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URINARY TRACT INFECTIONS: BASIC PRINCIPLES OF THERAPY

URINARY TRACT INFECTIONS: BASIC PRINCIPLES OF THERAPY

Bibliography

Many controversies about the treatment of urinary tract infections remain unresolved. Bacteriuria may be asymptomatic and not require antimicrobial therapy or may be associated with upper or lower tract infection. Although the treatment of cystitis differs significantly from that of pyelonephritis, the physician may not know with certainty where the infection is localized. Despite these controversies and uncertainties, there are several well-documented guidelines for the treatment of urinary tract infection:

1.
Patients with upper tract symptoms require 10 days to 2 weeks of antimicrobial therapy.

2.
Patients with high fever, chills, and elevated WBC counts require initial IV antimicrobial therapy, guided by urine Gram’s stain.

3.
Patients with community-acquired upper urinary tract infection who have gram-negative bacilli on urine Gram’s stain can be treated with a wide range of antimicrobial agents. Agents such as third-generation cephalosporins, aztreonam, trimethoprimsulfamethoxazole, and ureidopenicillins are widely recommended. Ampicillin and sulfonamides are not used in this setting because of the increasing resistance of Escherichia coli.

4.
In patients with hospital-acquired pyelonephritis, a history of recurrent infection, or prior infection with a resistant organism, initial antimicrobial therapy must have an antipseudomonal spectrum. Depending on the institution’s antimicrobial resistance profile, agents such as ceftazidime, tobramycin or amikacin, imipenem, ticarcillin-clavulanic acid, or ciprofloxacin may be initiated. When results of antimicrobial susceptibility tests become available, therapy can be revised. If aminoglycoside therapy was begun in an elderly patient or a patient with renal insufficiency, a safer antimicrobial should be chosen once susceptibility results define all options.

5.
Bacteria should be cleared from the urine within 24 to 48 hours of therapy. If bacteriuria persists, antimicrobial therapy should be changed based on susceptibility results.

6.
Patients who have persistent fever or toxicity despite appropriate antimicrobial therapy should be investigated for perinephric or renal cortical abscess.

7.
In patients with uncomplicated upper tract infection, antimicrobial therapy can be switched from IV to oral after a few days of defervescence. The quinolones, particularly ciprofloxacin, have been used extensively in this setting. Selected patients can be treated with oral therapy initially, provided they are not toxic, immunosuppressed, pregnant, or vomiting.

8.
Many studies have found that short-course therapy for lower urinary tract infection (3 days or even one dose) is as effective as a 7- to 14-day course. These studies have generally been performed in young women with symptoms of cystitis. Many different oral regimens have been used, including trimethoprim-sulfamethoxazole, norfloxacin, ciprofloxacin, cephalexin, and amoxicillin-clavulanate (Augmentin). Recent reviews have warned that single-drug therapy for cystitis is somewhat less effective than 3-day regimens. Men with cystitis generally receive at least 7 days of antibiotic therapy because of concern for complicating factors, particularly prostatitis.

9.
Cystitis in elderly women has not been well studied. Long-term eradication of bacteriuria is less likely to be seen in elderly women, particularly if their functional status is poor. Elderly women with typical symptoms of cystitis should probably be treated for 3 days with a quinolone or trimethoprim-sulfamethoxazole. Relapse after 3 days should be considered evidence for upper tract disease, and treatment guidelines, as previously described, should be followed.

10.
Prospective studies have confirmed the value of in vitro antimicrobial susceptibility testing. The initial disappearance of bacteriuria is closely correlated with the susceptibility of the microorganism to the concentration of the antimicrobial agent achieved in the urine.

11.
The relative importance of antimicrobial concentrations obtained in the serum and urine in the treatment of urinary tract infections remains controversial. When concomitant bacteremia occurs, blood levels achieve critical importance, and parenteral administration of drugs is required. Urinary tract infections can be cured with drugs that achieve therapeutic concentrations only in the urine. The majority sentiment is that cure of urinary tract infections depends on antimicrobial concentrations in the urine rather than in the serum.

12.
Many infectious disease experts prefer to administer a bactericidal drug for urinary tract infections, but there is no documentation that a bactericidal compound has greater efficacy than a bacteriostatic drug. There is no evidence that unselected combinations of multiple antimicrobials given simultaneously produce a higher cure rate than does an effective member of the combination given singly.

