Understanding Urinary Tract Infection NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES NIH Publication No. 88-2097 April 1988 Urinary tract infections are a serious health problem affecting millions of people each year. The urinary tract is a vital, finely balanced system whose task is to extract and dispose of the body's liquid wastes. Infections of the urinary tract are among the most common in the human body--so common that only respiratory infections occur more often. Each year, patients with symptoms of a urinary tract infection (UTI) account for 5 million visits to a doctor's office. Among women, UTI's are especially troublesome; it is estimated that up to 20 percent of women develop a UTI sometime in their lives. The urinary system, made up of the kidneys, ureters, bladder, and urethra, eliminates liquid waste products and helps maintain a stable balance of salts and other dissolved substances in the blood. The key players in the system are the kidneys, a pair of purplish-brown organs located below the ribs toward the middle of the back. These highly complex organs remove liquid waste material from the bloodstream in the form of urine and produce a hormone that regulates the formation of red blood cells. Two narrow tubes called ureters carry urine from the kidneys to the bladder, a triangle-shaped chamber in the lower abdomen. Urine is stored in the bladder and emptied through another passageway, the urethra. The average adult passes about 1,500 milliliters (about a quart and a half) of urine each day. The amount of urine varies, depending on the amount and type of food and fluids consumed. The volume formed at night is about half as much as that formed in the daytime. CAUSES Normal urine is sterile. It contains fluids, salts, and waste products, but it is free of microorganisms such as bacteria, viruses, or fungi. An infection occurs when microorganisms, usually bacteria from the digestive tract, adhere to the opening of the urethra and begin to multiply. Most infections can be traced to one type of colon bacteria, called Escherichia coli. Recently, microorganisms called Chlamydia and Mycoplasma have been found to cause urinary tract infections in both men and women, but these tend to remain limited to the urethra and genital system. Unlike the majority of UTI' s, infections caused by these two microbes are sexually transmitted, are not detected by standard culturing methods, and require treatment of both sexual partners. As they reproduce, bacteria colonize the urethra. An infection that is limited to the urethra is called urethritis. Often the bacteria migrate from the urethra to the bladder, causing cystitis (a bladder infection). It is important to treat the infection promptly, before bacteria that invade the lower urinary tract have a chance to travel upward, causing a kidney infection (pyelonephritis) and possibly kidney damage. The urinary system is structured in a way that helps guard against infection. For instance, the ureters normally prevent the backup of urine toward the kidneys, and the flow of urine from the bladder helps wash harmful bacteria out of the body. In men, the prostate gland produces secretions that kill or inhibit infection-causing bacteria. In both sexes, various immune defenses also play a role in keeping infection at bay. Despite these and other safeguards, infections still occur. Scientists are not sure why women have more urinary infections than men. RISK FACTORS Some people are more prone to getting a urinary infection than others. Any abnormality of the urinary tract that obstructs or slows the flow of urine makes it easier for bacteria to grow. When the urine does not empty freely, it may stagnate in the bladder. A stone in the kidney or any part of the urinary tract can form such a blockage, creating the conditions for a UTI. In men, an enlarged prostate gland can obstruct urine flow and make infection difficult to treat. One of the most common sources of infection is catheters, or tubes, placed in the bladder. Patients who cannot void, are unconscious, or critically ill, often need a catheter that remains in place for a period of time. Because of the risk that bacteria inhabiting the catheter can enter and infect the bladder, hospital staff take special care to prevent the catheter from becoming contaminated. Also, physicians try to remove the catheter as soon as possible. Some patients, especially the elderly or those with diseases of the nervous system who lose bladder control, may need a catheter for life. People who have diabetes mellitus have a higher risk of a UTI because of changes of the immune system. Any disorder that involves suppression of the immune system sets the stage for urinary infection. UTI's occur in a small percentage of infants due to congenital abnormalities that sometimes require surgery. They are rarely seen in boys and young men, but the rate of UTI's in females gradually increases as they age. Scientists are not sure why women have more urinary infections than men. One factor may be that in women the urethra is short, allowing easy migration of bacteria to the bladder. Also, a woman's urethral opening is near sources of bacteria from the anus and vagina. For many