Pharmacologic Therapy for Acute Cystitis in Adults: A Review of Treatment Options

Karen A. Karlowicz, MSN, RN, CURN


This article is reprinted with permission of the Society of Urologic Nurses and Associates (SUNA) from Urologic
Nursing, March 1997, 17(3) , p. 106-116 (published by Mosby Yearbook Incorporated).
This article is a review of the current pharmacologic treatment options for acute cystitis in adults. It is intended to provide the urologic nurse with practical information regarding the administration of the most frequently prescribed antimicrobial drugs. Pharmacologic agents discussed are of the following classes of antimicrobials: beta-lactam antibiotics, fluoroquinolones, sulfonamides, and urinary-specific antiinfectives. The discussion of each drug class includes information about the indications, pharmacodynamics, pharmacokinetics, and recommended dosage regimens. Specific factors that will influence the health care provider's choice of the most appropriate antimicrobial for the treatment of acute cystitis are examined. Key teaching points that should be incorporated into patient education by the nurse are reviewed. Urol Nurs 1997;17:106-16.
                     
It has been estimated that reports of irritative voiding, characteristic of lower urinary tract infection (UTI), account for more than 6 million patient visits annually to health care providers. A 7- to 10-day course of an appropriate urinary antimicrobial was once considered the standard treatment for acute cystitis in adults. However, in recent years considerable effort has been devoted toward decreasing the emergence of resistant organisms and simplifying the management, improving the cost effectiveness, and enhancing the patient compliance of treatment by investigating the efficacy of shorter dosage regimens. At present, most adults with uncomplicated acute cystitis often caused by Escherichia coli, the most common urinary pathogen, are treated with a 3-day course of an oral urinary antimicrobial. Single-dose therapy, although attractive, is generally considered to be less effective in fully eradicating bacteria than 3-, 5- or 7-day regimens.*






*The recent release of Fosfomycin tromethamine (monurol) for single-dose treatment of uncomplicated UTI represents an important advancement. A full review of this drug including its efficay compound to other agents will be featured in the next issue of Urologic Nursing.

For all patients with acute cystitis, the prompt eradication of symptomatic infection and the prevention of disease progression to the kidneys are the primary goals of treatment. Antimicrobials that are commonly prescribed for the treatment of adult acute cystitis include beta-lactam antibiotics, fluoroquinolones, sulfonamides, and urinary-specific antiinfectives. The specific antimicrobial agent selected to accomplish treatment goals should have the ability to achieve higher urine than serum concentrations for a prolonged period, selectively affect the susceptibility of bacterial cells, impede the development of clinically significant bacterial resistance, and demonstrate a clinical response with few adverse reactions, all at a reasonable cost.

Pharmacologic Treatment Options

Beta-lactam antibiotics

Penicillin and cephalosporin drugs are classified as beta-lactam antibiotics. Of the penicillin-type drugs, ampicillin (Omnipen, Principen) and amoxicillin (Amoxil, Wymox) may be for the treatment of an initial acute UTI and for the treatment of bacterial persistence. Penicillin-susceptible organisms causing

   
Karen A. Karlowicz is Adjunct Instructor in the School of Nursing College of Health Sciences at Old Dominion University in Norfolk, Virginia.

Copyright © 1997 by the Society of Urologic Nurses and Associates, Inc.

1053-816X/97/$5.00 + 0 33/1/83841

 





UTI include strains of E. coli, Klebsiella sp., and Enterobacter sp. Ampicillin and amoxicillin are also sometimes effective against gram-positive urinary pathogens such as streptococci, enterococci, and Staphylococcus saprophyticus.

Cephalosporin drugs are used for the treatment of acute UTI and for perioperative prophylaxis of UTI. First-generation cephalosporins such as cefadroxil (Duricef, Ultrasef), cephalexin monohydrate (Cefanex, Cephalexin, Keflex), and cephradine (Velosef) are appropriate for the treatment of uncomplicated acute UTI caused by staphylococci, streptococci, E. coli, Proteus mirabilis, and Klebsiella species. Third-generation cephalosporins such as cefoperazone (Cefobid) and ceftazidime (Fortaz, Pentacef, Tazidime) are high-power, broad-spectrum agents used for complicated acute UTI caused by resistant E. coli and Proteus and by Pseudomonas aeruginosa. Preliminary in vitro and clinical studies on cefepime, a fourth-generation cephalosporin, suggest this drug may be beneficial in the parenteral treatment of complicated acute UTI.1 Second-generation cephalosporins are not usually prescribed for the treatment of UTIs because they offer no therapeutic advantage over other pharmacologic agents.2

