Antibiotic Toxicities Agents

Aminoglycosides. These are used for gram-negative infections.
Most of them have some gram-positive activity, but you would never use it for a gram-positive infection unless you're using it with other drugs. The most common that we still use in kids is gentamicin, also tobramycin, not much with kanamycin, even less with streptomycin. Pulmonologist are using inhaled tobra for some CS patients. The main type of toxicities that we see from aminoglycosides are ototoxicity and nephrotoxicity.
There are two kinds of toxicity to the ear. The direct ototoxicity is actually destruction of the cochlear hair cells and it produces a
high-frequency, irreversible hearing loss. This can occur early. It can occur late. It can occur after you've gone through you're
therapy. It's most commonly seen with amikacin and kanamycin. The vestibular dysfunction, which causes damage to the vestibular hair cells is most commonly seen with gentamicin and streptomycin. These can occur at any time during therapy.
Risk factors. The very young and the very old. Those may be some people to worry about. Ototoxicity is usually directly related to the peak level that you get. So, if you give 10 x the dose of
aminoglycoside, that's the kind of patient that I would worry about
their ears. If something could happen to their ears. Pre-existing renal disease, obviously if you are not getting rid of it and you're having high peaks for whatever reason you're not following them and you don't check peaks and troughs, there is a data suggesting that maybe we don't need to do that all the time anymore and maybe it doesn't really suggest efficiency of therapy. Let's say your patient had renal disease that you didn't pay attention, so you're getting too much of it producing high peaks. If you use other agents which also have Ototoxic potential in combination vancomycin and
other loop diuretics. Prior exposure to aminoglycosides or loud sound. Again, the very young, the very old. If you have a hereditary tendency for any ear problems you need to be concerned with
aminoglycosides and the exact amount of ototoxicity we always think is rare in infants but they're hard to evaluate, especially the premature infants. All premature infants should get their hearing screened usually before they leave the premature nursery and I talk about the micro-preemies. The 500 to 1000 gm infants, but if they have hearing loss was it to the multiple courses of aminoglycosides they got or the fact that they had intraventricular hemorrhage or a
brain abscess or was it the fact that they were exposed to multiple loud noises. So the exact mechanism is not well known.
Nephrotoxicity, I think of the patients who had high troughs. They're not clearing their aminoglycoside. They really need to be on it twice a day which is clearly just enough to get their peaks down but still
maintains a very high level which is hurting their kidneys as time
goes by. What we see is a gradual onset which could complete the kidney shut down. Usually we'll see elevations of BUN or creatine or hypertension and excessive urine protein. Risk for nephrotoxicity. Again, high doses or prolonged courses of therapy, especially for hemoglobin. Liver disease, concurrent use of other nephrotoxic medications, again, vancomycin, salt and water deprivation.
With each kind of drug we are going to talk about adverse effects and drug interactions. The interactions, mostly we worry about increased nephrotoxicity. Again, increased nephrotoxicity when you
use aminoglycosides in combination with all other potential
nephrotoxicity drugs. Cyclosporine, amphotericin B, some of the loop diuretics, indomethacin, most people don't realize that cephalothin is one of those. One of the interesting things aminoglycosides do or potentially potentiate is the respiratory suppression of nondepolarizing neuromuscular agents, but if you think about it too, in the old days before the cephalosporins when we used ampicillin and gentamicin exclusively when the newborn babies came in or you had the baby that presented with a little constipation, some cranial nerve findings, just kind of being floppy,
you put him on amp and gent and all of a sudden boom they got a lot worse, so it potentiates that neuromuscular blockade. I don't think anybody's going to use a lot of oral kanamycin, but oral
kanamycin and methotrexate can increase methotrexate toxicity.
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