Quantitative Bronchoalveolar Lavage Research Articles

Fucoxanthin, a Marine Carotenoid, Suppresses Mycoplasma pneumoniae-Triggered Inflammatory Cytokine Production and Promotes Bacterial Clearance in a Murine Model.

Mycoplasma pneumoniae (MP), an atypical bacterium, is a common pathogenetic organism of respiratory infection in children. In the present study, we analyzed the beneficial role of fucoxanthin (Fx), a marine carotenoid, in a murine model of MP. C57BL/6 mice were inoculated once intranasally with 107 CFU of M. pneumoniae, and we found that Fx treatment markedly decreased BAL (quantitative bronchoalveolar lavage) M. pneumoniae concentrations and alleviated airway obstruction in the infected mice. Moreover, the concentrations of proinflammatory cytokines, including IL-6, TNF-α and IL-1β, were significantly decreased by Fx treatment in the BAL samples of infected mice. In vitro study further indicated that Fx treatment markedly suppressed the production of proinflammatory cytokines in mouse peritoneal macrophages after M. pneumoniae infection. In conclusion, this may be the first study to report the protective role of Fx against M. pneumoniae infection, providing a potential therapeutic agent for MP.

The Impact of Multiple Viral Respiratory Infections on Outcomes for Critically Ill Children.

Advances in molecular diagnosis have led to increased testing for single and multiviral respiratory infection in routine clinical practice. This study compares outcomes between single and multiviral respiratory infections in children younger than 5 years old admitted to the PICU with respiratory failure. Retrospective, single-center, cohort study. Tertiary-care, freestanding children's hospital. Children younger than 5 years old admitted to the PICU with respiratory failure and positive respiratory molecular panel. Children with comorbidity or history of similar infections were excluded. After exclusions, the children were divided into single or multiviral groups. Their demographics and PICU outcomes were compared and analyzed. None. Four hundred seventy-seven children with respiratory failure tested positive on respiratory panel, out of which 432 had single and 45 had multiple viruses. Children with multiple viruses had a longer PICU stay (4.5 d) compared with the single viral group (3 d; p < 0.002). Multiviral infections were associated with higher utilization of central line (odds ratio, 2.4; 95% CI, 1.3-4.6; p = 0.008) but not with the need of invasive ventilation requirement or cardiovascular dysfunction. Further analysis among invasively ventilated patients showed multiviral infections resulted in higher association of prolonged ventilation (> 7 d) (odds ratio, 3.4; 95% CI, 1.2-9.4; p = 0.01) and bacterial lower respiratory tract infection confirmed by quantitative bronchoalveolar lavage (odds ratio, 2.1; 95% CI, 1.1-11.2; p = 0.03). Infections with human rhinovirus/Enterovirus, Adenovirus, parainfluenza, and influenza formed a significantly larger proportions of cases (p = 0.00089) as multiviral infections compared with individual infections. Multiviral infections were associated with longer PICU stay, with prolonged mechanical ventilation, with bacterial lower respiratory infections, and with central line requirement. Certain common viruses resulted in higher percentages of PICU admission as multiviral infections.

Use of endotracheal tubes with subglottic secretion drainage reduces ventilator-associated pneumonia in trauma patients.

Patients sustaining traumatic injuries have a higher incidence of ventilator-associated pneumonia (VAP) compared with other critically ill patient populations. Previous studies of patients with predominantly medical diagnoses and use of endotracheal tubes allowing subglottic secretion drainage (ETT-SSD) have shown significant reduction in VAP rates. We hypothesized that the use of ETT-SSD would reduce VAP in trauma patients. A retrospective review from 2010 to 2014 of adult trauma patients orotracheally intubated for more than 48 hours was performed at a Level 1 trauma center. Patients were compared based on standard endotracheal tube (ETT) versus ETT-SSD for the primary outcome VAP per 1,000 ventilator days. The diagnosis of VAP was made by quantitative bronchoalveolar lavage cultures as defined by Centers for Disease Control and Prevention criteria. Patients with ETT-SSD were matched to patients with ETT based on age group, sex, mechanism of injury, head and chest Abbreviated Injury Scale (AIS) score, and Injury Severity Score (ISS). Of 1,135 patients included in the study, 667 patients had ETT and 468 had ETT-SSD. Groups did not differ by demographics, mechanism of injury, Glasgow Coma Scale (GCS) score, alcohol intoxication, or ISS. Patients with ETT-SSD had significantly higher head AIS score but lower chest AIS score. In matched cohorts, ETT-SSD had a lower VAP rate (5.7 vs. 9.3 for ETT, p = 0.03), decreased ventilator days (12 vs. 14, p = 0.04), and decreased intensive care unit length of stay (13 days vs. 16 days, p = 0.003). After controlling for confounding factors, ETT-SSD decreased VAP rate, ventilator days, and intensive care unit length of stay in trauma patients. In this high-risk patient population, we recommend routine use of ETT-SSD to decrease VAP. Therapeutic/care management study, level III.