Penicillins and cephalosporins act similarly to inhibit mucopeptide synthesis in the bacterial wall, thereby causing destruction of the bacterial cell. They are most effective when administered in high concentrations during the peak of an infectious process when bacteria are multiplying and growing at rapid rates. Beta-lactam antibiotics are considered bactericidal, with the primary difference between penicillins and cephalosporins being their antibacterial spectrum. Penicillins and cephalosporins have the ability to permeate most body tissues and fluids and are primarily excreted unchanged in the urine by glomerular filtration and active tubular secretion (Table 1).		  

At one time beta-lactam antibiotics, in particular amoxicillin, were among the most popular drugs used to treat acute UTI. However, recent studies have shown a dramatic decrease in the sensitivity rates of E. coli to ampicillin from 91.4% in 1971 to 65% in 19893 to 38% in 1993.4 There are also anecdotal reports of lower cure rates and an increased frequency of bacterial persistence or episodes of reinfection when ampicillin, amoxicillin, or oral cephalosporins are used. More significant is the fact that bacterial eradication could not be effectively accomplished when these drugs were prescribed as a single-dose or 3-day regimen.4-6 Thus UTI culture-sensitive to beta-lactam antibiotics requires treatment for the traditional period of 7 to 10 days. The usual oral dosage for amoxicillin is 250 mg every 8 hours; the oral dosage for cephalexin is 500 mg every 12 hours.

Fluoroquinolones

Fluoroquinolones are recommended for use in adults with uncomplicated and complicated UTI. Because of their ability to achieve high therapeutic levels in urine, ciprofloxacin (Cipro), enoxacin (Penetrex), norfloxacin (Noroxin), levofloxacin (Levaquin), and ofloxacin (Floxin) are particularly effective against bacteria infecting the urinary tract. Urinary pathogens sensitive to the fluoroquinolones include Entero-bacteriaceae, gram-positive organisms such as staphylococci, some enterococci, and most strains of P. aeruginosa.2,7 Although oral fluoroquinolones offer a broad spectrum of activity and have proven to be safe and clinically effective against many community-acquired organisms, concerns have been raised about the emerging resistance of Staphylococcus aureus, P. aeruginosa, and Serratia marcescens to ciprofloxacin.8,9 For this reason it is suggested that the use of oral fluoroquinolones be restricted to persons with complicated UTI caused by bacteria resistant to other antimicrobials, those unable to tolerate other oral agents, those for whom parenteral agents may be the only alternative, and infections in which other oral agents have failed.10 When prescribed empiri-

 
cally for the treatment of uncomplicated acute UTI, the minimum effective dosage should be used.

Fluoroquinolones are bactericidal. The bacterial-killing mechanism of these drugs works to inhibit DNA gyrase (an enzyme) and to interfere with DNA replication, repair, and transcription before ultimately causing bacterial cell death. When given in high concentrations, fluoroquinolones cause a dose-dependent inhibition of RNA synthesis, which actually results in decreased bacterial killing.7 These drugs also tend to exhibit a distinct postantibiotic effect for gram-negative and gram-positive bacteria, meaning that bacterial growth does not occur for several hours after transient exposure to the drug. It is this property of the fluoroquinolones that enables these drugs to be given according to the short dosage regimens now recommended for UTI.9

After oral administration each of the fluoroquinolone drugs is absorbed rapidly, but with some degree of variability, from the gastrointestinal tract. Ofloxacin and levofloxacin are highly absorbed, ciprofloxacin and enoxacin are considered to be moderately absorbed, and norfloxacin is absorbed least well.7 Ciprofloxacin, enoxacin, levofloxacin, and ofloxacin are widely distributed, with high concentrations achieved in the urine and in most tissues including the kidney and prostate. Norfloxacin does not attain a high serum concentration but does concentrate well in urine and the gastrointestinal tract. The elimination of enoxacin, levofloxacin, and ofloxacin is primarily by renal excretion. Ciprofloxacin elimination is a combination of renal, biliary, and transintestinal excretion, whereas norfloxacin undergoes biotransformation in the liver followed by biliary and renal excretion.

