Andrew F. Shorr

Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study

BACKGROUND Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia. METHODS This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated. RESULTS Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). CONCLUSIONS For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.

Increase in Adult Clostridium difficile–related Hospitalizations and Case-Fatality Rate, United States, 2000–2005

Virulence of and deaths from Clostridium difficile–associated disease (CDAD) are on the rise in the United States. The incidence of adult CDAD hospitalizations doubled from 5.5 cases per 10,000 population in 2000 to 11.2 in 2005, and the CDAD-related age-adjusted case-fatality rate rose from 1.2% in 2000 to 2.2% in 2004.

Critical care delivery in the United States: distribution of services and compliance with Leapfrog recommendations.

Objectives:To describe the organization and distribution of intensive care unit (ICU) patients and services in the United States and to determine ICU physician staffing before the publication and dissemination of the Leapfrog Group ICU physician staffing recommendations. Design and Setting:Stratified, weighted survey of ICU directors in the United States, performed as part of the Committee on Manpower for the Pulmonary and Critical Care Societies (COMPACCS) study. Using lenient definitions, we defined an ICU as “high intensity” if ≥80% of patients were cared for by a critical care physician (intensivist) and defined an ICU as compliant with Leapfrog if it was both high-intensity and providing some form of in-house physician coverage during all hours. Subjects:Three hundred ninety-three ICU directors. Interventions:None. Measurements and Main Results:We obtained a 33.5% response rate (393/1,173). We estimated there were 5,980 ICUs in the United States, caring for approximately 55,000 patients per day, with at least one ICU in all acute care hospitals. The predominant reasons for admission were respiratory insufficiency, postoperative care, and heart failure. Most ICUs were combined medical-surgical ICUs (n = 3,865; 65%), were located in nonteaching, community hospitals (n = 4,245; 71%), and were in hospitals of <300 beds (n = 3,710; 62%). One in four ICUs were high-intensity (n = 1,578; 26%), half had no intensivist coverage (n = 3,183; 53%), and the remainder had at least some intensivist presence (n = 1,219; 20%). High-intensity units were more common in larger hospitals (p = .001) and in teaching hospitals (p < .001) and more likely to be surgical (p < .001) or trauma ICUs (p < .001). Few ICUs had any in-house physician coverage outside weekday daylight hours (20% during weekend days, 12% during weeknights, and 10% during weekend nights). Only 4% (n = 255) of all adult ICUs in the United States appeared to meet the full Leapfrog standards (a high-intensity ICU staffing pattern plus dedicated attending coverage during daytime plus dedicated coverage by any physician during nighttime). Conclusions:ICU services are widely distributed but heterogeneously organized in the United States. Although high-intensity ICUs have been associated previously with improved outcomes, they were infrequent in our study, especially in smaller hospitals, and virtually no ICU met the Leapfrog standards before their dissemination. These findings highlight the considerable challenge to any efforts designed to promote either 24-hr physician coverage or high-intensity model organization.

Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant

Pulmonary hypertension (PH) may complicate idiopathic pulmonary fibrosis (IPF) but the prevalence of PH in IPF remains undefined. The present authors sought to describe the prevalence of PH in IPF. The lung transplant registry for the USA (January 1995 to June 2004) was analysed and IPF patients who had undergone right heart catheterisation (RHC) were identified. PH was defined as a mean pulmonary arterial pressure (P̄pa) ≥25 mmHg and severe PH as a P̄pa >40 mmHg. Independent factors associated with PH were determined. Of the 3,457 persons listed, 2,525 (73.0%) had undergone RHC. PH affected 46.1% of subjects; ∼9% had severe PH. Variables independently associated with mild-to-moderate PH were as follows: need for oxygen, pulmonary capillary wedge pressure (Ppcw) and forced expiratory volume in one second (FEV1). Independent factors related to severe PH included the following: carbon dioxide tension, age, FEV1, Ppcw, need for oxygen and ethnicity. A sensitivity analysis in subjects with Ppcw <15 mmHg did not appreciably alter the present findings. Pulmonary hypertension is common in idiopathic pulmonary fibrosis patients awaiting lung transplant, but the elevations in mean pulmonary arterial pressure are moderate. Lung volumes alone do not explain the pulmonary hypertension. Given the prevalence of pulmonary hypertension and its relationship with surrogate markers for quality of life (e.g. activities of daily living), future trials of therapies for this may be warranted.

Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database.

