Nipping contamination in the blood
It’s practically an axiom of laboratory science: If you want
the highest sensitivity, you have to sacrifice some specificity.
And in the case of blood cultures, where false positive results
are routine, the tradeoff is considered justified because of the
risk of failing to detect an active infection.
"Laboratorians tend to think of blood culture contamination as
a kind of necessary evil," says Ron B. Schifman, MD, chief of pathology
and laboratory medicine with Southern Arizona VA Health Care System,
associate professor of pathology at the University of Arizona, and
a former member of the CAP’s Quality Practices Committee.
But new data from the CAP’s Q-Tracks program demonstrate that
taking two measures could significantly reduce false positive blood
cultures: Use tincture of iodine to disinfect patients’ skin, and
collect the maximum amount of blood recommended by the instrument
Those are recommendations the College is making to laboratories
based on the first year’s worth of blood culture contamination data
from the Q-Tracks program. Underscoring what previous research has
suggested, the Q-Tracks studies found that iodophor, the most common
agent used to sterilize skin for blood draws, is not as effective
as tincture of iodine, and that fewer false positives occurred the
higher the volume of blood collected. The laboratories with the
lowest contamination rates, when asked by Q-Tracks staff, also counted
technique, training, and monitoring as key contributors to their
Costly false positives
Relatively infrequent contamination of blood cultures can have a
disproportionate impact on patient care and the hospital’s bottom
line. While only a small percentage of blood cultures are contaminated,
a positive result can be false 20 percent to 50 percent of the time.
And false positives lead not only to repeat tests, but also significant
downstream patient care costscosts that in an era of sharp
managed-care accounting should set off alarms.
People in the laboratory often see false positives differently
from clinicians. "False positives create a cycle of extra work for
the lab," says Emily Vetter, MT(ASCP), supervisor of the bacteriology
laboratory at Mayo Clinic in Rochester, Minn. But to the clinician
they mean additional cultures collected, repeat tests, additional
antibiotic use, and longer lengths of stay.
"The high cost of blood culture contamination to the health care
system is not typically in the equation," says Dr. Schifman. "It’s
just now entering the consciousness of most pathologists and infectious
disease people, and maybe even hospital administrators."
The evidence has been in for nearly 10 years. In a 1991 article
in the Journal of the American Medical Association (JAMA.
1991;265: 365-369), David W. Bates, MD, and others studied charge
and length of stay data for episodes in which blood cultures were
obtained from hospitalized adults. They found false-positive episodes,
compared to negative episodes, were associated with longer subsequent
hospital stays (eight days versus 12.5 days), higher total charges
($8,731 versus $13,116), higher laboratory charges ($2,057 versus
$1,426), and sharply higher pharmacy charges ($798 versus $1,456).
Leaving aside other factors, contaminants were independently correlated
with a 20 percent increase in total subsequent laboratory charges
and a 39 percent increase in intravenous antibiotic charges. These
findings have been borne out by a 1999 study that calculated the
difference in mean total hospital costs for patients with contaminated
blood cultures and those with sterile blood cultures was $4,100
(Little JR, Murray PR, Traynor PS, Spitznagel E. Am J Med.
"Most blood culture tests in use are broth systems," Dr. Schifman
notes. "This limits the amount of information you have when a positive
culture is first detected. All you can report at that time is the
gram stain reaction and morphology of the organism. We know a high
proportion of contaminations are coagulase-negative staphylococcus.
These are typically contaminants. So when you report out a gram-positive
coccus in a blood culture as an initial finding, the lab doesn’t
know and the clinician doesn’t know whether it’s a coagulase-negative
staphylococcus, which is likely to be a contaminant, or, for example,
a coagulase-positive staphylococcus, which is probably not a contaminant."
It may take 12 to 18 hours before the final result is available,
he adds. In the meantime, the clinician often has to make a decision
whether to keep the patient in the hospital longer, use empiric
antibiotics, or order more diagnostic tests.
Dr. Bates’ study was the first to point out the high cost of blood
culture contamination, Dr. Schifman notes. "But I haven’t seen a
lot of attention paid to it either in textbooks or by other people
writing about blood culture contamination. While everybody knows
blood culture contamination is a concern, I don’t think the connection
to the high cost is widely appreciated."