Numerous comparative studies have evaluated the overall effectiveness of fluoroquinolones versus other urinary antimicrobials and the efficacy and safety of various dosing Regimens 8, 11-13 current evidence suggests that the short-term efficacy of fluoroquinolones




is comparable to that of trimethoprim-sulfamethoxazole (TMP-SMZ).7-9 Single-dose therapy of any of the fluoroquinolone drugs is less effective (75% to 96% bacterial response) than 3-, 5-, and 7-day regimens (92% to 100% bacterial response) in eradicating uncomplicated acute UTI.

Ciprofloxacin is the most frequently prescribed fluoroquinolone. It is preferred by health care providers because it enables them to treat difficult urinary infections with an oral medication that in the past would have required parenteral therapy.14 For treatment of uncomplicated acute UTI, ciprofloxacin is as effective as TMP-SMZ and is superior to nalidixic acid or trimethoprim alone; it is better than TMP-SMZ for the treatment of complicated UTI. A series of multicenter, prospective, randomized, double-blind trials demonstrated that the minimum effective dose of Ciprofloxacin for uncomplicated acute UTI was 100 mg twice daily for 3 days.12 This dosing schedule was found to have a bacterial and clinical response equivalent to a regimen of 250 mg twice daily for 3 days.

Sulfonamides

Sulfonamides may be prescribed for the treatment of uncomplicated acute UTI caused by community-acquired organisms such as E. coli, Klebsiella, Enterobacter, S. aureus, P. mirabilis, P. vulgaris, and S. saprophyticus. They are not useful for treating urinary infections caused by P. aeruginosa. For patients with a first-time urinary infection, sulfonamides should be considered a viable treatment option because of their ease of administration, low cost, safety, and effectiveness.

Most gram-positive and gram-negative urinary pathogens are sensitive to the broad-spectrum bacteriostatic activity of the sulfonamides. The mechanism of action of a sulfonamide, such

 

as sulfamethoxazole (Gantanol) or sulfisoxazole (Gantrisin) is competitive inhibition of para-aminobenzoic acid, a necessary element in bacterial folate synthesis, which ultimately prevents bacterial cell replication. Sulfamethoxazole and sulfisoxazole are considered intermediate-acting sulfonamides with a great degree of solubility in urine. An alkaline urine tends to enhance the efficacy of the sulfonamides.

Seventy percent to 100% of an oral dose of a sulfonamide is rapidly absorbed by the gastrointestinal tract and is distributed throughout all body tissues. Biotransformation occurs in the liver and is followed by elimination primarily through renal excretion by glomerular filtration; small amounts may also be eliminated in other bodily secretions such as stool, bile, and breast milk. A nonalkaline urine and inadequate fluid intake may cause sulfonamides to precipitate, contributing to the development of crystalluria and sometimes the formation of calculi.

When administering sulfamethoxazole, an initial loading dose is required to quickly establish a therapeutic concentration of the drug in the urine. An initial loading dose is considered unnecessary when sulfisoxazole is administered, because the drug is rapidly absorbed and promptly appears in high concentrations in the urine. A 3-day regimen is suggested for patients with a first-time UTI; treatment for up to 7 days may be required for bacterial persistence and reinfection.

Urinary-specific antiinfectives

Cinoxacin (Cinobac). Cinoxacin is recommended for the treatment of initial uncomplicated acute UTI and instances of persistent bacteriuria and reinfection. Microorganisms usually susceptible to cinoxacin include E. Coli, Klebsiella sp. Enterobacter sp., P. mirabilis, and P. vulgaris. Cinoxacin is a quinolone-type drug chemically related to nalidixic acid. It is considered a bactericidal agent that acts by inhibiting DNA replication and is active within the full range of urinary pH that is normally 4.5 to 8.0. After oral administration,

 

cinoxacin is rapidly absorbed into the bloodstream, however, a 30% decrease in the peak serum concentration may result when the drug is taken concurrently with food. Oral cinoxacin is excreted by the kidneys, with 97% of the drug present in the urine within 24 hours of ingestion.

