1. Comparison of the Systemic Inflammatory Response Syndrome between Monomicrobial and Polymicrobial Pseudomonas aeruginosa Nosocomial Bloodstream Infections Alexandre R. Marra, Gonzalo Bearman, Richard P. Wenzel and Michael B. Edmond Federal University of São Paulo, Escola Paulista de Medicina, São Paulo, Brazil and Virginia Commonwealth University, Richmond, Virginia ABSTRACT METHODS RESULTS (continued) Background: Some studies of nosocomial bloodstream infection (nBSI) have demonstrated higher mortality rates due to polymicrobial bacteremia when compared to monomicrobial nBSI. Methods: We performed a historical cohort study on 98 adults with P. aeruginosa (Pa) nBSI to define the associated systemic inflammatory response syndrome (SIRS). We examined SIRS scores 2 days prior through 14 days after the first positive blood culture. Monomicrobial (n=77) and polymicrobial BSIs (n=21) were compared. Bacteremia was defined as polymicrobial if microorganisms other than P. aeruginosa were isolated from the blood culture. Coagulase-negative staphylococci were considered contaminants unless they grew in two or more blood cultures. Variables significant in univariate analysis were entered into a logistic regression model. Results: 78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa) and 21.4% by polymicrobial P. aeruginosa infection (PPa). Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p=0.64). No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score  20 at BSI onset, Charlson weighted comorbidity index  3, burn injury, and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p<0.001) and APACHE II score  20 at BSI onset (p=0.007) independently predicted death. Conclusions: The incidence of septic shock and organ failure was high in both groups. Additionally, patients with PPa BSI were not more acutely ill, as judged by APACHE II score prior to blood culture positivity than those with MPa BSI. Using multivariable logistic regression analysis, the development of hematologic failure and APACHE II score  20 at BSI onset were independent predictors of death; however, PPa BSI was not. INTRODUCTION P. aeruginosa is an important nosocomial BSI pathogen with a high associated mortality. Although the frequency of Gram-negative sepsis has diminished over the last 20 years, the incidence of polymicrobial nBSI infection has increased. Prior studies of nosocomial bloodstream infection (nBSI) have reported a higher associated mortality with polymicrobial nBSI than with monomicrobial nBSI. Little information exists about the systemic inflammatory response in polymicrobial BSI. The purpose of this study was to evaluate and compare the inflammatory response, clinical course, and outcome of monomicrobial and polymicrobial nosocomial BSI due to Pseudomonas aeruginosa. Setting: The Virginia Commonwealth University Medical Center is a 820-bed tertiary care facility in Richmond, Virginia. The hospital houses 9 intensive care units and a burn unit; approximately 30,000 patients are admitted annually. Study design: Historical cohort study of 98 randomly selected patients with monomicrobial (n=77) and polymicrobial (N=21) P. aeruginosa nBSI from 1996- 2003. The clinical condition of each patient was classified according to systemic inflammatory response syndrome (SIRS) criteria [SIRS, sepsis, severe sepsis or septic shock] and APACHE II scores from two days prior to positive blood culture through 14 days afterwards. Definitions: Bacteremia was defined as polymicrobial if microorganisms other than P. aeruginosa were recovered from the blood culture within a 24 h period. SIRS was defined as two or more of the following: (1) temperature >38ºC or 90 beats/minute, (3) respiratory rate >20 breaths/ minute or PaCO 2 12,000/  L or 10% immature neutrophils. Sepsis was defined as SIRS associated with P. aeruginosa