13.
Drug efficacy can be enhanced by awareness of the fact that the antibacterial activity of many chemotherapeutic agents used in the treatment of urinary tract infections is affected by changes in urinary pH.

Alkalinization of urine increases the activity of the aminoglycosides (streptomycin, kanamycin, gentamicin, tobramycin, amikacin), benzylpenicillin, and erythromycin.

Acidification of the urine increases the activity of the tetracyclines, nitrofurantoin, and methenamine mandelate.
Controlled studies have demonstrated that efficacy will be enhanced by appropriate modification of urinary pH. (S.L.B.)
Bibliography
Dembry LM, Andriole VT. Renal and perirenal abscesses. Infect Dis Clin North Am 1997;11:663.
Renal carbuncles and corticomedullary abscesses usually resolve after 1 week of antibiotic therapy. The patient should then be evaluated by an appropriate imaging technique.
Fihn SD, et al. Trimethoprim-sulfamethoxazole for acute dysuria in women: a single-dose or 10-day course. A double-blind, randomized trial treatment. Ann Intern Med 1985;108:350.
A history of urinary tract infection, use of spermicide, and the presence of more than 105 bacteria correlate with failure of the single-treatment regimen.
File TM Jr, Tan JS. Urinary tract infections in the elderly. Geriatrics 1989;44 (Suppl A):15.
Describes different approaches to managing urinary tract infection in the elderly.
Gleckman R, et al. Therapy of symptomatic pyelonephritis in women. J Urol 1985; 133:176.
Reports that a 10-day course of therapy is adequate for acute pyelonephritis in elderly women.
Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 1997;11:551.
Detailed literature review of treatment for cystitis and uncomplicated pyelonephritis in both men and women.
Johnson JR, Stamm WE. Diagnosis and treatment of acute urinary tract infections. Infect Dis Clin North Am 1987;1:773.
Recommends antimicrobial therapy based on changing susceptibility patterns of gram-negative bacilli.
Naber KG. Use of quinolones in urinary tract infections and prostatitis. Rev Infect Dis 1989;11 (Suppl 5):S1321–S1337.
Reviews the role of quinolones in complicated and uncomplicated urinary tract infections.
Norby SR. Short-term treatment of uncomplicated lower urinary tract infections in women. Rev Infect Dis 1990;12:458.
Reviews of large numbers of patients indicate that short-course therapy for cystitis is not as effective as traditional regimens.
Philbrick JT, Bracikowski JP. Single-dose antibiotic treatment for uncomplicated urinary tract infections. Less for less? Arch Intern Med 1985;145:1672.
Single-dose therapy is not recommended for uncomplicated urinary tract infection.
Raz R, et al. Comparison of single-dose administration and 3-day course of amoxicillin with clavulanic acid for treatment of uncomplicated urinary tract infection in women. Antimicrob Agents Chemother 1991;35:1688.
A 3-day regimen is better than single-dose therapy only in the population with recurrent urinary tract infection.
Ronald AR, et al. Complicated urinary tract infection. Infect Dis Clin North Am 1997;11:583.
Urinary tract infections may be complicated by structural abnormalities, metabolic abnormalities, immunologic deficiencies, or unusual organisms. Complicated infections usually require longer periods of therapy, although better data are needed to make definitive recommendations.
Sobel JD, Kaye D. Urinary tract infections. In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practice of infectious disease, 3rd ed. New York: Churchill Livingstone, 1990.
Expert discussion includes flow diagram of management decisions.
Stamey TA. Recurrent urinary tract infections in female patients: an overview of management and treatment. Rev Infect Dis 1987;9 (Suppl 2):S195.
Single-dose therapy is not effective in all patients with lower urinary tract infection; a 3-day course gives better overall results.
Stamm WE, McKevitt M, Counts GW. Acute renal infection in women: treatment with trimethoprim-sulfamethoxazole or ampicillin for 2 or 6 weeks. A randomized trial. Ann Intern Med 1987;106:341.
Supports 2-week course of antimicrobial therapy for uncomplicated pyelonephritis.
Trienekens TA, et al. Different lengths of treatment with co-trimoxazole for acute uncomplicated urinary tract infections in women. Br Med J 1989;299:1319.
Three days of therapy for cystitis was as effective as 7 days.
Yoshikawa TT, Nicolle LE, Norman DC. Management of complicated urinary infection in older patients. J Am Geriatr Soc 1996;44:1235.
Describes treatment for recurrent urinary tract infection and catheter-related bacteriuria, including the special considerations in the elderly.

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