Comparison of the Systemic Inflammatory Response Syndrome between Monomicrobial and Polymicrobial Pseudomonas aeruginosa Nosocomial Bloodstream Infections

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
K-1941
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 (n77) and
polymicrobial BSIs (n21) 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 (p0.64). 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
(plt0.001) and APACHE II score ?20 at BSI onset
(p0.007) 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.  
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 (n77) and polymicrobial (N21) 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
gt38ºC or lt36ºC, (2) heart rate gt90 beats/minute,
(3) respiratory rate gt20 breaths/ minute or PaCO2
lt32mm HG, or (4) white blood cell count
gt12,000/?L or lt4,000/?L or the presence of gt10
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 gt5?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 ?2 test. All tests of significance were
2-tailed, and a 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.
Table 2 Characteristics of 26 co-pathogens
isolated in 21 cases of polymicrobial P.
aeruginosa BSI
Microorganisms (n26) Polymicrobial BSI cases (n21) Polymicrobial BSI cases (n21)
Microorganisms (n26) 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
RESULTS
CNScoagulase-negative staphylococci Two
methicillin-resistant S. aureus One
vancomycin-resistant E. faecium
Table 1 Patient characteristics and outcomes,
stratified by polymicrobial infection (MPa vs.
PPa) and underlying severity of illness before
infection (APACHE II score gt vs. lt 20)
Figure 1 Severe sepsis, septic shock and death
in patients with P. aeruginosa nBSI stratified
by polymicrobial infection
Table 3 Risk factors for death in patients with
P. aeruginosanosocomial bloodstream infection
Total (n98) PPa (n21) MPa (n77) AP2lt20 (n33) AP2gt20 (n65)
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 gt20 at day 0 (median) 23 23 22
Charlson score gt3 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
Univariate Analysis Univariate Analysis Multivariate Analysis Multivariate Analysis
Risk factor OR P OR P
Apache II score ?20 12.7 lt0.001 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 lt0.001 2.6 0.14
Hematologic failure 10.7 lt0.001 16.9 lt0.001
Respiratory failure 3.6 0.011 1.4 0.70
Renal failure 3.9 0.003 1.3 0.69
Only significant univariate variables are shown
CONCLUSIONS
INTRODUCTION
Figure 2 Mean APACHE II scores in patients with
P. aeruginosa nBSI stratified by polymicrobial
infection

• 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.

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.
                                                             UNIVERSIDADE FEDERAL DE SÃO PAULOHospital São Paulo                      
Plt.05
Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior (CAPES) Grants/Research Support
Alexandre R. Marra, MD a.marra_at_uol.com.br