Objective:To gain a better understanding of the epidemiology, microbiology, and outcomes of early-onset, culture-positive, community-acquired, healthcare-associated, and hospital-acquired bloodstream infections. Design:We analyzed a large U.S. database (Cardinal Health, MediQual, formerly MedisGroups) to identify patients with bacterial or fungal bloodstream isolates from 2002 to 2003. Setting:The data set included administrative and clinical variables (physiologic, laboratory, culture, and other clinical) from 59 hospitals. Bloodstream infections were identified in those hospitals collecting clinical and culture data for at least the first 5 days of admission. Patients:Patients with bloodstream infection within 2 days of admission were classified as having community-acquired bloodstream infection. Those with a prior hospitalization within 30 days, transfer from another facility, ongoing chemotherapy, or long-term hemodialysis were classified as having healthcare-associated bloodstream infection. Bloodstream infections that developed after day 2 of admission were classified as hospital-acquired bloodstream infection. A total of 6,697 patients were identified as having bloodstream infection. Interventions:None. Measurements and Main Results:Healthcare-associated bloodstream infection accounted for more than half (55.3%) of all bloodstream infections. Nearly two thirds (62.3%) of hospitalized patients with bloodstream infection suffered from either hospital-acquired bloodstream infection or healthcare-associated bloodstream infection and had higher morbidity and mortality rates than those with community-acquired bloodstream infection. Of all bloodstream infection pathogens, fungal organisms were associated with the highest crude mortality, longest length of stay in hospital, and greatest total charges. Of all bacterial bloodstream infections, methicillin-resistant Staphylococcus aureus was associated with the highest crude mortality rate (22.5%), the longest mean length of stay (11.1 ± 10.7 days), and the highest median total charges (

Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics

36,109). After we controlled for confounding factors, methicillin-resistant S. aureus was associated with the highest independent mortality risk (odds ratio 2.70; confidence interval 2.03–3.58). S. aureus was the most commonly encountered pathogen in all types of early-onset bacteremia. Conclusions:Healthcare-associated bloodstream infection constitutes a distinct entity of bloodstream infection with its unique epidemiology, microbiology, and outcomes. Methicillin-resistant Staphylococcus aureus carries the highest relative mortality risk among all pathogens.

Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens

Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little is known about the epidemiology of PH in sarcoidosis. The current authors reviewed the records of patients with sarcoidosis listed for lung transplantation in the USA between January 1995 and December 2002. PH was defined as a mean pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery pressure of ≥40 mmHg. The cohort included 363 patients of whom 73.8% had PH. Neither spirometric testing nor the need for corticosteroids was associated with PH. Subjects with PH required more supplemental oxygen (2.7±1.8 L·min−1 versus 1.6±1.4 L·min−1). The cardiac index was lower in individuals with PH, whereas the pulmonary capillary wedge pressure was higher. In multivariate analysis, supplemental oxygen remained an independent predictor of PH, whereas the relationship between cardiac index and PH was no longer significant. As a screening test, the need for oxygen had a sensitivity and specificity of 91.8% and 32.6%, respectively. Pulmonary hypertension is common in advanced sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.

Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs?

The results from two methodologically identical double-blind studies indicate that telavancin is noninferior to vancomycin based on clinical response in the treatment of hospital-acquired pneumonia due to Gram-positive pathogens.

Red blood cell transfusion and ventilator-associated pneumonia: A potential link?

Objective:To determine the financial impact of a sepsis protocol designed for use in the emergency department. Design:Retrospective analysis of a before-after study testing the implications of sepsis protocol. Setting:Academic, tertiary care hospital in the United States. Patients:Persons with septic shock presenting to the emergency department. Interventions:A multifaceted protocol developed from recent scientific literature on sepsis and the Surviving Sepsis Campaign. The protocol emphasized identification of septic patients, aggressive fluid resuscitation, timely antibiotic administration, and appropriateness of antibiotics, along with other adjunctive, supportive measures in sepsis care. Measurements and Main Results:We compared patients treated before the protocol with those cared for after the protocol was implemented. Overall hospital costs represented the primary end point, whereas hospital length of stay served as a secondary end point. All hospital costs were calculated based on charges after conversion to costs based on department-specific cost-to-charge ratios. We also attempted to measure the independent impact of the protocol on costs through linear regression. We conducted a sensitivity analysis assessing these end points in the subgroup of subjects who survived their hospitalization. The total cohort included 120 subjects (evenly divided into the before and after cohorts) with a mean age of 64.7 ± 18.2 yrs and median Acute Physiology and Chronic Health Evaluation II score of 22.5 ± 8.3. There were more survivors following the protocols adoption (70.0% vs. 51.7%, p = .040). Median total costs were significantly lower with use of the protocol (

Invasive approaches to the diagnosis of ventilator-associated pneumonia: A meta-analysis

16,103 vs.