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Antibiotics, Bacteria and (usually not) Viruses



What are antibiotics?

Antibiotics are medicines that help your body fight bacteria and viruses, either by directly killing the offending bugs or by weakening them so that your own immune system can fight and kill them more easily. The vast majority of antibiotics are bacteria fighters; although there are millions of viruses, we only have antibiotics for half-a-dozen or so of them. Bacteria, on the other hand, are more complex (while viruses must "live" in a "host" (us), bacteria can live independently) and so are easier to kill.

(A note for the purists out there: strictly speaking, an "antibiotic" is a bacteria-fighting medicine that is derived from a biological source (plant, mold, or other bacteria). Since most people use the term "antibiotic" for any anti-infection medicine, I am doing the same here.)

Antibiotic Resistance

Bacteria (and viruses) aren't particularly intelligent. However, it is possible -- and unfortunately all too common -- for bacteria and some viruses to "learn" how to survive even with antibiotics around.

There are several ways that bacteria can become resistant. All of them involve changes in the bacteria's genes.

Human and animal viruses can also develop resistance to antiviral antibiotics, usually through mutation. This isn't a big issue, since there aren't a lot of antiviral antibiotics. However, antiviral resistance has become a major problem in HIV (AIDS) therapy, where the virus rapidly becomes resistant to the first-line antivirals such as AZT. Resistance develops particularly fast in patients who do not take their medicines properly, and in those whose immune systems can't help clean up after the antibiotics. This is one reason why tuberculosis (which is caused by a bacteria that multiplies very slowly and that is specifcally fought by the part of the immune system that HIV disables) has resurged since the appearance of AIDS.

Kinds of Antibiotics

There are now so many different antibiotics on the market that it's hard for us to keep track of them all. Personally, I almost always look up the dose of an antibiotic when I prescribe it, just to make sure that I'm giving the right medicine in the right dose. I also tend to stick to a few antibiotics in my practice, so that I can stay familiar with their effects and side-effects; most pediatricians I know do the same.

Penicillins and Cephalosporins

In the early 20th century, Alexander Fleming discovered that a mold called Penicillium (the cells are pencil-shaped when you look at them under a microscope) produces chemicals which kills most of the bacteria nearby. (The mold is green when it grows in large amounts, and is often found on bread. This, however, does not mean that eating moldy bread will cure your ear ache -- or anything else. Molds produce other things, too...) He was able to isolate these chemicals, which are now known as "penicillins". Sometime later, another mold was found which produced a bacteria-killing chemical, and this chemical's molecule was found to be very similar to the penicillin molecule; this chemical and its cousins were called "cephalosporins" after the mold it came from. The majority of antibiotics are either penicillins or cephalosporins; chemical changes have been made to the molecules over the years to improve their bacteria-fighting abilities and to help them overcome breakdown and "immunity" of resistant bacteria.

Most bacterial cells have double layers on their outside. The outermost layer -- the "cell wall" -- is similar to the outer layer of plant cells, but is missing in human and animal cells. This wall must grow along with the cell, or the growing cell will eventually become too big for the wall and burst and die. Penicillins and cephalosporins kill bacteria by messing up the wall-building system. Since we don't have cell walls, and plants have a different wall-building system, neither we, nor animals, nor plants are affected by the medicine.

There are a very few bacteria that don't have cell walls, either. These bugs are immune to penicillins and cephalosporins for the same reasons we are. Most bacteria do have cell walls, but many have changed their wall-building systems so that penicillins can't interfere, or have come up with ways to break down the medicines before the medicines can work. When we first started using penicillin in the 40's and 50's, most bacteria could be killed by plain penicillin. Now, because we have used penicillins and cephalosporins so often (and, in many cases, when we really shouldn't have), there are many bacteria that can't be killed any more by plain penicillin or even by the "super-penicillins" and "super-cephalosporins".

Penicillins and cephalosporins usually don't cause many problems for a patient. Like all antibiotics, they can cause mild side effects like diarrhea. Less common side effects include rashes (which may or may not imply a true allergy) and hives (which usually means you're allergic to the medicine). The rarest -- and scariest -- side effect is "anaphylactic" allergy, in which your airway swells up when you take a dose of the medicine, sometimes to the point where you can't breathe. Although the reaction can be treated if you are close to help, the safest thing if you are that allergic to the medicine is never to take it at all. (In cases where you have an anaphylactic allergy to penicillin or cephalosporins and must have it to treat an infection, doctors can "desensitize" you temporarily, using very small doses that are given frequently and in increasing amounts. That is almost always done in a hospital.)

