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Background: Nosocomial and ventilator-associated pneumonia (VAP) are causes of significant morbidity and mortality in hospitalized patients. We analyzed a) the incidence and the outcome of pneumonias caused by different pathogens in the intensive care unit (ICU) of a medium-sized twenty-four bed community hospital and b) the incidence of complications of such pneumonias requiring surgical intervention such as thoracotomy and decortication., Results: We retrospectively reviewed the charts of patients diagnosed with nosocomial and ventilator-associated pneumonia in our ICU. Their bronchoalveolar lavage (BAL) and sputum cultures, antibiograms, and other clinical characteristics, including complications and need for tracheostomy, thoracotomy and decortication were studied. In a span of one year (2011-12), 43 patients were diagnosed with nosocomial pneumonia in our ICU. The median simplified acute physiology score (SAPS II) was 39. One or more gram negative organisms as the causative agents were present in 85% of microbiologic samples. The three most prevalent gram negatives were Stenotrophomonas maltophilia (34%), Pseudomonas aeurginosa (40%), and Acinetobacter baumannii (32%). Twenty eight percent of bronchoalveolar samples contained Staphylococcus aureus. Eight three percent of patients required mechanical ventilation postoperatively and 37% underwent tracheostony. Thirty five percent underwent thoracotomy and decortication because of further complications such as empyema and non-resolving parapneumonic effusions. A. baumannii, Klebsiella pneumonia extended spectrum beta lactam (ESBL) and P. aeurginosa had the highest prevalence of multi drug resistance (MDR). Fifteen patients required surgical intervention. Mortality from pneumonia was 37% and from surgery was 2%., Conclusion: Nosocomial pneumonias, in particular the ones that were caused by gram negative drug resistant organisms and their ensuing complications which required thoracotomy and decortication, were the cause of significant morbidity in our intensive care unit. Preventative and more intensive and novel infection control interventions in reducing the incidence of nosocomial pneumonias are strongly emphasized.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant hospital-acquired infections worldwide and remains a public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often affects patients in intensive care units with substantial morbidity, mortality and associated costs. A guideline-based approach to empirical treatment with an antibacterial agent active against MRSA can improve the outcome of patients with MRSA NP, including those with ventilator-associated pneumonia. New methods may allow more rapid or sensitive diagnosis of NP or microbiological confirmation in patients with MRSA NP, allowing early de-escalation of treatment once the pathogen is known. In Europe, available antibacterial agents for the treatment of MRSA NP include the glycopeptides (vancomycin and teicoplanin) and linezolid (available as an intravenous or oral treatment). Vancomycin has remained a standard of care in many European hospitals; however, there is evidence that it may be a suboptimal therapeutic option in critically ill patients with NP because of concerns about its limited intrapulmonary penetration, increased nephrotoxicity with higher doses, as well as the emergence of resistant strains that may result in increased clinical failure. Linezolid has demonstrated high penetration into the epithelial lining fluid of patients with ventilator-associated pneumonia and shown statistically superior clinical efficacy versus vancomycin in the treatment of MRSA NP in a phase IV, randomized, controlled study. This review focuses on the disease burden and clinical management of MRSA NP, and the use of linezolid after more than 10 years of clinical experience., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Doripenem is approved in the Asia-Pacific (APAC) region for treating nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP), complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs). Clinical usage of doripenem (500mg intravenously, infused over 1h or 4h every 8h for 5-14 days) in APAC was evaluated in a prospective, open-label, non-comparative, multicentre study of inpatients (≥18 years) with NP, VAP, cIAI or cUTI. A total of 216 [intention-to-treat (ITT)] patients received doripenem: 53 NP (24.5%); 77 VAP (35.6%); 67 cIAI (31.0%); and 19 cUTI (8.8%). Doripenem MIC90 values for Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were 32, 32, 0.094 and 0.64μg/mL, respectively. Doripenem was used most commonly as monotherapy (86.6%) and as second-line therapy (62.0%). The clinical cure rate in clinically evaluable patients was 86.7% at the end of therapy (EOT) and 87.1% at test of cure (TOC) (7-14 days after EOT). In the ITT population, overall clinical cure rates were 66.2% at EOT and 56.5% at TOC. The median duration of hospital stay, intensive care unit (ICU) stay and mechanical ventilation was 20, 12 and 10 days, respectively. Of 146 discharged patients, 7 were re-admitted within 28 days of EOT; 1 VAP patient was re-admitted to the ICU. The all-cause mortality rate was 22.7% (49/216). The most common treatment-related adverse events were diarrhoea (1.4%) and vomiting (1.4%). Doripenem is a viable option for treating APAC patients with NP, VAP, cIAI or cUTI. [ClinicalTrials.gov: NCT 00986102]., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17-95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n=93); (ii) colistin and tigecycline (n=43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n=30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR)=1.11; P<0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR=1.01; P=0.002 for each hour delay), underlying malignancy (aOR=3.46; P=0.01) and chronic kidney disease (aOR=2.85; P=0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Background: Ongoing educational programs targeting health care professionals have shown positive outcomes by reducing the morbidity and mortality associated with health care-associated infections (HAIs). We undertook this study to measure the impact of such a program in a pediatric critical care unit of a developing country., Methods: This prospective study was conducted in 2 time periods of 6 months each, with an educational intervention for resident doctors and nurses in between. The rates of ventilator-associated pneumonia (VAP) during the preintervention and postintervention periods were estimated by active surveillance., Results: The incidence density of VAP was reduced by 28% (20.2 vs 14.6 per 1,000 ventilator-days; P = .21, Z test) despite a significant increase in the ventilator utilization ratio during the postintervention period (0.64 vs 0.88; P < .0001, Pearson's χ² test). There was a statistically significant reduction in mortality among patients who received mechanical ventilation for ≥48 hours in the postintervention period (49.3% vs 31.4%; P = .029, Pearson's χ² test)., Conclusions: Educational programs have a positive impact on reducing the morbidity and mortality associated with HAIs. Incidence rates based on device-days should be compared by keeping the variations in device utilization ratio in mind., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Acinetobacter baumannii is characterized by a rapid development of resistance to the commonly used antimicrobial agents. We investigated the risk factors, clinical features, and outcomes in ventilator-associated pneumonia (VAP) caused by extensive drug-resistant Acinetobacter baumannii (XDRAB). Clinical parameters and overall in-hospital mortality rates were compared between the VAP with and without XDRAB infection groups. This study showed that VAP caused by XDRAB was not associated with in-hospital mortality. However, it was related to high Simplified Acute Physiology Score II scores and increasing durations of hospital stays., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: The objective of this analysis was to evaluate the association between gender and clinical outcomes in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) since data thus far are controversial., Methods: Data from a convenience sample of ICU patients with HAP, including ventilator-associated and health care-associated pneumonia, were retrospectively collected from four academic institutions (Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia [IMPACT-HAP] study). Outcomes included 28-day mortality, clinical failure at day 14, hospital and ICU length of stay (LOS), and duration of mechanical ventilation. We compared baseline characteristics and performed multivariate analysis to identify factors independently associated with mortality., Results: Among 416 patients, 271 were men and 145 were women. Women were older (62.4±16.9 vs. 55.7±16.5 years, p<0.001) and more critically ill, with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 21 vs. 19 (p=0.004). Day-28 mortality was 30% for women and 24% for men (p=0.25). Increased 28-day mortality was associated with severity of illness, age, ventilator-associated pneumonia, vascular disease, and hospital LOS prior to pneumonia diagnosis. No significant differences were found in the distribution of bacteria pathogens or in clinical failure rates (36% vs. 31%) between genders. Duration in days of mechanical ventilation, ICU LOS and hospital LOS after the diagnosis of pneumonia were not significantly different between men and women. Analyzing data for women based on presumed pre- or postmenopausal status (age breakpoint of 50 years), showed an increased in ICU LOS (15 vs. 25 days; p=0.0026) and hospital LOS (22 vs. 30 days; p=0.05) for women ≤50 years. No differences were noted in 28-day mortality (24.3% vs. 13.1%; p=0.18) in women ≤50 years of age., Conclusions: In ICU patients with pneumonia, female gender was not associated with worse outcomes or increased resource utilization compared to male gender. Further studies are needed to evaluate menopausal status and outcomes in women with pneumonia.

