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SAL KHAN: We're here at Stanford Medical School with fourth year medical student Morgan Theis and Dr. Charles Prober. MORGAN THEIS: OK, Dr. Prober, what are we going to talk about today? DR. CHARLES PROBER: So Morgan, I thought we'd talk about bacterial meningitis in children. MORGAN THEIS: OK. DR. CHARLES PROBER: And what I'd like to do, in reflecting on bacterial meningitis is go back to some lessons that we learned in "The Prudent Prescribing of Antibiotics," a prior video. And one of the things that was mentioned as a general principle in that particular video was trying to understand where the site of infection is in a child, in order to pick the right antibiotics and the right management. So in this case, because I'm referring to bacterial meningitis, a question might be, what would make you think that a child has bacterial meningitis? That is, what are the signs and symptoms of bacterial meningitis? MORGAN THEIS: So this is kind of thinking about the site, knowing that there's an infection in the cerebrospinal fluid or fluid around the brain and spinal cord. You have to look for that in a variety of ways, as a doctor. DR. CHARLES PROBER: Exactly. And one of the things which will make a physician suspicious that there may be an infection in the cerebrospinal fluid or that is, in the central nervous system is, a child may not be behaving normally. That is, they'll have an altered state of consciousness. They'll be very, very sleepy. Or they'll be very irritable. MORGAN THEIS: OK, so I guess I would say, the signs here-- irritable children. And what was the other one you said? DR. CHARLES PROBER: And I mentioned they might be very sleepy. Some people might use the word lethargic, as an altered state of consciousness. And at the extreme of that, the child would be in a coma. But that would be more advanced in the infection. And then, the child would almost invariably have a fever associated with it, with this illness. And on examination, when the physician examines the child, they may detect what are called meningeal signs. And those meningeal signs include a stiff neck, especially if the child is over one or two years of age. MORGAN THEIS: And how can you tell if someone has a stiff neck? DR. CHARLES PROBER: So what's the physician will often do is hold the child behind the head and try to flex the head on the next, try to flex the neck. And stiff would be literally that. The child's neck would not bend, when the head is elevated from the bed. MORGAN THEIS: Oh, wow. So it just stays really linear. You can't really curve it well. DR. CHARLES PROBER: Exactly. The other meningeal signs that may be present in addition to the stiff neck are the child may have some seizures, abnormal movements. The child might also assume an abnormal posture, stiffening of the body, so not just the next being stiff but the rest of the body being stiff as well. And on examination of the neurologic system, the nervous system, the child may have what are referred to as focal. signs. That is asymmetry between the two sides of the body. MORGAN THEIS: Oh, and what kind of things would you see that were asymmetrical? DR. CHARLES PROBER: It could be that one side of the body is weaker than the other. It could be that one side of the body has different reflexes than the other side of the body. So these are all signs and symptoms that may be associated with bacterial meningitis, that would make the physician suspicious of the diagnosis of meningitis. MORGAN THEIS: OK. So we talked about some of the things you look for as a doctor. Now, just going back a minute, you said, we're talking about bacterial meningitis. Does that assume that there are other types of meningitis that we're not addressing in this lecture? DR. CHARLES PROBER: That's a very important point. So I am focusing on bacterial meningitis. There are other types of organisms, that is, non-bacteria that can cause meningitis. And the most prominent of those other organisms are viruses. So you can have a viral meningitis, sometimes referred to as aseptic meningitis. And that, in fact, is more common than bacterial meningitis. So it's very important to consider. There are also some parasites that can cause meningitis. And there are some fungi that can cause meningitis. The fungi and parasites are uncommon in the general population, but they may occur in patients who have an abnormal immune system. Viral meningitis, on the other hand, is really, as I mentioned, quite common. But for today, I'm focusing on bacterial meningitis. So you suspect that the infection may be present, based upon those signs and symptoms that we've spoken about. And then to prove or determine whether or not meningitis is present, cerebral spinal fluid has to be examined. And cerebral spinal fluid, which is typically abbreviated CSF. MORGAN THEIS: CSF is cerebrospinal fluid. We already got that but OK. Sorry. DR. CHARLES PROBER: And that's obtained by doing something called a lumbar puncture, by putting a needle in the back to obtain fluid. MORGAN THEIS: OK. Is that also what a spinal tap is? DR. CHARLES PROBER: And that's also called a spinal tap, exactly, a Lumbar puncture or a spinal tap. When that's obtained using a needle into the lumber area, the fluid is then sent to the laboratory, who will examine the fluid in different ways. One is to look under the microscope and determine if there are an abnormal number of white blood cells present. MORGAN THEIS: So abnormal meaning high or low? DR. CHARLES PROBER: Meaning just high actually. MORGAN THEIS: OK. DR. CHARLES PROBER: The normal number of white blood cells in the CSF is 0. So high is something greater than 0. MORGAN