women, sexual intercourse seems to precipitate an infection. The reasons for this association are unclear, but some doctors think that, in women predisposed to vaginal colonization of bacteria, intercourse may propel bacteria in to the urethra. Yet another factor is the method of birth control: according to several studies, women who use the diaphragm are more likely to develop a UTI than women who use other forms of contraception. UTI's are a recurrent problem for many women, also for reasons that are poorly understood. In the vast majority of cases, the new infection stems from a strain or type of bacteria that is different from the infection that preceded it. (Even when several infections in a row are traced to E. coli, there are usually slight differences in the bacteria, indicating that each infection was caused by a distinct strain.) Researchers at Tulane University in New Orleans, supported by the National Institute of Diabetes and Digestive and Kidney Diseases, suggest that one factor behind recurrent UTI's may be the ability of bacteria to adhere to the mucous tissue of the urinary tract. Another may be that local immune responses in some women are less effective in preventing the growth of bacteria. Pregnant women seem no more susceptible to UTI's than nonpregnant women. However, when an infection does occur, it may be more serious because it is more likely to travel to the kidneys. According to some reports, about 2 to 4 percent of pregnant women develop a urinary tract infection. Scientists think that hormonal changes and shifts in the positioning of the urinary tract during pregnancy make it easier for bacteria to travel up the ureters to the kidneys. For this reason, many doctors recommend periodic testing of the urine. A pregnant woman who develops a UTI should be treated promptly to avoid premature delivery of her baby and other risks such as high blood pressure and toxemia. In selecting an antibacterial drug, the physician considers both its effectiveness and toxic effects to the fetus. SYMPTOMS Not everyone with a urinary tract infection has symptoms, but most people get at least some. Such symptoms include a frequent urge to urinate and a painful, burning feeling during urination. It is not unusual to feel bad all over--tired, shaky, washed out--and to feel pain even when not urinating. Often, women feel an uncomfortable pressure above the pubic bone, and some men experience a fullness in the rectum. It is common for a person with a urinary infection to complain that, despite the urge to urinate, only a small amount of urine is passed. The urine itself may appear milky or cloudy--even reddish if blood is present. A fever may indicate that the infection has reached the kidneys. Other symptoms of a kidney infection include pain in the back or side below the ribs, nausea, or vomiting. In children, symptoms of urinary infection often are not noticed, or they may be attributed to some other disorder. A UTI should be considered when a child, or infant, seems irritable, is not eating normally, vomits, has incontinence or loose bowels, or is not thriving. The child should be seen by a doctor if there are any questions about these symptoms, especially when accompanied by increased frequency of urination. DIAGNOSIS A urinary infection can easily be diagnosed by testing a sample of urine for the presence of pus and bacteria. A "clean catch" urine sample is obtained by washing the genital area and collecting a "midstream" sample of urine in a sterile container. (This method of collecting a urine sample helps prevent bacteria around the genital area from contaminating the urine and confusing the test results.) Usually, the sample is sent to a laboratory, although some doctors' offices are equipped to do the testing on site. First, the urine is examined for white and red blood cells and bacteria in a test called urinalysis. The bacteria then are grown in a culture and tested against various antibiotics to determine which drug most effectively destroys the bacteria. This step is called a sensitivity test. Some microbes, like Chlamydia and Mycoplasma, require special bacterial cultures in order to be detected. A doctor should suspect one of these infections if the patient has symptoms of a UTI and has pus in the urine, but a laboratory culture fails to grow any bacteria. When a patient has a persistent infection-one that does not clear up with appropriate treatment and is traced to the same strain of bacteria--the doctor orders an intravenous pyelogram (IVP). This examination gives x-ray images of the bladder, kidneys, and ureters. An opaque dye visible on x-ray film is injected into a vein, and a series of x-rays are taken. The film shows an outline of the urinary tract, revealing even small changes in the contours of these organs that might contribute to infection. Some doctors may also recommend an IVP for women patients who have five or more infections in a year. (As stated before, most recurring infections are caused by a different strain or type of bacteria.) Another test that may be useful for patients with recurring infections is a cystoscopy. A cystoscope is an instrument made of a hollow tube with several lenses and a light source, which