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Nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), are the most common nosocomial infections occurring in critically ill patients requiring intensive care. However, challenges exist in making a timely and accurate diagnosis of HAP and VAP. Under diagnosis of HAP and VAP can result in greater mortality risk, especially if accompanied by delays in the administration of appropriate antimicrobial treatment. Over diagnosis of HAP and VAP results in the unnecessary administration of broad spectrum antibiotics that can lead to further escalation of antibiotic resistance. Optimal diagnosis and management of HAP and VAP require a systematic approach that combines clinical and radiographic assessments along with proper microbiologic techniques. The use of more invasive sampling methods (bronchoalveolar lavage and protected specimen brush) may enhance specimen collection resulting in more specific diagnoses to limit unnecessary antibiotic exposure. Molecular techniques, currently in use and investigational technique, may improve the diagnosis of HAP and VAP by allowing more rapid identification of offending pathogens, if present, thus increasing both appropriate antibiotic treatment and avoiding unnecessary drug exposure., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The first 70 years of critical care can be considered a period of "industrial revolution-like" advancement in terms of progressing the understanding and care of critical illness. Unfortunately, like the industrial revolution's impact on the environment, advancing ICU care of increasingly elderly, immunosuppressed, and debilitated individuals has resulted in a greater overall burden and complexity of nosocomial infections within modern ICUs. Given the rapid evolution of nosocomial infections, the authors provide an updated review., Data Sources and Study Selection: We searched PubMed and OVID for peer-reviewed literature dealing with nosocomial infections in the critically ill, as well as the websites of government agencies involved with the reporting and prevention of nosocomial infections. Search terms included nosocomial infection, antibiotic resistance, microbiome, antibiotics, and intensive care., Data Extraction and Data Synthesis: Nosocomial infections in the ICU setting are evolving in multiple domains including etiologic pathogens plus novel or emerging pathogens, prevalence, host risk factors, antimicrobial resistance, interactions of the host microbiome with nosocomial infection occurrence, and understanding of pathogenesis and prevention strategies. Increasing virulence and antimicrobial resistance of nosocomial infections mandate increasing efforts toward their prevention., Conclusions: Nosocomial infections are an important determinant of outcome for patients in the ICU setting. Systematic research aimed at improving the prevention and treatment of nosocomial infections is still needed., Competing Interests: Dr. Kollef’s efforts are supported by the Barnes-Jewish Hospital Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials., Research Question: What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia?, Study Design and Methods: Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission., Results: Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days., Interpretation: Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Nosocomial pneumonia due to antimicrobial-resistant pathogens is associated with high mortality. We assessed the efficacy and safety of the combination antibacterial drug ceftolozane-tazobactam versus meropenem for treatment of Gram-negative nosocomial pneumonia., Methods: We conducted a randomised, controlled, double-blind, non-inferiority trial at 263 hospitals in 34 countries. Eligible patients were aged 18 years or older, were undergoing mechanical ventilation, and had nosocomial pneumonia (either ventilator-associated pneumonia or ventilated hospital-acquired pneumonia). Patients were randomly assigned (1:1) with block randomisation (block size four), stratified by type of nosocomial pneumonia and age (<65 years vs ≥65 years), to receive either 3 g ceftolozane-tazobactam or 1 g meropenem intravenously every 8 h for 8-14 days. The primary endpoint was 28-day all-cause mortality (at a 10% non-inferiority margin). The key secondary endpoint was clinical response at the test-of-cure visit (7-14 days after the end of therapy; 12·5% non-inferiority margin). Both endpoints were assessed in the intention-to-treat population. Investigators, study staff, patients, and patients' representatives were masked to treatment assignment. Safety was assessed in all randomly assigned patients who received study treatment. This trial was registered with ClinicalTrials.gov, NCT02070757., Findings: Between Jan 16, 2015, and April 27, 2018, 726 patients were enrolled and randomly assigned, 362 to the ceftolozane-tazobactam group and 364 to the meropenem group. Overall, 519 (71%) patients had ventilator-associated pneumonia, 239 (33%) had Acute Physiology and Chronic Health Evaluation II scores of at least 20, and 668 (92%) were in the intensive care unit. At 28 days, 87 (24·0%) patients in the ceftolozane-tazobactam group and 92 (25·3%) in the meropenem group had died (weighted treatment difference 1·1% [95% CI -5·1 to 7·4]). At the test-of-cure visit 197 (54%) patients in the ceftolozane-tazobactam group and 194 (53%) in the meropenem group were clinically cured (weighted treatment difference 1·1% [95% CI -6·2 to 8·3]). Ceftolozane-tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure. Treatment-related adverse events occurred in 38 (11%) of 361 patients in the ceftolozane-tazobactam group and 27 (8%) of 359 in the meropenem group. Eight (2%) patients in the ceftolozane-tazobactam group and two (1%) in the meropenem group had serious treatment-related adverse events. There were no treatment-related deaths., Interpretation: High-dose ceftolozane-tazobactam is an efficacious and well tolerated treatment for Gram-negative nosocomial pneumonia in mechanically ventilated patients, a high-risk, critically ill population., Funding: Merck & Co., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Central-line-associated bloodstream infections (CLABSIs) are responsible for ∼1/3 of all deaths from healthcare-associated infections in the United States. Of these, multidrug-resistant organisms (MDROs) are responsible for 20% to 67%. However, whether catheter removal affects clinical outcomes for MDRO CLABSIs has not been studied. Our objective was to determine the relationship between failure to remove a central venous catheter (CVC) and 30-day all-cause mortality in patients with MDRO CLABSIs. We used a retrospective cohort from Barnes-Jewish Hospital (1/1/2009-10/1/2015) to study patients with a multidrug-resistant Staphylococcus aureus, Enterococcus species, Enterobacteriaceae, Acinetobacter species, or Pseudomonas aeruginosa CLABSI. Risk factors for 30-day mortality, including catheter removal, were assessed for association with 30-day mortality using Cox proportional hazards models. The CLABSIs were assessed prospectively at the time of occurrence by infection prevention specialists. A total of 430 patients met inclusion criteria, 173 (40.2%) with Enterococcus, 116 (27.0%) Enterobacteriaceae, 81 (18.8%) S aureus, 44 (10.2%) polymicrobial, 11 (2.6%) P aeruginosa, and 5 (1.2%) Acinetobacter CLABSIs. Removal of a CVC occurred in 50.2% of patients, of which 4.2% died by 30 days (n = 9). For patients whose CVC remained in place, 45.3% died (n = 97). Failure to remove a CVC was strongly associated with 30-day all-cause mortality with a hazard ratio of 13.5 (6.8-26.7), P < .001. Other risk factors for 30-day mortality included patient comorbidities (cardiovascular disease, congestive heart failure, cirrhosis), and being in an intensive care unit at the time of MDRO isolation. Failure to remove a CVC was strongly associated with 30-day all-cause mortality for patients with MDRO CLABSIs in this single center retrospective cohort. This suggests that patients presenting with MDRO CLABSIs should all undergo CVC removal.