Adherence to an established diagnostic threshold for ventilator-associated pneumonia contributes to low false-negative rates in trauma patients.

The diagnosis of ventilator-associated pneumonia (VAP) in our institution has followed an established diagnostic threshold (DT) of equal to or greater than 10 colony-forming units (CFU) per milliliter on bronchoalveolar lavage (BAL) based on our previous study (PS). Because mortality from VAP is related to treatment delay, some have advocated a lower DT. The purpose of the current study (CS) was to evaluate the impact of adherence to this DT for VAP on false-negative (FN) rates and mortality in trauma patients. Consecutive patients over 9 years with VAP (defined as ≥10 CFU/mL in the BAL effluent) subsequent to the PS were identified. Data regarding each BAL performed and the colony counts of each organism identified were recorded. An FN BAL result was defined as any patient who had less than 10 CFU/mL and developed VAP with the same organism up to 7 days after the previous culture. The CS was then compared with the PS. Over 9 years, 1,679 patients underwent 3,202 BALs. Of these, 79% were male, 88% experienced blunt injury, mean age and Injury Severity Score (ISS) were 44 years and 31, respectively. Overall, there were 73 FN BAL results (2.3%) in the CS compared with 3% in the PS (p = 0.092). In those patients with 10 organisms, the FN rate was reduced (7.5% vs. 11%, p = 0.045), and mortality was unchanged (5.4% vs. 8.3%, p = 0.361) in the CS compared with the PS. The use of the threshold equal to or greater than 10 resulted in a cumulative reduction in antibiotic charges of $1.57 million. Continued adherence to the diagnostic threshold of equal to or greater than 10 for quantitative BAL in trauma patients has maintained a low incidence of FN BALs and reduced patient charges without impacting mortality. The purported benefit of a lower threshold is not supported. In addition, the potential sequelae of increased resistant organisms, antibiotic-related complications, and costs associated with prolonged unnecessary antibiotic exposure are minimized. Prognostic study, level III.

Anesthesia Literature Review

Anesthesia Literature Review

Early Antibiotic Discontinuation in Patients With Clinically Suspected Ventilator-Associated Pneumonia and Negative Quantitative Bronchoscopy Cultures*

Preliminary data suggest that antibiotic discontinuation in patients with negative quantitative bronchoscopy and symptom resolution will not increase mortality. Because our hospital algorithm for antibiotic discontinuation rules out ventilator-associated pneumonia in the setting of negative quantitative bronchoscopy cultures, we compared antibiotic utilization and mortality in empirically treated, culture-negative ventilator-associated pneumonia patients whose antibiotic discontinuation was early versus late. Retrospective, observational cohort study. Eight hundred sixty-seven bed, tertiary care, teaching hospital in Hartford, CT. Eighty-nine patients with clinically suspected ventilator-associated pneumonia and a negative (<10 colony forming units/mL) quantitative bronchoscopy culture between January 2009 and March 2012. Early discontinuation patients (n = 40) were defined as those who had all antibiotic therapy stopped within one day of final negative culture report, whereas late discontinuation patients (n = 49) had antibiotics stopped later than one day. Univariate analyses assessed mortality, antibiotic duration, and frequency of superinfections. Multivariate logistic regression was performed to assess the effect of early discontinuation on hospital mortality. Patients had a mean ± SD Acute Physiology and Chronic Health Evaluation II score of 26.0 ± 6.0. Mortality was not different between early discontinuation (25.0%) and late discontinuation (30.6%) patients (p = 0.642). Antibiotic duration (days) was also not different for patients who died vs. those who survived (Median [interquartile range]: 3 [1-7.5] vs. 3 [1.75-6.25], respectively, p = 0.87), and when controlling for baseline characteristics and symptom resolution, only Acute Physiology and Chronic Health Evaluation II score was associated with hospital mortality on multivariate analyses. There were fewer superinfections (22.5% vs. 42.9%, p = 0.008), respiratory superinfections (10.0% vs. 28.6%, p = 0.036), and multidrug resistant superinfections (7.5% vs. 35.7%, p = 0.003), in early discontinuation compared with late discontinuation patients. In this severely ill population with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoalveolar lavage cultures, early discontinuation of antibiotics did not affect mortality and was associated with a lower frequency of MDR superinfections.

