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Bloodstream Infections After Invasive Nonsurgical Cardiologic Procedures
Patricia Muñoz, MD, PhD;
Jose Ramón Blanco, MD, PhD;
Marta Rodríguez-Creixéms, MD, PhD;
Eulogio García, MD, PhD;
Juan Luis Delcan, MD, PhD;
Emilio Bouza, MD, PhD
Arch Intern Med. 2001;161:2110-2115.
ABSTRACT
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Objective To define the incidence, risk factors, and characteristics of bloodstream
infections (BSIs) after invasive nonsurgical cardiologic procedures (ICPs).
Methods Retrospective case-control study; multivariate analysis.
Results Between January 1991 and December 1998, 22 006 ICPs were performed
in our hospital and 25 BSIs were documented within 72 hours after ICP. Overall
incidence of bacteremia was 0.11% (25 cases) (0.24% after percutaneous transluminal
coronary angioplasty [14 cases of 5625 patients], 0.6% after diagnostic cardiac
catheterization [9 cases of 14 034 patients], and 0.8% after electrophysiologic
studies [2 cases of 2347 patients]). These 25 patients with bacteremia were
compared with 50 controls randomly selected among patients who underwent an
ICP but did not have BSIs. Patient-related risk factors for BSI were age older
than 60 years (20 cases [80%] vs 28 controls [56%]), valvular disease (4 [16%]
vs 1 [2%]), congestive heart failure (7 [28%] vs 1 [2%]), indwelling bladder
catheter before the ICP (5 [20%] vs 1 [2%]), more than 1 puncture for the
ICP (5 [20%] vs 3 [6%]), a prolonged procedure (83.7 vs 65.1 minutes); and/or
more than 1 ICP performed (2 [8%] vs 0). Multivariate analysis identified
the presence of congestive heart failure (odds ratio, 21; 95% confidence interval,
6.8-66.0) and age older than 60 years (odds ratio, 1.9; 95% confidence interval,
1.9-6.3) as independent risk factors for BSI after ICP. Bloodstream infection
was detected a median of 1.7 days after the procedure. Gram-negative bacteremia
accounted for 17 cases (68%) of the BSIs. Among the patients with BSI, the
duration of hospital stay was significantly increased (21 vs 6 days). The
overall mortality rate was 0.009% for patients who underwent an ICP (8.0%
for the 25 patients with bacteremia documented within 72 hours after ICP).
Conclusions Bloodstream infection should be included among the potential complications
of ICP. Elderly patients with recent congestive heart failure episodes constitute
a subgroup with a higher risk of postprocedure bacteremia. Therapy with antimicrobial
agents against gram-positive and gram-negative bacteremia should be initiated
after performing blood cultures in patients with signs suggestive of infection.
INTRODUCTION
IN MODERN hospitals many invasive nonsurgical cardiologic procedures
(ICPs) are performed every day. Although these techniques are safe, a wide
array of systemic and local potential complications associated with these
procedures have been reported. Systemic adverse effects include cerebrovascular
accidents (0.07%-0.30%), myocardial infarction (0.06%-4.80%), and even death
(0.10%-1.10%).1-8
Related infectious complications are not commonly reported, and local
problems predominate.6, 8-24
However, patients undergoing ICP may develop bloodstream infections (BSIs)
that may cause death or significantly extend the hospital stay, which increases
the cost.
An ICP-related BSI is an infrequent finding, and most of the available
literature consists of isolated case reports that do not allow for an accurate
definition of risk factors.14, 16-17,19-22
Herein we report what is to our knowledge the largest case-control series
of early BSI after ICP from a single center. Our objective was to define the
incidence, risk factors, and clinical characteristics of early BSI in patients
who have undergone ICP.
POPULATION, MATERIALS, AND METHODS
Our institution is a 2000-bed teaching hospital with a very active invasive
cardiology department and heart transplantation program. The records of ICPs
performed in the Cardiology Department were cross referenced with the records
of BSI detected in the Clinical Microbiology Laboratory. Patients with BSI
detected within 72 hours after ICP were selected as "cases." This period was
chosen to maximize the likelihood of only including BSIs related to the ICPs.
For each case subject with ICP-related BSI, 2 "control" subjects were elicited
from a random number table from patients who had undergone ICP in the same
period but had not developed a subsequent BSI.
Blood cultures were ordered when the patients experienced fever, chills,
or others signs suggestive of infection. Only significant bacteremic episodes
were included, and all blood cultures were obtained through direct venipuncture
rather than through an intravascular device. When a case of Staphylococcus epidermidis bacteremia was found, the episode was only
included when at least 2 blood culture sets yielded the same microorganism
and the patient showed clinical signs suggestive of infection. Blood samples
were processed with an automated monitoring system (BACTEC NR; Becton, Dickinson
and Company, Franklin Lakes, NJ). Isolates were identified with standard microbiological
tests and automated methods (MicroScan; Dade International Inc, West Sacramento,
Calif). None of the patients received prophylactic treatment, and ICPs were
performed using standard sterile techniques and infection prevention measures.25 Femoral access was undertaken in all instances.