isolated from at least one blood culture. Sepsis with the presence of hypotension or systemic manifestations of hypoperfusion constituted severe sepsis. Septic shock was defined as sepsis associated with hypotension unresponsive to intravenous fluid challenge or the need for >5  g/kg/minute of dopamine or any other vasopressor agent. Organ system failure was assessed using the criteria described by Fagon. Statistical methods: Mean values were compared using 2 sample t tests for independent samples. Proportions were compared using a χ 2 test. All tests of significance were 2-tailed, and α was set at 0.05. Independent predictors of mortality were identified by means of stepwise logistic regression analysis, using variables found to be significant in univariate analysis. In patients with P. aeruginosa nBSI: -One-fifth of cases are polymicrobial; -The incidence of septic shock and organ failure is high Patients with PPa BSI are not more severely ill prior to infection than those with MPa BSI, and APACHE II score  20 at BSI onset and the development of hematologic failure are independent predictors of death. Table 1: Patient characteristics and outcomes, stratified by polymicrobial infection (MPa vs. PPa) and underlying severity of illness before infection (APACHE II score > vs. < 20) Figure 1: Severe sepsis, septic shock and death in patients with P. aeruginosa nBSI stratified by polymicrobial infection CONCLUSIONS Table 2: Characteristics of 26 co-pathogens isolated in 21 cases of polymicrobial P. aeruginosa BSI RESULTS Figure 2: Mean APACHE II scores in patients with P. aeruginosa nBSI stratified by polymicrobial infection Total (n=98) PPa (n=21) MPa (n=77) AP2<20 (n=33) AP2>20 (n=65) Mean age (years)5554555256 Male sex64.3%81.0%59.7%75.8%58.5% Mean LOS prior to nBSI (days)3226332436 Mechanical ventilation63.371.4%61.0%42.4%73.8% Hemodialysis15.314.3%15.6%3.0%21.5% TPN24.514.3%27.3%21.2%26.2% Transfusion22.638.1%26.0%15.2%35.4% ICU83.7%90.5%81.8%72.7%89.2% Central venous line84.7%90.5%83.1%66.7%93.8% Burn injury17.3%42.9%10.4%9.1%21.5% Diabetes mellitus22.4%23.8%22.1%24.2%21.5% Neoplasia20.4%4.8%24.7%24.2%18.5% Gastrointestinal complication20.4%19.0%20.8%21.2%20.0% Polymicrobial infection18.2%23.1% Imipenem resistance26.5%28.6%26.0%12.1%33.8% AP2 >20 at day 0 (median)23 22 Charlson score >327.6%19.0%29.9%21.2%30.8% Inadequate antibiotic therapy43.9%85.7%48.1%45.5%43.1% Mean time to appropriate antimicrobial therapy (days) 2.03.41.72.41.8 Respiratory failure74.5%71.4%75.3%45.5%89.2% CV failure37.8%33.3%39.0%9.1%52.3% Renal failure39.8%52.4%36.4%18.2%50.8% Hematologic failure32.7%28.6%33.8%21.2%38.5% Liver failure12.2%9.5%13.0%3.0%16.9% 7-day mortality22.4%28.6%20.8%3.032.3 Overall mortality45.9%38.1%48.1%12.1%63.1% K-1941 P<.05 Univariate Analysis*Multivariate Analysis Risk factorORP P Apache II score  20 12.7<0.0019.70.007 Charlson score2.60.0372.70.13 Burn injury3.50.0253.20.18 Cardiovascular failure5.2<0.0012.60.14 Hematologic failure10.7<0.00116.9<0.001 Respiratory failure3.60.0111.40.70 Renal failure3.90.0031.30.69 Table 3: Risk factors for death in patients with P. aeruginosa nosocomial bloodstream infection *Only significant univariate variables are shown Alexandre R. Marra, MD a.marra@uol.com.br UNIVERSIDADE FEDERAL DE SÃO PAULO Hospital São Paulo Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Grants/Research Support Microorganisms (n=26) Polymicrobial BSI cases (n=21) N% CNS415.4 Staphylococcus aureus*311.5 Enterococcus faecalis13.8 Enterococcus faecium27.7 Streptococcus pneumoniae13.8 Acinetobacter baumannii415.4 Burkholderia cepacia27.7 Enterobacter cloacae13.8 Klebsiella pneumoniae311.5 Klebsiella oxytoca13.8 Serratia marcescens13.8 Candida albicans311.5 CNS=coagulase-negative staphylococci; *Two methicillin-resistant S. aureus; **One vancomycin-resistant E. faecium