Background: Ventilator-associated pneumonia (VAP) accounts for almost 90% of infections in mechanically ventilated patients and more than one-quarter of all patients requiring intubation, with associated mortality rates as high as 70%. The rise in methicillin resistance within the community has led to a national increase in methicillin-resistant Staphylococcus aureus (MRSA) rates in early VAP and associated healthcare expenditure., Methods: Trauma patients identified via an institutional VAP database were stratified by gender, age, severity of shock (24-h transfusions), and severity of injury. The primary outcome measure was evaluation of the incidence and trend of early MRSA VAP over a 6-y period. Secondary outcomes examined the adequacy of our current empiric antibiotic regimen as it pertained to outcome variables, including mortality., Results: A total of 997 episodes of VAP were identified in 727 patients. Linear regression showed that the incidence of early Staphylococcus aureus (SA) VAP was stable over the 6-y period (slope=-0.911; p=0.490). Over the same 6 y, however, the percentage of MRSA in early SA VAP (slope=3.95; p=0.0154) and the incidence of early MRSA VAP increased. No difference in mortality was detected between early methicillin-susceptible SA and early MRSA VAP. After adjustment for age, ISS, and 24-h transfusion requirements, early MRSA was not an independent predictor of mortality (odds ratio [OR], 0.815; p=0.59)., Conclusions: Although the incidence of early SA VAP with methicillin resistance increased significantly within the first 7 d of admission, this study showed no difference in mortality and resource utilization between early VAP from MRSA and other causative organisms, despite lack of empiric MRSA coverage.

Objectives: In this prospective clinical trial we aimed to answer if spontaneous exhaled breath condensate (EBC) in the trap of the expiratory arm of the ventilator could replace EBC collected by coolant chamber standardized with Argon as an inert gas. Second, if EBC pH could predict ventilator associated pneumonia (VAP) and mortality., Patients: We included 34 critically ill patients (males = 26), aged = 54.85 ± 19.86 (mean ± SD) yrs, that required mechanical ventilation due to non-pulmonary direct cause (APACHE II score = 23.58 ± 14.7; PaO(2)/FiO(2) = 240.00 ± 98.29)., Setting: ICU with 9 beds from a regional teaching hospital., Intervention and Results: The patients were followed up until development of VAP, successful weaning or death. There were significant differences between mean EBC pH from the 4 procedures with the exception of spontaneous EBC de-aerated with Argon (n = 79; 6.74 ± 0.28) and coolant chamber deaerated with Argon (n = 79; 6.70 ± 0.36; p = NS by Tukey's Multiple Comparison Test). However, none of the procedures were extrapolated between each other according to Bland & Altman method. The mean EBC pH from the trap without Argon was 6.50 ± 0.28. From the total of 34 patients, 22 survived and were discharged and 12 patients died in the ICU., Conclusion: Spontaneous EBC pH could not be extrapolated to EBC pH from coolant chamber and it did not change in subjects who dead, neither subject with VAP in comparison with baseline data. The lack of other biomarker in EBC and the lack of a control group determinate the need for further studies in this setting., (Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.)

Objective: To describe the clinical characteristics and outcomes of neonatal intensive care unit patients with a radiographic diagnosis of pneumatocele., Study Design: Retrospective chart review., Results: Our cohort (n = 27) had a gestational age of 27 ± 5 weeks, birth weight of 1038 ± 760 g, and a predominance of females (59%) and black infants (74%). All infants were ventilated at the time of diagnosis at a median age of 12 days (range: 5 to 105 days). Endotracheal cultures sent from 25 infants revealed bacteria in 20 (80%). Clinical diagnosis of pneumonia was made in 18 (67%) infants. Pneumatoceles resolved in 17 (63%) infants, but persisted in 10 (37%) infants. Compared with infants with resolution of pneumatoceles, mortality (70% versus 0%, p < 0.001), positive endotracheal cultures (100% versus 67%, p = 0.05), and clinical diagnosis of pneumonia (100% versus 47%, p = 0.005) were significantly higher in infants with persistent pneumatoceles., Conclusions: In infants with pneumatoceles, positive endotracheal culture is a frequent finding and correlates with persistence. Persistence of pneumatoceles is associated with a higher mortality., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

