Insurgents in the Bloodstream

By Captain Chas Henry, U.S. Marine Corps (Retired)

Emery's mother recalls that the hazard was not confined to her son's limbs.

"He ended up getting it in his stomach," says Connie Emery, "and they tried to close his stomach back up, but when they did, the stitches ended up pulling away because the infection was taking over."

An Army infectious disease physician says the germ has spread rapidly since the wars in Afghanistan and Iraq began. "Prior to the war, we were seeing one to two cases of acinetobacter infection per year," remembers Lieutenant Colonel Kimberly Moran, deputy director for tropical public health at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. "Now that's much different. We've had hundreds of positive cultures over the last four years."

And the toll has been serious, observes Army Colonel Glenn Wortmann, acting chief of infectious disease at Walter Reed Army Medical Center in Washington, D.C. "Of the infectious disease problems that have come out of the conflict," notes Dr. Wortmann, "it is the most important complication we've seen."

Most striking about the problem is that men and women wounded in combat have acquired the bacteria in the very hospitals where aggressive surgery has, in many cases, saved their lives. "The outbreak," acknowledges a Defense Department fact sheet, "appears to have started during the care of patients (both U.S. military and non-U.S.) in the combat support hospitals of Iraq and Afghanistan."

"They go to what's called 'far forward' surgical outfits where the main concern is keeping them alive," explains Dr. Rox Anderson of Harvard Medical School, "and in the process there's not a hundred percent of the [anti-contamination] controls. Despite a great effort by the military medical people, there's a high risk of infection anyway."

Once established at frontline surgical sites, the bacteria began "traveling with patients or on patients," says Dr. Moran, "from Iraq all the way back to Walter Reed, with stops along the way through the evacuation chain and getting into our hospitals." There, she adds, "it was spread from patient to patient through various means, just being on surfaces and having one person come in a room after another person has left."

Most evidence of the bacteria has been confirmed at military hospitals in Germany, the Washington, D.C. area, and Texas—though cases have also been confirmed on board the hospital ship USNS Comfort (T-AH-20) and at Tripler Army Medical Center in Hawaii. After Canadian soldiers injured in Afghanistan began testing positive for acinetobacter infection, public health officials began warning Canadian hospitals to take precautions against spread of the germs if they treated anyone who had been wounded overseas.

(As Proceedings went to press, the Baltimore Sun reported an outbreak of acinetobacter baumannii infections at the University of Maryland Medical Center.)

The persistence of the outbreak has pushed it to momentous proportions. "I believe this is the largest in-hospital acinetobacter outbreak in history," asserts Dr. Timothy Endy, a retired Army colonel now teaching infectious disease medicine at the State University of New York, Upstate Medical University. Endy battled the bacteria while attending to patients at Walter Reed.

Where Did it Come From?

Researchers say they don't know exactly how acinetobacter baumannii first made its way into frontline treatment facilities. Early suspicions pointed to the possibility that the germs, mixed with soil, were blown deep into penetrating wounds. Some physicians speculated that bacteria residing in the combat zone had settled onto the skin of service members—lying dormant until open wounds allowed the bugs to create havoc. Small-sample testing, however, has indicated little or no evidence of problem-causing acinetobacter in Iraqi soil. And the only Iraq or Afghanistan veterans so far showing signs of acinetobacter colonization on their skin are those who have spent time in casualty treatment centers. 

Moreover, say scientists, nothing in the character of the outbreak would indicate that it originated as a result of intentional biological attack.

The bug's dangerous effects were first noticed just weeks into the March 2003 assault on Iraq. During April of that year, then-Lieutenant Commander Kyle Petersen, a Navy physician treating battle casualties on board the Comfort, observed a number of not-easily-explained patient deaths. He contacted fellow infectious disease specialists via online message boards, describing his American and Iraqi patients' symptoms—and, when they were eventually available, their lab results. The interaction helped rapidly identify the problem and initiated testing of frontline medical facilities.

