Daraprim

Definition

Antibiotics are drugs that are used to treat infections caused by bacteria and other organisms, including protozoa, parasites, and fungi.

Purpose

Many treatments for cancer destroy disease-fighting white blood cells, thereby reducing the body's ability to fight infection. For example, bladder, pulmonary, and urinary tract infections may occur with chemotherapy. Single-celled organisms called protozoa are rarely a problem for healthy individuals. However, they can cause serious infections in individuals with low white blood cell counts. Because of the dangers that infections present for cancer patients, antibiotic treatment often is initiated before the exact nature of the infection has been determined; instead, the choice of antibiotic may depend on the site of the infection and the organism that is likely to be the cause. Often, an antibiotic that kills a broad spectrum of bacteria is chosen and several antibiotics may be used together.

Description

The common antibiotics that are used during cancer treatment include:

• Atovaquone (Mapren): antiprotozoal drug used to prevent and treat a very serious type of pneumonia called Pneumocystis carinii pneumonia (PCP), in individuals who experience serious side effects with SMZ-TMP (Sulfamethoxazole/Trimethoprim, brand name Bactrim).

• Aztreonam (Azactam): monobactam antibiotic used to treat gram-negative bacterial infections of the urinary and lower respiratory tracts and the female organs, and infections that are present throughout the body (systemic infections or septicemia).

• Cefepime (Maxipime), ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime), and ceftriaxone sodium (Rocephin): members of a group of antibiotics called cephalosporins used to treat bacterial infections of the urinary and lower respiratory tracts, and infections of the skin, bones, joints, pelvis, and abdomen.

• Ciprofloxacin (Cipro): fluoroquinolone antibiotic used to treat certain gram-negative and gram-positive bacteria and some mycobacteria.

• Clindamycin phosphate (Cleocin): used to treat gram-positive and gram-negative bacterial infections and, in individuals who are allergic to sulfadiazine, toxoplasmosis caused by a parasitic protozoa.

• Gentamicin (gentamycin) sulfate (generic name product, Garamycin, G-Mycin, Jenamicin): aminoglycoside antibiotic used to treat serious infections by many gram-negative bacteria that cannot be treated with other medicines.

• Metronidazole hydrochloride (Flagyl, Metric 21, Metro I.V., Protostat): used for anaerobic bacteria and protozoa.

• Pentamidine (generic name product, Pentam 300): used to treat PCP if serious side effects develop with SMZ-TMP.

• Pyrimethamine (Daraprim): antiprotozoal medicine used together with sulfadiazine to treat toxoplasmosis; or in combination with other medicines for treating mild to moderate PCP, in individuals who cannot tolerate the standard treatment.

• Sulfadiazine (generic name product): sulfonamide antibiotic used with pyrimethamine to treat toxoplasmosis.

• Sulfamethoxazole-Trimethoprim (SMZ-TMP) (generic name product, Bactrim, Cofatrim Forte, Cotrim, Septra, Sulfatrim): the sulfonamide antibiotic, sulfamethoxazole, used in combination with trimethoprim, to prevent and treat PCP and bacterial infections, such as bronchitis and middle ear and urinary tract infections.

• Trimethoprim (generic name product, Proloprim, Trimpex): primarily used to prevent or treat urinary tract infections.

• Vancomycin hydrochloride (generic name product, Vancocin): glycopeptide antibiotic used to treat a variety of serious gram-positive bacterial infections for which other medicines are ineffective, including strains of Staphylococcus that are resistant to most oral antibiotics.

Most of these antibiotics kill bacteria by preventing them from making protein for their cell walls. Ciprofloxacin and metronidazole prevent bacteria from reproducing by interfering with their ability to make new DNA. All of these drugs are approved for prescription by the U.S. Food and Drug Administration.

Recommended dosage

Dosages of antibiotics depend on the individual, the infection that is being treated, and the presence of other medical conditions. For children, the dosage usually is based on body weight and is lower than the adult dosage. To be effective, an entire treatment with antibiotics must be completed, even if the symptoms of infection have disappeared. Furthermore, it is important to keep the level of antibiotic in the body at a constant level during treatment. Therefore, the drug should be taken on a regular schedule. If a dose is missed, it should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped. Doubling up doses is generally not recommended.

Average adult dosages of common antibiotics for cancer patients are as follows:

• Atovaquone: for PCP treatment, 750 mg oral suspension twice a day, or tablets three times per day, for 21 days; for PCP prevention, 1,500 mg oral suspension, once a day; must be taken with balanced meals.

• Aztreonam: 1-2 gm every 6-12 hours, injected into a vein, over a 20-60 minute-period.

• Cefepime: 500 mg to 2 gm, injected into a vein or muscle, every 8-12 hours for 7-10 days.