Cinoxacin should be administered in two to four divided doses to equal a total daily dosage of 1 gm for the treatment of uncomplicated acute UTI, bacterial persistence, and episodes of reinfection. No evidence suggests that cinoxacin is effective for short-course therapy; therefore treatment should be maintained for 7 to 14 days and until follow-up urine cultures are negative. A low daily dosage of cinoxacin may also be used for long-term prevention of bacteriuria. In women with a history of frequent episodes of urinary reinfection, cinoxacin may be used continuously for up to 5 months as preventative therapy.

Nalidixic acid (NegGram). Nalidixic acid may be used for primary treatment of uncomplicated acute UTI and for prolonged treatment for persistent bacteriuria or episodes of reinfection. It is particularly effective in treating UTI caused by gram-negative bacteria including E. coli, most strains of Proteus, Klebsiella sp., and Enterobacter sp.

Nalidixic acid is a quinolone drug that acts by interfering with DNA and RNA synthesis in susceptible gram-negative organisms for a bactericidal effect in urine. Like cinoxacin, it is effective over the full range of urinary pH. Nalidixic acid is quickly absorbed, then undergoes biotransformation in the liver to hydroxynalidixic acid before being rapidly excreted by the kidney; approximately 4% of the drug is also excreted in the feces. Impaired renal function may significantly alter renal excretion of nalidixic acid, thereby causing an increase in serum concentration levels and a decrease in urine levels.

Nalidixic acid should be administered to achieve a total daily dosage of 4 gm. For many patients, however, this dosage level is associated with a high incidence of adverse affects. As an alternative, nalidixic acid can be administered




  in a dose of 0.5 gm every 8 hours. This regimen seems to be better tolerated while maintaining the optimal bactericidal effect of the drug.6 After the initial treatment period the dosage of nalidixic acid may be reduced to 2 gm/day or less for prolonged or suppressive treatment.

Methenamine (Hiprex, Mandelamine). Methenamine is used for long-term prophylactic or suppressive therapy of UTI in patients who are at risk for bacterial reinfection. This drug is not appropriate for the treatment of acute symptomatic infection but instead should be initiated after the UTI has been eradicated with another culture-sensitive antimicrobial. Methenamine exerts a bactericidal effect by decomposing in the urine to produce ammonia and formaldehyde. The formaldehyde is the by-product to which most bacteria are sensitive when its concentration in urine rises to more than 20 µg/ml. For methenamine to be effective, an acidic urine with a pH < 5.5 must be maintained. The combination of methenamine with acid salts (hippurate and mandelate) helps to maintain the urinary pH in the desired range.

Methenamine is quickly absorbed after oral administration. It undergoes biotransformation in the liver and is excreted by glomerular filtration and tubular secretion. The effectiveness of methenamine depends on an adequately maintained urine concentration of formaldehyde that is easily altered by an increase in the pH of the urine, an increased fluid intake and high urine output, and the duration that urine is retained in the bladder. Peak urine concentrations of formaldehyde usually occur 2 hours after a single dose of methenamine hippurate and 3 to 8 hours after a single dose of methenamine mandelate. Formaldehyde concentration levels in the urine should stabilize at a constant level within 2 to 3 days after a methenamine treatment regimen is initiated, assuming an acidic urine can be maintained.

A total daily adult dosage of 1 gm of methenamine should be administered		   in two divided doses for suppressive or preventive therapy of UTI. Some suggest, however, that treatment with methenamine should be used only when suppressive therapy with other antimicrobials has failed.15 Because there is little risk of toxicity with prolonged use with methenamine, treatment may continue for 6 months or longer.

Nitrofurantoin (Furadantin, Macrodantin). Although nitrofurantoin may be used for primary treatment of uncomplicated acute UTI, it also is among the few drugs considered safe for the treatment of acute UTI during pregnancy.2,16-18 The benefit of nitrofurantoin versus other agents is its ability to combat the development of resistant microorganisms. In most patients, however, it is more effective when used for prolonged treatment for persistent bacteriuria or episodes of reinfection caused by E. coli, enterococci, some strains of Klebsiella and Enterobacter sp., and S. aureus; it is ineffective against Proteus sp.