Data collected included age; sex; underlying diseases (diabetes mellitus,
malignancy, central nervous system disorders, chronic renal failure, liver
disease, human immunodeficiency virus, valvular heart disease, congestive
heart failure in the previous 14 days, presence of intravascular prosthetic
material, chronic obstructive pulmonary disease, and previous myocardial infarction);
risk factors (alcoholism, current smoking, drug abuse, steroid treatment,
central venous catheters, and indwelling urinary tract catheter); type of
ICP (percutaneous transluminal coronary angioplasty [PTCA], diagnostic cardiac
catheterization, or electrophysiologic studies); priority of the ICP (urgent
or not); procedure variables (duration of the procedure, number of punctures,
and number of days the sheath was left in place); complications and outcome
during or after ICP (fever, chills, vascular lesion, neurologic lesion, hematoma
at the site of puncture, primary BSI, catheter-related BSI, urosepsis, pneumonia,
meningitis, endocarditis, shock, intensive care unit admission, and death);
analytical data (white blood cell count, left deviation, platelet count);
microorganism identified from blood cultures (gram-positive, gram-negative,
or polymicrobial); duration of hospital stay; and empirical treatment (adequate
or inadequate). Antimicrobial therapy was considered adequate if 1 or more
antimicrobial agents with in vitro activity against the corresponding isolate
were administered for a minimum of 5 days. Death was attributed to the infectious
process if the patient died within 10 days of the bacteremic episode with
a clinical course suggesting persistent infection; it was always attributed
if the patient died during the phase of acute infection and death could not
be clearly attributed to any other cause.
Assessment of significant risk factors for BSI was performed by univariate
and multivariate analyses. Quantitative variable analysis was analyzed with
the Mann-Whitney test. The study of qualitative variables was performed with
the  2 test with the Yates correction or the Fisher exact test
(2-tailed) whenever possible. Adjusted risk ratios with 95% confidence intervals
were assessed by stepwise logistic regression analysis (SPSS software; SPSS
Inc, Chicago, Ill). Nonrelated variables identified as significant in the
univariate analysis were entered into the logistic regression analysis. Statistical
significance was defined as P<.05.
RESULTS
During the study period (January 1991 to December 1998), 68 patients
had an episode of BSI among the 22 006 who underwent an ICP. Of these
episodes, 25 occurred within 72 hours after the procedure, resulting in an
overall incidence of 0.11%. Incidence of early BSI was significantly higher
after PTCA: 14 (0.24%) of 5625 patients who underwent PTCA followed by 9 (0.06%)
of 14 034 patients who underwent cardiac catheterization and 2 (0.08%)
of 2347 patients who underwent electrophysiologic studies (P = .001). However, the type of cardiologic procedure was not an independent
risk factor in the multivariable study.
RISK FACTORS FOR BSI
Risk factors predisposing to BSI were grouped into those present before
the procedure (the first group) and those related to the procedure itself
(the second group) (Table 1).
Among the first group, age older than 60 years (20 cases [80%] vs 28 controls
[56%]), prior valvular disease (4 [16%] vs 1 [2%]), congestive heart failure
(7 [28%] vs 1 [2%]), and indwelling bladder catheterization (5 [20%] vs 1
[2%]) were more common among patients with BSI. Among the second group, more
than 1 ICP performed (2 [8%] vs 0), number of punctures needed (mean of 1.2
vs 1.05), duration of the procedure (mean of 83.7 vs 65.1 minutes), and development
of inguinal hematoma (4 [16%] vs 1 [2%]) were associated with a higher risk
of developing BSI in the univariate analysis. Multivariate analysis identified
the presence of congestive heart failure (odds ratio [OR], 21; 95% confidence
interval, 6.8-66.0) and age older than 60 years (OR, 1.9; 95% confidence interval,
1.9-6.3) as independent risk factors for BSI after ICP.
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Table 1. Characteristics and Underlying Diseases of Cases and Controls*
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CLINICAL PRESENTATION OF BSI AFTER AN ICP
Bloodstream infection was detected a median of 1.7 days after ICP (range,
0-3 days); 9 (36%) of them were detected in the first 24 hours after ICP and
21 (84%) in the first 48 hours. The main clinical signs of BSI were fever
(25 [100%]) and chills (16 [64%]), which were both only present in patients
with BSI. One patient developed endocarditis, which was possibly related to
an episode of Staphylococcus aureus BSI after an
electrophysiologic study. However, it was not included in this analysis because
the BSI occurred 7 days after the procedure. None of the patients with both
bacteremia and valvular heart lesions who were included in this study developed
endovascular infection. No local infection was documented in this series.
