Guidelines for Treatment of Uncomplicated Cystitis and Pyelonephritis in Healthy, Community-Dwelling Women

For the treatment of acute pyelonephritis, the guidelines emphasize that all patients should have urine culture and susceptibility testing in order to tailor empiric therapy to the specific uropathogen.

Background

Uncomplicated cystitis is one of the most common indications for prescribing antimicrobial therapy to otherwise healthy women, but wide variation in prescribing practices has been described.^1-2 This has prompted the need for guidelines to help providers in their selection of empiric antimicrobial regimens. Antibiotic selection should take into consideration the efficacy of individual agents, as well as their propensity for inducing resistance, altering gut flora, and increasing the risk of colonization or infection with multi-drug resistant organisms.

Guideline Update

In March 2010, the Infectious Diseases Society of America (IDSA) and the European Society for Microbiology and Infectious Diseases (ESCMID) published new guidelines for the treatment of uncomplicated cystitis and pyelonephritis in healthy, community-dwelling women.³

First-line recommended agents for empiric treatment of uncomplicated cystitis are:

• nitrofurantoin for five days;
• trimethoprim-sulfamethoxazole for three days;
• fosfomycin in a single dose; or
• pivmecillinam (where available) for three to seven days.

Although highly efficacious, fluoroquinolones are not recommended as first-line treatment for acute cystitis because of their propensity for causing “collateral damage,” especially alteration of gut flora and increased risk of multi-drug resistant infection or colonization, including methicillin-resistant Staphylococcus aureus. Oral beta-lactams (other than pivmecillinam) have generally demonstrated inferior efficacy and more adverse effects when compared with the above agents, and should be used only if none of the preferred agents can be used. Specifically, amoxicillin and ampicillin are not recommended as empiric therapy due to their low efficacy in unselected patients, though may be appropriate when culture data is available to guide therapy. Narrow spectrum cephalosporins are also a potential agent for use in certain clinical situations, although the guidelines do not make any recommendation for or against their use, given a lack of studies.

For the treatment of acute pyelonephritis, the guidelines emphasize that all patients should have urine culture and susceptibility testing in order to tailor empiric therapy to the specific uropathogen. A 5-7 day course of an oral fluoroquinolone is appropriate when the prevalence of resistance in community uropathogens is ≤10%. Where resistance is more common, an initial intravenous dose of ceftriaxone or an aminoglycoside can be administered prior to starting oral therapy. Other alternatives include a 14-day course of trimethoprim-sulfamethoxazole or an oral beta-lactam.

Women requiring hospitalization for pyelonephritis should initially be treated with an intravenous antimicrobial regimen, the choice of which should be based on local resistance patterns. Recommended intravenous agents include fluoroquinolones, aminoglycosides (with or without ampicillin), extended-spectrum cephalosporins / penicillins, or carbapenems.

Analysis

Previous guidelines for the treatment of uncomplicated cystitis and pyelonephritis were published by the IDSA in 1999.⁴ The guidelines were updated based on the following factors:

• continued variability in prescribing practices;1-2
• increase in antimicrobial resistance among uropathogens;
• awareness of the unintended consequences of antimicrobial therapy, such as selection of drug-resistant organisms and colonization or infection with multi-drug resistant organisms; and
• study of newer agents and different durations of therapy.

Two important differences exist between the 1999 and 2010 guidelines:

• Nitrofurantoin has taken on more prominence in the 2010 guidelines for uncomplicated cystitis. The 1999 guidelines recommended trimethoprim-sulfamethoxazole as a first-line agent and mentioned nitrofurantoin and fosfomycin as potential alternative agents, but had few studies available to inform comparative efficacy or duration of therapy.
• For the outpatient treatment of mildly-ill patients with acute pyelonephritis, the 1999 guidelines recommended 14 days of therapy regardless of the agent used; in contrast, the 2010 guidelines recommend a five- to seven-day course for oral fluoroquinolones.