Nitrofurantoin is a drug that is bacteriostatic in low concentrations and bactericidal in concentrations greater than 10 µ/ml. Its mechanism of action is inhibition of bacterial acetyl coenzyme A with disruption of cell wall formation. An oral dose of nitrofurantoin is fully absorbed from the gastrointestinal tract. The macrocrystalline form of the drug dissolves slower; therefore the rate of absorption is slower. When taken with food, the bioavailability of nitrofurantoin is enhanced, and there is less gastrointestinal upset. Biotransformation occurs rapidly before the drug is excreted by way of glomerular filtration and tubular secretion. As much as 30% to 50% of the drug is excreted in the urine unchanged. An alkaline urine decreases the antimicrobial activity of nitrofurantoin.

Many health care providers have "rediscovered" nitrofurantoin and now consider it among the drugs of choice for the treatment of UTI. Nitrofurantoin has been in use for nearly 30 years and continues to be a safe, economical treatment option. Most notable is the fact that no clinically significant bacterial resistance has		   developed to this drug over the years.19 Nitrofurantoin may be administered as a 3-day regimen for treatment of uncomplicated acute UTI and symptomatic bacteriuria during pregnancy; the usual dosage is 50 mg every 8 hours. For instances of persistent bacteriuria or reinfecion, treatment should continue for 7 to 10 days. Patients who require long-term prophylaxis may safely take a lower dose of nitrofurantoin nightly for many months. In fact, it can be used for the duration of pregnancy if necessary.16

Trimethoprim (Proloprim). Whether it is given alone or in combination with sulfamethoxazole (Bactrim, Cotrim, Septra), trimethoprim is recommended for the initial treatment of uncomplicated acute UTI and for prolonged treatment for persistent bacteriuria or episodes of reinfection. Bacteria often susceptible to trimethoprim include E. coli. P. mirabilis, K. pneumoniae, Enterobacter sp., and S. saprophyticus. Bacteria often susceptible to TMP-SMZ include E. coli, Morganella morganii, P. mirabilis, P. vulgaris, and Klebsiella and Enterobacter sp.

Trimethoprim works to inhibit the enzymedihydrofolate reductase by blocking the production of tetrahydrofolic acid from dihydrofolic acid. Trimethoprim is effective because it binds much more strongly to bacterial dihydrofolate reductase than to human dihydrofolate reductase. The ability of trimethoprim to interfere with bacterial metabolism of dihydrofolic acid results in inhibition of bacterial biosynthesis of nucleic acids and proteins. When combined with sulfamethoxazole, there is a two-step synergistic inhibition of bacterial metabolism of dihydrofolic acid. The combination of trimethoprim and sulfamethox-azole is more effective in delaying the emergence of bacterial resistance than when either drug is used separately.

Oral trimethoprim is rapidly absorbed, achieving higher peak urine concentration than serum concentration levels within the first 1 to 4 hours after a single dose. Less than 20% of the drug undergoes biotransformation, whereas approximately 80% of trimethoprim is excreted unchanged. Excretion of trimethoprim is primarily by glomerular filtration and tubular secretion, but approximately 4% of the drug may be excreted in feces. The pairing of trimethoprim with sulfamethoxazole does not affect




  The biotransformation or excretion patterns of either drug.

A 3-day regimen of oral trimethoprim, either alone or in combination with sulfamethoxazole, is as effective as the 7-day regimen but with fewer adverse effects and a much lower cost. Dosing options for the 3-day course of treatment with trimethoprim may range from 300 mg taken once daily to 100 mg taken every 12 hours. As preventive therapy, 100 mg of trimethoprim every night or every other night is generally effective.

Of all the drugs available to treat UTI, most agree that TMP-SMZ is the best choice for single-dose therapy.2,5,6 However, the use of this regimen should be limited to the treatment of initial infections in healthy, sexually active women caused by community-acquired E. coli. For single-dose therapy to be effective, treatment must be initiated immediately on the onset of irritative voiding symptoms. Two double-strength (DS) tablets of TMP-SMZ is the suggested single dose; one DS tablet every 12 hours is the suggested dose for 3-day therapy.


Factors Influencing the Choice of Antimicrobial

The choice of the most appropriate antimicrobial for the treatment of acute UTI in adults should ultimately be based on urine culture and sensitivity testing results. Choosing the most effective pharmacologic agent also requires the incorporation of other factors into the decision-making process.

