College of American Pathologists
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Nipping contamination in the blood

May 2000
Anne Paxton

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 manufacturer.

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 success.

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 costs—costs 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. August 1999;107:119-125).

Limited information
"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 the bottle."

Most systems, though, require the sample to be inoculated from a syringe into the bottle—creating 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 variable—dedicated teams—was 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 percent—a 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. Valenstein adds.

The role of controls
Some of the Q-Tracks participants express concern about their own contamination rates.

"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 blood—the 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 problem—but 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 are—I don’t want to say unexplainable—but are typically the we-don’t-know-why variety." Most are due to carelessness or just random error, Hastings says.

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 low—under one percent—for 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.

Tracking results
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," Vetter says.

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 technique—usually 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 believes.

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 each—which 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 rate."

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.