Some pathologists call for caution in estimating the dollar impact
of contamination. "The downstream cost of false positives may have
been overstated," says Washington Winn, MD, director of clinical
microbiology and professor of pathology at Fletcher Allen Health
Care, Burlington, Vt. "Most of the time they aren’t that confusing
and don’t make that much difference, but occasionally they can produce
severe disruptions in the course of trying to figure out a diagnosis,
and they may lead to inappropriate therapy. Once you get into cost-accounting
you can come up with any number you want."
However, he adds, that is not to detract from the importance of
reducing contamination rates. The average contamination rate is
about 2.5 percent, says Dr. Schifman, and since rates typically
range between one percent and five percent, "There’s a pretty wide
variation, which means there are probably factors accounting for
the differences. So it’s something we have control over that can
reduce costs and improve quality."
Keeping skin flora out
The causes of contamination are no mystery. "Skin flora is usually
the cause, and they can be on the patient’s skin, on the collector’s
skin, and potentially on the skin of somebody in the lab who processes
the specimen," says Dr. Winn. Determining the best measures to keep
skin flora out of the culture, however, is the critical task.
"If you just wanted to have a blood count done, you would swab
the arm with alcohol to keep it clean and prevent bacteria from
entering the bloodstream," says Dr. Schifman. "But for a blood culture
we want to go one step further and decontaminate the venipuncture
site in a much more effective way."
Making sure any bacteria on the skin are killed is the first priority,
but the other source of contamination is in processing the specimen
in the laboratory. "With some systems you collect the sample from
the patient straight into a broth bottle," Dr. Schifman notes. "That’s
ideal because there’s no break from the needle into the vein to
Most systems, though, require the sample to be inoculated from
a syringe into the bottlecreating controversy over whether
double-needling is necessary to avoid contamination. "Since the
needle that entered the patient’s vein may contain skin flora, there
is the practice of replacing the first needle with another fresh
sterile one on the syringe before inoculating the bottle. But this
practice has been shown to have a very marginal effect on contamination,"
Dr. Schifman says. "It probably does lower it, but so slightly that
I personally do not recommend it. There is an increased risk any
time you change needles of sticking yourself, so it’s best to avoid
having the phlebotomist or anyone else changing needles during procedures."
What makes a difference
The first year of Q-Tracks data confirmed that the double-needle
method made no difference in contamination rates. Wiping the rubber
septum on top of the bottle with antiseptic appeared not to have
an impact either. But the data give strong backing to other practices.
The annual summary of results, released in April, reports an overall
blood culture contamination rate of 2.94 percent for the 155 institutions
that submitted data to the CAP. Two aspects of practice had a statistically
significant association with lower overall contamination rates,
says Paul Valenstein, MD, director of microbiology and the computer
section at St. Joseph Mercy Health Hospital, Ann Arbor, Mich., and
a member of the CAP’s Quality Practices Committee. Collection of
higher blood culture volumes and use of tincture of iodine as a
disinfectant appeared to be the key factors for the top 20 laboratories.
Higher volume of blood collected does appear to be directly related
to lower contamination rates, Dr. Valenstein says, and the College
is recommending that institutions collect the maximum amount recommended
by the manufacturer. "Collecting a higher volume increases detection
of real pathogens, and it also is associated with lower contamination
rates," he says.
Many laboratory professionals believe lower contamination rates
will be found if dedicated phlebotomy teams are used. When this
variablededicated teamswas examined on its own, Dr.
Valenstein says, it was in fact associated with lower rates of contamination.
But "most of the improvement associated with dedicated teams appears
to be due to the fact that they are more likely to use tincture
of iodine as a decontaminant," he explains. When this difference
was taken into account, the use of dedicated phlebotomy teams was
no longer associated with lower contamination rates.
"This finding does not mean dedicated phlebotomy teams are a bad
idea or that they don’t impact blood culture contamination rates,"
Dr. Valenstein says. However, "in our data set, the improvement
that was associated with dedicated phlebotomy teams seemed to be
due to the fact that they were more likely to use tincture of iodine
than iodophor compounds in preparing the patient’s skin before phlebotomy."
