Call them stealth bacteria.
For years, chronic ear infections have presented a puzzle. Even when children exhibited all the symptoms of infection, doctors often were unable to grow bacteria from their middle-ear fluids. Now, though, researchers in Pittsburgh have found genetic evidence of active bacteria in the ears of such children.
They suspect that the bacteria have learned to band together in a cooperative community called a biofilm, a sort of germ city that not only protects them from antibiotics but actually makes them much harder to detect than free-floating bugs. If the theory proves true, it has significant implications for the way doctors treat ear infections -- the No. 1 reason for pediatric visits. It could also help explain chronic infections in other parts of the body, such as the sinuses.
"It just changes your whole mental picture of what's happening in kids' ears," said Bill Costerton, a microbiologist who runs the Center for Biofilm Engineering in Bozeman, Mont.
While most children clear an infection after a course of antibiotics, in some children the infection becomes stubborn and persistent. Doctors try to treat such infections with long-term antibiotics or tubes that drain fluid from the middle ear. Clearing up chronic infections is important because they can lead to hearing loss and language-development problems.
In a report in the current issue of the Journal of the American Medical Association, the researchers offer a new explanation for why antibiotics often don't work. Because biofilms are a thousand times more antibiotic resistant than isolated bacteria, the most these drugs can do is keep infections at bay.
"The data are very clear," said J. Christopher Post, an otolaryngologist at Allegheny University of the Health Sciences Center for Genomic Sciences, who was involved in the study while at the University of Pittsburgh School of Medicine. "Prolonged antibiotic use is not effective in this disease, and it probably is contributing to the development of resistant bacterial organisms."
He's not talking about the 10-day courses of antibiotics that pediatricians typically prescribe for acute ear infections, but rather the months of drugs some children receive when they can't shake the infections. "You're not winning the war that way," he said.
Post and fellow researcher Garth Ehrlich, a molecular biologist, believe the key is disrupting the biofilm. Their research now focuses on, first, proving that biofilms exist in the middle ear and then figuring out how to break the bacteria apart genetically. Certain genes are turned on only when bacteria form biofilms. The trick will be figuring out which ones they are, then turning them off.
But some infectious disease experts are skeptical of Post and Ehrlich's theory, saying it is an inadequate explanation for why some ear fluids culture negative in laboratory testing. Other types of biofilms, those found on catheters, for example, readily produce culturable bacteria.
"This is incredibly speculative," said Sarah Long, chief of infectious disease at St. Christopher's Hospital for Children in Philadelphia.
Because doctors have often been unable to culture or grow bacteria from some middle-ear fluids, they have guessed that children's symptoms were a prolonged inflammatory response to a past infection. Long said the excess fluids in some children's ears are more likely the result of a viral infection or of malfunctioning Eustachian tubes, tiny tubes of the ear that normally drain fluid.
But Post and Ehrlich were able to detect messenger RNA of "Haemophilus influenzae," a common ear pathogen, in samples that cultured negative. Messenger RNA is a blueprint for a specific protein. It survives intact for no more than a few minutes, so its presence was proof of active bacteria, they said.
But if the bacteria were there, why weren't antibiotics killing them? And why didn't they grow in cultures?
A possible answer came to Ehrlich one night when he was avoiding writing a complicated grant application. As a distraction, he read an article in Science magazine about biofilms. Microbiologists long have recognized such bacterial colonies as a problem in engineering. Slimy biofilms gum up the works in nuclear cooling towers. They clog city water systems. They can infect catheters and artificial joints. There is no cure, save removal of the device. They also cling to dead bone and tissue, causing infections in weakened lungs and prostate glands. They cause bedsores. The plaque on your teeth is a biofilm.
Costerton, who coined the word "biofilm" 20 years ago, thinks VTC many scientists have long ignored its importance. They have studied bacteria as individuals swimming freely in petri dishes. In the real world, the vast majority of bacteria -- 99.9 percent is a "conservative" estimate, he says -- live in biofilms, where they behave in surprisingly complex ways.
They communicate chemically. They create channels so that fluids can reach their innermost members. And they find that in numbers, they are far stronger than they are alone.
Some researchers believe that bacteria within biofilms reproduce much more slowly and that that might keep them from growing quickly enough to show up in a standard culture.
Pub Date: 2/17/98