ME1071, a maleic acid derivative, is a novel, specific inhibitor of metallo-β-lactamases (MBLs). In vitro, ME1071 can potentiate the activity of carbapenems against MBL-producing Pseudomonas aeruginosa. To confirm the clinical efficacy of ME1071 in ventilator-associated pneumonia (VAP) caused by MBL-producing P. aeruginosa, a mouse model that mimics VAP by placement of a plastic tube in the bronchus was used. Biapenem (100 mg/kg) or ME1071 plus biapenem (each 100 mg/kg) was administered intraperitoneally every 12 h beginning at 12 h after inoculation. Survival was evaluated over 7 days. At 30 h post infection, mice were sacrificed and the numbers of viable bacteria in the lungs and bronchoalveolar lavage fluid (BALF) were compared. Histopathological analysis of lung specimens was also performed. The pharmacokinetics of ME1071 was analysed after initial treatment. The ME1071 plus biapenem combination group displayed significantly longer survival compared with the control and biapenem monotherapy groups (P<0.05). Furthermore, the number of viable bacteria in the lungs was significantly lower in the combination group (P<0.05). Histopathological examination of lung specimens indicated that progression of lung inflammation was prevented in the combination group. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in BALF were significantly decreased (P<0.05) in the combination group. The percentage time above the MIC (%T>MIC) for biapenem without ME1071 was 0% in plasma; however, this value was elevated to 10.8% with ME1071. These results suggest that ME1071 is potent and effective for treatment of VAP caused by MBL-producing P. aeruginosa., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objective: To investigate prospectively the clinical course and risk factors for ventilator-associated tracheobronchitis (VAT) and the impact of VAT on intensive care unit (ICU) morbidity and mortality., Design: Prospective cohort study., Setting: University Hospital Larissa, Larissa, Greece., Patients: Critical care patients who received mechanical ventilation for more than 48 hours were prospectively studied between 2009 and 2011., Methods: The modified Clinical Pulmonary Infection Score, white blood cell count, and C-reactive protein level were systematically assessed every 2 days for the first 2 weeks of ICU stay. Bronchial secretions were assessed daily. Quantitative cultures of endotracheal secretions were performed on the first ICU day for every patient and every 2 days thereafter for the first 2 weeks or more at the discretion of the attending physicians. Definition of VAT was based on previously published criteria., Results: A total of 236 patients were observed; 42 patients (18%) presented with VAT. Gram-negative pathogens, which were usually multidrug resistant, were responsible for 92.9% of cases. Patients with a neurosurgical admission presented with VAT significantly more often than did other ICU patients (28.5% vs 14.1%; . The occurrence P=.02) of VAT was a significant risk factor for increased duration of ICU stay (OR [95% CI], 3.04 [1.35–6.85]; P=.01). Age (OR [95% CI], 1.04 [1.015–1.06]; P=.02), Acute Physiology and Chronic Health Evaluation II score (OR [95% CI], 1.08 [1.015–1.16]; P=.02), and C-reactive protein level at admission (OR [95% CI], 1.05 [1.01–1.1]; P=.02) were independent factors for ICU mortality., Conclusions: VAT is a nosocomial infection that might be associated with prolonged stay in the ICU, especially in neurocritical patients. VAT was not associated with increased mortality in our study.

Background: Oral decontamination is proposed to be an effective prevention of ventilator-associated pneumonia (VAP)., Aim: The objective of this paper was to evaluate the effectiveness of oral decontamination in adult patients undergoing ventilation for more than 48h., Methods: We included all randomized controlled trials that used oral topical decontamination in adult patients from any population requiring mechanical ventilation for more than 48h, versus placebo, normal saline, or standard oral care., Findings: Sixteen trials involving 2399 participants were included. Meta-analysis showed that oral topical antiseptics significantly reduced the incidence of VAP [risk ratio (RR): 0.66; 95% confidence interval (CI): 0.49-0.88]. There was a significant reduction of VAP in studies which investigated decontamination with antibiotic agents other than iseganan (RR: 0.27; 95% CI: 0.18-0.42). Neither antiseptics nor antibiotics affected all-cause mortality, duration of ventilation, or duration of intensive care unit (ICU) stay., Conclusion: Oral decontamination reduced the incidence of VAP in adults undergoing ventilation, but did not affect all-cause mortality, duration of ventilation, or duration of ICU stay in ventilated patients. Further evidence from higher quality trials is necessary., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Background: Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention., Methods: We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores., Findings: Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58)., Interpretation: The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay., Funding: None., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The objectives of this study were to evaluate if a strategy based on routine endotracheal aspirate (ETA) cultures is better than using the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines to prescribe antimicrobials in ventilator-associated pneumonia (VAP)., Methods: This was a prospective, observational, cohort study conducted in a 15-bed ICU and comprising 283 patients who were mechanically ventilated for ≥48 h. Interventions included twice-weekly ETA; BAL culture was done if VAP was suspected. BAL (collected at the time of VAP) plus ETA cultures (collected≤7 days before VAP) (n=146 different pairs) were defined. We compared two models of 10 days of empirical antimicrobials (ETA-based vs ATS/IDSA guidelines-based strategies), analyzing their impact on appropriateness of therapy and total antimicrobial-days, using the BAL result as the standard for comparison., Results: Complete ETA and BAL culture concordance (identical pathogens or negative result) occurred in 52 pairs; discordance (false positive or false negative) in 67, and partial concordance in two. ETA predicted the etiology in 62.4% of all pairs, in 74.0% of pairs if ETA was performed≤2 days before BAL, and in 46.2% of pairs if ETA was performed 3 to 7 days before BAL (P=.016). Strategies based on the ATS/IDSA guidelines and on ETA results led to appropriate therapy in 97.9% and 77.4% of pairs, respectively (P<.001). The numbers of antimicrobial-days were 1,942 and 1,557 for therapies based on ATS/IDSA guidelines and ETA results, respectively (P<.001)., Conclusions: The ATS/IDSA guidelines-based approach was more accurate than the ETA-based strategy for prescribing appropriate, initial, empirical antibiotics in VAP, unless a sample was available≤2 days of the onset of VAP. The ETA-based strategy led to fewer days on prescribed antimicrobials.

Ventilator-associated pneumonia (VAP) is the primary hospital-acquired infection contracted by critically ill patients who receive mechanical ventilation. This retrospective study evaluated the efficacy of a multifaceted VAP prevention protocol in an adult trauma population. Ventilator-associated pneumonia was defined according to the National Healthcare Safety Network (2009) criteria. The number of days to onset of VAP in the postprotocol period was longer than the preprotocol period despite a concomitant increase in the number of mechanical ventilation days.

