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Note: This section has health/medical information. It was not written by a health care professional, however, the author has an MS in biochemistry and has a good knowledge of drugs and how they work. The medical references are at the bottom of this page.
Children on chemotherapy take antibiotics two to three days each week to prevent pneumocystis pneumonia (PCP). They will probably continue to take the antibiotics six months to a year following cessation of chemotherapy. The prescription of preventative or prophylactic antibiotics is somewhat at the discretion of the oncologist. If the risks outweigh the benefits, the child will not be on the antibiotics. Also, some parts of the country are less prone to PCP, a fact which may weigh in the doctor's decision.
Children that are HIV positive or have AIDS also take these same antibiotics.
The antibiotic of choice for PCP prevention is a combination drug consisting of sulfamethoxazole and trimethoprim:
This combination drug is called "co-trimoxazole". It is sold under the brand names "Bactrim®" and "Septra®". Read your child's prescription label carefully and it should list the two above ingredients. It is supplied as a tablet or suspension to be administered orally as a preventative (if your child were to develop PCP, co-trimoxazole would be administered IV). Here are the doses:
- According to the CCG 1952 protocol, the dose is 5 mg/kg/day, divided into two doses a day. This translates to 114 mg per day for a 50 pound child, and 228 mg per day for a 100 pound child.
- Oral suspensions: carefully follow the doctor's directions.
- According to the manufacturer, the dose is 2 - 400 mg tablets twice a day for adult-sized people; children's doses calculated on a per weight value. (1 tab per 44 pounds, 1 1/2 per 66, 2 for 88.) (note: the manufacturers values do not correlate with the CCG 1952 study protocol numbers.)
- It can be purchased as 800 mg tablets, but these are HUGE, hard for even teens to swallow.
Children swear that different brand names and/or generic formulations of this antibiotic taste different, either in pill or suspension form. My teen hates even the pills; for awhile I had to crush them up and put them in gel caps. I can just imagine how awful the suspension might taste. (Try it yourself!) If you are having problems getting your child to take this oral medication, you might try a different brand or pharmacy. The antibiotic is cheap, so it's not a lot out of your pocket if you have to look around, even if you have to go outside your health insurance coverage. These antibiotics are very important, and have to be taken for several years, so it's worth taking the time to work out an arrangement that your child likes. Give them some power to try different ones and make their own choice.
Note: You can buy these tablets in a very large size, over 100, so you don't have to keep going back for refills.
Antibiotics should be taken with plenty of water or other fluids.
Pneumocystis Carinii Pneumonia (PCP)
Co-trimoxazole is essentially 100% effective in preventing PCP in children on chemotherapy. PCP is aggressive, fast-moving, and sometimes hard to detect. Any pneumonia is a real concern for children on chemo, but PCP is particularly nasty pneumonia. It is caused by pneumocystis carinii, thought to be a fungus which is usually dormant in the hosts lung. PCP presents as:
- dry, nonproductive cough
- fluid in lungs on X-ray BUT 10 to 20% of patients have normal chest x-rays
- arterial blood gases show low oxygen levels
Your child's oncologist will likely do a check for PCP in the event of the above symptoms. PCP is diagnosed by checking lung fluid for the pneumocystis carinii. PCP progresses very quickly and must be treated with immediate and aggressive treatment. It's treated by IV administration of co-trimoxazole (or alternative, see below). According to the Merck Manual:
"the overall mortality with treatment is 10 to 30%"
This is pretty scary, for a disease that can be entirely prevented by taking pills a couple days a week.
It is probably not a concern, but the literature states that PCP can be transmitted from patient to patient. I can't see this as a problem, unless your child is sharing a hospital room with a child who has PCP.
Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA, yes, the sunscreen compound). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and inhibiting the required enzyme. Combined, the two antibiotics block two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria. This data was presented for bacteria, I am assuming that it can be extrapolated to the possibly fungal pneumcystis carinii. (This information is according to Danbury Pharmaceutical, the manufacturer who printed the slip included with co-trimoxazole.)
The most common adverse reactions are: (again, from the slip of paper provided by the manufacturer with the prescription)
- gastrointestinal disturbances (nausea, vomiting, anorexia)
- allergic skin reactions (rash) (including increased sun sensitivity)
Co-trimoxazole can cause adverse reactions in some children, including severe allergic, hematological, respiratory, and neurological problems. These reactions are rare, but they can and do occur. Realistically, with all the chemotherapy the kids are taking and with their own nasty side effects, it can be difficult to attribute problems to the antibiotic. Still, be aware.
Children undergoing chemotherapy are particularly susceptible to neutropenia due to co-trimoxazole. Listening to online chat for several months, more than one child was taken off co-trimoxazole in order to allow the ANC -- the "counts" -- to come back up. Usually, Pentamidine or Dapsone is substituted during the suspension from co-trimoxazole.
I included the biochemical actions of sulfamethazole and trimethoprim above for a reason (other than my own chemist nature). Note that these antibiotics work on the same pathway as does methotrexate, a chemotherapy agent common in the treatment of many childhood cancers, especially ALL. According to the manufacturer, the antibiotic:
- interferes with serum methotrexate assay
- displaces methotrexate from plasma binding sites, thus increasing serum methotrexate concentrations
Therefore, your child should not be taking co-trimoxazole on the same say as he or she receives a dose of methotrexate (MT). The serum concentrations of the antibiotic peak 1-4 hours after oral administration, so it can likely be given the day before. Always ask your doctor if they tell you otherwise.
Alternatives to co-trimoxazole
A significant number of children need to discontinue co-trimoxazole because of a drop in blood counts attributed to this antibiotic. Or, the child has an allergic reaction to the co-trimoxazole. Substitutes include:
- Pentamidine, administered as an aerosol, or nebulized (the choice, supposedly fewer side-effects, but it reportedly can be difficult for the child because it takes 20 minutes and it smells bad) or IV, usually on a once a month basis.
- Pneumocystis pneumonia in children receiving chemotherapy. "Intravenous pentamidine may not be as effective as previously considered and should be used with caution." 2008 Pediatric Blood and Cancer article (Abstract).
- Intravenous pentamidine is effective as second line Pneumocystis pneumonia prophylaxis in pediatric oncology patients. 2008 Pediatric Blood and Cancer article (Abstract).
- Link to an article on nebulized pentamidine on the UK Institute of Child Health web site.
- Dapsone, given orally but more frequently than co-trimoxazole and it comes as smaller pills.
- Atovaquone. Taken daily, PO. Some clinics go right to this alternative. MedLinePlus link and PubMed abstract. The brand name is Mepron®.
In patients with HIV infection, Pentamidine is clearly not as good as co-trimoxazole at preventing PCP. The general consensus that I found from reading Web sources is that co-trimoxazole is always the first choice, and Pentamidine and Dapsone are very good alternatives, but not as well-thought of as co-trimoxazole for preventing and treating PCP, and perhaps have unwanted side-effects. Still, things change with time, so keep an eye on the AIDS-related Web pages for new alternative preventative treatments for PCP.
- Merck Manual (accessed 2011)
- The Body: an AIDS and HIV information resource: PCP and the main reference page. (accessed 2011)
- Hughes WT, Rivera G, Schell M, et al: Successful intermittent chemoprophylaxis for pneumocystis carinii pneumonitis. N Engl J Med 316:1627, 1987
- Drugs for parasitic infections. The Medical Letter 37:99, 1995.