Urinary Tract Infection - Medications

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Urinary Tract Infection - Medications

Description
An in-depth report on the causes, diagnosis, treatment, and prevention of urinary infections.

Medications
Antibiotics are the mainstay treatment for all UTIs. A variety of antibiotics are available and choices depend on many factors, including whether the infection is complicated or uncomplicated or primary or recurrent. Treatment decisions are also based on the type of patient (e.g., man or woman, a pregnant or nonpregnant woman, child, hospitalized or nonhospitalized patient, person with diabetes.) Treatment should not necessarily be based on the actual bacteria count. For example, if a woman has symptoms, even if bacterial count is low or normal, infection is probably present and antibiotic treatment should be considered.

Bacterial Resistance to Antibiotics. Of major concern for physicians and the public is the emergence of strains of common bacteria, including E. coli, that are resistant to specific antibiotics. The prevalence of such bacteria has dramatically increased worldwide, in large part due to widespread use of antibiotics in people and animal feeds.

Resistance to antibiotics is most often observed in the hospital setting. Unfortunately, there has been a major worldwide increase within the community in E. coli resistance to standard antibiotics used for UTIs. A major study, the ECO.SENS Project, has been designed to investigate resistant UTI bacteria in 17 European countries. In a 2003 report, 42% of E. coli were resistant to one or more of the 12 antibiotics investigated. Resistance was highest to ampicillin (29.8%). Resistance to TMP-SMX (Bactrim, Cotrim, Septra) was 14.1%. (E. coli is the most common bacteria in urinary tract infections.) Resistance to other common UTI antibiotics, including mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin, and ciprofloxacin still averaged under 3%. The rates vary, however, depending on regions. In general, regions and institutions with the highest rate of resistance are those in which antibiotics are heavily prescribed. In the European study, for example, resistance rates were highest in Portugal and Spain and lowest in the Nordic countries and Austria.

Specific Antibiotics Used for Most UTIs
Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins, cephalosporins, and some newer similar agents. Their primary actions to interfere with bacterial cell walls. Many have been important in the treatment of urinary tract infections.

Penicillins (Amoxicillin). Until recent years, the standard treatment for a UTI was 10 days of amoxicillin, a penicillin antibiotic, but it is now ineffective against E. coli bacteria in up to 25% of cases. A combination of amoxicillin-clavulanate (Augmentin) is now sometimes given for drug-resistant infections. Amoxicillin or Augmentin may be useful for UTIs caused by gram-positive organisms, including Enterococcus species and S. saprophyticus.

Cephalosporins. Antibiotics known as cephalosporins are also alternatives for infections that do not respond to standard treatments or for special populations. They are often classed in the following:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation include cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation include cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of gram-negative bacteria.
Other Beta-Lactam Agents. Other beta-lactam antibiotics have been developed. For example, pivmecillinam (a form of mecillinam), is commonly used in Europe for UTIs. It appears to be safe during pregnancy.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

The current typical treatment is a three-day course of the combination drug trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A one-day course is somewhat less effective but poses a lower risk for side effects. Longer courses (7 to 10 days) are no more effective than the three-day course and have a higher rate of side effects. It should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious. Trimethoprim (Proloprim, Trimpex) is sometimes used alone in those allergic to sulfa drugs. It should be noted that TMP-SMX interferes with the effectiveness of oral contraceptives. High rates of bacterial resistance to TMP-SMX are being observed in parts of the US, such as the Southeast, Southwest, and southern California. Still, even regional rates approach 30%, cure rates with TMP-SMX reach 80% to 85%.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) interfere with the bacteria's genetic material so they cannot reproduce. They are the standard alternatives to TMP-SMX. Examples of quinolones include ofloxacin (Floxacin), ciprofloxacin (Cipro), norfloxacin (Noroxin), levofloxacin (Levaquin), gatifloxacin (Tequin), and sparfloxacin (Zagam). These antibiotics are effective against a wide range of organisms but are expensive and, in general, used in the following circumstances:

In patients with complicated or catheter-induced UTIs.
In patients who do not respond or who are allergic to TMP-SMX.
In communities where there are high rates of bacteria resistant to TMP-SMX.
In elderly patients. A 2001 study of older women with UTIs (mean age 80), about half of whom were living in nursing homes, found that 96% responded to ciprofloxacin, compared with 87% to TMP-SMX.
Pregnant women should not take fluoroquinolone antibiotics. They also have more adverse effects in children than other antibiotics and should not be the first-line option in most situations.