The type of infection is among the first variables to consider when choosing an appropriate antimicrobial for the treatment of UTI. Patients with a first-time or occasional acute UTI will require an antimicrobial that can effectively treat the infection with a single dose or 3-day regimen. Episodes of bacterial persistence or frequent reinfection, especially if complicated by the presence of a urinary tract abnormality or a coexisting illness, may require a more potent agent with a broader antibacterial spectrum. Sometimes		   a longer treatment period is necessary (e.g., the traditional 7 to 14 days).

To cure a UTI, an antimicrobial must be able to achieve a higher urine than serum concentration to successfully eradicate infectious pathogens from the urinary system. Those antimicrobials proven to be most effective in treating UTI often excrete more than 50% of the drug into the urine and demonstrate urinary levels several hundred times greater than serum levels.20 Based on the single criterion of urine concentration, Cephalexin with a urine concentration of 800 ug/ml, or ciprofloxacin with aurine concentration of up to 700 mg/ml would seem to be optimal treatment choices (Table 2).

The ability of an antimicrobial to achieve a therapeutic urine level also requires adequate renal function. Patients with renal insufficiency require either reduced dosages or lengthened dosage intervals to avoid retaining the drug and having development of nephrotoxicity. Their urine also must be carefully monitored to ensure that the bacteria is being effectively eliminated, because the inhibitory action of the antimicrobial is dependent on an adequate urine level.

Another important consideration for pharmacologic treatment of UTI is the ability of the antimicrobial to selectively affect the susceptibility of bacterial cells. In vitro testing has established which microorganisms will most likely be susceptible to a given agent. However, it is important to keep in mind that an institution's bacterial environment, the presence of a structural or functional urinary tract abnormality, and the accuracy of culture techniques and sensitivity testing create a certain degree of unpredictability regarding the effectiveness of any drug used for the treatment of UTI. Still, it is widely accepted that TMP-SMZ has a proven efficacy against community-acquired E. coli and thus is often the best choice for the empiric treatment of an initial uncomplicated acute UTI. Careful consideration should also be given to using a fluoroquinolone, because these drugs have shown good activity against a variety of gram-negative organisms, most importantly P. aeruginosa.		   The ability of an antimicrobial to impede the development of clinically significant bacterial resistance is extremely important. Nitrofurantoin is one antimicrobial that has developed little bacterial resistance in more than 30 years of use apparently because of its ability to attack multiple sites within the bacterial cell, whereas other antimicrobials typically act on a single target.19 The combination of TMP-SMZ has a synergistic effect that too limits the emergence of resistant bacterial strains. Despite the good track record of nitrofurantoin and TMP-SMZ, it has been estimated that 33% of all pathogens causing uncomplicated acute cystitis show in vitro resistance to sulfonamides, whereas 15% to 20% now show resistance to nitrofurantoin, and 5% to 15% are resistant to TMP-SMZ and trimethoprim.5

Although regional and environmental factors have some bearing on the development of bacterial resistance, so do practice patterns. All too often the doses of antimicrobials are too high, the treatment periods too long, and the antimicrobial spectrum too broad. This is especially true for fluoroquinolones, which have caused the emergence of bacterial resistance at a rate far greater than was anticipated because of the wide, sometimes indiscriminate, use of these drugs for treatment of UTI.10 For this reason the minimum effective dosage and shortest treatment regimen of other equally effective agents should be used to avoid the development of bacterial resistance, especially before a broad-spectrum drug like ciprofloxacin is used to treat UTI.

The practice of treating UTI with an appropriate antimicrobial for 3 days, or in some cases a single dose, has dramatically decreased the cost of treating this condition. Even when treatment is limited to 3 days, some antimicrobials cost considerably less, but with an efficacy equal to other more costly agents. A comparison of the average wholesale price for urinary antimicrobials commonly prescribed shows the cost of a 3-day regimen as follows: ciprofloxacin, $16.20; nitrofurantoin, $5.40; sulfisokazole, $4.23; cotrimoxazole DS, $2.40; and trimethoprim, $1.80. Although sulfisoxazole is a relatively inexpensive alternative, the popularity of TMP-SMZ and Fluoroquinolones for the treatment of UTI has caused a notable decline in the production and availability of this and other sulfonamides in the marketplace. In all cases the selection of an appropriate antimicrobial for treatment of UTI should be guided first by urine culture and sensitivity reports, second by the overall efficacy and risk of adverse reactions, and third by the cost effectiveness of the treatment.21





 

Patient Education

First and foremost, patients should be taught the importance of completing the entire course of treatment. Although shorter dosage regimens have significantly enhanced patient compliance, there is still the tendency to discontinue the drug once the symptoms of UTI have resolved. Emphasize to patients that the infection could persist and symptoms recur without strict adherence to the treatment schedule. To enhance compliance, explain to the patient or the caregiver the premise underlying the action of all urinary antimicrobials: the ability to achieve a therapeutic concentration in the urine.

