function and systemic inflammation in chronic obstructive pulmonary disease (COPD) patients. Azithromycin (AZ) is active against HP and reduces the risk of COPD exacerbation. We determined whether HP infection status modifies the effects of AZ in COPD patients. METHODS: Plasma samples from 1018 subjects with COPD who participated in the Macrolide Azithromycin (MACRO) in COPD Study were used to determine the HP infection status at baseline and 12 months of follow-up using a serologic assay. Based on HP infection status and randomization to either AZ or placebo (PL), the subjects were divided into 4 groups: HP+/AZ, HP-/AZ, HP+/PL, and HP-/PL. Time to first exacerbation was compared across the 4 groups using Kaplan-Meier survival analysis and a Cox proportional hazards model. The rates of exacerbation were compared using both the Kruskal-Wallis test and negative binomial analysis. Blood biomarkers at enrolment and at follow-up visits 3, 12, and 13 (1 month after treatment was stopped) months were measured. RESULTS: One hundred eighty one (17.8%) patients were seropositive to HP. Non-Caucasian participants were nearly three times more likely to be HP seropositive than Caucasian participants (37.4% vs 13.6%; p < 0.001). The median time to first exacerbation was significantly different across the four groups (p = 0.001) with the longest time in the HP+/AZ group (11.2 months, 95% CI; 8.4-12.5+) followed by the HP-/AZ group (8.0 months, 95% CI; 6.7-9.7). Hazard ratio (HR) for exacerbations was lowest in the HP+/AZ group after adjustment for age, sex, smoking status, ethnicity, history of peptic ulcer, dyspnea, previous hospital admission, GOLD grade of severity, and forced vital capacity (HR, 0.612; 95% CI, 0.442-0.846 vs HR, 0.789; 95% CI, 0.663-0.938 in the HP-/AZ group). Circulating levels of soluble tumor necrosis factor receptor-75 were reduced only in the HP+/AZ group after 3 months of AZ treatment (-0.87 ± 0.31 µg/L; p = 0.002); levels returned to baseline after discontinuing AZ. CONCLUSIONS: AZ is effective in preventing COPD exacerbations in patients with HP seropositivity, possibly by modulating TNF pathways related to HP infection.

Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

BACKGROUND: Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. METHODS: We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. RESULTS: Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. CONCLUSION: We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model.

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006-2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47-4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04-0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method.

Filimonas aurantiibacter sp. nov., an orange-pigmented bacterium isolated from lake water and emended description of the genus Filimonas.

A Gram-stain-negative bacterium was isolated from Lake Michigan water. 16S rRNA gene sequence analysis revealed that strain 1458T had a sequence similarity to Filimonas lacunae YT21T, Sediminibacterium goheungense HME7863T, Parasegetibacter terrae SGM2-10T, Sediminibacterium ginsengisoli DCY13T, Terrimonas ferruginea DSM 30193T, Lacibacter cauensis NJ-8T, Flavihumibacter solisilvae 3-3T, Parasegetibacter luojieneis RHYL-37T, Vibrionimonas magnilacihabitans MU-2T and Parafilimonas terrae 5GHs7-2T with values of 93.4, 92.3, 91.9, 91.9, 91.8, 91.6, 91.6, 91.6, 91.5 and 90.4 %, respectively. The primary cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1G and summed feature 3 (iso-C15 : 0 2-OH/C16 : 1ω7c). The primary polar lipids were phosphatidylethanolamine and an unidentified polar lipid only detectable after total polar lipid staining. The quinone system was menaquinone MK-7, and in the polyamine pattern, sym-homospermidine was predominant. Additional phenotypic characteristics included growth at 15 to 40 °C and pH 5.0 to 8.0, a salt tolerance range of 0 to 2.0 % (w/v), production of orange cell-bound pigment flexirubin, and gliding motility. After phenotypic, chemotaxonomic and molecular analyses, strain 1458T was identified as a novel species of the genus Filimonas, for which the name Filimonas aurantiibacter sp. nov. is proposed. The type strain is 1458T (=NRRL B-65305T=LMG 29039T). An emended description of the genus Filimonas is also provided.

The Effect of Macrolide Resistance on the Presentation and Outcome of Patients Hospitalized for Streptococcus pneumoniae Pneumonia.

RATIONALE: There are conflicting reports describing the effect of macrolide resistance on the presentation and outcomes of patients with Streptococcus pneumoniae pneumonia. OBJECTIVES: We aimed to determine the effect of macrolide resistance on the presentation and outcomes of patients with pneumococcal pneumonia. METHODS: We conducted a retrospective, observational study in the Hospital Clinic of Barcelona of all adult patients hospitalized with pneumonia who had positive cultures for S. pneumoniae from January 1, 2000 to December 31, 2013. Outcomes examined included bacteremia, pulmonary complications, acute renal failure, shock, intensive care unit admission, need for mechanical ventilation, length of hospital stay, and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: Of 643 patients hospitalized for S. pneumoniae pneumonia, 139 (22%) were macrolide resistant. Patients with macrolide-resistant organisms were less likely to have bacteremia, pulmonary complications, and shock, and were less likely to require noninvasive mechanical ventilation. We found no increase in the incidence of acute renal failure, the frequency of intensive care unit admission, the need for invasive ventilatory support, the length of hospital stay, or the 30-day mortality in patients with (invasive or noninvasive) macrolide-resistant S. pneumoniae pneumonia, and no effect on outcomes as a function of whether treatment regimens did or did not comply with current guidelines. CONCLUSIONS: We found no evidence suggesting that patients hospitalized for macrolide-resistant S. pneumoniae pneumonia were more severely ill on presentation or had worse clinical outcomes if they were treated with guideline-compliant versus noncompliant regimens.