Macrolides (Erythromycin and its Relatives)

Erythromycin is another antibacterial produced by a mold. There are a couple of new relatives of erythromycin (azithromycin and clarithromycin) that work the same way, but kill more bugs and have slightly fewer side effects. The erythromycin-like antibiotics are also known as macrolides.

Erythromycin works by blocking the bacterial cell's machinery for making new proteins. Since proteins both make up much of the cell's structure and make the enzymes that direct all the cell's chemical reactions, blocking protein manufacturing makes the cell unable to function. Erythromycin in low doses will stop bacteria from growing and multiplying, but you need a higher concentration to kill the bacteria. However, if you can stop growth until your immune system kicks in, that will help you get rid of the infection.

Since all protein making is affected, erythromycin can slow down or kill any bacteria, even those without cell walls. Because of this, we use the erythromycins for several diseases, including bacterial bronchitis, chlamydia, and whooping cough, that penicillins and cephalosporins can't touch.

Erythromycin and its cousins don't have anything like the allergy problems we see with the penicillins and cephalosporins, although there are rare people who have reactions to it. The biggest problem with these medicines is that they can irritate the stomach. I have seen one patient who ended up with bleeding stomach ulcers after taking erythromycin; this irritation seems to happen most often when someone tries to take the medicine on an empty stomach. Always take erythromycin with food or milk. (The same goes for clarithromycin. Azithromycin doesn't irritate the stomach nearly as much as the others.) Another problem with erythromycin -- but not with azithromycin -- is that it may cause enlargement of the pylorus, the muscle that serves as the valve at the outlet of the stomach -- in infants. This condition is known as pyloric stenosis, and is a surgical emergency if it occurs since nothing can leave the stomach properly. In the past we treated infants with erythromycin if they developed whooping cough. We now use azithromycin, which works just as well as erythromycin but doesn't affect the pylorus (and needs to be given for only five days; you need 14 days of erythromycin for complete treatment of whooping cough).

Sulfas

The sulfas (more properly "sulfanilamides" or "sulfonamides") were the first antibiotics to be developed; they are actually completely man-made. They interfere with certain "manufacturing" systems in the bacterial cell, including ones that bacteria use to produce new DNA for new bacteria. Sulfas can stop bacteria from growing, but they cannot actually kill the bacteria.

When they were first used, sulfas worked against many kinds of bacteria. Unfortunately, as with penicillin, the more we used the sulfas the more bacteria became resistant to it. Sulfas also have a tendency to produce allergic reactions -- different than those we see with the penicillins, for the most part, but including some that are rare but life-threatening. Because of this we don't use sulfas nearly as much we used to, and most often when we use sulfas it's in combination with another drug which attacks a different part of the bacteria (an attack on two fronts is usually better than an attack on one). The drugs we usually combine with sulfas are either erythromycin or "trimethoprim" (see below); these combinations usually can kill bacteria rather than just slowing them down. One frequent use of "plain" sulfas is in antibiotic eyedrops used for conjunctivitis ("pink eye").

Trimethoprim-Sulfamethoxazole

Trimethoprim (TMP) is another man-made antibiotic. Like the sulfas, trimethoprim blocks an important step in the bacteria's system for making new DNA -- but it's a different step. By itself, TMP can kill bacteria, but very slowly. Usually, though, we use TMP in combination with sulfamethoxazole (SMX), and the combination of TMP and a sulfa kills bugs better. In fact, bacteria that are partly resistant to either TMP or SMX can still be killed by the combination of the two. The side effects of the combination are the same as those of the two separate components.

Other Antibacterials

Nitrofurantoin

Nitrofurantoin is another synthetic antibiotic, used mainly for urinary tract infections. (Since it is excreted in the urine, it concentrates in the bladder very nicely.) Nitrofurantoin stops bacteria from growing, and can kill bacteria with a high enough level, by blocking the bacteria's ability to use energy it makes by "digesting" nutrients like sugar, and by blocking other chemical reactions that use the same system. It is not usually used for infections other than UTIs, and there are several side effects (ranging from stomach upset to (very rarely) malfunctioning nerves) which limit its use.

