Urinary Anti-Infectives

Definition
Purpose
Description
Recommended dosage
Precautions
Side effects
Interactions

Definition

Urinary anti-infectives are medicines used to treat or prevent infections of the urinary tract, which is the passage through which urine flows from the kidneys out of the body.

Purpose

Normally, no bacteria or other disease-causing organisms live in the bladder. Likewise, the urethra—the tube-like structure that carries urine from the bladder to the outside of the body—usually does not contain any bacteria, or not enough to cause problems. But the bladder, urethra, and other parts of the urinary tract may become infected when disease-causing organisms enter it from other body regions or from outside the body. Urinary anti-infectives are used to treat such infections.

Although many antibiotics and some sulfonamides are equally effective in treating urinary tract infections, urinary anti-infectives have the advantage of being active only in the urinary tract. This means they are less likely to cause development of resistant microorganisms, or cause diarrhea by destroying the bacteria in the large intestine.

Some urinary anti-infectives have been used to prevent urinary tract infections, but the evidence that they are effective for this purpose is limited.

Description

Commonly used urinary anti-infectives include methenamine (Urex, Hiprex, Mandelamine); nalidixic acid (NegGram); and nitrofurantoin (Macrobid, Fur-atoin, and other brands). Nalidixic acid belongs to a group of synthetic antibacterial drugs known as quinolones. The first quinolone to be approved for clinical use, nalidixic acid, has been used to treat urinary tract infections since 1967. Nitrofurantoin is also a synthetic antibacterial medication.

Urinary anti-infectives are available only with a physician’s prescription. They come in capsule, tablet, granular, and liquid forms.

Recommended dosage

Methenamine

For adults and children 12 years and over, the usual dosage is 1 gram, taken either twice a day or four times a day, depending on the form of the medication that the doctor prescribes. For children aged six to 12 years, the dosage ranges from 500 mg taken two to four times a day to 1 gram taken twice a day, again depending on the form of the drug. A physician must determine the dose for children under six years.

Urinary anti-infectives will not work properly unless the urine is acidic, with a pH reading of 5.5 or lower. The physician who prescribes the medicine will explain how to test the urine’s acidity. He or she may suggest dietary changes that will make the urine more acidic, such as eating more protein; drinking cranberry juice; eating plums and prunes while avoiding most other fruits; and cutting down on milk and other dairy products. The patient should also avoid taking antacids.

Nalidixic acid

The recommended dosage of this drug for adults and children 12 years and older is 1 gram every six hours. If the medicine is taken for more than one or two weeks, the dosage may be decreased to 500 mg every six hours. A physician must determine the correct dosage for children three months to 12 years old. Children under three months should not take nalidixic acid because it causes bone problems in young animals and could have the same effect in young children.

Nitrofurantoin

CAPSULES, TABLETS, OR LIQUID. The usual dose for adults and adolescents is 50-100 mg every six hours.

KEY TERMS

Altitude sickness— A set of symptoms that people who normally live at low altitudes may have when they climb mountains or travel to high altitudes. The symptoms include nosebleed, nausea, and shortness of breath.

Anemia— A low level of hemoglobin in the blood.

Anticoagulant— A type of medication given to prevent the formation of blood clots. Anticoagulants are sometimes called blood thinners.

Bacteria— Microscopically small one-celled forms of life that cause many diseases and infections.

Glaucoma— A condition in which fluid pressure in the eye is abnormally high. If not treated, glaucoma may lead to blindness.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency— An inherited disorder in which the body lacks an enzyme that normally protects red blood cells from toxic chemicals. Certain drugs can cause patients’ red blood cells to break down, resulting in anemia. This may also happen when they have a fever or an infection. The condition usually occurs in males. About 10% of black males have it, as do small percentage of people from the Mediterranean region.

Granule— A small grain or pellet. Medicines that come in granule form are usually mixed with liquids or sprinkled on food before they are taken.

Hemoglobin— The reddish-colored compound in blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from the cells to the lungs, where it is released

pH— A measure of the acidity or alkalinity of a substance or compound. The pH scale ranges from 0 to 14. Values below 7 are acidic; values above 7 are alkaline.

Psyllium— A herb whose seeds contain a water-soluble fiber that adds bulk to the contents of the digestive tract. The bulk helps to prevent constipation. Laxatives containing psyllium may interfere with the body’s absorption of urinary anti-infectives.

Quinolones— A group of synthetic antibacterial drugs originally derived from quinine. Nalidixic acid is the first quinolone that was approved for clinical use.