"There were bacteria," recalls Moran, "acinetobacter bacteria, on hospital surfaces like in operating rooms, on ventilator machines, or on light surfaces or environmental control units."

Putting Up a Heavy Resistance

At first glance, acinetobacter baumannii does not seem particularly fiendish. It is neither intensely virulent nor remarkably energetic. Its name, in fact, derives from the Greek word akinetos, meaning "unable to move." But, as hundreds of those wounded in combat have learned, it exhibits one particularly troubling genius. Noteworthy even among better-known, more-feared microorganisms, it is able to steal resistance capabilities from other bacteria with which it comes into contact.

"It's this smart," says Moran, "that it could put together this resistance island that makes it resistant to almost every antibiotic we have available."

Facing a bug able to counter many commonly used antibiotics, doctors and patients are sometimes forced to turn to increasingly toxic medications that might kill the bacteria but risk additional harm to a patient's health.

"We're having to dig old ones out of the closet," says Petersen, medications "that were not so good in the 1960s, and use those because they're the only effective treatment."

One such antibiotic is colistin. "It hadn't been used really since the 1970s, " says Walter Reed's Wortmann. "I had never used it—ever—until the last couple years. And the concern with colistin was that it would cause kidney damage or nerve damage."

In addition to agonizing over what treatment to use, physicians worry about when they should bring medications to bear. This is particularly difficult since tests to prove infection take days. So a doctor may have to wait up to 72 hours to learn if bacteria have colonized on a patient's skin or, more dangerously, insinuated themselves into a wound.

"Is my patient infected, or just colonized?" asks Petersen, recalling the dilemma faced when suspecting that acinetobacter is threatening a patient. "If [the person's skin] is colonized and I over-treat him, I could damage his kidneys. If he's infected, and I ignore that and say he's colonized, he could die."

"The infection, if it goes on," notes Anderson, "sometimes will lead to amputation, so these are tough choices."

Even when some degree of amputation is required to rid a patient of quickly spreading infection, military surgeons face the challenge of trying to remove only infected tissue—"to get rid of the devitalized tissue," explains Moran, "without taking too much in the way of good viable tissue and preserving limb length for a prosthetic."

Who's At Risk?

Defense Department records—provided in response to a December 2007 query from Proceedings —indicate that from March 2003 to March 2005 acinetobacter infections attacked more than 250 patients at U.S. military healthcare facilities. As of June 2006, the same documents say, seven deaths had been linked to acinetobacter-related complications. The records did not contain figures for the bacteria's impact during the remainder of 2006 and 2007. 

While the majority of those fighting acinetobacter infection in military hospitals have been deployed to Iraq or Afghanistan, up to a third have not—infants and the elderly among those apparently acquiring the bacteria in armed forces healthcare centers.

Those hit hardest are typically the weakest of the weak. In the case of men and women hurt on the battlefield, observes Anderson, those with "complex wounds, combination of burns, blast injury, and lacerations."

"A lot of patients are colonized with acinetobacter," adds Commander Eric Elster, a Navy surgeon involved in combat wound research, "but it's the patients that have additional injuries, they're very systemically ill, they have an associated arterial injury, an associated abdominal injury—those are the patients that run into trouble and become infected from a bug like acinetobacter."

Of the seven people the Defense Department acknowledges to have died because of acinetobacter-related complications, five were non-active duty patients being treated in the same hospital as infected service members—patients already weakened by such problems as organ failure, immune system deficiency, or multiple traumatic wounds.

There have, however, been frighteningly dissimilar cases. An apparently healthy nurse at the National Naval Medical Center in Bethesda, for instance, spent months near death after being exposed.

Good Antibiotics, Bad Antibiotics

Two key issues seem behind the persistence of the outbreak. A number of infectious disease specialists point to difficulties in completely ridding hospital environments of acinetobacter. Doing so, they say, requires more stringent cleaning than that typically sufficient to kill other bacteria. Additionally, several express concern that policies on antibiotic use differ at commands and hospitals along the casualty evacuation chain.