Postliver Transplantation Pulmonary Complications

We read the article by Levesque et al. (1) with great interest. We congratulate the authors for addressing this important issue in the critical care of liver transplant recipients. We have few queries regarding the study. Until date, to our knowledge, this is the first study in cohort of liver transplant recipients using modified clinical pulmonary infection score (CPIS) to diagnose pneumonia. CPIS has been originally devised for diagnosis of ventilator-associated pneumonia (VAP) (2), and the authors did not mention the incidence of VAP. The authors used the modified CPIS score to confirm the diagnosis of pneumonia, which excludes the culture results (3). CPIS is still not validated for the diagnosis of VAP and has low sensitivity, 60%, and specificity, 43%, if it excludes the culture results (4). It would be great to know the sensitivity and specificity of CPIS score in this cohort as compared with quantitative bronchoalveolar lavage culture. In this study, there were 55 episodes of pneumonia; out of that, only 39 are reported to be culture positive. It means that, for 16 times, no microorganism was isolated. The protocol for antibiotics is for 48 hr after transplantation; how many patients were on antibiotics when they were diagnosed to have pneumonia? History of acute cellular rejection is an independent risk factor for developing pneumonia (5). The incidence of rejection in the study population is not mentioned. It will be interesting to know the risk of pneumonia in this subset of patients. In the pulmonary complication group, how many patients were having associated renal dysfunction that required dialysis? It might affect pulmonary complications (5). Did the authors control the ascites and pleural effusion before performing the pulmonary function test because it might improve patient compliance? At one point, it is stated that age is not the risk factor, but is the P value significant? Patients with upper abdominal surgery are expected to have some pleural effusion during the immediate postoperative period; however, in this study, pleural effusion was evaluated on the seventh day after the transplantation on computed tomographic scan as per routine protocol. Are there any other methods (bedside chest x-ray and ultrasound) used to evaluate pleural effusion before 7 days? How many patients experienced early effusion? Shridhar V. Sasturkar 1 Viniyendra Pamecha1 Vijay Kant Pandey2 1 Department of Hepatico-Pancreatic-Biliary Surgery and Liver Transplantation Institute of Liver and Biliary Sciences New Delhi, India 2 Department of Anesthesiology and Intensive Care Institute of Liver and Biliary Sciences New Delhi, India

Point-Counterpoint: Quantitative Cultures of Bronchoscopically Obtained Specimens Should Be Performed for Optimal Management of Ventilator-Associated Pneumonia

ABSTRACT Ventilator-associated pneumonia (VAP) is a leading cause of health care-associated infection. It has a high rate of attributed mortality, and this mortality is increased in patients who do not receive appropriate empirical antimicrobial therapy. As a result of the overuse of broad-spectrum antimicrobials such as the carbapenems, strains of Acinetobacter , Enterobacteriaceae , and Pseudomonas aeruginosa susceptible only to polymyxins and tigecycline have emerged as important causes of VAP. The need to accurately diagnose VAP so that appropriate discontinuation or de-escalation of antimicrobial therapy can be initiated to reduce this antimicrobial pressure is essential. Practice guidelines for the diagnosis of VAP advocate the use of bronchoalveolar lavage (BAL) fluid obtained either bronchoscopically or by the use of a catheter passed through the endotracheal tube. The CDC recommends that quantitative cultures be performed on these specimens, using ≥10 4 CFU/ml to designate a positive culture ( http://www.cdc.gov/nhsn/TOC_PSCManual.html , accessed 30 October 2012). However, there is no consensus in the clinical microbiology community as to whether these specimens should be cultured quantitatively, using the aforementioned designated bacterial cell count to designate infection, or by a semiquantitative approach. We have asked Vickie Baselski, University of Tennessee Health Science Center, who was the lead author on one of the seminal papers on quantitative BAL fluid culture, to explain why she believes that quantitative BAL fluid cultures are the optimal strategy for VAP diagnosis. We have Stacey Klutts, University of Iowa, to advocate the semiquantitative approach.