OBJECTIVE To determine incidence of and risk factors for readmissions with multidrug-resistant organism (MDRO) infections among patients with previous MDRO infection. DESIGN Retrospective cohort of patients admitted between January 1, 2006, and October 1, 2015. SETTING Barnes-Jewish Hospital, a 1,250-bed academic tertiary referral center in St Louis, Missouri. METHODS We identified patients with MDROs obtained from the bloodstream, bronchoalveolar lavage (BAL)/bronchial wash, or other sterile sites. Centers for Disease Control and prevention (CDC) and European CDC definitions of MDROs were utilized. All readmissions ≤1 year from discharge from the index MDRO hospitalization were evaluated for bloodstream, BAL/bronchial wash, or other sterile site cultures positive for the same or different MDROs. RESULTS In total, 4,429 unique patients had a positive culture for an MDRO; 3,453 of these (78.0%) survived the index hospitalization. Moreover, 2,127 patients (61.6%) were readmitted ≥1 time within a year, for a total of 5,849 readmissions. Furthermore, 512 patients (24.1%) had the same or a different MDRO isolated from blood, BAL/bronchial wash, or another sterile site during a readmission. Bone marrow transplant, end-stage renal disease, lymphoma, methicillin-resistant Staphylococcus aureus, or carbapenem-resistant Pseudomonas aeruginosa during index hospitalization were factors associated with increased risk of having an MDRO isolated during a readmission. MDROs isolated during readmissions were in the same class of MDRO as the index hospitalization 9%-78% of the time, with variation by index pathogen. CONCLUSIONS Readmissions among patients with MDRO infections are frequent. Various patient and organism factors predispose to readmission. When readmitted patients had an MDRO, it was often a pathogen in the same class as that isolated during the index admission, with the exception of Acinetobacter (~9%). Infect Control Hosp Epidemiol 2018;39:12-19.

Purpose: To concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to the management of multidrug-resistant (MDR) bacteria, antibiotic use, and antimicrobial stewardship in the intensive care unit (ICU) setting., Methods: Narrative review based on a systematic analysis of the medical literature, national and international guidelines, and expert opinion., Results: The prevalence of infection of critically ill patients by MDR bacteria is rapidly evolving. Clinical studies aimed at improving understanding of the changing patterns of these infections in ICUs are urgently needed. Ideal antibiotic utilization is another area of uncertainty requiring additional investigations aimed at better understanding of dose optimization, duration of therapy, use of combination treatment, aerosolized antibiotics, and the integration of rapid diagnostics as a guide for treatment. Moreover, there is an imperative need to develop non-antibiotic approaches for the prevention and treatment of MDR infections in the ICU. Finally, clinical research aimed at demonstrating the beneficial impact of antimicrobial stewardship in the ICU setting is essential., Conclusions: These and other fundamental questions need to be addressed over the next decade in order to better understand how to prevent, diagnose, and treat MDR bacterial infections. Clinical studies described in this research agenda provide a template and set priorities for investigations that should be performed in this field.