Nosocomial pneumonia remains a significant cause of hospital-acquired infection, imposing substantial economic burden on the health care system worldwide. Various preventive strategies have been increasingly used to prevent the development of pneumonia. It is now recognized that patients with health care-associated pneumonia are a heterogeneous population and that not all are at risk for infection with nosocomial pneumonia pathogens, with some being infected with the same organisms as in community-acquired pneumonia. This review discusses the risk factors for nosocomial pneumonia, controversies in its diagnosis, and approaches to the treatment and prevention of nosocomial and health care-associated pneumonia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was higher in the tigecycline group versus the comparator group. Study-level mortality risk differences were pooled using a random-effects meta-analysis. Statistical models evaluated the association between patient-level all-cause mortality and baseline factors using logistic regression, recursive partitioning [classification and regression tree (CART) analysis] and survival techniques. The estimated risk difference (tigecycline minus comparator) in all-cause mortality from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical modelling identified baseline bacteraemia associated with mortality only in the tigecycline group. In patients with ventilator-associated pneumonia (VAP) and baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7% (1/13) for the comparator group. Study-level and patient-level analyses have identified that patients in the hospital-acquired pneumonia trial, particularly those with VAP with baseline bacteraemia, were at a higher risk of clinical failure and mortality., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Introduction: Ventilator-associated pneumonia (VAP) occurs in up to 25% of mechanically ventilated patients, with an associated mortality up to 50%. Early diagnosis and appropriate empiric antibiotic coverage of VAP are crucial. Given the multitude of noninfectious clinical and radiographic anomalies within trauma patients, microbiology from bronchioalveolar lavage (BAL) is often needed. Empiric antibiotics are administered while awaiting BAL culture data. Little is known about the effects of these empiric antibiotics on patients with negative BAL microbiology if a subsequent VAP occurs during the same hospital course., Methods: This is a retrospective chart review of intubated trauma patients undergoing BAL for suspected pneumonia over a 3-y period at a Level 1 trauma center. All patients with suspected VAP undergoing a BAL receive empiric antibiotics. If microbiology data are negative at 72 h, all antibiotics are stopped; however, if the BAL returns with ≥10(5) colony-forming units per milliliter, the diagnosis of VAP is confirmed. We divided patients into three groups. Group 1 consisted of patients in whom the initial BAL was positive for VAP. Group 2 consisted of patients with an initial negative BAL, who subsequently developed VAP at a later point in the hospital course. Group 3 consisted of patients with negative BAL who did not develop a subsequent VAP., Results: We obtained 499 BAL specimens in 185 patients over the 3-y period. A total of 14 patients with 23 BAL specimens initially negative for VAP subsequently developed VAP later during the same hospital stay. These patients did not have an increase in the hospital length of stay, intensive care unit days, ventilator days, or mortality compared with those who had a positive culture on the first suspicion of VAP. There was a significant increase in the percentage of Enterobacter (21% versus 8%) and Morganella (8% versus 0%) as the causative organism in these 14 patients when the VAP occurred. Furthermore, the profile of the top two organisms in each group changed. Enterobacter (21%) and Pseudomonas (17%) were the principal organisms in the initial BAL-negative group, whereas the two predominant strains in the initial positive BAL group were methicillin-sensitive Staphylococcus aureus (21%) and Haemophilus influenza (11%). Interestingly, methicillin-resistant S. aureus remained the third most common organism in both groups. Empiric antibiotics also did not seem to induce the growth of multidrug-resistant organisms, and there was no increased rate of secondary infections such as Clostridium difficile., Conclusions: Ventilator-associated pneumonia remains a significant cause of morbidity and mortality in mechanically ventilated trauma patients. The diagnosis and treatment of VAP continue to be challenging. Once clinically suspected, empiric coverage decreases morbidity and mortality. Our data demonstrate that patients who receive empiric coverage exhibit a significantly different microbiologic profile compared with those who had an initial positive BAL culture. Initial empiric antibiotics in BAL-negative patients were not associated with an increase in multidrug-resistant organisms, hospital, or intensive care unit length of stay, ventilator days, and mortality or secondary infections., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Comatose patients present a high risk of early-onset ventilator-associated pneumonia (EO-VAP) for which antibiotic prophylaxis has been proposed. Comatose patients were studied to evaluate the efficacy of a single-dose of antibiotic prophylaxis at intubation against EO-VAP., Methods: A prospective cohort of comatose patients (Glasgow Coma Score ≤ 8) who were admitted in 2009-2010 and administered a single-dose of antibiotic within 4 h of intubation was compared with comatose patients (admitted ≥ 4 h after intubation in 2009-2010 or admitted in 2007-2008) who did not receive antibiotic prophylaxis. We analyzed the incidence of EO-VAP, late-onset VAP, and ventilator-associated tracheobronchitis in both groups. Propensity scores for receiving antibiotic prophylaxis were derived on the basis of patients' characteristics (eg, age and severity) to assess its impact on EO-VAP development., Results: We included 129 patients (71 in the prophylaxis group and 58 in the control group). The global incidence of VAP and incidence of EO-VAP were lower in the prophylaxis group: 10.8 vs 28.4 episodes/1,000 days on mechanical ventilation (P = .015) and 4.4 vs 23.1 episodes/1,000 days on mechanical ventilation (P = .02), respectively. The incidence of late-onset VAP did not differ. The prophylaxis group tended toward lower incidence of ventilator-associated tracheobronchitis (15.5% vs 25.9%, P = .14). No differences in mortality were found between groups. The propensity-score regression analysis confirmed that a single dose of antibiotic prophylaxis was independently associated with lower incidence of EO-VAP (OR, 0.11; 95% CI, 0.02-0.58; P = .009)., Conclusions: A single dose of antibiotic prophylaxis at intubation might lower the incidence of EO-VAP. However, a randomized clinical trial should be conducted to confirm our findings.

Aim: to investigate the role of combined Lipopolysaccharide-Binding Protein (LBP) and Procalcitonin (PCT) ) as prognostic marker of mortality in patients with Ventilator-Associated Pneumonia (VAP)., Methods: this prospective cohort study was held in ICU/HCU of Cipto Mangunkusumo hospital between 2006 to 2007 by taking the subjects consecutively. Thirty five patients with VAP were studied. For analysing the data, chi-square or its alternative Fisher exact test were used. Based on a previous study for evaluation, we used cut off pants of 5 ng/ml and 0.5 ng/ml for PCT and 30 µg/ml and 25 µg/ml for LBP after three-day and seven-day treatment respectively. Receiver operating curve was made to determine the sensitivity and specificity of PCT and LBP as infection markers., Results: 35 patients participated in this study. After three days of therapy, if the level of PCT >5 ng/mL and LBP >30 µg/mL the prognosis would be bad (p<0.05) with a sensitivity of 88.5%, specificity of 53.2% and AUC value 0.69. Poor prognosis was also found if after seven day therapy PCT level was >0.5 ng/mL and LBP level >25 µg/mL (p<0.05) with sensitivity of 96.3%, specificity of 66.7% and AUC value 0.81., Conclusion: examination of combined PCT and LBP can be taken as a good prognostic markers to predict mortality in patients with VAP.