Adequate fluid intake is extremely important for the patient taking a urinary antimicrobial and should approximate 2000 ml/24 hours. A higher fluid intake may compromise the efficacy of the prescribed antimicrobial by making the urine too dilute. Water is preferred over other types of beverages, and in most instances a full glass of water should be consumed with each oral dose of the drug. After the UTI has resolved and antimicrobial therapy has been discontinued, the high fluid intake should be maintained to keep urine dilute.

Although the role of cranberry juice in preventing bacteriuria and pyuria remains unclear, there is evidence that the beverage does have bacteriostatic properties.22 Therefore patients at risk for UTI should be encouraged to consume approximately 300 ml of cranberry (or blueberry) juice daily. Fluids to avoid that may irritate the bladder include alcohol, citrus juices, and caffeine products.

The absorption of urinary antimicrobials may be enhanced or compromised by the concomitant intake of food, representing another important teaching point. Those drugs that should be consumed with food include methenamine, nalidixic acid, and nitrofurantoin. The sulfonamides, fluoroquinolones, and most penicillins should be taken at least 2 hours after meals or on an empty stomach. Amoxicillin, cinoxacin, trimethoprim, and cephalosporin antibiotics may be administered without regard for meal times.

Those patients who require long-term suppressive or prophylactic therapy should be taught the importance of taking their medication just before going to bed. Urinary antimicrobials used for this purpose are more effective when they are able to reach peak urine concentration levels during the longest natural period of urinary retention: while the patient is asleep. Patients taking methenamine for suppressive therapy should be taught to monitor the pH of their urine to ensure the effectiveness of the drug.

  Although urinary antimicrobials are relatively safe, patients should be taught about the potential adverse effects for their prescribed medication (Table 1). Signs and symptoms of a hypersensitivity reaction to the medication, particularly if a sulfonamide has been prescribed, should be provided along with suggested strategies for managing a hypersensitive response.

Regular and complete bladder emptying should be stressed to all patients. A regular schedule of bladder emptying will allow the urinary system to reestablish its natural defense against infection. Maintaining a dilute urine along with a consistent voiding pattern is a preventive strategy that patients should adopt as a life-long habit. For female patients, voiding before and soon after intercourse is an important reminder.

Risk factors that contribute to the development of subsequent UTI should be reviewed. Among young women of childbearing age, there is a strong correlation between the use of a diaphragm and spermicidal gel for birth control and episodes of acute bacterial reinfection.23 Other factors commonly linked to the development of UTI, but not scientifically substantiated, remain important teaching points. Among these are the importance of regular adequate hygiene, wiping from front to back after defecation, discontinuing the use of tampons and feminine hygiene sprays, use of a shower instead of a tub for bathing, use of cotton versus synthetic underwear, and avoiding tight-fitting pants.

Finally, patients should be taught to recognize the signs and symptoms of UTI. Urinary frequency, urgency, and dysuria are classic signs of acute cystitis. Patients should also be cautioned not to ignore a dull ache or tenderness in the flank region and to be alert to urine that appears cloudy or that looks like it contains blood or smells different. Most important, patients need to be reminded to promptly contact their health care provider for treatment with an antimicrobial should any of these symptoms occur.		   References

1. Sharifi R, Geckler R, Childs S. Treatment of urinary tract infections: selecting an appropriate broad-spectrum antibiotic for nosocomial infections. Am J Med 1996;100:76S-82S.

2. Carson CC. Antimicrobial agents in urinary tract infections in patients with spinal cord injury. Urol Clin North Am 1993;20:443-52.

3. Gruneberg RN. Changes in the sensitivities of urinary pathogens, 1971-1989. J Antimicrob Chemother 1990;26(Suppl F):3-11.