Seizure— A sudden attack, spasm, or convulsion.

EXTENDED-RELEASE CAPSULES. For adults and children 12 years and older, the usual dosage is 100 mg every 12 hours for seven days.

A physician must determine the correct dose of all forms of nitrofurantoin for children one month and older according to the child’s body weight. Children under one month should not be given this medicine.

Precautions

Methenamine

Methenamine may produce adverse effects in some patients with systemic disorders. For example, it may worsen the symptoms of people with severe liver disease. People who are dehydrated or who have severe kidney disease may be more likely to have side effects that affect the kidneys.

Nalidixic acid

Some people feel drowsy, dizzy, or less alert than usual when using this drug. Nalidixic acid may also cause blurred vision or other visual problems. Because of these possible side effects, anyone who takes nalidixic acid should not drive, operate machinery, or do anything else that might be dangerous until they have found out how the drugs affect them.

Nalidixic acid may increase sensitivity to sunlight. Even brief exposure to sunlight may cause severe sunburn or a rash. Patients treated with this medication should avoid sun exposure, especially during high sun (between 10 A.M. and 3 P.m.). They should wear a hat or scarf and tightly woven clothing that covers the arms and legs; use a sunscreen with a sun protection factor (SPF) of at least 15; protect the lips with a lip balm containing sun block; and avoid the use of tanning beds, tanning booths, and sunlamps.

Diabetic patients should be aware that nalidixic acid may cause false results on some urine sugar tests. They should check with a physician before making any changes in their diet or diabetes medicine based on the results of a urine test.

In laboratory studies, nalidixic acid has been found to interfere with bone development in young animals. The drug’s effects have not been studied in pregnant women, but because of its effects in animals, it is not recommended for use during pregnancy.

This medicine does not cause problems in most nursing babies whose mothers are taking it during lactation. However, nursing babies with glucose-6-phosphate dehydrogenase (G6PD) deficiency (an inherited disorder that affects mainly black males) may have blood problems if their mothers take nalidixic acid.

People with certain medical conditions may be more likely to have particular side effects if they take this medicine. For example, people with a history of seizures or severe hardening of the arteries in the brain may be more likely to have side effects that affect the nervous system. People with glucose-6-phosphate dehydrogenase (G6PD) deficiency are more likely to have side effects that affect the blood. In addition, people with liver disease or severe kidney disease are at increased risk of having any of the drug’s possible side effects.

Nitrofurantoin

Pregnant women should not take this medicine within two weeks of their delivery date. They should not use it during labor and delivery, as this could cause problems in the baby.

Women who are breastfeeding should check with their physicians before using this medicine. It passes into breast milk and could cause problems in nursing babies whose mothers take it. This is especially true of babies with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The medicine also should not be given directly to babies up to one month of age, as they are particularly sensitive to its effects.

Older people may be more likely to have side effects when taking nitrofurantoin, because they are more sensitive to the drug’s effects.

Taking nitrofurantoin may cause problems for people with certain medical conditions. Side effects may be greater, for example, in people with lung disease or nerve damage. In people with kidney disease, the medicine may not work as well as it should, but may cause more side effects. Those with glucose-6-phosphate dehydrogenase (G6PD) deficiency who take nitrofurantoin may develop anemia.

Diabetic patients should be aware that this medicine may cause false results on some urine sugar tests. They should check with a physician before making any changes in diet or diabetes medicine based on the results of a urine test.

General precautions for all urinary anti-infectives

The symptoms of a urinary tract infection should improve within a few days of starting to take a urinary anti-infective. If they do not, or if they become worse, the patient should consult a physician right away. Patients who need to take this medicine for long periods should see their doctors regularly, so that their improvement and any side effects can be monitored.

Anyone who has had unusual reactions to urinary anti-infectives in the past should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances. Patients taking nalidixic acid should tell their physicians if they have ever had reactions to such other quinolones as cinoxacin (Cinobac), ciprofloxacin (Cipro), enoxacin (Penetrex), norfloxacin (Noroxin), or ofloxacin (Floxin), all of which are also used to treat or prevent infections. Anyone taking nitrofurantoin should let the physician know if he or she has had an unusual reaction to such drugs as furazolidone (Furoxone) or nitrofurazone (Furacin).

Side effects

Methenamine

Nausea and vomiting are not common, but may occur. These side effects do not need medical attention unless they are severe. One side effect that should be brought to a physician’s attention immediately is a skin rash.