Antibiotic resistance has emerged as a key determinant of outcome in patients with serious infections along with the virulence of the underlying pathogen. Within the intensive care unit (ICU) setting, ventilator-associated pneumonia (VAP) is a common nosocomial infection that is frequently caused by multidrug-resistant bacteria. Antimicrobial resistance is a growing challenge in the care of critically ill patients. Escalating rates of antibiotic resistance add substantially to the morbidity, mortality, and cost related to infection in the ICU. Both gram-positive organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-intermediate S. aureus , and gram-negative bacteria, including Pseudomonas aeruginosa , Acinetobacter species, carbapenem-resistant Enterobacteriaceae , such as the Klebsiella pneumoniae carbapenemase-producing bacteria, and extended spectrum β-lactamase organisms, have contributed to the escalating rates of resistance seen in VAP and other nosocomial infections. The rising rates of antimicrobial resistance have led to the routine empiric administration of broad-spectrum antibiotics even when bacterial infection is not documented. Moreover, there are several new broader-spectrum antibiotics that have recently become available and others scheduled for approval in the near future. The challenge to ICU clinicians is how to most effectively utilize these agents to maximize patient benefits while minimizing further emergence of resistance. Use of rapid diagnostics may hold the key for achieving this important balance. There is an urgent need for integrating the administration of new and existing antibiotics with the emerging rapid diagnostic technologies in a way that is both cost-effective and sustainable for the long run., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Hospital-acquired pneumonia arising in non-ventilated patients (NVHAP) is traditionally thought to be caused by bacteria, and little is known about viral etiologies in this syndrome. We sought to describe the prevalence of viruses causing NVHAP and to determine factors independently associated with the isolation of a virus., Methods: We identified patients with NVHAP over one year and reviewed their cultures to determine etiologies. Patients with a viral process were compared to those with either negative cultures or a bacterial infection to determine variables independently associated with the recovery of a virus., Results: Among 174 cases, cultures were positive in 46.0%, with viruses identified in 22.4%. Bacterial pathogens arose 23.6% of subjects. The most common viruses included rhinovirus, influenza, and parainfluenza. We noted no seasonality in the isolation of viral organisms, and most cases of viral NVHAP developed after more than a week length of stay (LOS). Outcomes in viral NVHAP were similar to those with bacterial NVHAP. Patients with viral and bacterial NVHAP were generally similar. Two variables were independently associated with isolation of a virus: a history of coronary artery disease (adjusted odds ratio: 5.16, 95% CI: 1.14-22.44) and a LOS of greater than 10 days prior to NVHAP diagnosis (adjusted odds ratio: 2.97, 95% CI: 1.35-6.51). As a screening test for a virus, neither had a good sensitivity or specificity., Conclusions: Viruses represent a common cause of NVHAP. Clinicians should consider viral diagnostic testing in NVHAP, as this may represent a means to enhance antimicrobial stewardship., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Nonventilated hospital-acquired pneumonia (NVHAP) is a serious nosocomial infection that is increasingly attributed to antibiotic-resistant bacteria., Methods: This is a retrospective case-control study comparing patients with and those without NVHAP from January 1, 2014 to December 31, 2014 at Barnes-Jewish Hospital, a 1,300-bed urban academic medical center in St. Louis, Missouri., Results: One hundred seventy-four consecutive patients with NVHAP were enrolled. A random sample of 696 control patients matched by age, sex, race, and hospital admission date were selected from a total of 5,322 potential matched control subjects. NVHAP was pathogen-negative in 98 cases (56.3%). Respiratory viruses were identified in 42 patients (24.1%), gram-negative bacteria were seen in 25 patients (14.4%), and gram-positive bacteria were identified in 20 patients (11.5%). Individuals in whom NVHAP developed were more likely to die (15.5% vs 1.6%; P < .01), to require intensive care (56.3% vs 22.8%; P < .01) or mechanical ventilation (19.0% vs 3.9%; P < 0.01), and to have a longer hospital length of stay (15.9 days [range, 9.8-26.3 days] vs 4.4 days [range, 2.9-7.3 days]; P < 0.01). This case-control study identified a strong association between hospital mortality and NVHAP, with patients who acquired NVHAP having an 8.4 times greater odds of death (95% CI, 5.6-12.5)., Conclusions: The occurrence of NVHAP was associated with significant increases in mortality, the use of intensive care and mechanical ventilation, and hospital length of stay. We also found that respiratory viruses were an important cause of NVHAP. These findings suggest that efforts aimed at the successful prevention of NVHAP could improve patient outcomes and reduce health-care costs., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

This was a randomized controlled pilot study of Lactobacillus rhamnosus GG versus standard of care to prevent gastrointestinal multidrug-resistant organism colonization in intensive care unit patients. Among 70 subjects, there were no significant differences in acquisition or loss of any multidrug-resistant organisms (P>.05) and no probiotic-associated adverse events.

Objective: To describe and compare the mortality associated with nosocomial pneumonia due to Pseudomonas aeruginosa (Pa-NP) according to pneumonia classification (community-onset pneumonia [COP], hospital-acquired pneumonia [(HAP], and ventilator-associated pneumonia [VAP])., Design: We conducted a retrospective cohort study of adults with Pa-NP. We compared mortality for Pa-NP among patients with COP, HAP, and VAP and used logistic regression to identify risk factors for hospital mortality and inappropriate initial antibiotic therapy (IIAT)., Setting: Twelve acute care hospitals in 5 countries (United States, 3; France, 2; Germany, 2; Italy, 2; and Spain, 3)., Patients/participants: A total of 742 patients with Pa-NP., Results: Hospital mortality was greater for those with VAP (41.9%) and HAP (40.1%) compared with COP (24.5%) (P<.001). In multivariate analyses, independent predictors of hospital mortality differed by pneumonia classification (COP: need for mechanical ventilation and intensive care; HAP: multidrug-resistant isolate; VAP: IIAT, increasing age, increasing Charlson comorbidity score, bacteremia, and use of vasopressors). Presence of multidrug resistance was identified as an independent predictor of IIAT for patients with COP and HAP, whereas recent antibiotic administration was protective in patients with VAP., Conclusions: Among patients with Pa-NP, pneumonia classification identified patients with different risks for hospital mortality. Specific risk factors for hospital mortality also differed by pneumonia classification and multidrug resistance appeared to be an important risk factor for IIAT. These findings suggest that pneumonia classification for P. aeruginosa identifies patients with different mortality risks and specific risk factors for outcome and IIAT.

Introduction: Pseudomonas aeruginosa nosocomial pneumonia (Pa-NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality., Methods: We conducted a retrospective cohort study of adult patients with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality., Results: Of 740 patients with Pa-NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis., Conclusions: Among patients with Pa-NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa-NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival.