Antibiotics Used Specifically for UTIs

Nitrofurantoin. Nitrofurantoin (Furadantin, Macrodantin) is a relatively inexpensive antibiotic that is used specifically for urinary tract infections. It is an effective alternative to TMP-SMX or a quinolone. Unlike many of the other drugs, however, it must be given seven to 10 days, even in cases of simple cystitis. (Shorter course treatments are being investigated.) It is not useful for treating kidney infections. Nitrofurantoin frequently causes stomach upset and interacts with many drugs. Other chronic or serious medical conditions may also affect its use. It should not be used in pregnant women within a week or two of delivery, in nursing mothers, or in those with kidney disease.

Fosfomycin. The antibiotic fosfomycin (Monurol), which comes in an orange-flavored, soluble powder, is proving to be another good alternative. It can be an effective one-dose treatment for many women, including those who are pregnant. To date, bacterial resistance rates to this antibiotic are very low.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Long-term treatment with tetracycline or doxycycline may be used for infections that are caused by Mycoplasma or Chlamydia. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Gentamicin is the most commonly used aminoglycoside for serious UTIs. They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.


Treatment for Uncomplicated UTIs
Studies are now reporting that uncomplicated UTIs in low-risk women can often be successfully treated over the phone. In such cases, a health professional, usually a nurse, provides the patients with three-day antibiotic regimens without even requiring an office urine test. This course is now recommended only for women at low risk for recurrent infection and who do not have symptoms suggesting other problems, such as vaginitis. In some centers, women who are treated over the phone have to be less than 55 years old; all other patients need to see a physician for evaluation.

Antibiotic Regimen. Oral antibiotic treatment cures 94% of uncomplicated urinary tract infections, although the rate of recurrence remains high. The following are antibiotics used for uncomplicated UTIs.

The standard regimen is a three-day course of trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A single oral dose of TMP-SMX is sometimes prescribed in mild cases, but cure rates are generally lower (87%) than with the three-day regimens. (Longer-term therapy, given for seven to 10 days, is now mostly limited to men, children, the elderly, people with diabetes with any UTI, and women with pyelonephritis or who are pregnant.)
An antibiotic called a fluoroquinolone, such as ciprofloxacin (Cipro), is usually the second choice. In fact, it is often the first choice where there are the high rates of bacterial resistant to TMP-SMX. Fluoroquinolones can also be given in a three-day course. Pregnant women should not take these agents.
Nitrofurantoin (Furadantin, Macrodantin) is a third option. This agent must be given for longer than three days.
Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Resistance rates to this drug are also very low.
After a week of antibiotic treatment, most patients are free of infection. If the symptoms do not clear up within the first few days of therapy, physicians generally suggest that women discontinue their antibiotic and provide a urine sample for culturing in order to identify the specific organism causing the condition.

Treatment for Relapsing Infection. A relapsing infection (caused by treatment failure) occurs within three weeks in about 10% of women. Relapse is treated similarly to a first infection but the antibiotics are continued for at least two weeks. (Relapsing infections may be due to structural abnormalities, abscesses, or other problems that may require surgery, and such conditions should be ruled out.)

Antibiotic Treatment for Recurrent Infections
Preventive antibiotics may be required for women who experience two or more symptomatic UTIs within six months or three or more over the course of a year. There are various approaches that are available. A woman's own perception of discomfort can generally guide her decisions on whether to use preventive antibiotics or not. All women should use life-style measures to prevent recurrences.

Intermittent Self Treatment. Many, if not most, women with recurrent UTIs can effectively self treat recurrent UTIs without going to a physician. In general, she takes the following steps:

As soon as the patient develops symptoms, she takes the antibiotic. Infections that occur less than twice a year are usually treated as if they were an initial attack, with single-dose or three-day antibiotic regimens.
At that time, she also performs a clean-catch urine test and sends it to the physician for culturing to confirm the infection.
A physician should be consulted under the following circumstances:

If symptoms have not completely resolved within 48 hours.
If there is a change in symptoms.
If the patient suspects that she is pregnant.
If the patient has more than four infections a year.
Women who are not good candidates for self-treatment are those who are unable to diagnose themselves or women with impaired immune systems, previous kidney infections, structural abnormalities of the urinary tract, or a history of infection with antibiotic-resistant bacteria.