The right disinfectant
The 1999 American Journal of Medicine study supports the Q-Tracks
findings on disinfectant. In that study, 3,851 patients were randomized
to have the skin site disinfected with one of two solutions: 10 percent
povidone-iodine and two percent iodine tincture. Before the iodine
tincture was applied, a 70 percent isopropyl alcohol applicator was
applied for one minute. The tincture was allowed to dry for two minutes
before phlebotomy proceeded.
Overall, nearly 10 percent of the blood cultures were positive and one third of these were determined
to be false positives; that is, the cultures grew skin microflora.
But the difference between the groups was significant. The povidone-iodine
group had 3.8 percent skin contamination while the iodine tincture
group had only 2.5 percenta 36 percent reduction in blood
culture contamination rate. This finding compares to a 1993 study
which found a 6.25 percent contamination for cultures using iodophor
and 3.74 percent for cultures using the iodine tincture (Strand
CL, Wajsbort RR, Sturmann K. JAMA. 1993;269:1004-1006).
Studies in both research settings and in the field thus confirm
that tincture of iodine can lower contamination rates, says Dr.
Valenstein. The recommendation is especially noteworthy because
iodophors, most commonly Betadyne, are more heavily marketed and
more expensive than tincture of iodine. Previous studies have found
almost twice as many laboratories use iodophor as tincture of iodine.
"This is one of those rare situations where higher quality really
does cost less," he points out.
To further explore the factors associated with low contamination
rates, the Q-Tracks study asked the best performers open-ended questions
about why they perform well. "Sites with consistently low rates
throughout 1999 did not differ particularly in the type of services
their hospitals offer," Dr. Valenstein says. "Many had trauma centers,
almost all had intensive-care units, and none had a particularly
easy patient population to care for.
"Best performers all reported that they trained their phlebotomy
personnel about blood cultures specifically, and all of them give
some sort of refresher training. Sixteen of 24 indicated that nonlaboratory
people collect blood cultures, so it’s not that they’re achieving
high performance just by using a dedicated phlebotomy team.
"Interestingly, all but one of the best performers give their
lab personnel feedback about their individual blood culture contamination
rates, and most, but not all, of them provide nonlaboratory staff
feedback about their rates. The fact that they know they’re being
watched may influence the care with which they draw blood," Dr.
The role of controls
Some of the Q-Tracks participants express concern about their own
"We have a relatively high rate [of false positives] at our institution,"
says Barbara Reisner, PhD, associate director of the clinical microbiology
laboratory at the University of Texas Medical Branch, Galveston.
In the most recent tally, the contamination rate was about four
percent, meaning about 30 percent of the positive results are false.
Loose control over the collection of samples may be the main culprit,
Dr. Reisner says. "We’re a training and teaching institution, so
a variety of people collect bloodthe residents, the faculty,
nurses. Our phlebotomists do not collect the blood cultures here.
If you have the ability to get phlebotomists to do the majority
of collections, that would be the best way to attack the problembut
we just don’t have the means to do that."
The training on how to collect specimens for a blood culture is
also inconsistent, she says. "People may get written instruction
or they may simply observe somebody, then follow what they’ve seen."
As a result, the procedures are not always followed correctly. "We
package our blood culture bottles in kits with disinfectants, but
I know you can get bottles independently of the kits too. So sometimes
if they cannot easily access the disinfectant, they may go ahead
and collect without the proper materials at hand," Dr. Reisner explains.
At Wyoming Medical Center, where he is team leader for the laboratory,
Kirk Hastings says training is one of the first priorities, and
one reason the contamination rate is low. When phlebotomists (or
laboratory resource technicians, as they are called) are hired,
"We actively stress aseptic technique in blood culture collection.
We are very religious about leaving the Betadyne on for one minute,
so they are trained that way from the beginning. If we go down to
collect a blood culture for an IV start, we’re adamant that the
nurse starting the IV must follow our protocol," he says.
Nevertheless, there are a lot more contaminations in the emergency
room. Hastings believes it is because the "ER environment and culture
lends itself to going fast" and they aren’t as attuned to details
of laboratory policy as are the laboratory personnel. "Unfortunately,
they get in a hurry; a lot of times they don’t want to wait that
minute. They like to put [the disinfectant] on and stick the patient
about 10 seconds later, and it’s very hard to get them to slow down
and to understand the significance that both false positives and
true positives have for the institution."
