Marcos I. Restrepo

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.

Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NASCENT randomized trial

CONTEXT Ventilator-associated pneumonia (VAP) causes substantial morbidity. A silver-coated endotracheal tube has been designed to reduce VAP incidence by preventing bacterial colonization and biofilm formation. OBJECTIVE To determine whether a silver-coated endotracheal tube would reduce the incidence of microbiologically confirmed VAP. DESIGN, SETTING, AND PARTICIPANTS Prospective, randomized, single-blind, controlled study conducted in 54 centers in North America. A total of 9417 adult patients (> or = 18 years) were screened between 2002 and 2006. A total of 2003 patients expected to require mechanical ventilation for 24 hours or longer were randomized. INTERVENTION Patients were assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal tubes, similar except for a silver coating on the experimental tube. MAIN OUTCOME MEASURES Primary outcome was VAP incidence based on quantitative bronchoalveolar lavage fluid culture with 10(4) colony-forming units/mL or greater in patients intubated for 24 hours or longer. Other outcomes were VAP incidence in all intubated patients, time to VAP onset, length of intubation and duration of intensive care unit and hospital stay, mortality, and adverse events. RESULTS Among patients intubated for 24 hours or longer, rates of microbiologically confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%] [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal tube was associated with delayed occurrence of VAP (P = .005). No statistically significant between-group differences were observed in durations of intubation, intensive care unit stay, and hospital stay; mortality; and frequency and severity of adverse events. CONCLUSION Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00148642.

Systematic Review of the Use of Retrievable Inferior Vena Cava Filters

PURPOSE To review the available literature on retrievable inferior vena cava (IVC) filters to examine the effectiveness and risks of these devices. MATERIALS AND METHODS Investigators searched MEDLINE for clinical trials evaluating retrievable filters and reviewed the complications reported to the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. Food and Drug Administration (FDA). RESULTS Eligibility criteria were met by 37 studies comprising 6,834 patients. All of the trials had limitations, and no studies were randomized. There were 11 prospective clinical trials; the rest were retrospective studies. Despite the limitations of the evidence, the IVC filters seemed to be effective in preventing pulmonary embolism (PE); the rate of PE after IVC placement was 1.7%. The mean retrieval rate was 34%. Most of the filters became permanent devices. Multiple complications associated with the use of IVC filters were described in the reviewed literature or were reported to the MAUDE database; most of these were associated with long-term use (> 30 days). At the present time, the objective comparison data of different filter designs do not support superiority of any particular design. CONCLUSIONS In high-risk patients for whom anticoagulation is not feasible, retrievable IVC filters seem to be effective in preventing PE. Long-term complications are a serious concern with the use of these filters. The evidence of the effectiveness and the risks was limited by the small number of prospective studies.

Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial.

IMPORTANCE In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. OBJECTIVE To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. INTERVENTIONS Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. MAIN OUTCOMES AND MEASURES The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. RESULTS There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). CONCLUSIONS AND RELEVANCE Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00908713.

COPD is associated with increased mortality in patients with community-acquired pneumonia

Patients with chronic obstructive pulmonary disease (COPD) who develop community-acquired pneumonia (CAP) may experience worse clinical outcomes. However, COPD is not included as a distinct diagnosis in validated instruments that predict mortality in patients with CAP. The aim of the present study was to evaluate the impact of COPD as a comorbid condition on 30- and 90-day mortality in CAP patients. A retrospective observational study was conducted at two hospitals. Eligible patients had a discharge diagnosis and radiological confirmation of CAP. Among 744 patients with CAP, 215 had a comorbid diagnosis of COPD and 529 did not have COPD. The COPD group had a higher mean pneumonia severity index score (105±32 versus 87±34) and were admitted to the intensive care unit more frequently (25 versus 18%). After adjusting for severity of disease and processes of care, CAP patients with COPD showed significantly higher 30- and 90-day mortality than non-COPD patients. Chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia exhibited higher 30- and 90-day mortality than patients without chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease should be evaluated for inclusion in community-acquired pneumonia prediction instruments.

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.

Late admission to the ICU in patients with community-acquired pneumonia is associated with higher mortality

BACKGROUND Limited data are available on the impact of time to ICU admission and outcomes for patients with severe community acquired pneumonia (CAP). Our objective was to examine the association of time to ICU admission and 30-day mortality in patients with severe CAP. METHODS A retrospective cohort study of 161 ICU subjects with CAP (by International Classification of Diseases, 9th edition, codes) was conducted over a 3-year period at two tertiary teaching hospitals. Timing of the ICU admission was dichotomized into early ICU admission (EICUA, direct admission or within 24 h) and late ICU admission (LICUA, >or= day 2). A multivariable analysis using Cox proportional hazard model was created with the primary outcome of 30-day mortality (dependent measure) and the American Thoracic Society (ATS) severity adjustment criteria and time to ICU admission as the independent measures. RESULTS Eighty-eight percent (n = 142) were EICUA patients compared with 12% (n = 19) LICUA patients. Groups were similar with respect to age, gender, comorbidities, clinical parameters, CAP-related process of care measures, and need for mechanical ventilation. LICUA patients had lower rates of ATS severity criteria at presentation (26.3% vs 53.5%; P = .03). LICUA patients (47.4%) had a higher 30-day mortality compared with EICUA (23.2%) patients (P = .02), which remained after adjusting in the multivariable analysis (hazard ratio 2.6; 95% CI, 1.2-5.5; P = .02). CONCLUSION Patients with severe CAP with a late ICU admission have increased 30-day mortality after adjustment for illness severity. Further research should evaluate the risk factors associated and their impact on clinical outcomes in patients admitted late to the ICU.

Impact of statins and ACE inhibitors on mortality after COPD exacerbations

BackgroundThe purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.MethodsWe conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.ResultsWe identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.ConclusionUse of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.

Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia

Recent studies suggest that statins and angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for some types of infections. The present study aimed to examine the association of outpatient use of these medications on 30-day mortality for subjects aged >65 yrs and hospitalised with community-acquired pneumonia. A retrospective national cohort study was conducted using the Department of Veterans Affairs administrative data including subjects aged ≥65 yrs hospitalised with community-acquired pneumonia, and having ≥1 yr of prior Veterans Affairs outpatient care. In total, 8,652 subjects were identified with a mean age of 75 yrs, 98.6% were male, and 9.9% of subjects died within 30 days of presentation. In this cohort, 18.1% of subjects were using statins and 33.9% were using ACE inhibitors. After adjusting for potential confounders, current statin use (odds ratio (OR) 0.54, 95% confidence interval (CI) 0.42–0.70) and ACE inhibitor use (OR 0.80, 95% CI 0.68–0.89) were significantly associated with decreased 30-day mortality. Use of statins and angiotensin-converting enzyme inhibitors prior to admission is associated with decreased mortality in subjects hospitalised with community-acquired pneumonia. Randomised controlled trials are needed to examine whether the use of these medications in patients hospitalised with community-acquired pneumonia may be beneficial.

A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia

IntroductionThe aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria.MethodsThis was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011).ResultsThe study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0).ConclusionsAmong patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome.Trial RegistrationClinicalTrials.gov: NCT00589693