Aminoglycosides

The aminoglycosides are drugs which stop bacteria from making proteins; they work by attaching permanently to the protein machinery. Since they attach permanently, the bacterial cell will die if it gets enough of the drug. They can be used by themselves, or along with penicillins or cephalosporins to give a two-pronged attack on the bacteria.

Aminoglycosides work quite well, but bacteria can become resistant to them. The drawbacks are large, though. Since aminoglycosides are broken down easily in the stomach, they can't be given by mouth and must be injected or given IV (although we can use them as eyedrops for "pink eye"). When injected, their side effects include possible damage (temporary or permanent) to the ears and to the kidneys; this can be minimized by checking the amount of the drug in the blood and adjusting the dose so that there is enough drug to kill bacteria but not too much of it. Generally, aminoglycosides are given for short time periods, and in the hospital where we can check both the drug levels and the bacteria's sensitivity easily.

Quinolones

The quinolones, of which the best known is ciprofloxacin (Cipro®:), interfere with an enzyme called DNA gyrase that is essential for duplication of bacterial DNA. (Bacteria have only one long chromosome (DNA molecule); the chromosome gets twisted during replication, like a telephone cord, and, again like the telephone cord, the chromosome can become so twisted that nothing more can be done with it. DNA gyrase is the "untwisting" enzyme.) This interference is completely different from the interference of other antibiotics with bacterial "machinery", and so bacteria that are resistant to other antibiotics may be sensitive to the quinolones.

However, bacteria can develop resistance to the quinolones, too. Also, researchers have noticed that young animals given quinolones can have damage to their cartilage (the hard but slippery material that connects some bones and covers the slding surfaces of joints). In the past we have avoided using quinilones in children because of this finding, but we sometimes have to give some children quinolones when there is no alternative antibiotic available.

Polymyxin B

Polymyxin B is an antibacterial that is produced by another bacteria. (We usually take our antibiotics wherever we can find them...) It kills bacteria by damaging the cell wall chemically -- just the way soap does. It can't be taken internally, but it's very useful for skin infections (it's part of "Polysporin") and for conjunctivitis ("pink eye").

Tetracyclines

Tetracyclines are yet another family of antibiotics oringinally found in bacteria. They also block the protein-making machinery of certain bacteria. One of the tetracyclines, doxycycline, is often used to treat certain sexually transmitted diseases (such as chlamydia and gonorrhea) in older patients. One known side effect of the tetracyclines is that they affect development of bone and of tooth enamel in young children, and because of this we do not usually give tetracyclines to children under age 8 years. However, tetracycline may be the best antibiotic for some life-threatening infections, such as cholera and anthrax, and in such cases we may use tetracycline to treat a young child (tetracycline often leaves a permanent brown stain on developing teeth, but that's better than death...).

Antifungals

Some microorganisms, known as fungi (fungus in the singular), are cells that are biologically more similar to animal cells than to bacteria. Since many of the antibacterial antibiotics take advantage of the difference between bacterial cells and animal cells, the fungi's similarlity to animal cells makes them immune to the antibacterial antibiotics. However, there are antibiotics available for fungi such as Candida. These include nystatin, the azoles (including fluconazole, ketoconazole, and similar antibiotics), and amphotericin B. These work by disrupting the fungal cells' machinery. Some of these antibiotics may be applied to the skin or taken by mouth, while others must be given IV.

Antivirals

Since viruses can't live outside the person or animal they infect, they are much harder to kill off. Our immune system can find and kill many of the viruses that attack us, but sometimes a virus can multiply and overwhelm the immune system before the immune system "comes up to full speed". We immunize or vaccinate people against diseases -- mostly viral, but some bacterial -- so that their immune systems do have that head start. That seems to be the most succesful way to kill viruses permanently. An example is smallpox, which has been eradicated due mainly to the use of vaccines against it -- without which the virus killed thousands, if not millions, in epidemics. Some viruses, such as HIV (which specifically attacks the immune system), are very hard to become immune to, but a great deal of research is being aimed at producing a working vaccine for those diseases.