THEIS: OK. DR. CHARLES PROBER: And with bacterial meningitis, it tends to be really quite high, 1,000 or 2,000 or more than that. With viral meningitis, it may not be quite as high. MORGAN THEIS: And that's per some unit of volume of this fluid. DR. CHARLES PROBER: Exactly. A glucose concentration is also measured when the fluid is sent to the lab. And with bacterial meningitis, the glucose in the spinal fluid tends to be low, less than 40. MORGAN THEIS: Now, why would it be low? DR. CHARLES PROBER: It's low because with meningitis, you have an abnormal penetrability or lack of penetrability of the meninges, which are the coverings of the brain, reducing the amount of glucose that's transported into the spinal fluid. And then, most importantly, the fluid is examined with something called a Gram stain, a special kind of stain. It's Gram with a capital G, named after Dr. Gram. And a Gram stain can determine whether or not there are bacteria present. MORGAN THEIS: OK. So you're actually staining the bacteria. DR. CHARLES PROBER: Exactly. And if there are sufficient bacteria present, the Gram stain will reveal those bacteria. And so with bacterial meningitis, the second prudent principle is to know the usual pathogens. So if a spinal fluid is obtained, there are lots of white cells, the glucose is low. Even with a negative Gram stain, one can guess the usual pathogens, because the list is short in normal children. And those bacteria, the short list includes a bacteria called Haemophilus influenzae, type B. MORGAN THEIS: Is there an A on that? I mean, an E at the end? DR. CHARLES PROBER: There is an E on the end. A second bacteria is the new pnuemococcus. MORGAN THEIS: Now, that's funny. It sounds like it causes pneumonia. DR. CHARLES PROBER: And it does indeed cause pneumonia as well. But it also causes bacterial meningitis. And a third bacteria is called meningicoccus. And those are the prominent bacteria in normal children with bacterial meningitis. The reason though, we're not seen as much bacterial meningitis in 2011 as we were seeing 10 and 20 years ago is, we now have vaccination against each of those three different pathogens. MORGAN THEIS: All of them? DR. CHARLES PROBER: We do. We vaccinate against Haemophilus influenzae, type B, starting at two months of age. And by the time the child is about a year and a half, they're completely protected against that particular bacteria. The pneumococcus, we also vaccinate against. And it's very successful. The vaccine is very successful at reducing the frequency of pneumococcal meningitis. It also starts at two months of age. And meningicoccus, the vaccine is relatively new and is used in children who are a bit older. They're over two years of age, under special circumstances. So that means that we still can see, and do see, cases of meningicoccal meningitis, because it occurs in children under two years of age. MORGAN THEIS: I see. DR. CHARLES PROBER: But those are the usual pathogens. And when you go to other parts of the world who don't use vaccines, those are the pathogens that will be prominent in causing bacterial meningitis. And knowing those pathogens, we go to the third principle of antibiotic prescribing, which is knowing what antibiotics typically kill those bacteria. MORGAN THEIS: OK. So what should I call that category, like matching? DR. CHARLES PROBER: That's called the pathogen sensitivity, knowing what antibiotics work against the likely bug, so pathogen sensitivity. MORGAN THEIS: Pathogen sensitivity, OK, great. DR. CHARLES PROBER: Sensitivity to the antibiotics. MORGAN THEIS: And I think you were mentioning in you last lecture, that varies by the location in the body and the location in the world that you're using the antibiotic. Is that right? DR. CHARLES PROBER: It varies according to the location in the world. MORGAN THEIS: But not in the body. DR. CHARLES PROBER: Not in what part of the body they're in. And fortunately, for the treatment of bacterial meningitis, to cover all three of the bacteria that are on the list of pathogens, two antibiotics cover all three of them. And I'll just mention their names as I end this. One antibiotic is cefotaxime. And a reasonable facsimile of cefotaxime is ceftriaxone. They're very similar antibiotics. So we give one or the other of those two antibiotics. And because some of the new pneumococci are resistant to so-called beta lactam drugs, penicillin and cephalosporins, vancomycin also is used to initiate therapy for suspected bacterial meningitis. MORGAN THEIS: OK. So we use vancomycin if we think you have sort of resistant bugs, bugs that are resistant to the first two antibiotics you mentioned. DR. CHARLES PROBER: Exactly. MORGAN THEIS: And there's some kind of lab tests you might be able to do to find that out. DR. CHARLES PROBER: Exactly. So those are the principles of antibiotic prescribing, in terms of the diagnosis of bacterial meningitis-- knowing the site of infection-- that is, the spinal fluid-- knowing how to diagnose it, what the pathogens, and what antibiotics wold work against those pathogens at that site of infection. MORGAN THEIS: OK. And just my last question is, just because we've learned a lot about how there is a tight barrier between the blood and the cerebrospinal fluid, are these antibiotics that you've listed here-- are those able to sort of penetrate through that barrier and get into the cerebrospinal fluid? DR. CHARLES PROBER: An extraordinarily important question, which got to another principle of antibiotics, which is, you have to make sure they can be delivered to the suspected site of infection. And for those particular antibiotics, the answer is, yes. MORGAN THEIS: OK. Thank you so much.