4. Ansbach RK, Dybus, KR, Bergeson R. Uncomplicated E. Coli urinary tract infection in college women: a retrospective study of E. Coli sensitivities to commonly prescribed antibiotics. J Am Coll Health 1995;43:183-5.

5. Hooten TM. A simplified approach to urinary tract infections. Hosp Pract 1995;30:23-30.

6. Baily RR. Managment of lower urinary tract infections. Drugs 1993;45(Suppl 3):139-44.

7. Hendershot EF. Fluoroquinolones. Infect Dis Clin North Am 1995;9:715-30.

8. Gottlieb PL. Comparison of enoxacin versus trimethoprim-sulfamethoxazole in the treatment of patients with complicated urinary tract infections. Clin Ther 1995;17:493-502.

9. Ponte CD, Fisher ME. Use of fluoroquinolones: practical considerations. Am Fam Phys 1993;47:1243-9.

10. Thomas KS, Sanders WE, Sanders CC. USA resistance patterns among UTI pathogens. J Antimicrob Chemother 1994;33(Suppl A):9-15.

11. Donabedian H, O'Donnell E, Drill C, et al. Prevention of subsequent urinary tract infections in women by the use of anti-adherence antimicrobial agents: a double-blind comparison of enoxacin with co-trimoxazole. J Antimicrob Chemother 1995;35:409-20.

12. Iravani A, Tice AD, McCarty J, et al. Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infections in women. Arch Intern Med 1995;155:485-94.

13. Swedish Urinary Tract Infection Study Group. Interpretation of the bacteriologic outcome of antibiotic treatment for uncomplicated cystitis: impact of the definition of significant bacteriuria in a comparison of ritipenem acoxil with norfloxacin. Clin Infect Dis 1995;20:507-13.

14. Louie TJ. Ciprofloxacin: an oral quinolone for the treatment of infections with gram-negative pathogens. Can Med Assoc J 1994;150:669-76.

15. Kunin CM. Chemoprophylaxis and suppressive therapy in the management of urinary tract infections. J Antimicrob Ther 1994;33(Suppl A):51-62.

16. Mikhail MS, Anyaegbunam A. Lower urinary tract dysfunction in pregnancy: a review. Obstet Gynecol Survey 1995;50:675-83.

17. Bint, AJ, Hill D. Bacteriuria of pregnancy - an update on significance, diagnosis, and management. J Antimicrob Chemother 1994;33(Suppl A):93-7.

18. Kinningham RB. Asymptomatic bacteriuria in pregnancy. Am Fam Phys 1993;47:1232-8.

19. McOsker CC, Fitzpatrick PM. Nitrofurantoin: mechanism of action and implications for resistance development in common uropathogens. J Antimicrob Chemother 1994;33(Suppl A):23-30.

20. Schaeffer AJ. Infections of the urinary tract. In: Walsh PC, Retik AB, Stamey TA Vaughan ED, editors. Campbell's Urology (6th ed). Philadelphia: WB Saunders; 1992:731-806.

21. McDonald TM. The economic evaluation of antibiotic therapy: relevance to urinary tract infection. J Antimicrob Chemother 1994;33(Suppl A):137-45.

22. Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA 1994;271:751-4.

23. Hooten TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med 1996;335:468-74.


CE POST TEST



Pharmacologic Therapy for Acute Cystitis in Adults: A Review of Treatment Options



SUNA has been approved as a provider of Continuing Education by the California Board of Nursing, Provider #05556;
Florida Board of Nursing, Provider #27I0971; and Iowa Board of Nursing, Provider #169.



Answers to the post-test will be graded, and you will be advised that you have passed or failed within 60 days of receipt of your completed test. A score of 80% or above will comprise a passing grade. One contact hour will be awarded to participants who successfully complete the test.

Objectives

By reading this article, the learner will be able to achieve the following objectives:

1. Differentiate among the various antimicrobial drugs and the effectiveness of dosage regimens used to treat acute cystitis in adults.

2. Discuss factors influencing the choice of antimicrobial for the treatment of acute cystitis in adults.

3. Identify critical teaching points that should be incorporated into patient education concerning the management of
acute cystitis and the prevention of reinfection of the urinary tract.

CE Post-Test



Go to CE Test Questions

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