Unfortunately, since viruses are completely dormant outside a "host" (an infected human or animal), they can't be attacked biologically unless they infect someone. The immune system can't go after the virus unless it's in the body, and all of the antiviral medicines we have work only when the virus is trying to reproduce in the body. We can destroy viruses in the environment if we know they are there (an example is using household bleach to kill HIV that might be on equipment contaminated with body fluids -- but bleach won't kill HIV in the body, even if we could get it into the body safely). Once the virus is in the body, however, all we can do is let the immune system do its work, and in very rare cases (perhaps half-a-dozen viruses at most) give drugs that slow down the infection so that the body can clear it out more easily.

Acyclovir

One often-used antiviral medicine is acyclovir; ganciclovir and valciclovir are similar to acyclovir. These medicines slow down infections with viruses of a certain family, which include both varicella (chickenpox and shingles) and the herpes viruses. Acyclovir slows down the virus' multiplication and therefore slows down the infection. The problem is that the varicella and herpes viruses are never actually eradicated -- they stay in the body forever, and "reactivate" later (sometimes years later). The recurrent sores of herpes, and the appearance of shingles years after you have chickenpox, are examples of reactivation, and although acyclovir can help you get over the reactivation infection, it can't actually get rid of the viruses.

AZT and other Reverse-Transcriptase Inhibitors

Another very well-known antiviral is triazidothymidine, better known as zidovudine or AZT. This drug, and others like it, are used to inhibit an enzyme called "reverse transcriptase" which HIV uses to "copy" its own genes into the genes of the cells it infects. Once the HIV genes are copied, the infected cell and all its offspring can produce more HIV. (This is why an AIDS patient cannot actually get rid of all of the virus once infected: the virus may lie dormant as inactive genes for months or years, and the anti-AIDS drugs cannot get to the gene copies.) Like bacteria, viruses can mutate, changing their structure so that drugs that used to work no longer help; this explains why AZT and other reverse-transcriptase inhibitors eventually lose their effectiveness in many patients.

Protease Inhibitors

A newer class of anti-AIDS drugs, the protease inhibitors, work by blocking a different HIV enzyme. HIV uses reverse transcriptase to copy its genes into the cell it's infecting; it uses "protease" (an enzyme that breaks down protein) to get into the cell in the first place. Many people with AIDS have been able to eliminate the virus from their bloodstream -- or almost eliminate it -- by using both reverse-transcriptase inhibitors and protease inhibitors at the same time. However, since the virus has copied itself into cells where neither kind of drug can attack it, a patient must keep taking the drugs forever to keep the virus from reactivating.

Note, by the way, that the antiviral drugs, even more than the antibacterials, are tailored to the kind of viruses they are intended to attack. AZT won't do anything for a cold, and neither will acyclovir. In fact, there are -- so far -- no antivirals that will do anything for the common cold. And, since there are many different viruses in several different families that can cause colds, we are not likely to have any anti-common-cold drugs in the near future.

The Common Cold

Since most colds are due to viruses attacking the mucus membranes of the nose and throat, the only way to get over the cold is to wait for your immune system to get rid of the virus, and for your body to produce a new, virus-free mucus membrane surface. Resurfacing the mucus membranes takes 3-4 days (you automatically resurface the membranes every 3-4 days), but getting rid of the virus takes a week or two, and until the virus is gone the new membranes will keep getting infected. Since we have no medicines that will slow down the cold viruses, we can't do anything to speed up this process. Antibacterial antibiotics will do nothing to help get rid of the virus, and giving antibacterial antibiotics when there is a viral cold will likely do nothing except help the bacteria in the nose and throat become resistant -- which makes the next bacterial infection much harder to treat. I never give antibiotics to someone who has only a cold, unless there seems to me to be a very good chance that he or she may develop a bacterial infection on top of the cold -- or unless there is clearly a bacterial infection already.

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PLEASE NOTE: As with all of this Web site, I try to give general answers to common questions my patients and their parents ask me in my (real) office. If you have specific questions about your child you must ask your child's regular doctor. No doctor can give completely accurate advice about a particular child without knowing and examining that child. I will be happy to try and answer general questions about children's health, but unless your child is a regular patient of mine I cannot give you specific advice.

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Copyright © 1997, 1998, 1999, 2000, 2004, 2005, 2007, 2008, 2011, 2014 Vinay N. Reddy, M.D. All rights reserved.
Written 02/24/97; major revision 09/16/04, major revision 04/28/05, major revision 05/02/2007; last revised 09/10/14 counter