allows the doctor to see the inside of the bladder. TREATMENT Urinary tract infections are treated with antibacterial drugs. The choice of drug and length of treatment depends on the patient's history and the urine tests that identify the offending bacteria. The sensitivity test is especially useful in helping the doctor select the most effective drug. Several clinical trials have shown that an uncomplicated infection in women can be cured with 1 or 2 days of treatment. However, many physicians prefer to have their patients take antibiotics for a longer period (e.g., 7 to 14 days) to assure that the infection has been cured. Single-dose treatment is not recommended for certain groups of patients, for example, those who have delayed treatment or have signs of bacterial invasion of tissue, patients with diabetes or structural abnormalities, or men who have infections in the prostate gland. Lengthier treatment is also needed by patients with infections caused by Mycoplasma or Chlamydia, who are usually treated with tetracycline, trimethoprim/ sulfamethoxazole (TMP/SMZ), or doxycycline. A follow-up urinalysis helps to confirm that the urinary tract is infection free. It is important to take the full course of treatment, even after symptoms disappear. Severely ill patients with kidney infections may be hospitalized until they are able to take fluids and needed drugs on their own. The consensus among physicians is that kidney infections require several weeks of antibiotic therapy. A recent clinical trial at the University of Washington found that 2-week therapy with TMP/SMZ was as effective as 6 weeks of treatment with the same drug in women with "uncomplicated" kidney infections. (Uncomplicated infections are those in which there is no underlying obstruction or nervous system disorder. In such cases, kidney infections rarely lead to kidney damage or kidney failure unless they go untreated.) Moreover, the research showed that 2-week TMP/SMZ treatment was more effective and better tolerated than either 2- or 6-week treatment with ampicillin. Various drugs are available to relieve the pain of a UTI. A heating pad or a warm bath may help. Physicians have different opinions on the importance of drinking extra fluids, but most suggest that drinking plenty of water helps cleanse the urinary tract of harmful bacteria. Others feel that increasing fluid intake is unnecessary because the infection is so quickly cured by antibiotics. For the time being, it is best to avoid irritants like coffee, alcohol, and spicy foods. (And one of the kindest favors a smoker can do for his or her bladder is to quit smoking. Smoking is the most important known risk factor for bladder cancer.) RECURRENT INFECTIONS IN WOMEN About four out of five women who have a UTI get another one within 18 months. Many women have them even more frequently. Women who have frequent recurrences (e.g., three or more a year) may benefit from preventive therapy. Doctors use several approaches to manage these patients after the most recent infection has been eradicated. One of the most common is for the patient to take low doses of an antibiotic daily for 6 months or longer. (If taken at bedtime, the drug remains in the bladder longer and may be more effective.) Another is to take a single dose of an antibiotic after sexual intercourse. Even after long-term treatment, however, some women continue to have recurrent infections. Many doctors suggest steps that a woman can take on her own to avoid an infection: * Drink plenty of water every day; (Some doctors suggest drinking cranberry juice, which in large amounts inhibits the growth of some bacteria by acidifying the urine.) * Don't put off urinating when you feel the need; * Wipe from front to back to prevent bacteria around the anus from entering the vagina or urethra; * Cleanse the genital area before sexual intercourse; * Empty the bladder shortly before and after sexual intercourse; and * Avoid using feminine hygiene sprays and scented douches. COMPLICATED INFECTIONS In both sexes, curing "complicated" infections--those involving an obstruction of urine or disorder of the nervous system-depends on finding and correcting the underlying problem, sometimes with surgery. If the root cause is not treated effectively, this group of patients is at risk of kidney damage. Also, such infections tend to arise from a wider range of bacteria, and occasionally from more than one organism at a time, so choosing the best antibiotic therapy can be a more complex process. As discussed earlier, UTI's are unusual in men. When they do occur, it is likely that the patient has some kind of obstruction--for example, a urinary stone or enlarged prostate--or recently had a medical procedure involving a catheter. The first step is to identify the infecting organism and the drugs to which it is sensitive. Usually, doctors recommend lengthier therapy in men than in women, in part to prevent infection of the prostate gland. When infection does involve the prostate (prostatitis), it is harder to cure' because antibacterial drugs are unable to penetrate prostatic tissue very well. For this reason, men with prostatitis often need long-term treatment with a carefully selected antibiotic. RESEARCH