Reasons for Low Bacterial Yields from Quantitative Cultures of Bronchoalveolar Lavage Fluid

Reasons for Low Bacterial Yields from Quantitative Cultures of Bronchoalveolar Lavage Fluid

Bacterial Yield from Quantitative Cultures of Bronchoalveolar Lavage Fluid in Patients with Pneumonia on Antimicrobial Therapy

Background/AimsEarly diagnosis and appropriate antimicrobial choice are crucial when managing pneumonia patients, and quantitative culture of bronchoalveolar lavage (BAL) fluid is considered a useful method for identifying pneumonia pathogens. We evaluated the quantitative yield of BAL fluid bacterial cultures in patients being treated with antimicrobials and attempted to identify factors predictive of positive BAL cultures.MethodsPatients over 18 years old and whose BAL fluid was subjected to quantitative culture to identify the organism causative of pneumonia between January 1, 2005, and December 31, 2009, were included. We reviewed the results of BAL fluid bacterial cultures and the clinical records, laboratory tests, and radiographic findings of the patients.ResultsBAL was performed on 340 patients with pneumonia. A positive BAL culture, defined as isolation of more than 104 colony forming units/mL bacteria, was documented in 18 (5.29%) patients. Of these, 9 bacteria isolated from 10 patients were classified as probable pathogens. The most frequently isolated bacteria were methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. No independent predictive factor for positive BAL cultures was identified.ConclusionsThe yield of quantitative BAL fluid bacterial culture in patients already on antimicrobials was low. Clinicians should be cautious when performing a BAL culture in patients with pneumonia who are already on antimicrobials.

Pre-Hospital Intubation Factors and Pneumonia in Trauma Patients

We reported similar rates of ventilator-associated pneumonia (VAP) previously in trauma patients intubated either in a pre-hospital (PH) venue or the emergency department. A subset of PH intubations with continuous quality assessment was re-examined to identify the intubation factors associated with VAP. The subgroup was derived from an existing data set of consecutive adult trauma patients intubated prior to Level I trauma center admission July 2007-July 2008. Intubation details recorded included bag-valve mask ventilation (BVM) and the presence of material in the airway. The diagnosis of VAP was made preferentially by quantitative bronchoalveolar lavage (BAL) cultures (≥ 10⁴ colony-forming units indicating infection). Baseline data, injury characteristics, and circumstances of intubation of patients with and without VAP were compared by univariable analysis. Detailed data were available for 197 patients; 32 (16.2%) developed VAP, on average 6.0±0.7 days after admission. Baseline characteristics were similar in the groups, but diabetes mellitus was more common in the VAP group (4 [12.5%] vs. 5 [3.0%]; p=0.02). There was a higher rate of blunt injury in the VAP patients (28 [87.5%] vs. 106 [64.2%]; p=0.01) and higher injury severity scores (33.1±2.8 vs. 23.0±1.0; p=0.0002) and chest Abbreviated Injury Scores (2.6±0.3 vs. 1.5±0.1; p=0.002). Lower Glasgow Coma Scale scores (7.9±0.9 vs. 9.9±0.4; p=0.04) and greater use of BVM (18 [56.3%] vs. 56 [34.0%]; p=0.02) were observed in patients who developed VAP. Among aspirations, 10 (31.3%) of patients with emesis developed VAP compared with only 4 (12.5%) with blood in the airway (p=0.003). Aspiration, along with depressed consciousness and greater injury severity, may predispose trauma patients to VAP. Prospective studies should focus on the quality and timing of aspiration relative to intubation to determine if novel interventions can prevent aspiration or decrease the risk of VAP after aspiration.