"We have a pretty good handle on the training side of things,"
he says. "The majority of false positives we have areI don’t
want to say unexplainablebut are typically the we-don’t-know-why
variety." Most are due to carelessness or just random error, Hastings
The experience factor
Nurses at St. Luke’s Hospital in Cedar Rapids, Iowa, have official
guidelines for drawing regular blood samples off IV lines, but nothing
specific for blood cultures, says laboratory supervisor Sue Smith,
MT (ASCP), SM. The institution is now revising its nursing procedures
to address that need.
"The predominant way we draw is directly into the bottle, but
if the nurses are drawing off an IV start it’s pretty hard to do
it that way," Smith says. "They usually have to attach and detach
a syringe, and once you put on a new needle and start transferring
the blood to other tubes, there’s a chance of contamination."
The contamination rate at St. Luke’s has been lowunder one
percentfor a year and a half, she says, and the hospital received
a letter from the College congratulating it on good practices for
drawing blood cultures. She credits yearly in-service training for
phlebotomists, preparation kits, and a constant stress on correct
procedures such as letting the disinfectant dry.
One training tool she has employed is a video prepared for the
laboratory staff. In it, a phlebotomist shows the correct way to
swab and draw, a microbiologist explains how bottles are monitored
and when the organisms start to grow, and Smith discusses the difference
between organisms in blood cultures that are true positives versus
coagulase-negative staph or skin flora. "Then we talk about the
medical costs associated with contaminated blood cultures, so they
really get the point of why it’s important," she says. After noticing
a little contamination in the neonatal intensive care unit, the
laboratory sent up the video and plans to distribute it to other
nursing departments as well.
Dr. Winn agrees that good sterile technique can avert most contamination,
but he also stresses the importance of experience and skill. In
a study he conducted in the 1980s, the contamination rate of a team
of infectious disease nurses was compared with that of phlebotomists,
in one group, and medical students, house staff, and other nurses
in another group. The ID nurses always had a rate under one percent,
he says. "So it was clearly expertise, consciousness, and willingness
to be compulsive about following all the steps that made the difference,"
Dr. Winn says. The contamination rate of phlebotomists was between
that of ID nurses and the other group.
Vetter’s laboratory at the Mayo Clinic, which collects some 40,000
blood cultures annually, already made the switch to tincture of
iodine a few years ago, encouraged by results of earlier CAP Q-Probes
studies. "Based on data provided to CAP, it looked as though tincture
of iodine was superior to other disinfectants," she says. Also,
the skin contact time required for tincture of iodine is less than
for povidone-iodine. For busy phlebotomists, that’s an improvement,"
Contamination rates at the Mayo Clinic have improved in the last
few years. "I think because we’ve become more and more focused on
continuous improvement activities," Vetter says. In addition, the
two hospitals that are part of the Mayo Foundation in Rochester
have recently focused on collection of blood cultures from different
vascular access devices. "We realized we were seeing an increasing
number of patients with these," she says.
Many laboratories report they keep close track of which phlebotomist
drew a particular contaminated culture and make an effort to correct
individual technique. The best performers in the Q-Tracks annual
report often said that tracking rates by individual accounts for
their low overall rate.
"If we get a false positive, as determined by our pathologist,
the phlebotomist gets a small note, saying, ’You had a false positive,’"
says Hastings, and is asked to think how the collection was performed
and if there was anything unusual about it. "After you get three
[false positives], then our professional development specialist
in charge of education, training, and coordination will require
direct observation of your techniqueusually several collections."
Feedback may be a useful check on contamination, according to
research. A 1997 study conducted at a tertiary-care teaching hospital
in Calgary compared blood culture contamination rates of phlebotomists
in a pre-feedback year to a post-feedback year and found they dropped
from 2.65 to 1.4 percent (Gibb AP, Hill B, Chorel B, Brant R. Arch
Pathol Lab Med. 1997;121:503-507). Although there was a rise
in the total number of positive cultures regarded as significant,
the number of significant coagulase-negative staph actually fell.