IN URINARY SYSTEM DISORDERS The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) was established by Congress in 1950 as an institute of the National Institutes of Health (NIH), whose mission is to improve human health through biomedical research. The NIH is the research arm of the Public Health Service under the U.S. Department of Health and Human Services. The NIDDK conducts and supports a variety of research in diseases of the kidney and urinary tract. Much of the research targets disorders of the lower urinary tract, including urinary tract infection, urinary obstruction, vesicoureteral reflux, prostatitis, urinary stones, and other urinary disorders. The knowledge gained from these studies is advancing scientific understanding of why UTI's develop and may lead to improved methods of diagnosing, treating, and preventing urinary infections. In one such study, researchers at the University of Wisconsin have developed a vaccine, until now tested only in animals, that stimulates a strong immune response against bacteria entering the bladder. The scientists found that this vaginal immunization elicited an immune response that protected the entire lower urinary tract. The investigators are conducting further studies to determine the safety of this technique before their vaccine can be tested in humans. Recently, the NIDDK established six new research centers around the country with the goal of reducing the major causes of kidney and urinary tract diseases through innovative research. The lead investigators, their institutions, and research focus are listed on the following pages. GEORGE M. O'BRIEN KIDNEY AND UROLOGICAL RESEARCH CENTERS Barry M. Brenner, M.D. Division of Nephrology Brigham and Women's Hospital 721 Huntington Avenue Boston, Massachusetts 02115 (617) 732-5850 Kidney Disease of Diabetes Mellitus Kidney Transplant Rejection Richard L. Tannen, M.D. Division of Nephrology University of Michigan D3238 South Ambulatory Care Building Ann Arbor, Michigan 48109 (313) 936-4890 Glomerulonephritis Harry R. Jacobson, M.D. Vanderbilt University School of Medicine Nashville, Tennessee 37232 (615) 322-4794 Progressive Glomerular Sclerosis Kidney Transplant Rejection Robert G. Luke, M.D. Division of Nephrology University of Alabama at Birmingham University Station Birmingham, Alabama 35294 (205) 934-3585 Effects of High Blood Pressure on the Kidney Glomerulonephritis Interstitial Nephritis Ahmad Elbadawi, M.D. SUNY Upstate Center 750 East Adams Street Syracuse, New York 13210 (315) 473-4750 Urinary Tract Obstruction John T. Grayhack, M.D. Department of Urology Northwestern University Medical School 303 East Chicago Avenue Chicago, Illinois 60611 (312) 649-8145 Enlargement of the Prostate Gland SUGGESTIONS FOR ADDITIONAL READING The following materials can be found in medical libraries, many college and university libraries, and through interlibrary loan in most public libraries. "Chlamydia," Information sheet prepared by and available from the National Institute of Allergy and Infectious Diseases, Building 31, Room 7A32, Bethesda, MD 20892, Aug. 1985. Corriere, Joseph N., Jr., et al., "Cystitis: Evolving Standard of Care," Patient Care, Feb. 29, 1988, pp. 33-47. Fowler, Jackson E., Jr., "Urinary Tract Infections in Women," Urologic Clinics of North America, Nov. 1986, pp. 673-683. Gillenwater, Jay Y., et al., eds. Adult and Pediatric Urology, vol. 1. Chicago: Year-book Medical Publishers, 1987. Komaroff, Anthony L., "'Simple' Cystitis: It's Not So Simple Anymore," Modern Medicine, Feb. 1985, pp. 116-127. Krieger, John N., "Complications and Treatment of Urinary Tract Infections During Pregnancy," Urologic Clinics of North America, Nov. 1986, pp. 685-693. Kunin, Calvin M. Detection, Prevention and Management of Urinary Tract Infections, 4th edition. Philadelphia: Lea and Febiger, 1987. Roberts, James A., "Bacterial Adherence and Urinary Tract Infection," Southern Medical Journal, March 1987, pp. 347-351. Spencer, Julia R., and Schaeffer, Anthony J., "Pediatric Urinary Tract Infections," Urologic Clinics of North America, Nov. 1986, pp. 661-672. Stamm, Walter E., et al., "Acute Renal Infection in Women: Treatment with Trimethoprim-Sulfamethoxazole or Ampicillin for Two or Six Weeks: A Randomized Trial," Annals of Internal Medicine, March 1987, pp. 341-345. Walsh, Patrick C., et al., eds. Campbell's Urology, vol 1.5th edition. Philadelphia: W.B. Saunders, 1986. ADDITIONAL INFORMATION The NIDDK sponsors the newly formed National Kidney and Urologic Diseases Information Clearinghouse, which collects, produces, and distributes information about kidney and urinary tract disorders to health professionals and the public. For information about kidney and urinary tract disorders, contact the National Kidney and Urologic Diseases Information Clearinghouse, Box NKUDIC, Bethesda, MD 20892, telephone (301) 468-6345. This booklet was written by Joan Chamberlain of NIDDK's Office of Health Research Reports. The draft was reviewed by NIDDK scientists as well as urologists Philip Hanno, M.D., of the Hospital of the University of Pennsylvania, and Jay Gillenwater, M12), of the University of Virginia Medical School, who kindly provided their thoughtful comments.