Diagnostic use of serum procalcitonin levels in pulmonary aspiration syndromes*

To assess the predictive accuracy of serum procalcitonin in distinguishing bacterial aspiration pneumonia from aspiration pneumonitis. Prospective observational study. Intensive care unit of a university-affiliated hospital. Sixty-five consecutive patients admitted with pulmonary aspiration and seven control subjects intubated for airway protection. None. Quantitative cultures from bronchoalveolar lavage fluid were conducted on all participants at the time of admission. Serial serum procalcitonin levels were measured on day 1 and day 3 using the procalcitonin enzyme-linked fluorescent assay. There were no differences in the median serum concentrations of procalcitonin between patients with positive bronchoalveolar lavage cultures (n = 32) and patients with negative bronchoalveolar lavage cultures (n = 33) on either day 1 or day 3 postadmission. The areas under the receiver operator characteristic curves were 0.59 (95% confidence interval, 0.47-0.72) and 0.63 (95% confidence interval, 0.5-0.75), respectively (p = .74). However, duration of mechanical ventilation and antibiotic therapy were shorter in those who had a decrease in their procalcitonin levels on day 3 from baseline compared with those who did not (6.7 ± 7.1 days and 11.1 ± 13.5 days, p = .03; and 8.2 ± 2.6 days vs. 12.8 ± 4.6 days; p < .001, respectively). Hospital mortality was associated with radiographic multilobar disease (adjusted odds ratio, 1.14; 95% confidence interval, 1.01-1.31; p = .04) and increasing procalcitonin levels (adjusted odds ratio, 5.63; 95% confidence interval, 1.56-20.29; p = .008). Serum procalcitonin levels had poor diagnostic value in separating bacterial aspiration pneumonia from aspiration pneumonitis based on quantitative bronchoalveolar lavage culture. However, serial measurements of serum procalcitonin may be helpful in predicting survival from pulmonary aspiration.

Bronchoalveolar Lavage in the Diagnosis of Ventilator-Associated Pneumonia: To Quantitate or Not, That is the Question

Quantitative bronchoalveolar lavage (BAL) is used to diagnose ventilator-associated pneumonia (VAP). We prospectively compared semiquantitative (SQ) and quantitative (Qu) culture of BAL for VAP diagnosis. Ventilated patients suspected of VAP underwent bronchoscopic BAL. BAL fluid was examined by both Qu (colony-forming units [CFUs]/mL) and SQ culture (none, sparse, moderate, or heavy) and results were compared. VAP was defined as 10⁵ CFU/mL or greater on Qu culture. Over 36 months, 319 BALs were performed. Sixty-three of 319 (20%) showed diagnostic growth by Qu culture identifying a total of 81 organisms causing VAP. All 63 specimens showed growth of some organism(s) on SQ culture with 79 of 81 causative organisms identified and two (Pseudomonas, one; Corynebacterium, one) not identified. The remaining 256 specimens did not meet the threshold for VAP by the Qu method. Among these, 79 did not show any growth on SQ culture. Among the 240 specimens showing some growth on SQ culture, a total of 384 organisms were identified. VAP rates in relation to strength of growth on SQ culture were: sparse, 10 of 140 (7%); moderate, 24 of 147 (16%); and heavy, 45 of 97 (46%). Sensitivity (Sn), specificity (Sp), positive (PPV), and negative (NPV) predictive values of SQ culture of BAL fluid for the diagnosis of VAP were 97, 21, 21, and 97 per cent, respectively. Nonquantitative culture of BAL fluid is fairly accurate in ruling out VAP (high Sn and NPV). It however has poor Sp and PPV and using this method will lead to unnecessary antimicrobial use with its attendant complications of toxicity, cost, and resistance.

Usefulness of Quantitative Endotracheal Aspirate Cultures in Intensive Care Unit Patients with Suspected Pneumonia

It is difficult to differentiate pathogens responsible for pneumonia or colonization in patients with an endotracheal tube or in patients that have undergone tracheostomy. We evaluated the clinical usefulness of quantitative endotracheal aspirates cultures and sought to determine the result threshold level for positivity. The authors performed this retrospective cohort study between December 1, 2004 and January 31, 2006. Forty-five suspected pneumonia patients admitted to an intensive care unit (ICU) with quantitative bronchoalveolar lavage (BAL) and endotracheal aspirate (EA) culture results were enrolled. Using a threshold of 105 cfu/mL, 10 of the 45 (22.2%) quantitative EA cultures were positive, as compared with 7 (15.6%) BAL cultures. When BAL culture findings were used as the reference, the sensitivity and specificity of quantitative EA cultures were 85.7% and 89.5%, respectively, at a threshold of 105 cfu/mL, and 85.7% and 94.7%, respectively, at a threshold of 106 cfu/mL. Of the 10 EA culture positive patients, 2 patients with a result of -105 cfu/mL were BAL culture negative. The quantitative EA culture is a useful non-invasive tool for the diagnosis of pneumonia pathogens. It is suggested that a threshold level of 106 cfu/mL is appropriate.