Postcoital Antibiotics. If recurrent infections are clearly related to sexual activity and episodes recur more than two times within a six-month period, a single preventive dose taken immediately after intercourse has proven to be very effective. Antibiotics in such cases include TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (such as ciprofloxacin). (Fluoroquinolones are not appropriate during pregnancy.)

Continuous Preventive Antibiotics (Prophylaxis). Continuous preventive (prophylactic) antibiotics are an option for some women who do not respond to other measures. With this approach, low-dose antibiotics are taken continuously for six months or longer.

Typical prophylactic regimens include one dose of nitrofurantoin (50 mg), 1/2 tablet of TMP-SMX, or cephalexin (250 mg) daily. Taking the antibiotic at bedtime may be most effective. Studies suggest that continuous prophylactic antibiotics reduces recurrences by up to 95% and may prevent kidney infection.

Adverse effects mostly include gastrointestinal problems and yeast infections. (Taking probiotic supplements or eating yogurt may help prevent yeast infections.) Although there is concern that continuous risk increases the risk for bacteria that are resistant to the antibiotics, studies to date have not reported any significant risk even up to five years of use.

Antibiotics for Kidney Infections (Pyelonephritis)
Treating Uncomplicated Kidney Infections. Patients with uncomplicated kidney infections (pyelonephritis) may be treated at home with oral antibiotics. Such patients are healthy and non pregnant. They typically are experiencing fever, chills, and flank pain. However, they are not nauseous or vomiting and show no symptoms or signs of kidney involvement or complicated infection.

The standard treatment for uncomplicated pyelonephritis is a 14-day course of oral antibiotics, usually trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone. Sometimes patients with uncomplicated pyelonephritis are first given an antibiotic injection, if indicated.

Oral amoxicillin or amoxicillin-clavulanate (Augmentin) may be prescribed for women with bacteria that do not respond to standard regimens (e.g., gram-positive organisms, including Enterococcus species and S. saprophyticus).

A urine culture is may be obtained within one week of completion of therapy and again four weeks later.

Treating Moderate to Severe Kidney Infections. Patients with moderate to severe acute kidney infection and those with severe symptoms or other complications may need to be hospitalized. In such cases, antibiotics (ceftriaxone and gentamicin) are usually given intravenously for three to five days or until symptoms are relieved and patients have not shown any signs of fever for 24 to 48 hours. One study reported that oral cefixime may be as effective as intravenous antibiotics in small children with UTIs and fever. In any case, adult patients are switched to oral antibiotic therapy after symptoms have subsided and continued for another two weeks; treatment for longer than this has no additional benefit.

If fever and back pain persist after 72 hours of antibiotic administration, the physician will usually order imaging tests to see if abscesses, obstructions, or other abnormalities are present.

Treating Chronic Kidney Infections. Patients with chronic pyelonephritis are often treated with long-term antibiotics, even during periods when they have no symptoms.

Treatments for Specific Populations
Treating the Pregnant Woman. Pregnant women should be screened for UTIs, since they are at high risk for UTIs and their complications. The antibiotics used during pregnancy are amoxicillin, ampicillin, nitrofurantoin, or an oral cephalosporin. Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Resistance rates to this drug are also very low. They should not take fluoroquinolones.

Pregnant women with even asymptomatic bacteriuria (evidence of infection but no symptoms) have a 30% risk for acute pyelonephritis in their second or third trimester. Therefore they need screening and treatment for this condition. In such cases, they should be treated with a short course of antibiotics (three to five days). If this condition is recurrent, they can take low-dose nitrofurantoin. For an uncomplicated UTI, pregnant women may need longer-term antibiotics (seven to 10) for urinary tract infections.

Women with pyelonephritis have, to date, been hospitalized for treatment. One study suggested that outpatient treatment may be safe and effective if the condition develops in the early months of pregnancy. In the study, women were given an injection of ceftriaxone in the emergency room, observed for a few hours, and then administered a second injection. After this, they were sent home with a prescription for an oral antibiotic.

Treating Women with Diabetes. Women with diabetes have more frequent and more severe UTIs than women without the disease. Many experts recommend that patient with diabetes and UTI, even an uncomplicated infection, be treated with antibiotics for seven to 14 days. People with diabetes have higher than average rates of asymptomatic bacteriuria, but it is unclear whether they should be screened and treated for this condition. A 2003 study indicated that treating this condition had little value in these women and did not prevent complications.