Microorganisms responsible for BSI are listed in Table 2. Of the episodes, 17 (68%) were caused by gram-negative
microorganisms. None of them were polymicrobial and no grouping of cases was
detected. Our 4 patients with previous valvular heart lesions had a gram-negative
bacteremia (Pseudomonas cepacia, Klebsiella pneumoniae, Enterobacter cloacae,
and Escherichia coli), and none of them had endocarditis
or endarteritis. The origins of the bacteremia in the patients with an indwelling
bladder catheter were S aureus in 2; Enterococcus faecalis in 1; Serratia marcescens
in 1; and E coli in 1.
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Table 2. Microorganisms Isolated From the 25 Patients With Bloodstream
Infection After an Invasive Nonsurgical Cardiologic Procedure
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Antimicrobial therapy was considered adequate in 75% of cases. Five
patients did not receive therapy (1 patient died before treatment was initiated,
and the other 4 had already been released from the hospital or were asymptomatic
when the results were available). All of them survived, and the origins of
these bacteremias were Klebsiella oxytoca in 2; E faecalis in 1; and E coli in
1.
Three patients (12%) developed septic shock, and 2 of them died (the
overall mortality was 12%, and the related mortality was 8% for the 25 patients
with bacteremia that was detected within 72 hours after ICP). The median hospital
stay was significantly longer for patients with bacteremia (21 vs 6 days)
(Table 1).
COMMENT
The use of ICP has experienced a rapid expansion in recent years, and
a large number of patients undergo these procedures every day. More than 300 000
PTCAs were performed in the United States in 199023
and more than 600 000 in 1999.
Although infectious complications are uncommon, the great number of
procedures performed every year implies that even a low incidence of infection
may have significant consequences. We are reporting what is to our knowledge
the largest series of early BSIs after ICP. In our hospital, 0.11% of all
patients who had undergone an ICP had a clinically significant procedure-related
BSI in the following 3 days. Incidence of BSI was significantly higher among
patients who underwent PTCA (0.24%), although the type of procedure was not
an independent risk factor in our multivariate model. In the literature, incidence
of bacteremia after PTCA ranges from 0.20 to 0.80,9-11,19
although the study by Samore et al11 includes
bacteremias that were detected in the first 7 weeks following PTCA.
To identify patients with a higher risk of severe infectious complications
who would require a closer follow-up or even prophylaxis, we performed a case-control
study and literature review. Risk factors proposed in previous studies (all
but 2 were derived from series with less than 6 patients with bacteremia)
are summarized in Table 3.
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Table 3. Summary of Studies That Identify Risk Factors for Infection
After ICPs*
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Congestive heart failure was the most significant risk factor in our
multivariate model (OR, 21; 95% confidence interval, 6.8-66.0). This factor
was also identified by Samore et al11 in the
only other comparative series of patients with bacteremia after PTCA (OR,
43.3). The reason for this association is not clear. In our series, patients
with bacteremia and previous congestive heart failure were younger than those
without BSI (median age, 61 vs 71 years; P = .04),
had a greater incidence of valvular diseases (3 cases [42%] vs 1 control [5%]; P = .02) and diabetes mellitus (4 [57%] vs 1 [5%]; P = .003), were more commonly receiving mechanical ventilation
(2 [28%] vs 0; P = .01), required more central venous
catheters (3 [43%] vs 1 [5%]; P = .02), and needed
more than 1 puncture for the ICP (4 [57%] vs 1 [5%]; P
= .03).
The second independent risk factor was age older than 60 years, which
was also suggested in previous works.11 In
our series, patients older than 60 years were more commonly heavy smokers
(10 [50%] vs 0; P = .04). In the literature, cohorts
of older patients who underwent PTCA include more women, more patients with
unstable angina, and more patients with left ventricular dysfunction and congestive
heart failure. Age older than 75 years was reported to be an independent risk
factor for death, acute myocardial infarction, need for transfusion, and need
for arterial repair after PTCA.3
In contrast to the results of Samore et al,11
we could not find a correlation between the risk of bacteremia and any of
the factors related to the procedure itself, although some of them were significant
in the univariate analysis (Table 1).
Samore et al found that duration of the procedure (OR, 6.8), number of catheterizations
in the same site (OR, 4.0), difficult vascular access (OR, 15.0), and length
of time the sheath was left in place (OR, 6.8) increased the risk of bacteremia.
