Systemic Inflammatory Response Syndrome in Adult Patients with Nosocomial Bloodstream Infection due to Pseudomonas aeruginosa Alexandre R. Marra, Katharine Bar, 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) ground: Pseudomonas aeruginosa has the highest crude mortality among m-negative pathogens causing nosocomial bloodstream infection (nBSI). ods: We performed a historical cohort study on 57 adults with P.aeruginosa nBSI to define the associated systemic inflammatory response syndrome S). We examined SIRS scores 2 days prior through 14 days after the first ve blood culture. Imipenem resistant (n=15) and susceptible infections 2) were compared. Variables significant in univariate analysis were entered logistic regression model. lts: 73.7% of BSI were caused by imipenem susceptible P. aeruginosa ) and 26.3% by imipenem resistant P. aeruginosa (IRPa). Median APACHE P2) score on the day of BSI was 22. Appropriate antimicrobials were begun n 24 hours in 59.6%. Septic shock occurred in 40.4% and severe sepsis in dditional 15.7%. Incidence of organ failure was as follows: respiratory 73.7%, 36.8%, hematologic 24.6%, hepatic 8.8%. Crude mortality was 45.6%. ession to septic shock was associated with death (OR 5.5, CI9 51.7-17.4, 003). There was no difference in AP2 scores on days -2, -1 and 0 between SPa and IRPa groups. Maximal SIR (severe sepsis, septic shock or death) seen on day 0 for IRPa BSI vs. day 1 for ISPa. No significant difference was d in the incidence of organ failure, 7-day or overall mortality between the two ps. Univariate analysis revealed that AP2≥20 at BSI onset, time to opriate therapy >24 hours and cardiovascular and hematologic failure were ciated with death, but age, respiratory, renal, and hepatic failure, and ion due to IRPa were not. Multivariate analysis revealed that hematologic e (OR 7.4; CI95 2.7-213.5, p=0.006), AP2≥20 at BSI onset (OR 6.0; CI95 19.9, p=0.014) and time to appropriate therapy >24 hours (OR 4.7; CI95 1.2- p=0.031) independently predicted death. clusions: In patients with P. aeruginosa nBSI, (1) the incidence of septic k and organ failure is high, (2) patients with IRPa BSI are not more acutely ill to infection than those with ISPa BSI, and (3) the development of atologic failure, AP2≥20 at BSI onset and the time to appropriate therapy >24 s were independent predictors of death. INTRODUCTION domonas aeruginosa is the third most common gram-negative gen causing nosocomial bloodstream infections (BSIs), and has the st crude mortality among bacteria causing nosocomial BSI. The crude ality of P. aeruginosa BSI in immunocompromised patients ranges from o 33%. In a study of patients with P. aeruginosa pneumonia, mination of the APACHE (Acute Physiological and Chronic Health ation) II score at admission was not useful as a prognostic marker, progression of organ dysfunction after the infection due to P. ginosa proved to be an ominous sign. There exist only a few small- studies evaluating the effect of antimicrobial resistance in hospital gens on clinical outcome. This study was conducted to explore the mmatory response, clinical course and outcome of nBSI due to P. ginosa. 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 57 randomly selected patients with monomicrobial 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: SIRS was defined as two or more of the following: (1) temperature >38ºC or <36ºC, (2) heart rate >90 beats/minute, (3) respiratory rate >20 breaths/ minute or PaCO 2 <32mm HG, or (4) white blood cell count >12,000/µL or <4,000/µL or the presence of >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 >5µg/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. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (days) Patients (%) SIRS 0 SIRS 1 SIRS 2 SIRS 3 SIRS 4 Severe sepsis Shock Dead The overall morbidity and mortality of patients with P. aeruginosa high. Patients with IRPa BSI are not more acutely ill prior to infection tha with ISPa BSI. When controlling for underlying severity of illness in patien P. aeruginosa nBSI, the hematologic failure, AP≥ 20 at BSI onset time to appropriate therapy >24 hours were independent predictors fo Table 1: Patient characteristics and outcomes, stratified by resistance pattern of infecting organism (ISPa vs. IRPa and underlying severity of illness before infection (APACHE II score > vs. < 20) Figure 1: Systemic Inflammatory response (SIRS) over time CONCLUSIONS Figure 3: Severe sepsis, septic shock and death in patients with P. aeruginosa nBSI stratified by imipenem resistance pattern RESULTS Figure 2: Severe sepsis, septic shock and death in patients with P. aeruginosa nBSI stratified by APACHE II score 1.6 1.9 3.3 1.4 1.7 Mean time to appropriate antimicrobial therapy (days) 64.9% 10.0% 46.7% 45.2% 45.6% Overall mortality 27.0% - 13.3% 19.0% 17.5% 7-day mortality 10.8% 5.0% 13.3% 7.1% 8.8% Liver failure 29.7% 15.0% 26.7% 23.8% 24.6% Hematologic failure 45.9% 20.0% 46.7% 33.3% 36.8% Renal failure 56.8% 10.0% 53.3% 35.7% 40.4% CV failure 94.6% 35.0% 86.7% 69.0% 73.7% Respiratory failure 22 22 22 AP2> 20 at day 0 32.4% 15.0% 26.3% Imipenem resistance 5.4% 10.0% 13.3% 4.8% 7.0% Neutropenia 91.9% 70.0% 100.0% 78.6% 84.2% Central venous line 89.2% 70.0% 86.7% 81.0% 82.5% ICU 83.8% 90.0% 73.3% 90.5% 86.0% Prior antibiotics 21.6% 10.0% 26.7% 14.3% 17.5% Transfusion 27.0% 35.0% 33.3% 28.6% 29.8% TPN 16.2% - 20.0% 7.1% 10.5% Hemodialysis 75.7% 35.0% 86.7% 52.4% 61.4% Mechanical ventilation 42 22 67 23 35 Mean LOS prior to nBSI (days) 51.4% 20.0% 33.0% 42.9% 40.4% Women 57 53 50 57 55 Mean age (years) AP2> 20 (n=37) AP2<20 (n=20) IRPa (n=15) ISPa (n=42) Total (n=57) 74 P<.05 4.7 0.045 3.0 Time to appropriate therapy >24 hours 1.0 0.003 5.5 Cardiovascular failure 6.0 <0.001 16.6 Apache II score ≥20 7.5 0.001 12.4 Hematologic failure OR P OR Risk factor Multivariate A Univariate Analysis* Table 2: Risk factors for death in patients with P. aeruginosa nosocomial bloodstream infection *Only significant univariate variables are shown Alexand a.m 0 10 20 30 40 50 60 70 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time (days) ISPa IR 0 10 20 30 40 50 60 70 80 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (days) A2<20 A2>=20 UNIVERSIDADE FEDERAL DE SÃO PAULO Hospital São Paulo Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (C Grants/Research Support Patients with severe sepsis, septic shock or death (%) Patients with severe sepsis, septic shock or death (%)