Objective: While incidence, mortality, morbidity, and recurrence rates of C. difficile infection (CDI) among the critically ill have been investigated, the impact of its recurrence on 30-day rehospitalization (ReAd), an important policy focus, has not been examined., Design: Secondary analysis of a multicenter retrospective cohort study Patients Adult critically ill patients who survived their index hospitalization complicated by CDI METHODS: CDI was defined by diarrhea or pseudomembranous colitis and a positive assay for C. difficile toxins A and/or B. CDI recurrence (rCDI) was defined as diarrhea, positive C. difficile toxin and need for retreatment after cessation of therapy. Descriptive statistics and a logistic regression examined ReAd rates and characteristics, and factors that impact it., Results: Among 287 hospital survivors, 76 (26.5%) required ReAd (ReAd+). At baseline, the ReAd+ group did not differ significantly from the ReAd- group based on demographics, comorbidities, APACHE II scores, or ICU type. ReAd+ patients were more likely to have hypotension at CDI onset (48.7% vs 34.1%, P=.025) and to require vasopressors (40.0% vs 27.1%, P=.038); they were less likely to require mechanical ventilation (56.0% vs 77.3%, P<.001). A far greater proportion of ReAd+ than ReAd- had developed a recurrence either during the index hospitalization or within 30 days after discharge (32.89% vs 2.84%, P<.001). In a logistic regression, rCDI was a strong predictor of ReAd+ (adjusted odd ratio, 15.33, 95% confidence interval, 5.68-41.40)., Conclusions: Greater than 25% of all survivors of critical illness complicated by CDI require readmission within 30 days of discharge. CDI recurrence is a strong predictor of such rehospitalizations.

Background: Macrolide-based treatment has been associated with survival benefit in patients hospitalized with community-acquired pneumonia (CAP). However, the influence of macrolide therapy in all patients hospitalized with pneumonia, including healthcare-associated pneumonia (HCAP), is unclear., Methods: Analysis of a retrospective single-center cohort., Results: Community-acquired pneumonia was present in 220 (22.5%) of all patients with pneumonia admitted through the emergency department of Barnes-Jewish Hospital, and HCAP was present in 757. Macrolide-based treatment was administered to 411 patients (42.1%). These patients were more likely to have CAP than were patients not receiving macrolide-based therapy (35.3% vs. 13.3%; p<0.001) and had lower scores on the CURB-65 tool, a measure of the severity of illness (2.4±1.5 vs. 3.1±1.3; p<0.001). Patients receiving macrolides also had a lower hospital mortality rate in univariable analysis (12.7% vs. 27.2%; p<0.001). A propensity score analysis showed that macrolide-based treatment was associated with a lower in-hospital mortality rate (adjusted odds ratio [AOR] 0.67; 95% confidence interval [CI] 0.54-0.81; p=0.043). Separate propensity score analyses of patients with CAP (AOR 0.20; 95% CI 0.11-0.34; p=0.003) and HCAP (AOR 0.81; 95% CI 0.65-1.01; p=0.337) produced discordant findings., Conclusions: Macrolide-based treatment was associated with better survival in patients hospitalized with pneumonia. The survival advantage appeared predominantly among patients with CAP.

Objective: Determine whether daily bathing with chlorhexidine-based soap decreased methicillin-resistant Staphylococcus aureus (MRSA) transmission and intensive care unit (ICU)-acquired S. aureus infection among ICU patients., Design: Prospective pre-post-intervention study with control unit., Setting: A 1,250-bed tertiary care teaching hospital., Patients: Medical and surgical ICU patients., Methods: Active surveillance for MRSA colonization was performed in both ICUs. In June 2005, a chlorhexidine bathing protocol was implemented in the surgical ICU. Changes in S. aureus transmission and infection rate before and after implementation were analyzed using time-series methodology., Results: The intervention unit had a 20.68% decrease in MRSA acquisition after institution of the bathing protocol (12.64 cases per 1,000 patient-days at risk before the intervention vs 10.03 cases per 1,000 patient-days at risk after the intervention; β, -2.62 [95% confidence interval (CI), -5.19 to -0.04]; P = .046). There was no significant change in MRSA acquisition in the control ICU during the study period (10.97 cases per 1,000 patient-days at risk before June 2005 vs 11.33 cases per 1,000 patient-days at risk after June 2005; β, -11.10 [95% CI, -37.40 to 15.19]; P = .40). There was a 20.77% decrease in all S. aureus (including MRSA) acquisition in the intervention ICU from 2002 through 2007 (19.73 cases per 1,000 patient-days at risk before the intervention to 15.63 cases per 1,000 patient-days at risk after the intervention [95% CI, -7.25 to -0.95]; P = .012)]. The incidence of ICU-acquired MRSA infections decreased by 41.37% in the intervention ICU (1.96 infections per 1,000 patient-days at risk before the intervention vs 1.15 infections per 1,000 patient-days at risk after the intervention; P = .001)., Conclusions: Institution of daily chlorhexidine bathing in an ICU resulted in a decrease in the transmission of S. aureus, including MRSA. These data support the use of routine daily chlorhexidine baths to decrease rates of S. aureus transmission and infection.

Background: ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results., Objective: To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection., Methods: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011)., Results: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329)., Conclusions: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Acute respiratory failure represents the most common condition requiring admission to an adult intensive care unit. Ventilator-associated pneumonia (VAP) has been used as a marker of quality for patients with respiratory failure. Hospital-based process-improvement initiatives to prevent VAP have been successfully used. The use of ventilator-associated complications (VACs) has been proposed as an objective marker to assess the quality of care for this patient population. The use of evidence-based bundles targeting the reduction of VACs, as well as the conduct of prospective studies showing that VACs are preventable complications, are reasonable first-steps in addressing this important clinical problem., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Objective: To evaluate the economic impact of ventilator-associated pneumonia (VAP) on length of stay and hospital costs. Design. Retrospective matched cohort study., Setting: Premier database of hospitals in the United States., Patients: Eligible patients were admitted to intensive care units (ICUs), received mechanical ventilation for ≥2 calendar-days, and were discharged between October 1, 2008, and December 31, 2009., Methods: VAP was defined by International Classification of Diseases, Ninth Revision (ICD-9), code 997.31 and ventilation charges for ≥2 calendar-days. We matched patients with VAP to patients without VAP by propensity score on the basis of demographics, administrative data, and severity of illness. Cost was based on provider perspective and procedural cost accounting methods., Results: Of 88,689 eligible patients, 2,238 (2.5%) had VAP; the incidence rate was 1.27 per 1,000 ventilation-days. In the matched cohort, patients with VAP ([Formula: see text]) had longer mean durations of mechanical ventilation (21.8 vs 10.3 days), ICU stay (20.5 vs 11.6 days), and hospitalization (32.6 vs 19.5 days; all [Formula: see text]) than patients without VAP ([Formula: see text]). Mean hospitalization costs were $99,598 for patients with VAP and $59,770 for patients without VAP ([Formula: see text]), resulting in an absolute difference of $39,828. Patients with VAP had a lower in-hospital mortality rate than patients without VAP (482/2,144 [22.5%] vs 630/2,144 [29.4%]; [Formula: see text])., Conclusions: Our findings suggest that VAP continues to occur as defined by the new specific ICD-9 code and is associated with a statistically significant resource utilization burden, which underscores the need for cost-effective interventions to minimize the occurrence of this complication.