Empiric, Broad-Spectrum Antibiotic Therapy with an Aggressive De-Escalation Strategy Does Not Induce Gram-Negative Pathogen Resistance in Ventilator-Associated Pneumonia

Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU. After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early (January-June 2005) and late (July-December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the on-line Simple Interactive Statistical Analysis tool. Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p = 0.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p = 0.73) and Acinetobacter baumannii (early 80%; late 100%; p = 0.13). Further, both TOB (early 77.1%; late 70.0%; p = 0.49) and LEV (early 74.3%; late 70.0%; p = 0.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%. In our SICU, early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogen-specific agents did not alter antimicrobial resistance and is a valid practice. Further, our compliance with de-escalation practices was higher than published rates.

Respuesta inflamatoria a nivel intrapulmonar en enfermos críticos con neumonía

Objective To evaluate the relationship between the microbiology result and cytokine expression in bronchoalveolar lavage (BAL). Design An observational, prospective study. Setting A 17-bed medical and surgical intensive care unit. Patients Mechanically-ventilated patients with suspected pneumonia admitted to the ICU during a 27-month time period were consecutively enrolled. Interventions BAL was performed with 150 ml sterile isotonic saline solution in three aliquots of 50 ml. Local anesthetics were not used during the procedure. A BAL sample was processed for a microbiologic quantitative culture and BAL cytokines IL-6, IL 8, TNFα, granulocyte colony-stimulating factor (G-CSF) and granulocyte–monocyte colony-stimulating factor (GM-CSF) were measured. Main variables of interest Age, APACHE II score within the first 24 hours of admission, time on mechanical ventilation, ICU length of stay, mortality, previous antibiotic therapy, isolated bacteria and cytokines concentration were analyzed. Results Fifty-nine consecutive patients were included, and most of the patients (79.7%) had prior antibiotic therapy. Twenty-two patients (37.2%) had a positive BAL. In the group of patients with positive BAL, the TNFα concentration was significantly higher in the group of patients with positive BAL than in the BAL negative group. Conclusions There is a significant correlation between the microbiology result and the TNFα concentration in the BAL fluid. In mechanically-ventilated patients, TNFα in BAL has been associated with positive cultures despite prior antibiotic therapy.

Insulin Resistance Heralds Positive Cultures after Severe Injury

Insulin resistance and hyperglycemia are common in acutely injured patients, and associated with poor outcomes. In the era of tight glucose control, measures of insulin responsiveness (IR) may provide a better indicator of patient status than does the serum glucose concentration. We hypothesized that measures of IR during tight glycemic control protocols are associated with infection and may be more predictive than the serum glucose concentration. All critically injured, mechanically ventilated patients undergo protocolized tight glycemic control with the aid of a computer-based system that calculates the insulin dose using an adapting multiplier (insulin dose = [blood glucose - 60) x M). Consecutive patients on protocol were studied to identify the incidence of positive sterile-site or quantitative bronchoalveolar lavage cultures (>10(4) colony-forming units/mL). Patients were stratified by presence and number of positive cultures and analyzed by both serum glucose measures and measures of IR (average multiplier and average insulin infusion rate). During the six-month study period, 356 patients were placed on the tight glycemic control protocol. Of these, 101 patients had 192 positive cultures. Patients with positive cultures required significantly more hourly insulin than those without a positive culture (3.7 vs. 2.8 units/h; p = or<0.001). Logistic regression showed the insulin dose (odds ratio 2.1; 95% confidence interval 1.6, 3.0; p = <0.001) and the adapting multiplier to be independent predictors of the patient having a positive culture among other factors associated with nosocomial infection. Insulin resistance, quantified by hourly insulin dose and median multiplier, confers a higher risk of systemic nosocomial infection. Patients with positive cultures actually had lower admission and median blood glucose values over their intensive care unit stays, highlighting the decreased value of this measure as a predictor of outcome in the setting of tight glucose control. A greater insulin requirement suggesting resistance may be used as a marker of a higher risk of nosocomial infection.