Hojabr Majlessi, MD, director of laboratories at Kessler Memorial
Hospital, Hammonton, NJ, says all contaminated cases are reviewed
thoroughly and "the cause and nature of the contamination are discussed
with the responsible individuals and shared with the rest of the
employees." An investigation of the cause of any deficiency, as
well as continuing education and practice updates, is a key factor
behind Kessler Memorial’s successful laboratory performance, he
But the Mayo Foundation, which has 250 phlebotomists, believes
associating contamination with individual phlebotomists may not
be useful. "At present, we do not track contamination rates by phlebotomist,"
says Vetter. "We do know that the more highly skilled phlebotomists
probably draw the very difficult patients, who are easier to contaminate.
We don’t want phlebotomists to shy away from doing difficult draws."
In planning training for phlebotomists, her laboratory tries to
stress visual demonstrations. "It’s hard to envision what you are
trying to remove from someone’s arm when you can’t see it," Vetter
notes. "The arm looks clean. So we show phlebotomists photographs
of actual skin cultures taken before and after prepping the venipuncture
site, so they can see the bacteria present. Seeing the visual makes
more of an impression."
Rewards of reduction
More than 85 percent of the blood cultures collected at the Mayo
Clinic in Rochester are drawn by dedicated phlebotomy teams. In
some units, specialized phlebotomy teams, called vascular access
teams, perform arterial blood draws, place IVs, and do point-of-care
testing in addition to phlebotomy. (All are part of the Department
of Laboratory Medicine and Pathology.) Vetter believes dedicated
teams help keep the contamination rate low, and a multi-institutional
study conducted by Dr. Schifman lends support to this idea.
"We found," says Dr. Schifman, "that the contamination rate was
lower by about four tenths of a percent when a trained phlebotomy
team was doing blood cultures (Schifman RB, Strand CL, Meier FA,
Howanitz PJ. Arch Pathol Lab Med. 1998;122:216-221). That
doesn’t sound high, but when you look at each contamination costing
$4,000, using round figures, the cost of blood cultures to the total
health care system would be reduced by $20 eachwhich certainly
justifies hiring phlebotomists to perform them."
Some clinical research has addressed the issue of false positives
from another direction.
"It’s clear from the data that extra dollars are associated with
contaminated blood cultures, and it’s not easy to rapidly separate
false from true positives," says Dr. David Bates, a co-author of
the 1991 JAMA study of costs and chief of the division of
general medicine at Brigham & Women’s Hospital, Boston.
One of his current interests is developing clinical prediction
rules to help physicians assess the probability that a positive
culture represents a true positive. The key factors include the
number of cultures that are positive for the specific isolate, the
type of isolate, whether the result is gram positive or gram negative,
the site of the body, and whether another positive culture results
from another site with the same organism.
It is impossible to eliminate all contaminated blood cultures,
Dr. Schifman says. Mock venipuncture studies on healthy, normal
subjects using a very sensitive blood culture technique found a
small number of positive cultures, usually less than one percent,
with coagulase-negative staph even though the person had no clinical
symptoms (Zierdt CH. J Clin Microbiol. 1983; 17:628-630).
"So it could be that some of these episodes we’re calling contaminants
are just transient bacteremias," perhaps caused by something as
innocuous as a cut on a finger.
"There’s nothing you can do about that no matter how carefully
you prep the skin or process the specimen in the lab," he says,
noting that these cases are technically true positives, not false
positives. "So I think labs that report the very lowest blood culture
contamination rates, one percent or lower, may be as low as you
can reasonably expect to get, because some may be unpreventable."
Eliminating preventable contamination will pay off in several
ways, he adds. "If you can maintain the same level of sensitivity
of blood cultures, at the same time reducing the contamination rate,
you’ll be much more cost-effective," Dr. Schifman maintains. In
addition, "One of the most important quality indicators you can
use in microbiology on a systemwide basis is the blood culture contamination
The College can take pride in using Q-Tracks to probe the factors
that influence and can reduce contamination, Dr. Valenstein says.
"Here’s a quality measure that can be easily tracked which is clearly
associated with both cost and outcome. If you set out today to do
something in microbiology that you could be proud of when you retire,
reducing contamination rates would be a good place to start."
Anne Paxton is a freelance writer in Seattle.