Inappropriate initial antimicrobial therapy (IIAT) has been associated with decreased survival in patients with health care-associated pneumonia (HCAP). We performed a study to determine whether empiric HCAP antibiotic regimens targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are associated with greater appropriate therapy. A retrospective cohort study of culture-positive HCAP over 6 years (January 2003-December 2008) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. We identified 757 consecutive patients with HCAP. IIAT was administered to 213 (28%) patients. The pathogens most frequently associated with IIAT included P. aeruginosa (n=60, 28%), MRSA (n=58, 27%), and Acinetobacter species (n=32, 15%).Multivariate logistic regression analysis demonstrated that empiric anti-pseudomonal antibiotics (adjusted odds ratio [AOR], 1.75; 95% confidence interval [CI], 1.34-2.29; p=0.036), empiric anti-MRSA antibiotics (AOR, 1.71; 95% CI, 1.36-2.14; p=0.018), infection with Streptococcus pneumoniae (AOR, 2.82; 95% CI, 2.03-3.91; p=0.002), absence of Acinetobacter species infection (AOR, 10.57; 95% CI, 7.29-15.33; p<0.001), absence of P. aeruginosa infection (AOR, 1.69; 95% CI, 1.36-2.05; p=0.014), and absence of Stenotrophomonas maltophilia infection (AOR, 20.43; 95% CI, 9.35-44.66; p<0.001) are independent predictors of appropriate therapy for HCAP. Our study suggests that initial therapy for HCAP should include antibiotics targeting MRSA and P. aeruginosa in order to provide appropriate initial therapy. However, the selection of individual antibiotic agents should be based on local patterns of infection and adjusted when microbiology results become available.

Healthcare-associated pneumonia patients have worse outcomes and a different microbiologic profile than those with community-acquired pneumonia, including a greater risk for multidrug-resistant (MDR) organism infection. Risks include hospitalization for 2 or more days within 90 days, presentation from a nursing home or long-term care facility, attending a hospital or hemodialysis clinic, receiving intravenous therapy within 30 days, and immunosuppression. Ability to predict infection with MDR organisms varies, and the relative frequency of MDR organisms varies by geographic region. Initial treatment is broad-spectrum empiric antibiotics., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Traditionally, pneumonia developing in patients who receive healthcare services in the outpatient environment has been classified as community-acquired pneumonia (CAP). However, recent investigations suggest that this type of infection, known as healthcare-associated pneumonia (HCAP), is distinct from CAP in terms of its epidemiology, etiology, and risk for infection with multidrug-resistant (MDR) pathogens., Methods: A Medline literature review of available clinical studies using the term HCAP was conducted to determine outcomes compared to CAP and effective empiric treatment strategies., Results: Analysis of multi-institutional clinical data showed that mortality in hospitalized patients with HCAP is greater than that in CAP, and patients with HCAP received inappropriate initial empiric antibiotic treatment more frequently than CAP patients. The bacterial pathogens associated with HCAP also differed from CAP with potentially MDR Gram-positive and Gram-negative bacteria being more common in HCAP., Conclusions: All patients hospitalized with suspected HCAP should be evaluated for their underlying risk of infection with MDR pathogens. Because HCAP is similar to hospital-acquired pneumonia (HAP), both clinically and etiologically, it should be treated as HAP until culture data become available., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Nosocomial pneumonia is a difficult diagnosis to establish in the intensive care unit setting, due to the non-specific nature of the clinical and radiographic findings. Procalcitonin is a circulating biomarker that may become elevated in the presence of bacterial infection., Methods: We conducted a prospective single-center cohort study at Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital in St Louis, Missouri. In medical and surgical intensive care unit patients with suspected nosocomial pneumonia we measured plasma procalcitonin with an enzyme-linked fluorescent assay., Results: We evaluated 104 consecutive patients with suspected nosocomial pneumonia, 67 (64%) of whom met our predefined clinical and microbiologic criteria for definite nosocomial pneumonia. Though the mean procalcitonin concentration was greater in the 67 patients with definite nosocomial pneumonia (18.3 ± 99.1 ng/mL, median 0.8 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 43.1 ng/mL) than in the 12 patients with definite absence of nosocomial pneumonia (1.7 ± 2.0 ng/mL, median 1.0 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 6.7 ng/mL), this difference was not statistically significant (P = .66). A procalcitonin cutoff value of > 1 ng/mL yielded a diagnostic sensitivity of 50% and a specificity of 49% for definite nosocomial pneumonia. Receiver operating curve and multivariate logistic regression analyses demonstrated that procalcitonin is inferior to clinical variables for diagnosing nosocomial pneumonia. However, compared to patients with an initial procalcitonin > 1 ng/mL, those with lower procalcitonin had fewer total antibiotic days (13.0 ± 10.3 d vs 19.7 ± 12.0 d, P < .001) and fewer antibiotic days for treatment of nosocomial pneumonia (10.0 ± 5.9 d vs 14.7 ± 7.4 d, P < .001)., Conclusions: Plasma procalcitonin has minimal diagnostic value for nosocomial pneumonia.