Genetic Variation in Complement Component 2 of the Classical Complement Pathway is Associated With Increased Mortality and Infection: A Study of 627 Patients With Trauma

Trauma is a disease of inflammation. Complement Component 2 (C2) is a protease involved in activation of complement through the classical pathway and has been implicated in a variety of chronic inflammatory diseases. We hypothesized that genetic variation in C2 (E318D) identifies a high-risk subgroup of patients with trauma reflecting increased mortality and infection (ventilator-associated pneumonia [VAP]). Consequently, genetic variation in C2 may stratify patient risk and illuminate underlying mechanisms for therapeutic intervention. DNA samples from 702 patients with trauma were genotyped for C2 E318D and linked with covariates (age: mean 42.8 years, gender: 74% male, ethnicity: 80% white, mechanism: 84% blunt, injury severity score: mean 25.0, admission lactate: mean 3.13 mEq/L) and outcomes: mortality 9.9% and VAP: 18.5%. VAP was defined by quantitative bronchoalveolar lavage (> 10). Multivariate regression analysis determined the relationship of genotype and covariates to risk of death and VAP. However, patients with injury severity score > or = 45 were excluded from the multivariate analysis, as magnitude of injury overwhelms genetics and covariates in determining outcome. Fifty-two patients (8.3%) had the high-risk heterozygous genotype, associated with a significant increase in mortality and VAP. In 702 patients with trauma, 8.3% had a high-risk genetic variation in C2 associated with increased mortality (odds ratio = 2.65) and infection (odds ratio = 2.00). This variation: (1) identifies a previously unknown high-risk group for infection and mortality; (2) can be determined at admission; (3) may provide opportunity for early therapeutic intervention; and (4) requires validation in a distinct cohort of patients.

Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?

Ventilator-associated pneumonia (VAP) is a leading cause of mortality in critically ill patients. Although previous studies have shown that de-escalation therapy (DT) of antibiotics may decrease costs and the development of resistant pathogens, minimal data have shown its effect in surgical patients or in any patients with septic shock. We hypothesized that DT for VAP was not associated with an increased rate of recurrent pneumonia (RP) or mortality in a high acuity cohort of critically ill surgical patients. All surgical intensive care unit (SICU) patients from January 2005 to May 2007 with VAP diagnosed by quantitative bronchoalveolar lavage with a positive threshold of 10,000 CFU/mL were identified. Data collected included age, gender, Acute Physiologic and Chronic Health Evaluation Score III (A3), type of bacterial or other pathogen, antibiotics used for initial and final therapy, mortality, RP, and appropriateness of initial therapy (AIT). Patients were designated as receiving AIT, DT, or escalation of antibiotic therapy based on microbiology for their VAP. One hundred thirty-eight of 1,596 SICU patients developed VAP during the study period (8.7%). For VAP patients, the mean Acute Physiologic and Chronic Health Evaluation III score was 82.7 points with a mean age of 63.8 years. The RP rate was 30% and did not differ between patients receiving DT (27.3%) and those who did not receive DT (35.1%). Overall mortality was 37% (55% predicted by A3 norms) and did not differ between those receiving DT (33.8%) or not (42.1%). The most common pathogens for primary VAP were methicillin-resistant Staphylococcus aureus (14%), Escherichia coli (11%), and Pseudomonas aeruginosa (9%) whereas P. aeruginosa was the most common pathogen in RP. The AIT for all VAP was 93%. De-escalation of therapy occurred in 55% of patients with AIT whereas 8% of VAP patients required escalation of antibiotic therapy. The most commonly used initial antibiotic choice was vancomycin/piperacillin-tazobactam (16%) and the final choice was piperacillin-tazobactam (20%). Logistic regression demonstrated no specific parameter correlated with development of RP. Higher A3 (Odds ratio, 1.03; 95% confidence interval, 1.01-1.05) was associated with mortality whereas lack of RP (odds ratio, 0.31; 95% confidence interval, 0.12-0.80), and AIT reduced mortality (odds ratio, 0.024; 95% confidence interval, 0.007-0.221). Age, gender, individual pathogen, individual antibiotic regimen, and the use of DT had no effect on mortality. De-escalation therapy did not lead to RP or increased mortality in critically ill surgical patients with VAP. De-escalation therapy was also shown to be safe in patients with septic shock. Because of its acknowledged benefits and lack of demonstrable risks, de-escalation therapy should be used whenever possible in critically ill patients with VAP.

Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1beta [IL-1beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.