Background: Little data exist on the burden of device-associated health care-associated infection (DA-HAI) in China. This study examined the DA-HAI rate and evaluated its association with device use (DU), length of stay (LOS), and mortality in intensive care units (ICUs) in 4 Chinese hospitals., Methods: This was a prospective cohort surveillance study conducted in 7 ICUs in 4 hospitals. We applied International Nosocomial Control Consortium methods and Centers for Disease Control and Prevention (CDC)/National Health and Safety Network (NHSN) definitions to determine rates of central line-associated blood stream infection (CLABSI), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (CAUTI), DU, crude extra length of hospital stay (LOS), and mortality., Results: Between August 2008 and July 2010, there were a total of 2,631 admissions to the 7 ICUs in the study hospitals. The rate of VAP was 10.46/1,000 mechanical ventilator (MV)-days, the CLABSI rate was 7.66/1,000 central line (CL)-days, and the CAUTI rate was 1.29/1,000 urinary catheter (UC)-days. Pooled DU ratios were 0.43 for MV, 0.71 for CL, and 0.76 for UC. Crude extra LOS was 15 days for patients with CLABSI, 20.5 days for patients with VAP, and 27 days for patients with CAUTI. Crude extra mortality was 14% for patients with CLABSI, 22% for patients with VAP, and 43% for patients with CAUTI., Conclusions: In the study ICUs, VAP and CLABSI rates were higher than CDC/NHSN's reported data, and LOS and mortality were increased. Compared with the CDC/NHSN and INICC data, the pooled DU ratio for MV was similar, and DU ratios for CL and UC use ratios were slightly higher., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Purpose: This study was designed to compare the efficacy of polymyxin B with other antimicrobials in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT) by Pseudomonas aeruginosa or Acinetobacter baumannii., Methods: A prospective cohort study was performed. Patients >18 years of age with the diagnosis of VAP or VAT who received appropriate therapy for >48 h were analyzed. The primary outcome was 30-day mortality. Clinical covariates were assessed and compared between the groups., Results: A total of 67 episodes were analyzed: 45 (67 %) treated with polymyxin B and 22 (33 %) with comparators. The crude 30-day mortality was 53 % (24 of 45) in the polymyxin B group and 27 % (6 of 22) in the comparator group (P = 0.08). Multivariable analysis using Cox regression models indicated that polymyxin B treatment was independently associated with increased mortality., Conclusions: Polymyxin B treatment in the currently recommended dosage may be inferior to other drugs in the treatment of VAP and VAT caused by organisms tested as susceptible in vitro to this agent.

Background: Acinetobacter baumannii hospital-acquired pneumonia (HAP) is associated with a high mortality worldwide. Non-ventilated patients with HAP (NVHAP) caused by nosocomial pathogens are reported to have a more favorable outcome than those with ventilator-associated pneumonia (VAP). The current study was designed to determine whether bacteremic patients with A. baumannii NVHAP also have a lower mortality than those receiving assisted ventilation., Methods: This retrospective 10-year study was conducted at a 2900-bed teaching hospital located in Northern Taiwan. The population consisted of 144 patients with A. baumannii bacteremia and HAP. Of these 96 had VAP and 48 had NVHAP. Charts were reviewed for demographic characteristics, comorbidities, clinical manifestations, antimicrobial susceptibility, and 14-day mortality. Clonal relationships were determined by molecular typing., Results: There were no significant differences between the two groups in comorbidities (Charlson scores). Patients with NVHAP were more likely to have developed bacteremia earlier, outside the ICU and undergone fewer invasive procedures. They had significantly lower APACHE II scores, fewer bilateral pneumonias and lower rates of antimicrobial resistance. No specific clones were identified in either group. The unadjusted (crude) 14-day mortality rates were not significantly different between the groups (NVHAP 43.8% vs. VAP 31.3%, p = 0.196). The adjusted 14-day mortality risk was significantly lower in ventilator-assisted patients (odds ratio = 0.201; 95% confidence interval = 0.075-0.538; p = 0.001)., Conclusions: Patients with bacteremic NVHAP and VAP caused by A. baumannii had similar crude mortality rates, but on logistic regression analysis those receiving ventilator assistance had a significantly lower mortality. This may have been due to better airway protection, more intensive monitoring with earlier diagnosis and treatment in patients with VAP, greater innate susceptibility to infection in those with NVHAP and differences in the virulence of A. baumannii.

Background: Ventilator-associated pneumonia (VAP) is considered the most common nosocomial infection in the intensive care unit (ICU), but its features are not fully known in many hospitals in Brazil. We identified clinical and epidemiological aspects associated with VAP in an intensive care unit (ICU) in a general public hospital in northern Brazil and performed an analytical descriptive prospective cohort study., Methods: We analyzed data from thirty-three patients who developed VAP while in the ICU. Clinical and epidemiological data of patients were obtained and tracheal secretions were submitted to culture. Microbial isolates were identified and evaluated for resistance against antimicrobial agents by using the automated Vitek 2 system., Results: The frequency of VAP was 26.2% in patients submitted to invasive mechanical ventilation for at least 48 hours, and death occurred in 78.8% of cases. Only the presence of comorbidity showed a significant association (P = 0.029) with death. The most commonly found bacteria were Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacteriaceae. We also found a frequency of 54.5% of multiresistant bacteria associated with VAP, and previous antibiotic therapy was used in 97% of patients., Conclusions: VAP in our ICU presented with a high frequency and was mainly caused by multiresistant bacteria. Implementation of rational protocols for the use of antibacterial agents and rapid delivery of culture and susceptibility test results are essential. This may help decrease VAP-related mortality rates by multiresistant bacteria in the ICU.

Objectives: The aim was to assess the diagnostic and prognostic value of measuring pentraxin 3 (PTX3) together with C-reactive protein (CRP) in patients with ventilator-associated pneumonia (VAP)., Background: The PTX3 values increase rapidly during multiple inflammatory conditions, but little is known about its characteristics in VAP., Methods: Measurement of PTX3 and CRP levels in plasma from 136 consecutive patients receiving mechanical ventilation > 48 h in a prospective single center study., Results: A PTX3 threshold of >16.43 ng/ml provided a specificity of 74.0% and a sensitivity of 68.6% for the diagnosis of VAP. PTX3 correlated with severity of sepsis and peaked earlier than CRP in patients with confirmed VAP. Multivariate Cox regression analysis showed PTX3 was the independent predictor for mortality of VAP., Conclusions: PTX3 was not superior to CRP as a biomarker to diagnose VAP, but it was an early indicator of inflammation and had better prognostic value to predict mortality than CRP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The treatment of ventilator-associated pneumonia (VAP) secondary to methicillin-resistant Staphylococcus aureus (MRSA) remains controversial., Methods: We performed a review of all blunt trauma patients diagnosed with MRSA VAP from June 2005 to June 2011. VAP for the first 3 years was diagnosed by sputum aspiration and treated with vancomycin. For the last 3 years of the study period, VAP was diagnosed with bronchoalveolar lavage and treated with linezolid., Results: MRSA VAP patients treated with vancomycin had an average hospital length of stay (LOS) of 49 days (range 9-99 days), an average intensive care unit (ICU) LOS of 43 days (range 6-98 days), and average ventilator days of 34.4 (range 3-76 days). Seventeen MRSA VAP patients treated with linezolid had an average hospital LOS of 27 days (range 11-61), an average ICU LOS of 22 days (range 10-42) days, and average ventilator days of 16.6 (range 2-42)., Conclusions: Trauma patients who develop MRSA VAP appear to have fewer ventilator days and shorter ICU and hospital LOS when treated with linezolid., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa has increased over the past decade and a significant rise in these isolates in ventilator-associated pneumonia (VAP) has been observed. However, the impact of MDR on VAP outcome has not been analysed in depth. We investigated the risk factors for early and crude mortality in a retrospective study of microbiologically and clinically documented VAP. Ninety-one VAP episodes in 83 patients were included, 31 caused by susceptible P. aeruginosa and 60 by MDR strains, of which 42 (70 %) were extensively drug-resistant (XDR) P. aeruginosa. Thirteen episodes concomitantly presented P. aeruginosa bacteraemia, in seven of which the origin was the respiratory tract. Whereas susceptible P. aeruginosa episodes were more likely than MDR episodes to receive adequate empirical (68 % vs. 30 %; p < 0.001) and definitive antimicrobial therapy (96 % vs. 50 %; p < 0.001), susceptible P. aeruginosa VAP presented a trend towards early mortality (29 % vs. 15 %; p = 0.06). A logistic regression model with early mortality as the dependent variable identified multiorgan dysfunction syndrome (MODS) [odds ratio (OR) 10.4; 95 % confidence interval (CI) 1.7-63.5; p = 0.01] and inadequate antibiotic therapy (OR 4.27; 95 % CI 0.98-18.4; p = 0.052) as independent risk factors for early mortality. A similar analysis identified MODS (OR 4.31; 95 % CI 1.14-16.2; p = 0.03) as the only independent predictor of crude mortality. The severity of acute illness clinical presentation was the main predictor of mortality. Despite adequate antibiotic therapy, susceptible P. aeruginosa seems to cause major early mortality. Although adequate therapy is essential to treat VAP, the severity of acute illness is a more important factor than drug resistance.