Background: Ventilator-associated tracheobronchitis (VAT) is considered an intermediate condition between bacterial airway colonization and ventilator-associated pneumonia (VAP). The purpose of this prospective cohort study was to further characterize VAT in terms of incidence, etiology, and impact on patient outcomes., Methods: Patients intubated for >48 h in the surgical and medical ICUs of Barnes-Jewish Hospital were screened daily for the development of VAT and VAP over 1 year. Patients were followed until hospital discharge or death, and patient demographics, causative pathogens, and clinical outcomes were recorded., Results: A total of 28 patients with VAT and 83 with VAP were identified corresponding to frequencies of 1.4% and 4.0%, respectively. VAP was more common in surgical than medical ICU patients (5.3% vs 2.3%; P<.001), but the occurrence of VAT was similar between surgical and medical patients (1.3% vs 1.5%; P=.845). VAT progressed to VAP in nine patients (32.1%) despite antibiotic therapy. There was no significant difference in hospital mortality between patients with VAP and VAT (19.3% vs 21.4%; P=.789). VAT was caused by a multidrug-resistant (MDR) pathogen in nine cases (32.1%)., Conclusion: VAT occurs less commonly than VAP but at a similar incidence in medical and surgical ICU patients. VAT frequently progressed to VAP, and patients diagnosed with VAT had similar outcomes to those diagnosed with VAP, suggesting that antimicrobial therapy is appropriate for VAT. VAT is also frequently caused by MDR organisms, and this should be taken into account when choosing antimicrobial therapy.

Objective: Early therapy of sepsis involving fluid resuscitation and antibiotic administration has been shown to improve patient outcomes. A proactive tool to identify patients at risk for developing sepsis may decrease time to interventions and improve patient outcomes. The objective of this study was to evaluate whether the implementation of an automated sepsis screening and alert system facilitated early appropriate interventions., Design: Prospective, observational, pilot study., Setting: Six medicine wards in Barnes-Jewish Hospital, a 1250-bed academic medical center., Patients: Patients identified by the sepsis screen while admitted to a medicine ward were included in the study. A total of 300 consecutive patients were identified comprising the nonintervention group (n=200) and the intervention group (n=100)., Interventions: A real-time sepsis alert was implemented for the intervention group, which notified the charge nurse on the patient's hospital ward by text page., Measurements and Main Results: Within 12 hrs of the sepsis alert, interventions by the treating physicians were assessed, including new or escalated antibiotics, intravenous fluid administration, oxygen therapy, vasopressors, and diagnostic tests. After exclusion of patients without commitment to aggressive management, 181 patients in the nonintervention group and 89 patients in the intervention group were analyzed. Within 12 hrs of the sepsis alert, 70.8% of patients in the intervention group had received≥1 intervention vs. 55.8% in the nonintervention group (p=.018). Antibiotic escalation, intravenous fluid administration, oxygen therapy, and diagnostic tests were all increased in the intervention group. This was a single-center, institution- and patient-specific algorithm., Conclusions: The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early therapeutic and diagnostic interventions among nonintensive care unit patients at risk for sepsis.

Objectives: Classically, infections have been considered either nosocomial or community-acquired. Healthcare-associated infection represents a new classification intended to capture patients who have infection onset outside the hospital, but who, nonetheless, have interactions with the healthcare system. Regarding bloodstream infection (BSI), little data exist differentiating healthcare-associated bacteremia (HCAB) from community-acquired bacteremia (CAB). We studied the epidemiology and outcomes associated with HCAB., Methods: We conducted a multicenter, retrospective chart review at 7 US hospitals, of consecutive patients admitted with a BSI during 2006, who met pre-defined selection criteria. We defined HCAB as a BSI in a patient who met ≥ 1 of the criteria: 1) hospitalization within 6 months; 2) immunosuppression; 3) chronic hemodialysis; or 4) nursing home residence. The rest were classified as CAB. We examined patient demographics, severity of illness, and in-hospital mortality rates by HCAB vs. CAB status. A bootstrap logistic regression model was developed to quantify the independent association between HCAB and hospital mortality., Results: Of the total 1143 patients included, HCAB accounted for 63.7%, with the percentage ranging from 49.0% to 78.1% across centers. HCAB patients were older (58.5 ± 17.5 vs. 55.0 ± 19.9 years, p = 0.003) and slightly more likely to be male (56.1% vs. 50.2%, p = 0.044) than those with CAB. HCAB was associated with a higher mean Acute Physiology Score (12.6 ± 6.2 vs. 11.4 ± 5.7, p = 0.009) and recent hospitalization was the most prevalent criteria for defining HCAB (76.5%). Hospital LOS was longer in the HCAB (median 8, IQR 5-15 days) than CAB (median 7, IQR 4-13 days) group (p = 0.030). In a multivariable model, the risk of hospital death was 3-fold higher for HCAB compared to CAB (adjusted odds ratio 3.13, 95% CI 1.75-5.50, p < 0.001, AUROC = 0.812)., Conclusions: HCAB accounts for a substantial proportion of all patients with BSIs admitted to the hospital. HCAB is associated with a higher mortality rate than CAB. Physicians should recognize that HCAB is responsible for many BSIs presenting to the hospital and may represent a distinct clinical group from CAB., (Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens., Methods: Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7-21 days. The primary end point was clinical response at follow-up/test-of-cure visit., Results: A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, -5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, -4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, -0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, -7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%)., Conclusions: The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.