• Ceftazidime: 250 mg to 2 gm, injected into a vein or muscle, every 8-12 hours.

• Ceftriaxone: 1-2 gm, injected into a vein or muscle, every 24 hours.

• Ciprofloxacin: 500-750 mg of the tablet or suspension, every 12 hours, for 3-28 days, taken two hours after meals with 8 oz of water; bone and joint infections usually are treated for at least 4-6 weeks; 200-400 mg injected every 8-12 hours.

• Clindamycin: 150-300 mg of capsule or solution, every six hours; 300-600 mg every six to eight hours or 900 mg every eight hours, injected into a vein or muscle.

• Gentamicin: dosage determined by body weight, every 8-24 hours for at least 7-10 days, injected into a vein or muscle.

• Metronidazole: for bacterial infections, 7.5 mg per kg (3.4 mg per lb) of body weight up to a maximum of 1 gm, every six hours for at least seven days (capsules or tablets); 15 mg per kg (6.8 mg per lb) for the first dose, followed by half that dosage every six hours for at least seven days (injected into a vein); for protozoal infections caused by amebas, 500-750 mg of oral medicine, three times per day for 5-10 days; for trichomoniasis, 2 gm for one day or 250 mg three times per day for seven days (oral medicine); extended-release tablets for vaginal bacterial infections, 750 mg once a day for seven days.

• Pentamidine: for treating PCP, 4 mg per kg (1.8 mg per lb) of body weight, once per day for 14-21 days, injected into a vein over one to two hours, while lying down.

• Pyrimethamine: for toxoplasmosis, 25-200 mg tablets, taken with other medicine, for several weeks.

• Sulfadiazine: for bacterial and protozoal infections, 2-4 gm for the first dose, followed by 1 gm every four to six hours (tablets).

• SMZ-TMP: 800 mg of sulfamethoxazole and 160 mg of trimethoprim, (tablet or oral suspension), every 12 hours for bacterial infections and every 24 hours for prevention of PCP; dosage based on body weight for PCP treatment; injections based on body weight, every six, eight or 12 hours for bacterial infections and every six hours for PCP treatment.

• Trimethoprim: 100 mg tablet every 12 hours for 10 days; for prevention of urinary tract infections, once a day for a long period.

• Vancomycin: 7.5 mg per kg (3.4 mg per lb) of body weight, or 500 mg-1 gram, injected or taken orally, every 6-12 hours.

Precautions

Stomach or intestinal problems or colitis (inflammation of the colon) may affect the use of:

• Atovaquone

• Cephalosporins

• Clindamycin

Kidney or liver disease may affect the use of:

• Aztreonam

• Cefepime

• Ceftazidime

• Ciprofloxacin

• Clindamycin

• Gentamicin

• Metronidazole

• Pentamidine

• Pyrimethamine

• Sulfadiazine

• SMZ-TMP

• Trimethoprim

• Vancomycin

Central nervous system or seizure disorders may affect the use of:

• Ciprofloxacin

• Metronidazole

• Pyrimethamine

Anemia (low red blood cell count) or other blood disorders may affect the use of:

• Metronidazole

• Pentamidine

• Pyrimethamine

• Sulfadiazine

• SMZ-TMP

• Trimethoprim

Ciprofloxacin may not be suitable for individuals with tendinitis or with skin sensitivities to sunlight. Gentamicin may not be suitable for people with hearing problems, myasthenia gravis, or Parkinson's disease. Metronidazole may not be suitable for individuals with heart disease, oral or vaginal yeast infections, or a history of alcoholism. Pentamidine may not be suitable for individuals with heart disease, bleeding disorders, or low blood pressure. Pentamidine may affect blood sugar levels, making control of diabetes mellitus or hypoglycemia (low blood sugar) difficult. Vancomycin may not be appropriate for individuals with hearing problems.

Many antibiotics should not be taken during pregnancy or while breast-feeding. Older individuals may be more susceptible to the side effects of sulfadiazine, SMZ-TMP, or trimethoprim.

Side effects

Some individuals may have allergic reactions to antibiotics. If symptoms of an allergic reaction (such as rash, shortness of breath, swelling of the face and neck), severe diarrhea, or abdominal cramping occur, the antibiotic should be stopped and the individual should seek medical advice.

Because antibiotics can affect bacteria that are beneficial, as well as those that are harmful, women may become susceptible to infections by fungi when taking antibiotics. Vaginal itching or discharge may be symptoms of such infections. All patients may develop oral fungal infections of the mouth, indicated by white plaques in the mouth.

Injected antibiotics may result in irritation, pain, tenderness, or swelling in the vein used for injection. Antibiotics used in cancer patients may have numerous side effects, both minor and severe; however, most side effects are uncommon or rare.