Background: Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit, with substantial subsequent mortality. The mortality following VAP declined in the 1980s and 1990s. Experts suggest that little progress has been made in the outcomes from VAP since several novel interventions have failed. We nonetheless hypothesized that mortality following VAP has continued to decrease owing to advances in pulmonary critical care., Methods: We identified all adult patients with Centers for Disease Control and Prevention-defined, intensive care unit-acquired VAP between January 1, 1997, and December 31, 2008, from a prospectively collected database., Results: A total of 793 cases of VAP occurred in the study period. Cases were divided into four periods (1997-1999, 2000-2002, 2003-2005, or 2006-2008) to compare outcomes over time. Acute Physiology and Chronic Health Evaluation II scores were stable, while mortality was significantly lower in Period 4 when compared with Periods 1 and 2 (p = 0.004 and 0.009, respectively). A logistic regression model predicting death (c statistic = 0.871) revealed age (odds ratio, 1.03; 95% confidence interval, 1.02-1.05), Acute Physiology and Chronic Health Evaluation II score (1.09, 1.05-1.14), white blood cell count (1.03, 1.00-1.06), transplant recipient (3.45, 1.40-8.53), transfusions (3.25, 1.37-7.68), and pulmonary disease (3.01, 1.67-5.45) were independent predictors of death, as was the presence of trauma (0.10, 0.06-0.18), chronic steroid therapy (0.39, 0.17-0.91), and patient length of stay (0.99, 0.98-0.99), with odds ratios less than 1.0. In addition, those patients treated in Period 1 (2.23, 1.16-4.29) or Period 2 (2.13, 1.12-4.06) had twice the risk of death following an episode of VAP when compared with those treated in the most recent period., Conclusion: We have shown that mortality following an episode of VAP continues to decrease over time and attribute this to advancements in pulmonary and general critical care rather than any specific interventions., Level of Evidence: Prognostic study, level II.

Background: The incidence of hospital acquired pneumonia (HAP) varies according to the type of intensive care units (ICUs)., Aim: The aims of this study were to determine the frequency of hospital acquired pneumonia (HAP) and the effect of isolation rooms on the frequency of pneumonia in the ICU., Materials and Methods: The present investigation was carried out between January 2004 and July 2008. The ICU, which was 4-bed ward-type between January 2004 and February 2006 (1st period), was reconfigured as isolated rooms with only 2 beds each after March 2006 (2nd period). 153 and 379 patients were followed up in the ICU in the 1st and 2nd periods, respectively. Blood, sputum, and deep tracheal aspiration cultures were used for the isolation of the causative agents., Results: No significant difference was detected between the general characteristics of patients. HAP developed in 101 patients (19%). The prevalence of HAP was 22.9% in the 1st period and 17.4% in the 2nd period. During the 1st and 2nd periods, the HAP infection densities were 22.2 and 16.1/1000 patient-days and the ventilator-associated pneumonia densities were 48.1 and 37.6/1000 ventilator-days, respectively. Eighty-six percent of HAP was ventilator-associated pneumonia (VAP)., Conclusions: Isolation rooms in the ICU may be an effective strategy to control and decrease the rate of pneumonia in the ICU in addition to other preventive strategies.

Cell counts of leukocytes subpopulations are demonstrating to have an important value in predicting outcome in severe infections. We evaluated here the render of leukogram counts to predict outcome in patients with ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus. Data from patients admitted to the ICU of Hospital Clínico Universitario de Valladolid from 2006 to 2011 with diagnosis of VAP caused by S. aureus were retrospectively collected for the study (n = 44). Leukocyte counts were collected at ICU admission and also at VAP diagnosis. Our results showed that nonsurvivors had significant lower eosinophil counts at VAP diagnosis. Multivariate Cox regression analysis performed by the Wald test for forward selection showed that eosinophil increments from ICU admission to VAP diagnosis and total eosinophil counts at VAP diagnosis were protective factors against mortality in the first 28 days following diagnosis: (HR [CI 95%], P): (0.996 [0.993-0.999], 0.010); (0.370 [0.180-0.750], 0.006). Patients with eosinophil counts <30 cells/mm(3) at diagnosis died earlier. Eosinophil counts identified survivors: (AUROC [CI 95%], P): (0.701 [0.519-0.882], 0.042). Eosinophil behaves as a protective cell in patients with VAP caused by S. aureus.

Introduction: Ventilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy., Methods: This prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis., Results: Ninety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective., Conclusions: In patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment.

Whether ventilator-associated pneumonia is a manifestation of severity of illness or an independent cause of mortality in ventilator-dependent patients is not known. In this complex area, which cannot be readily subjected to randomized controlled trials, studies should focus on the underlying questions of relevance, how to improve care of ventilated patients.

Background: Hospital associated infections are major problems, which are increasing in incidence and very costly. However, most research has focused only on measuring consequences associated with the initial hospitalization. We explored the long-term consequences of infections in elderly Medicare patients admitted to an intensive care unit (ICU) and discharged alive, focusing on: sepsis, pneumonia, central-line-associated bloodstream infections (CLABSI), and ventilator-associated pneumonia (VAP); the relationships between the infections and long-term survival and resource utilization; and how resource utilization was related to impending death during the follow up period., Methods: Clinical data and one year pre- and five years post-index hospitalization Medicare records were examined. Hazard ratios (HR) and healthcare utilization incidence ratios (IR) were estimated from state of the art econometric models. Patient demographics (i.e., age, gender, race and health status) and Medicaid status (i.e., dual eligibility) were controlled for in these models., Results: In 17,537 patients, there were 1,062 sepsis, 1,802 pneumonia, 42 CLABSI and 52 VAP cases. These subjects accounted for 62,554 person-years post discharge. The sepsis and CLABSI cohorts were similar as were the pneumonia and VAP cohorts. Infection was associated with increased mortality (sepsis HR = 1.39, P < 0.01; and pneumonia HR = 1.58, P < 0.01) and the risk persisted throughout the follow-up period. Persons with sepsis and pneumonia experienced higher utilization than controls (e.g., IR for long-term care utilization for those with sepsis ranged from 2.67 to 1.93 in years 1 through 5); and, utilization was partially related to impending death., Conclusions: The infections had significant and lasting adverse consequences among the elderly. Yet, many of these infections may be preventable. Investments in infection prevention interventions are needed in both community and hospitals settings.