Treating Urethritis in Men. Urethritis in men has typically been treated with a seven-day regimen of doxycycline. Some research is showing that a single dose of azithromycin may be just as effective while causing fewer side effects. One-dose treatment also improves compliance, so cure rates may even be better than with a long-term regimen. Of concern, however, is an infection that spreads to the prostate gland, which is harder to treat, so most physicians still prefer the longer regimen. It should be noted that azithromycin and similar antibiotics do not cure the infection and may mask the symptoms of an accompanying sexually transmitted disease, such as gonorrhea. Tests for such diseases should be conducted if urethritis is diagnosed.

Treating Children with UTIs. Children with UTIs are generally treated with TMP-SMX or cephalexin (Keflex). The optimal duration is unclear. In one major 2003 analysis, a two- to four-day treatment was as effective as seven to 14 days. If initial therapy fails, then one injection of ceftriaxone or 10 days of intravenous gentamicin nearly always cure the infection.

Children can be treated effectively for acute pyelonephritis with oral cefixime (Suprax) or a short course (two to four days) of an intravenous (IV) antibiotic (typically gentamicin given in one daily dose). The IV antibiotic is then followed by an oral antibiotic.

Either long-term antibiotics or surgery to correct vesicoureteral reflux (VUR) are options to prevent infections in children (particularly girls) with VUR. It is unclear if either approach is any more effective than the other. Studies are finding no significant difference in kidney damage between children who are treated with antibiotics or surgery. Antibiotic treatment usually continues for years with the idea that the condition will resolve when the child has grown. A 2002 study reported that continuous antibiotics prevented infection in 72% of girls and all of boys over more than two years. Antibiotics were stopped after about four years on average, and 42% experienced UTIs or kidney infections afterward. The use of long-term antibiotics in VUR is controversial, however. There have been few well-conducted studies, and in one study, there was no difference in risk for UTI or kidney damage between patients who were taking the antibiotics and those who weren't. There is also the concern of increasing the rates of bacteria that are resistant to common antibiotics.

Management of Catheter-Induced Urinary Tract Infections
Preventing Catheter-Induced Infections

Catheter-induced urinary tract infections are very common and preventive measures are extremely important. Catheters should not be used unless absolutely necessary, and they should be removed as soon as possible. Reducing the risk for infections during long-term catheter use, however, remains problematic.

Catheter Coatings. Catheter coatings, such as silver nitrate, antibiotics, and other substances, are being tested and are showing some benefits, but the problem is still not resolved. One promising catheter (LoFric) uses a so-called hydrophilic coating consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the catheter surface, putting up a water barrier to reduce friction. In a 2003 study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters. If a catheter is required for long periods, it is best to use it intermittently if possible (as opposed to an indwelling catheter). Some physicians recommend replacing it every two weeks to reduce the risk of infection and irrigating the bladder with antibiotics between replacements.

Daily Hygiene. A typical catheter is one that has been preconnected and sealed and uses a drainage bag system. To prevent infection, some of the following tips may be helpful:

Drink plenty of fluids, including three glasses of cranberry juice a day.
The catheter tube should be free of any knots or kinks.
Clean the catheter and the area around the urethra with soap and water daily and after each bowel movement. (Women should be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area.
Never disconnect the catheter from the drainage bag without careful instructions from a health professional on strict methods for preventing infection.
Keep the drainage bag off the floor.
Stabilize the bag against the leg using tape or some other system.
Antibiotics for Catheter-Induced Infections

Patients using catheters who develop UTIs with symptoms should be treated for each episode with antibiotics and the catheter should be removed, if possible. A major problem in treating catheter-related UTIs is that the organisms involved are constantly changing. Because there are likely to be multiple species of bacteria, experts generally recommend an antibiotic that is effective against a wide variety of microorganisms. These medications include those in the fluoroquinolone group and drug combinations such as ampicillin plus gentamicin or imipenem plus cilastatin.

Although high bacteria counts in the urine (bacteriuria) occur in most catheterized patients, administering antibiotics to prevent a UTI is rarely recommended. Many catheterized patients do not develop symptomatic urinary tract infections even with high bacteria counts. If bacteriuria occurs without symptoms, antibiotic therapy has little benefit if the catheter is to remain in place for a long period.


Catheterization is accomplished by inserting a catheter (a hollow tube, often with and inflatable balloon tip) into the urinary bladder. This procedure is performed for urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured. Catheterization in males is slightly more difficult and uncomfortable than in females because of the longer urethra.