Objective: Inappropriate empiric therapy worsens outcomes in certain healthcare-associated infections (HCAI). We studied the association of inappropriate empiric therapy with outcomes in patients with HCA complicated skin and skin structure infections (cSSSI)., Design: A single-center retrospective cohort study., Patients: Hospitalized with a culture-positive cSSSI., Measurements: We defined HCA-cSSSI as having ≥1 of these risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, (4) transfer from a nursing home, and inappropriate treatment as no antimicrobial therapy active against the pathogen(s) within 24 hours of obtaining culture specimen. We performed descriptive and multivariate statistics to compute the impact of inappropriate empiric therapy on outcomes. Hospital length of stay (LOS) served as primary and mortality as secondary outcomes., Results: Of the 717 patients with culture-positive cSSSI, 527 (73.5%) had HCAI, of whom 405 (76.9%) received appropriate treatment. A higher proportion of those receiving inappropriate than appropriate treatment had a decubitus ulcer (29.5% vs. 10.9%, P < 0.001), a device-associated infection (42.6% vs. 28.6%, P = 0.004), or bacteremia (68.9% vs. 57.8%, P = 0.028). The frequency of methicillin-resistant Staphylococcus aureus (MRSA) did not differ between the groups. The low overall unadjusted mortality rate did not vary based on initial treatment. In a multivariable analysis adjusting for potential confounders inappropriate therapy had an attributable increase in hospital LOS of 1.8 days (95% CI, 1.4-2.3)., Conclusion: Similar to other populations with HCAI, HCA-cSSSI patients are likely to receive inappropriate empiric therapy for their infection. This early exposure is associated with a significant prolongation of the hospitalization by nearly 2 days., (Copyright © 2010 Society of Hospital Medicine.)

Objective: To test whether intensive care unit (ICU) nasal screening for methicillin-resistant Staphylococcus aureus (MRSA) predicts the presence or absence of MRSA infections requiring antimicrobial treatment., Design: A prospective cohort study., Setting: Medical ICU at Barnes-Jewish Hospital, a 1252-bed urban teaching hospital., Patients: Seven hundred forty-nine consecutive patients admitted to the medical ICU over a 7-mo period (November 2007 through June 2008)., Interventions: Nasal swabs were obtained at ICU admission and weekly thereafter for MRSA detection by using polymerase chain reaction. All subjects were followed for the development of MRSA infection during their ICU stay., Measurements and Main Results: One hundred sixty-four (21.9%) patients had positive nasal colonization with MRSA at the time of ICU admission. The predictive accuracy of MRSA nasal colonization for ICU-acquired MRSA infections, either lower respiratory tract infection or bloodstream infection, was poor (lower respiratory tract infection: sensitivity, 24.2%; specificity, 78.5%; positive predictive value, 17.7%; and negative predictive value, 84.4%; and bloodstream infection: sensitivity, 23.1%; specificity, 78.2%; positive predictive value, 11.0%; and negative predictive value, 89.7%). Addition of nasal-colonization results obtained during the ICU stay did not appreciably change the predictive accuracy of this test for identification of subsequent lower respiratory tract infections and bloodstream infections attributed to MRSA requiring antimicrobial treatment., Conclusions: In this analysis, nasal colonization with MRSA was found to be a poor predictor for the subsequent occurrence of MRSA lower respiratory tract infections and MRSA bloodstream infections requiring antimicrobial treatment. Clinicians should be cautious in using the results of nasal-colonization testing to determine the need for MRSA treatment among patients with ICU-acquired infections.

Nosocomial pneumonia (NP) is a difficult diagnosis to establish in the critically ill patient due to the presence of underlying cardiopulmonary disorders (e.g., pulmonary contusion, acute respiratory distress syndrome, atelectasis) and the nonspecific radiographic and clinical signs associated with this infection. Additionally, the classification of NP in the intensive care unit setting has become increasingly complex, as the types of patients who develop NP become more diverse. The occurrence of NP is especially problematic as it is associated with a greater risk of hospital mortality, longer lengths of stay on mechanical ventilation and in the intensive care unit, a greater need for tracheostomy, and significantly increased medical care costs. The adverse effects of NP on healthcare outcomes has increased pressure on clinicians and healthcare systems to prevent this infection, as well as other nosocomial infections that complicate the hospital course of patients with respiratory failure. This manuscript will provide a brief overview of the current approaches for the diagnosis of NP and focus on strategies for prevention. Finally, we will provide some guidance on how standardized or protocolized care of mechanically ventilated patients can reduce the occurrence of and morbidity associated with complications like NP.

Clinical trials evaluating antimicrobial therapy for nosocomial pneumonia face many hurdles in terms of producing data that are widely applicable, supportive of safe medical practices, and able to demonstrate distinct advantages of one form of therapy over the other. Adherence to strict performance measures in conducting such trials should improve their overall quality. Such measures include enrollment of clearly defined patient populations who have a high likelihood of nosocomial pneumonia, use of diagnostic measures to confirm the presence of lower respiratory tract infection, and inclusion of broad-based pathogen distributions to ensure that the trial is applicable to the majority of patients developing nosocomial pneumonia.

Traditionally, pneumonia developing in patients who receive health care services in the outpatient environment, such as nursing homes, long-term care facilities, and dialysis centers, has been classified and treated as community-acquired pneumonia (CAP). Recent studies, however, have shown that this type of infection, known as health care-associated pneumonia (HCAP) is distinct from CAP in terms of its epidemiology and etiology, and increases the risk for infection with multidrug-resistant (MDR) pathogens. A review of available clinical data about HCAP was conducted to determine effective empiric treatment strategies and improve clinical outcomes. Analysis of multi-institutional clinical data showed that mortality associated with HCAP is higher than with CAP, suggesting that patients with HCAP may have been treated as hospitalized patients with CAP and received inappropriate initial empiric antibiotic treatment. All patients presenting to the hospital with suspected HCAP or CAP should be evaluated for their underlying risk of infection with MDR pathogens. Because HCAP may be similar to hospital-acquired pneumonia (HAP) both clinically and etiologically, it should be treated as HAP until culture data become available. A greater recognition of HCAP as a new class of pneumonia with a distinct epidemiologic, microbiologic, and clinical profile should lead physicians to initiate appropriate empiric antibiotic therapy more often, thereby improving the likelihood for optimal clinical outcomes and patient care.