Background: Timely diagnosis and prognostic assessment of ventilator-associated pneumonia remain major challenges in critical care., Objective: To explore the value of soluble triggering receptor expressed on myeloid cells 1, procalcitonin, and the Clinical Pulmonary Infection Score in the diagnosis and prognostic assessment of ventilator-associated pneumonia., Methods: For 92 patients, bronchoalveolar lavage fluid was cultured for detection of microorganisms, serum levels of the receptor and procalcitonin and levels of the receptor in exhaled ventilator condensate were measured, and the Clinical Pulmonary Infection Score was calculated., Results: On the day of diagnosis, patients who had pneumonia had higher serum levels of the receptor, procalcitonin, and C-reactive protein; higher white blood cell counts; and higher pulmonary infection and Sequential Organ Failure Assessment scores than did patients without pneumonia. White blood cell count (odds ratio, 1.118; 95% CI, 1.139-1.204) and serum levels of the receptor (odds ratio, 1.002; 95% CI, 1.000-1.005) may be risk factors for VAP. Serum levels of the receptor plus the pulmonary infection score were the most reliable for diagnosis; the area under the receiver operating characteristic curve was 0.972 (95% CI, 0.945-0.999), sensitivity was 0.875, and specificity was 0.95. For 28-day survival, procalcitonin level combined with pulmonary infection score was the most reliable for prognostic assessment (area under the curve, 0.848; 95% CI, 0.672-1.025)., Conclusions: In patients with ventilator-associated pneumonia, serum levels of the receptor plus the pulmonary infection score are useful for diagnosis, and procalcitonin levels plus the pulmonary infection score are useful for prognostic assessment.

Background: Trauma produces profound inflammatory and immune responses. A second hit such as an infection further disrupts the inflammatory cascade. Inflammatory responses, following traumatic injuries, infections, or both, are emerging as biologic mediators of cardiac disease including myocardial ischemia and infarction. Inflammation-induced and stress-related cardiac damage are increasingly recognized in patients with critical illness. It is believed that cardiac dysfunction is the result of alterations in the inflammatory and immune cascades. Urinary tract infections (UTIs) and ventilator-associated pneumonia (VAP) are associated with increased mortality in trauma patients. UTIs and VAPs induced inflammatory responses. We postulate that increased mortality seen in trauma patients with infections is caused by increased rates of cardiac injury., Methods: This is a retrospective review of prospectively collected data. All trauma patients admitted to the intensive care unit at our Level I trauma center during 5 years were included in the analysis. Proportional hazard regression analysis was performed to predict suspicion of cardiac injury (troponin ordered), any cardiac injury (troponin > 0.15 ng/mL), or severe cardiac injury (troponin > 1 ng/mL) using age, sex, Injury Severity Score (ISS), pulmonary disease (chronic obstructive pulmonary disease), heart failure, hypertension, diabetes, and the presence of a UTI or VAP. A similar proportion hazard regression was performed to predict mortality., Results: In the model to predict any cardiac injury, chronic obstructive pulmonary disease (hazards ratio [HR], 1.9; p = 0.02), ISS (HR, 1.01; p = 0.04), VAP (HR, 5.6; p < 0.01), and UTI (HR, 2.4; p = 0.03) were significant. Neither VAP nor UTI predicted severe cardiac injury. In the model to predict death, any cardiac injury was not associated with mortality, but severe cardiac injury and UTI were associated with mortality as age increased., Conclusion: Infectious complications have been associated with increased mortality in trauma patients. Our data demonstrate that development of VAP or UTI is associated with an increased risk of developing cardiac injury in trauma patients, which may contribute to subsequent increased mortality., Level of Evidence: Prognostic/epidemiologic study, level III.

Introduction: Ventilator-associated pneumonia remains the most common nosocomial infection in the critically ill and contributes to significant morbidity. Eventual decisions regarding withdrawal or maximal therapy are demanding and rely on physicians' experience. Additional objective tools for risk assessment may improve medical judgement. Copeptin, reflecting vasopressin release, as well as the Sequential Organ Failure Assessment (SOFA) score, reflecting the individual degree of organ dysfunction, might qualify for survival prediction in ventilator-associated pneumonia. We investigated the predictive value of the SOFA score and copeptin in ventilator-associated pneumonia., Methods: One hundred one patients with ventilator-associated pneumonia were prospectively assessed. Death within 28 days after ventilator-associated pneumonia onset was the primary end point., Results: The SOFA score and the copeptin levels at ventilator-associated pneumonia onset were significantly elevated in nonsurvivors (P = .002 and P = .017, respectively). Both markers had different time courses in survivors and nonsurvivors (P < .001 and P = .006). Mean SOFA (average SOFA of 10 days after VAP onset) was superior in predicting 28-day survival as compared with SOFA and copeptin at ventilator-associated pneumonia onset (area under the curve, 0.90 vs 0.73 and 0.67, respectively)., Conclusions: The predictive value of serial-measured SOFA significantly exceeds those of single SOFA and copeptin measurements. Serial SOFA scores accurately predict outcome in ventilator-associated pneumonia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Device-associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30-day and in-hospital mortality in the intensive care unit (ICU)., Methods: Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality., Results: The overall rate of DAIs was 3.03 episodes per 1000 device-days. The most common DAI type was catheter-associated urinary tract infection (3.76 per 1000 urinary catheter-days). There was a decrease in DAI rates in 2005 and rates of ventilator-associated pneumonia (VAP, 3.18 per 1000 ventilator-days) have remained low since then (p < 0.001). The crude rates of 30-day (33.6%) and in-hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin-resistant Staphylococcus aureus (94.9%) and imipenem-resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30-day mortality (OR 2.51, 95% confidence interval [CI] 1.99-3.17, p = 0.001) and in-hospital mortality (OR 3.61, 95% CI 2.10-3.25, p < 0.001)., Conclusions: The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.