The more common side effects of atovaquone, aztreonam, cephalosporins, ciprofloxacin, clindamycin, gentamicin, metronidazole, and SMZ-TMP include:

• nausea and vomiting

• diarrhea

• loss of appetite

Eating active cultured yogurt may help counteract diarrhea, but if a patient has low white blood cells, this remedy is not recommended. For mild diarrhea with cephalosporins, only diarrhea medicines containing kaolin or attapulgite should be taken. With clindamycin, diarrhea medicines containing attapulgite should be taken several hours before or after the oral antibiotic. Diarrhea following antibiotics like clindamycin may indicate a bacterial infection that needs additional therapy, and a physician should be consulted.

Other side effects of atovaquone may include:

• fever

• skin rash

• cough

• headache

• insomnia

Other side effects of ciprofloxacin may include:

• abdominal pain

• increase in blood tests for kidney function

• dizziness or light-headedness

• inflammation or tearing of a tendon

• drowsiness

• insomnia

Other common side effects of clindamycin include abdominal pain and fever. Side effects may occur up to several weeks after treatment with this medicine.

Gentamicin and vancomycin may cause serious side effects, particularly in elderly individuals and newborn infants. These include kidney damage and damage to the auditory nerve that controls hearing. Other, more common side effects of gentamicin may include:

• changes in urination

• increased thirst

• muscle twitching or seizures

• headache

• lethargy

When gentamicin is injected into a muscle, vein, or the spinal fluid, the following side effects may occur:

• leg cramps

• skin rash

• fever

• seizures

Side effects from gentamicin may develop up to several weeks after the medicine is stopped.

More common side effects of metronidazole include:

• mouth dryness

• unpleasant or metallic taste

• dizziness or light-headedness

• headache

• stomach pain

Sugarless candy or gum, bits of ice, or a saliva substitute may relieve symptoms of dry mouth.

Pentamidine, pyrimethamine, sulfonamides, SMZ-TMP, and trimethoprim can lower the number of white blood cells, resulting in an increased risk of infection. These drugs also can lower the number of blood platelets that are important for blood clotting. Thus, there is an increased risk of bleeding or bruising while taking these drugs.

Serious side effects of pentamidine may include:

• heart problems

• low blood pressure

• high or low blood sugar

• other blood problems

• decrease in urination

• sore throat and fever

• sharp pain in upper abdomen

Some of these symptoms may not occur until several months after treatment with pentamidine.

Pyrimethamine and trimethoprim may lower the red blood cell count, causing anemia. Leucovorin or the vitamin folic acid may be prescribed for anemia.

Some individuals become more sensitive to sunlight when taking sulfonamides, SMZ-TMP, or trimethoprim. Other common side effects of sulfonamides and SMZ-TMP include:

• dizziness

• itching

• skin rash

• headache

• mouth sores or swelling of the tongue

• fatigue

If vancomycin is injected into a vein too quickly, it can cause flushing and a rash over the neck, face, and chest, wheezing or difficulty breathing, and a dangerous decrease in blood pressure.

Interactions

Many prescription and non-prescription medicines can interact with these antibiotics. Therefore, it is important to consult a complete list of known drug interactions. Among the more common or dangerous interactions:

• Antibiotics that lower the number of blood platelets, with blood thinners (anticoagulants), such as warfarin

• Aztreonam and metronidazole with alcohol; it is important not to consume alcohol until at least three days after treatment with these antibiotics

• Ciprofloxacin with antacids, iron supplements, or caffeine

• Pentamidine or pyrimethamine with previous treatments with x rays or cancer medicines (increased risk of blood cell damage)

• Trimethoprim with diuretics to remove excess fluid in the elderly

Many medicines can increase the risk of hearing or kidney damage from gentamicin. These include:

• cisplatin

• combination pain medicine with acetaminophen and aspirin or other salicylates (taken regularly in large amounts)

• cyclosporine

• inflammation or pain medicine, except narcotics

• lithium

• methotrexate

• other medicines for infection

The following drugs may increase the risk of liver effects with sulfadiazine or SMZ-TMP:

• acetaminophen, long-term, high-dose (eg Tylenol)

• birth control pills containing estrogens

• disulfiram (Antabuse)

• other medicines for infection

KEY TERMS

Gram-negative

Types of bacteria that do not retain Gram stain.

Gram-positive

Types of bacteria that retain Gram stain.

Mycobacteria

Rod-shaped bacteria, some of which cause human diseases such as tuberculosis.

pneumonia (PCP)

Serious type of pneumonia caused by the protozoan .

Protozoa

Single-celled animals.

Toxoplasmosis

Infection caused by the protozoan parasite , affecting animals and humans with suppressed immune systems.

Trichomoniasis

Infection caused by a protozoan of the genus ; especially vaginitis caused by