Objective: The aim of this study is to describe the initial antibiotic treatment regimens, severity of illness, and in-hospital mortality among culture-negative (CN) and culture-positive (CP) patients with health-care-associated pneumonia (HCAP)., Methods: We used a retrospective cohort study, examining adult patients with HCAP from Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital., Results: Eight hundred seventy patients with HCAP were identified over a 3-year period (January 2003 through December 2005) of whom 431 (49.5%) were CP. Among the non-CP patients, 290 (66.1%) had no respiratory cultures obtained, and 149 (33.9%) had no growth or nonpathogenic oral flora identified and were classified as CN. CN patients were more likely to have received an initial antibiotic regimen (ceftriaxone +/- azithromycin or moxifloxacin) targeting community-acquired pneumonia pathogens compared with CP patients (71.8% vs 25.5%, P < .001). Severity of illness as assessed by ICU admission and mechanical ventilation (MV) was statistically lower in CN compared with CP patients (ICU admittance 12.1% vs 48.7%, P < .001; MV: 6.7% vs 44.5%, P < .001). In-hospital mortality and hospital length of stay were also statistically lower for CN patients (mortality: 7.4% vs 24.6%, P < .001; hospital length of stay: 6.7 +/- 7.4 days vs 12.1 +/- 11.7 days, P < .001)., Conclusions: In this analysis, patients with CN HCAP had lower severity of illness, hospital mortality, and hospital length of stay compared with CP patients. These data suggest that patients with CN HCAP differ substantially from patients with HCAP with positive microbiologic cultures.

Objective: Healthcare-associated infections are likely to be caused by drug-resistant and possibly mixed organisms and to be treated with inappropriate antibiotics. Because prompt appropriate treatment is associated with better outcomes, we studied the epidemiology of healthcare-associated complicated skin and skin-structure infections (cSSSIs)., Patients: Persons hospitalized with cSSSI and a positive culture result., Methods: We conducted a single-center retrospective cohort study from April 2006 through December 2007. We differentiated healthcare-associated from community-acquired cSSSIs by at least 1 of the following risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, and (4) transfer from a nursing home. Inappropriate treatment was defined as no antimicrobial therapy with activity against the offending pathogen(s) within 24 hours after collection of a culture specimen. Mixed infections were those caused by both a gram-positive and a gram-negative organism., Results: Among 717 hospitalized patients with cSSSI, 527 (73.5%) had healthcare-associated cSSSI. Gram-negative organisms were more common (relative risk, 1.24 [95% confidence interval, 1.14-1.35) and inappropriate treatment trended toward being more common (odds ratio, 1.29 [95% confidence interval, 0.85-1.95]) in healthcare-associated cSSSI than in community-acquired cSSSI. Mixed cSSSIs occurred in 10.6% of patients with healthcare-associated cSSSI and 6.3% of those with community-acquired cSSSI (P = .082) and were more likely to be treated inappropriately than to be nonmixed infections (odds ratio, 2.42 [95% confidence interval, 1.43-4.10]). Both median length of hospital stay (6.2 vs 2.9 days; P < .001) and mortality rate (6.6% vs 1.1%; P = .003) were significantly higher for healthcare-associated cSSSI than community-acquired cSSSI., Conclusions: Healthcare-associated cSSSIs are common and are likely to be caused by gram-negative organisms. Mixed infections carry a >2-fold greater risk of inappropriate treatment. Healthcare-associated cSSSIs are associated with increased mortality and prolonged length of hospital stay, compared with community-acquired cSSSIs.

Purposes: Patients receiving prolonged acute mechanical ventilation (PAMV), although comprising a third of all mechanical ventilation (MV) patients, consume two-thirds of all the resources allocated to MV, and their numbers are projected to double by 2020. By virtue of their prolonged hospital length of stay (median LOS, 17 days), they are subject to such nosocomial infections as Clostridium difficile-associated disease (CDAD), the incidence and age-adjusted case fatality rate of which doubled between 2000 and 2005. We examined the rates and outcomes of CDAD among adult PAMV patients., Methods: We analyzed 2005 data from the Health Care Utilization Project/Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality. PAMV and CDAD were identified using the International Classification of Diseases, ninth revision, clinical modification codes 96.72 and 008.45, respectively., Results: Among 64,910 adult PAMV patients who were discharged in 2005, 3,468 patients (5.34%) had a concurrent diagnosis of CDAD (PAMV patients who were discharged with concomitant diagnosis of CDAD [CDAD+]). CDAD+ patients who were discharged were older (mean [+/- SD] age, 66.7 +/- 15.9 vs 63.7 +/- 16.9 years, respectively; p < 0.001) and were more likely to have been admitted to the hospital from a long-term care facility (5.7% vs 2.9%, respectively; p < 0.001) than PAMV patients who were discharged without CDAD (CDAD-). Although crude hospital mortality rates did not differ among PAMV patients who were discharged from the hospital by CDAD status (CDAD+, 32.6%; CDAD-, 33.0%; p = 0.598), both unadjusted calculations and propensity-score adjustment showed a substantial increase in LOS (6.1 days; 95% confidence interval [CI], 4.9 to 7.4) and total costs ($10,355; 95% CI, $7,540 to $13,170) among CDAD+ patients., Conclusions: PAMV patients have an order of magnitude higher risk of having CDAD than other hospitalized patients. Concurrent CDAD infection is associated with increased hospital LOS and costs. The PAMV population is an attractive target for aggressive measures aimed at CDAD prevention.