Background: This study determined the incidence, characteristics, risk factors, and outcomes of ventilator-associated pneumonia (VAP) in newborns hospitalized in a Neonatal Intensive Care Unit (NICU) in Tehran, Iran., Methods: A prospective cohort study was carried out in the NICU of Mahdieh Hospital over a period of one year, from December 2008 to November 2009, on all neonates mechanically ventilated for more than 48 hours. VAP was diagnosed in accordance with the CDC definition of nosocomial pneumonias for patients younger than 12 months. Risk factors relevant to the development of VAP were studied. Multiple logistic and Cox regression analysis were performed to determine independent predictors for VAP and survival rate, respectively., Results: There were 81 neonates enrolled. VAP occurred in 14 (17.3%), at a rate of 11.6/1000 days on the ventilator. Gram negative bacteria were the predominant etiologic agents. The most common bacterial isolates from the endotracheal aspirate were E. coli (21.4%), Klebsiella (21.4%), and Pseudomonas (14.1%). The only VAP predictor was sputum [odds ratio (OR) = 5.11, P = 0.02]. Mortality rate for VAP was 2/14 (14.3%). Duration of mechanical ventilation [hazard ratio (HR) = 0.96, P = 0.01], birth weight (HR = 0.81, P < 0.001), and purulent tracheal aspirate (HR = 0.25, P < 0.006) were independent predictors of overall survival., Conclusions: VAP occurs at a significant rate in mechanically ventilated newborns. Additional studies are needed to accurately determine the incidence and risk factors in order to develop effective preventive and therapeutic protocols.

Attributable risk has become an important concept in clinical epidemiology. In this paper, we suggest to estimate the attributable risk of nosocomial infections using a multistate approach. Recently, a multistate model (called progressive disability model in the literature) has been developed in order to take into consideration both the time-dependency of the risk factor (e.g., nosocomial infections) and the presence of competing risks (e.g., death and discharge) at each time point. However, this approach does not take into account the possible heterogeneity of the study population. In this paper, we investigate an extension of this model and suggest an adjusted disability multistate model including covariates in each transition. This new multistate model has led us to define the concepts of overall and profiled attributable risk. We use a classical semiparametric approach to estimate the model and the new attributable risk. A simulation study is investigated and we show, in particular, that neglecting the presence of covariates when estimating the model can lead to an important bias. The methodology developed in this paper is applied to data on ventilator-associated pneumonia in 12 French intensive care units., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The use of corticosteroids is frequent in critically-ill patients. However, little information is available on their effects in patients with intensive care unit-acquired pneumonia. We assessed patients' characteristics, microbial etiology, inflammatory response, and outcomes of previous corticosteroid use in patients with intensive care unit-acquired pneumonia., Design: Prospective observational study., Setting: Intensive care units of a university teaching hospital., Patients: Three hundred sixteen patients with intensive care unit-acquired pneumonia. Patients were divided according to previous systemic steroid use at onset of pneumonia., Interventions: None., Measurements and Main Results: Survival at 28 days was analyzed using Cox regression, with adjustment for the propensity for receiving steroid therapy. One hundred twenty-five (40%) patients were receiving steroids at onset of pneumonia. Despite similar baseline clinical severity, steroid treatment was associated with decreased 28-day survival (adjusted hazard ratio for propensity score and mortality predictors 2.503; 95% confidence interval 1.176-5.330; p = .017) and decreased systemic inflammatory response. In post hoc analyses, steroid treatment had an impact on survival in patients with nonventilator intensive care unit-acquired pneumonia, those with lower baseline severity and organ dysfunction, and those without etiologic diagnosis or bacteremia. The cumulative dosage of corticosteroids had no significant effect on the risk of death, but bacterial burden upon diagnosis was higher in patients receiving steroid therapy., Conclusions: In critically-ill patients, systemic corticosteroids should be used very cautiously because this treatment is strongly associated with increased risk of death in patients with intensive care unit-acquired pneumonia, particularly in the absence of established indications and in patients with lower baseline severity. Decreased inflammatory response may result in delayed clinical suspicion of intensive care unit-acquired pneumonia and higher bacterial count.

Background: The prompt initial use of appropriate antibiotics should improve mortality rates in adults with ventilator-associated pneumonia (VAP). However, the incidence of multidrug-resistant (MDR) pathogen infections is on the rise, and the choice of the initial empiric antibiotic may be challenging. We investigated whether appropriate initial antibiotic therapy, infective pathogens, and the clinical severity index influence hospital mortality in patients with VAP and determined independent risk factors for the same., Methods: This study evaluated 163 adult patients (aged ≥ 18 years) at Chang Gung Memorial Hospital, Kaohsiung, Taiwan, from January 1, 2007, to January 31, 2008. Eligibility was evaluated based on criteria for VAP. Sequential Organ Failure Assessment (SOFA) scores, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) scores, oxygenation index, underlying comorbidities, septic shock status, previous tracheostomy status, and factors related to pneumonia were collected for analysis., Results: Ninety-two patients survived from a total 163 patients with VAP during the course of their confinement in the intensive care unit. Multivariable logistic regression analysis identified that a pre-existing Charlson Comorbidity Index score (P = .011), initial oxygenation index (P = .025), SOFA score (P = .043), VAP caused by Acinetobacter baumanii (P = .030), and infection with MDR pathogens (P = .003) were independent risk factors for hospital mortality in patients with VAP., Conclusion: High Charlson Comorbidity Index score, high initial oxygenation index, high SOFA score, and infection with Acinetobacter baumannii or MDR pathogens significantly affect hospital mortality in patients with VAP., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: Candida spp. airway colonization could promote development of ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa, a potentially multidrug-resistant (MDR) bacteria, and worsen the outcome of VAP regardless of pathogen. We therefore address the question of the risk of MDR bacteria isolation within the airway of patients with suspected VAP, whether Candida spp. is present or not., Design and Setting: Prospective observational study in a teaching hospital., Patients and Methods: Consecutive patients with suspected VAP were included. Respiratory tract secretions were seeded on specific medium for yeast isolation in addition to standard culture. Outcome as well as presence of MDR bacteria were assessed according to fungal colonization., Results: 323 suspected VAP were analysed. Among these, 181 (56 %) cases presented with Candida spp. airway colonization. Colonized and noncolonized patients were similar regarding baseline characteristics, prior exposure to antibiotics and VAP severity. However, mortality rate was greater in patients with fungal airway colonization than in those without (44.2 versus 31.0 %, respectively; p = 0.02). In addition, MDR bacteria isolation was 31.5 % in patients with Candida spp. colonization versus 23.2 % in those without (p = 0.13). Moreover, Candida spp. airway colonization was one independent risk factor for MDR bacteria isolation [odds ratio (OR) = 1.79, 95 % confidence interval 1.05-3.05; p = 0.03], in addition to the time elapsed between intensive care unit (ICU) admission and VAP suspicion., Conclusions: In patients with suspected VAP, Candida spp. airway colonization is frequent and associated with increased risk for MDR bacteria isolation. This could worsen outcome and should therefore be considered when choosing an empiric antibiotic therapy.