Nalidixic acid

Some side effects are fairly minor and are likely to go away as the body adjusts to the drug. These include dizziness, drowsiness, headache, nausea or vomiting, stomach pain, and diarrhea. Unless these problems continue or are bothersome, they do not need medical attention.

Other side effects, however, should have prompt medical attention. Anyone who has such visual symptoms as blurred vision, double vision, decreased vision, changes in color vision, seeing halos around lights, or increased glare from lights should consult a physician immediately.

Nitrofurantoin

This medicine may discolor the urine, causing it to turn reddish-yellow or brown. Patients should not be concerned about this change in color. Other possible side effects that do not need medical attention, unless they are severe, include pain in the stomach or abdomen, stomach upset, diarrhea, loss of appetite, and nausea or vomiting.

Anyone who has chest pain, breathing problems, fever, chills, or a cough while taking nitrofurantoin should consult their physician immediately.

General advice on side effects for all urinary anti-infectives

Other side effects are possible when taking any urinary anti-infective. Anyone who has unusual symptoms while taking this type of medication should contact his or her physician.

Interactions

Methenamine

Certain medicines may make methenamine less effective. These include thiazide diuretics (water pills) and medicines that make the urine less acid, such as antacids, bicarbonate of soda (baking soda), and the drugs acetazolamide (Diamox), dichlorphenamide (Daranide), and methazolamide (Neptazane), which are used to treat glaucoma, epilepsy, altitude sickness, and other conditions.

Nalidixic acid

People who are taking blood thinners (anticoagulants) may be more likely to have bleeding problems if they take this medicine.

Nitrofurantoin

Nitrofurantoin may interact with many other medicines. For example, taking nitrofurantoin with certain drugs that include methyldopa (Aldomet), sulfonamides (sulfa drugs), vitamin K, and diabetes medicines taken by mouth may increase the chance of side effects that affect the blood. General side effects are more likely in people who take nitrofurantoin with the gout drugs probenecid (Benemid) or sulfinpyrazone (Anturane). The risk of side effects that involve the nervous system is higher in people who take nitrofurantoin with such drugs as lithium (Lithane); disulfiram (Antabuse); other anti-infectives; and the cancer drugs cisplatin (Platinol) and vincristine (Oncovin). Patients who have been vaccinated with DPT (diphtheria, tetanus, and pertussis) within the last 30 days or are vaccinated after taking nitrofurantoin are also more likely to have side effects that affect the nervous system. Because of the many possible interactions, anyone taking nitrofurantoin should be sure to consult a physician before combining it with any other medicine.

Laxatives containing psyllium and other bulk-forming substances may interfere with the body’s absorption of nitrofurantoin. Patients with constipation who are taking nitrofurantoin should consult their doctor before taking an over-the-counter laxative.

General advice about drug interactions

Patients should check with a physician or pharmacist before combining a urinary anti-infective with any other prescription or nonprescription (over-the-counter) medicine.

Patients who are taking any kind of herbal preparation or other alternative medicine should give their doctor and pharmacist a list of all the compounds that they use on a regular basis. Most of these preparations are unlikely to interact with urinary anti-infectives, but there is much that is still unknown about possible interactions between standard prescription medications and alternative medicines.

Resources

BOOKS

Mandell, G. L., et al. Principles and Practice of Infectious Diseases, 6th ed. London: Churchill Livingstone, 2005.

Wein, A. J., et al. Campbell-Walsh Urology, 9th ed. Philadelphia: Saunders, 2007.

PERIODICALS

Chang, S. L. “Pediatric urinary tract infections.” Pediatric Clinics of North America 53 (June 2006): 379–00.

Emmerson, A. M., and A. M. Jones. “The Quinolones: Decades of Development and Use.” Journal of Antimicrobial Chemotherapy 51 (May 2003): Supplement 1, 13–20.

Juthani-Mehta, M. “Asymtpomatic Bacteriuria and Urinary Tract Infections in Older Adults.” Clinics of Geriatric Medicine 23 (August 2007): 585–594.

ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000. http://www.ashp.org (accessed April 15, 2008).

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA. http://www.fda.gov (accessed April 15, 2008).

Nancy Ross-Flanigan

Sam Uretsky, PharmD

Urinary artificial sphincter seeArtificial sphincter insertion

Urinary catheterization, female seeCatheterization, female

Urinary catheterization, male seeCatheterization, male

Urinary diversion seeUreterostomy, cutaneous

Urinary diversion surgery seeIleal conduit surgery