Sometimes trying to err on the side of caution, doctors on the frontline prescribe wide-spectrum antibiotics prior to determining if a patient is actually carrying acinetobacter. In the long term, this has created problems.

"I think antibiotic use is probably driving some of this," suggests Petersen of the Comfort, "because when you keep people on prolonged antibiotics unnecessarily, it lets them be colonized with worse and worse bacteria."

In 2006, doctors at Walter Reed began successfully curbing acinetobacter infections using an antibiotic called imipenem. Soon thereafter, Endy recalls, frontline surgeons began using imipenem as a prophylactic antibiotic—infusing it into injured service members even when it was not clear the bacteria had colonized on the patients' skin or invaded their wounds. The result, he says: "We started to see increasing resistance to this antibiotic, resulting in the use of the more toxic drug, colistin."

Wortmann at Walter Reed understands the urge of frontline providers to "break out the big guns" right away, particularly when they know their facilities are contaminated with acinetobacter. But he counsels caregivers to first use antibiotics targeted toward more common bacteria, treating for acinetobacter only when tests show a patient has been colonized or infected. "When you give an antibiotic," he says, "you'll kill most of the bacteria that's on that patient, but if a bacteria either is resistant to that antibiotic or is able to rapidly become resistant to that antibiotic, then it will grow because all the other bacteria have been killed off.

A Bacterial Long War?

Researchers in military laboratories and elsewhere are exploring better means of fighting acinetobacter. Some are examining possible uses of radiation. At Harvard, Anderson is experimenting with a dye "painted" onto open wounds then activated with light. "Even the worst strains that are resistant to multiple antibiotics," he says, "will succumb to the light-activated dye approach." 

Another idea: creating tests to more quickly determine or rule out infection. This would allow faster closing of non-infected wounds—reducing contamination risk. "But these technologies are not ready for prime time as of tomorrow," cautions Elster. "Clinical trials take a while. You're looking two or three years down the road." And that's if the ideas pan out.

In mid-2007, a group of military infectious disease physicians convened in San Antonio to discuss the outbreak. They plan to write a medical journal article including recommendations for dealing with the problem.

Policies on infection control and antibiotic use, meantime, remain essentially unchanged from those in place when the war began. "There are guidelines," says Wortmann, "and sort of loose oversight of the practicing patterns of the physicians, but there is no one person that says, 'Doctor Jones in Baghdad, you must do this.'"

Timothy Endy, the former Walter Reed physician, is among those who believe that, in some measure, there should be. He urges defense leaders to bring a more systematic approach to the fight—across military service lines and command structures—citing "lessons that should be learned from this outbreak but have not been implemented to my knowledge."

A key reform he feels necessary, and past due: creating the means for military services and the Department of Veterans Affairs to gather and share real-time information on antibiotic-resistant infections in medical centers.

He also recommends application of unified policies on infection control and prophylactic use of antibiotics—and advocates that the service's most senior medical officers, employing a more global view than physicians at single points along casualty evacuation routes, be afforded authority to order clinical practice guidelines for infection control.

Most important, he adds, in order for treatment rules to work more swiftly than fast-adapting bacteria, such guidelines must be "executed in the war theater without delay."

Endy also counsels that hospitals treating the combat wounded be afforded space and staff to keep acinetobacter-positive patients isolated from other patients, and that attention be paid to preventing warehoused medical equipment from becoming breeding grounds for contamination.

During 2004, the outbreak's worst point so far, some 30 percent of all patients returning from Iraq and Afghanistan tested positive for acinetobacter. Four years into the fight, up to 20 percent of those returning wounded still face biological onslaught by this bloodstream insurgent.

"That's what really held me back," says Marine Sergeant Emery. "That's why I was laid up in the hospital for so long."

Captain Henry was a Marine public affairs officer. He now covers defense, intelligence, and homeland security for Washington, D.C. television outlets ABC7 and NewsChannel 8.

Captain Henry was a Marine public affairs officer. He now covers defense, intelligence, and homeland security for Washington, D.C. television outlets ABC7 and NewsChannel 8.

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