Drug Therapy of Urinary Tract Infections

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Chapter 74

Drug Therapy of Urinary Tract Infections

Laura D. Rosenthal DNP, ACNP, FAANP

Urinary tract infections (UTIs) are one of the most common infections encountered today. In the United States UTIs account for more than 7 million visits to health care providers each year. Among sexually active younger women, 25% to 35% develop at least one UTI a year. Among older women in nursing homes, between 30% and 50% have bacteriuria at any given time. UTIs occur much less frequently in males but are more likely to be associated with complications (e.g., septicemia, pyelonephritis).

Infections may be limited to bacterial colonization of the urine, or bacteria may invade tissues of the urinary tract. When bacteria invade tissues, characteristic inflammatory syndromes result: urethritis, cystitis, pyelonephritis, and prostatitis.

UTIs may be classified according to their location, in either the lower urinary tract (bladder and urethra) or upper urinary tract (kidney). Within this classification scheme, cystitis and urethritis are considered lower tract infections, whereas pyelonephritis is considered an upper tract infection.

UTIs are referred to as complicated or uncomplicated. Complicated UTIs occur in both males and females and are associated with some predisposing factor, such as calculi, prostatic hypertrophy, an indwelling catheter, or an impediment to the flow of urine (e.g., physical obstruction). Uncomplicated UTIs occur primarily in women of childbearing age and are not associated with any particular predisposing factor.

Several classes of antibiotics are used to treat UTIs. Among these are sulfonamides, trimethoprim, penicillins, aminoglycosides, cephalosporins, fluoroquinolones, and two urinary tract antiseptics: nitrofurantoin and methenamine. With the exception of the urinary tract antiseptics, these drugs are discussed in other chapters. The basic pharmacology of the urinary tract antiseptics is introduced here.

Organisms That Cause Urinary Tract Infections

The bacteria that cause UTIs differ between community-associated infections and hospital-associated infections. Most (more than 80%) uncomplicated, community-associated UTIs are caused by Escherichia coli. Rarely, other gram-negative bacilli—Klebsiella pneumoniae and Enterobacter, Proteus, Providencia, and Pseudomonas species—are the cause. Gram-positive cocci, especially Staphylococcus saprophyticus, account for 10% to 15% of community-associated infections. Hospital-associated UTIs are frequently caused by Klebsiella, Proteus, Enterobacter and Pseudomonas species, staphylococci, and enterococci; E. coli is responsible for less than 50% of these infections. Although most UTIs involve only one organism, infection with multiple organisms may occur, especially in patients with an indwelling catheter, renal stones, or chronic renal abscesses.

Specific Urinary Tract Infections and Their Treatment

In this section, we consider the characteristics and treatment of the major UTIs: acute cystitis, acute urethral syndrome, acute pyelonephritis, acute bacterial prostatitis, and recurrent UTIs. Most of these can be treated with oral therapy at home. The principal exception is severe pyelonephritis, which requires intravenous (IV) therapy in a hospital. Drugs and dosages for outpatient therapy in nonpregnant women are shown in Table 74.1.

TABLE 74.1

Regimens for Oral Therapy of Urinary Tract Infections in Nonpregnant Women

Drug Dose Duration
First-Line Drugs
Trimethoprim/sulfamethoxazole 160/800 mg 2 times/day 3 days
Nitrofurantoin (monohydrate/macrocrystals) 100 mg 2 times/day 5 days
Fosfomycin 3 g once 1 day
Second-Line Drugs
Ciprofloxacin 250 mg 2 times/day 3 days
Levofloxacin 250 mg once daily 3 days
First-Line Drugs
Trimethoprim/sulfamethoxazole 160/800 mg 2 times/day 14 days
Ciprofloxacin 250–500 mg 2 times/day 7–14 days
Levofloxacin 250 mg once daily* 5–10 days
Second-Line Drugs
Amoxicillin (with clavulanic acid) 500 mg 3 times/day 10–14 days
Cephalexin 500 mg 4 times/day 10–14 days
Cefotaxime 1 g 3 times/day 10–14 days
Ceftriaxone 1–2 g once daily 10–14 days
Trimethoprim/sulfamethoxazole 160/800 mg 2 times/day 7–14 days
Ciprofloxacin 500 mg 2 times/day 5–14 days
Levofloxacin 750 mg once daily 5–14 days
Amoxicillin (with clavulanic acid) 500 mg 3 times/day 7–14 days
Cephalexin 500 mg 3 times/day 7–14 days
Trimethoprim/sulfamethoxazole 40/200 mg at bedtime 3 times/wk 6 months
Trimethoprim 100 mg at bedtime 6 months
Nitrofurantoin 50–100 mg at bedtime 6 months

*For infection due to Escherichia coli without concurrent bacteremia.

Half of a single-strength tablet.

Acute Cystitis

Acute cystitis is a lower UTI that occurs most often in women of childbearing age. Clinical manifestations are dysuria, urinary urgency, urinary frequency, suprapubic discomfort, pyuria, and bacteriuria (more than 100,000 bacteria per milliliter of urine). It is important to note that many women (30% or more) with symptoms of acute cystitis also have asymptomatic upper UTI (subclinical pyelonephritis). In uncomplicated, community-associated cystitis, the principal causative organisms are E. coli (80%), S. saprophyticus (11%), and Enterococcus faecalis.

For community-associated infections, three types of oral therapy can be employed: (1) single-dose therapy; (2) short-course therapy (3 days); and (3) conventional therapy (7 days). Single-dose therapy and short-course therapy are recommended only for uncomplicated, community-associated infections in women who are not pregnant and whose symptoms began less than 7 days before starting treatment. As a rule, short-course therapy is more effective than single-dose therapy and hence is generally preferred. Advantages of short-course therapy over conventional therapy are lower cost, greater adherence, fewer side effects, and less potential for promoting emergence of bacterial resistance. Conventional therapy is indicated for all patients who do not meet the criteria for short-course therapy. Among these are males, children, pregnant women, and women with suspected upper tract involvement.

Several drugs can be used for treatment (see Table 74.1). For uncomplicated cystitis, trimethoprim/sulfamethoxazole and nitrofurantoin are drugs of first choice. In communities where resistance to these drugs exceeds 20%, the fluoroquinolones (e.g., ciprofloxacin, norfloxacin) are good alternatives. When adherence is a concern, fosfomycin, which requires just one dose, is a good choice. Beta-lactam antibiotics (e.g., amoxicillin; cephalexin and other cephalosporins) should be avoided because they are less effective than the alternatives, and less well tolerated.

Acute Uncomplicated Pyelonephritis

Acute uncomplicated pyelonephritis is an infection of the kidneys. The disorder is common in young children, older adults, and women of childbearing age. Clinical manifestations include fever, chills, severe flank pain, dysuria, urinary frequency, urinary urgency, pyuria, and, usually, bacteriuria (more than 100,000 bacteria per milliliter of urine). E. coli is the causative organism in 90% of initial community-associated infections.

Mild to moderate infection can be treated at home with oral antibiotics. Preferred options are trimethoprim/sulfamethoxazole, trimethoprim alone, ciprofloxacin, and levofloxacin. Treatment should last 14 days.

Severe pyelonephritis requires hospitalization and IV antibiotics. Options include ciprofloxacin, ceftriaxone, ceftazidime, ampicillin plus gentamicin, and ampicillin/sulbactam. After the infection has been controlled with IV antibiotics, a switch to oral antibiotics should be made, usually within 24 to 48 hours.

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Apr 8, 2017 | Posted by in PHARMACY | Comments Off on Drug Therapy of Urinary Tract Infections
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