The significantly lower incidence of bacteremia after PTCA in our study compared
with that of Samore et al11 (14 cases [0.24%]
vs 27 cases [0.64%]; P = .003) may be justified by
technical factors. For example, 20 (80%) of our patients vs 12 (44%) of the
patients required just 1 puncture, the duration of the procedure in our center
was less than 1 hour in 36% vs 11% of the cases, and the sheath always remained
in place less than 24 hours (mean time, 7.28 hours), while in the study by
Samore et al11 the sheath remained in place
less than 24 hours in only 7 cases (26%). In another series, duration of the
procedure was also not found to be a significant risk factor.9
Retention of the sheath (40 vs 22 hours) and bleeding around the insertion
site (43% vs 9% transfusion rate) were risk factors for infection in a prospective
series of 500 patients who underwent angioplasty with 6 related infections
(4 bacteremias).10 These factors were not found
to increase the risk of bacteremia in our series, but both our transfusion
rate (4%) and the length of time the sheath was left in place are significantly
less than those reported in the series by McHenry et al10.
Early repuncture of the ipsilateral femoral artery or repeated procedures
through a previously traumatized femoral access site have been proposed as
risk factors in some short series, mainly for local complications.16, 19-21,24
However, these findings were not confirmed by others.6, 12
Two of our 25 patients with bacteremia underwent a second cardiologic procedure,
but this factor was not independently related to a higher risk of bacteremia.
Local infections are very uncommon8;
there were none in our series, probably because we had focused on the early
onset of bacteremia. Blood cultures may remain negative even after severe
local infections,18 and femoral endarteritis
may be associated with osteoarticular metastases and peripheral emboli.22-23
Fever after ICP has been correlated with the use of contrast medium2 or with the introduction of bacterial endotoxin from
the surface of the catheter or from the skin.12, 24
However, the change to single-use pyrogen-free catheters has virtually eliminated
these problems as well as the potential for BSI due to unsterile catheters.
In our study, fever 25 (100%) of the cases vs none of the controls; P<.001) and chills were the most constant symptoms of
BSI after ICP. The association of fever after an ICP with real infection has
also been indicated by some authors (50% of cases vs 4% of controls).10
Gram-negative microorganisms were more commonly identified in our study
(17 [68%]). This finding has also been observed by other authors,15, 26-27 while gram-positive
bacteria (mainly Staphylococcus species) predominated
in other reports.9, 11, 19
In a series of 7 cases of bacteremia after coronary stenting, 3 episodes were
caused by S aureus, 2 by E cloacae, and 1 each by Proteus mirabilis and S marcescens.15 Gram-negative
bacteria are well-known colonizers of perineal and groin skin, mainly in patients
with indwelling bladder catheters. However, this was not the only reason,
since 3 of our 5 cases with indwelling bladder catheter had gram-positive
bacteremia.
Other potential reasons for the importance of gram-negative bacteremia
in our series is that our population was severely ill and older (mean age,
66.6 years), both well-recognized risk factors for colonization by gram-negative
bacteria. In some of the published series in which gram-positive bacteremia
predominated, blood cultures were obtained from the femoral catheter or from
the vessel from which the catheter had just been removed. Thus, some of these
isolates may represent contamination by skin pathogens.12
This practice is not useful for the diagnosis of BSI unless lysis centrifugation
techniques are used and another blood culture is obtained through the vein.
The overall mortality rate related to the bloodstream infection was
0.09 per 1000 ICPs (8% of the 25 patients with bacteremia that was detected
within 72 hours after ICP). In other series, 1.7% of the deaths were caused
by a related infection (0.16 per 1000 PTCAs).2
Patients with bacteremia had a much more prolonged hospital stay (21 vs 6
days), which also increased the cost.
CONCLUSIONS
Bloodstream infection complicates 0.11% of ICPs. Elderly patients with
recent congestive heart failure episodes constitute a subgroup with a higher
risk of postprocedure bacteremia. Antimicrobial agents against gram-positive
and gram-negative bacteria should be initiated after blood cultures are performed
in patients with signs suggestive of infection. The selection of a subgroup
of patients with a high risk of infection who could benefit from antimicrobial
prophylaxis merits further study.
AUTHOR INFORMATION
Accepted for publication February 12, 2001.
The authors are grateful for the help of the staff of the Cardiac Catheterization
Department and Microbiology Laboratory of the Hospital General Universitario
"Gregorio Marañón."
Corresponding author and reprints: Patricia Muñoz, MD, PhD,
Servicio de Microbiología, Hospital General Universitario "Gregorio
Marañón," Doctor Esquerdo 47, Madrid 28006, Spain (e-mail: pmunoz{at}micro.hggm.es).
From the Clinical Microbiology Laboratory (Drs Muñoz, Blanco,
Rodríguez-Creixéms, and Bouza) and the Cardiology Department
(Drs García and Delcan), Hospital General Universitario "Gregorio Marañón,"
Madrid, Spain.
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