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 <36ºC, (2) heart rate >90 beats/minute, (3) respiratory rate >20 breaths/ minute or

PaCO2 <32mm HG, or (4) white blood cell count >12,000/L or <4,000/L 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

>5g/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 χ2 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) 55 54 55 52 56

Male sex 64.3% 81.0% 59.7% 75.8% 58.5%

Mean LOS prior to nBSI (days) 32 26 33 24 36

Mechanical ventilation 63.3 71.4% 61.0% 42.4% 73.8%

Hemodialysis 15.3 14.3% 15.6% 3.0% 21.5%

TPN 24.5 14.3% 27.3% 21.2% 26.2%

Transfusion 22.6 38.1% 26.0% 15.2% 35.4%

ICU 83.7% 90.5% 81.8% 72.7% 89.2%

Central venous line 84.7% 90.5% 83.1% 66.7% 93.8%

Burn injury 17.3% 42.9% 10.4% 9.1% 21.5%

Diabetes mellitus 22.4% 23.8% 22.1% 24.2% 21.5%

Neoplasia 20.4% 4.8% 24.7% 24.2% 18.5%

Gastrointestinal complication 20.4% 19.0% 20.8% 21.2% 20.0%

Polymicrobial infection 18.2% 23.1%

Imipenem resistance 26.5% 28.6% 26.0% 12.1% 33.8%

AP2 >20 at day 0 (median) 23 23 22

Charlson score >3 27.6% 19.0% 29.9% 21.2% 30.8%

Inadequate antibiotic therapy 43.9% 85.7% 48.1% 45.5% 43.1%

Mean time to appropriate antimicrobial therapy (days)

2.0 3.4 1.7 2.4 1.8

Respiratory failure 74.5% 71.4% 75.3% 45.5% 89.2%

CV failure 37.8% 33.3% 39.0% 9.1% 52.3%

Renal failure 39.8% 52.4% 36.4% 18.2% 50.8%

Hematologic failure 32.7% 28.6% 33.8% 21.2% 38.5%

Liver failure 12.2% 9.5% 13.0% 3.0% 16.9%

7-day mortality 22.4% 28.6% 20.8% 3.0 32.3

Overall mortality 45.9% 38.1% 48.1% 12.1% 63.1%

K-1941

P<.05

Univariate Analysis* Multivariate Analysis

Risk factor OR P OR P

Apache II score 20 12.7 <0.001 9.7 0.007

Charlson score 2.6 0.037 2.7 0.13

Burn injury 3.5 0.025 3.2 0.18

Cardiovascular failure 5.2 <0.001 2.6 0.14

Hematologic failure 10.7 <0.001 16.9 <0.001

Respiratory failure 3.6 0.011 1.4 0.70

Renal failure 3.9 0.003 1.3 0.69

Table 3: Risk factors for death in patients with P. aeruginosanosocomial bloodstream infection

*Only significant univariate variables are shown

Alexandre R. Marra, MDa.marra@uol.com.br

                   

                                         

UNIVERSIDADE FEDERAL DE SÃO

PAULOHospital São Paulo

                  

   Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Grants/Research Support

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-2 -1 0 1 2 3 4 5 6 7 8 9 10 111213 14Time (days)

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MPa PPa

Microorganisms (n=26)

Polymicrobial BSI cases (n=21)

N %

CNS 4 15.4

Staphylococcus aureus* 3 11.5

Enterococcus faecalis 1 3.8

Enterococcus faecium 2 7.7

Streptococcus pneumoniae 1 3.8

Acinetobacter baumannii 4 15.4

Burkholderia cepacia 2 7.7

Enterobacter cloacae 1 3.8

Klebsiella pneumoniae 3 11.5

Klebsiella oxytoca 1 3.8

Serratia marcescens 1 3.8

Candida albicans 3 11.5

CNS=coagulase-negative staphylococci; *Two methicillin-resistant S. aureus; **One vancomycin-resistant E. faecium