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

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

Author(s)

Emily Tarvin, MD

Kelly Cunningham Sponsler, MD

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.

Although nitrofurantoin is favored as a first-line antimicrobial agent for cystitis in the 2010 IDSA-ESCMID guidelines, it might be problematic in hospitalized patients for several additional reasons.

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.

The American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine have endorsed the 2010 IDSA-ESCMID guidelines. The IDSA and ESCMID plan to evaluate the need for revisions to the 2010 guidelines based on an annual review of the current literature.

HM Takeaways

The 2010 IDSA-ESCMID guidelines are a resource available to hospitalists treating acute uncomplicated cystitis and pyelonephritis. As important differences exist between the target population and the hospitalist’s patient population, there are some key points to consider for clinicians treating cystitis or pyelonephritis in hospitalized patients.

Importantly, while nitrofurantoin is favored as a first-line antimicrobial agent for cystitis in the 2010 IDSA-ESCMID guidelines, it might be problematic in hospitalized patients for several reasons:

it is not approved or recommended for the treatment of pyelonephritis;

it is contraindicated in patients with creatinine clearance <60 ml/min; and

it is generally not recommended for use in patients >65 years old because of the risk of renal impairment (Beers Criteria).⁵

Additionally, the treatment of acute cystitis in men requires special consideration. Notably, nitrofurantoin is not recommended in men because of poor prostatic tissue penetration, and although studies are limited, some sources recommend a longer treatment duration of at least 7 days.⁶ Finally, hospitalized patients commonly have other conditions, such as urological abnormalities, indwelling Foley catheters, recent urinary tract instrumentation, recent use of antibiotics, risk for multi-drug resistant organisms, potential interactions with other medications, and immunosuppression. The presence of any of these factors will influence the choice of empiric therapy and may warrant treatment for complicated cystitis or pyelonephritis, which are not addressed by these guidelines.

Drs. Tarvin and Sponsler are academic hospitalists at Vanderbilt University School of Medicine in Nashville, Tenn.

References

Huang ES, Stafford RS. National patterns in the treatment of urinary tract infections in women by ambulatory care physicians. Arch Intern Med. 2006;166:635-639.

Kahan NR, Chinitz DP, Kahan E. Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money. J Clin Pharm Therap. 2004;29:59-63.

Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Inf Dis. 2011;52(5):e103-20.

Warren JW, Abrutyn E, Hebel JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America. Clin Inf Dis. 1999;29(4):745-58.

Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a U.S. consensus panel of experts. Arch Intern Med. 2003;163(22):2716-2724.

Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. A Fam Phys. 2005;72(3):451-456.

Issue

The Hospitalist - 2012(04)

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Author(s)

Kelly Cunningham Sponsler, MD

Author(s)

Emily Tarvin, MD

Kelly Cunningham Sponsler, MD

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.

Although nitrofurantoin is favored as a first-line antimicrobial agent for cystitis in the 2010 IDSA-ESCMID guidelines, it might be problematic in hospitalized patients for several additional reasons.

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.

The American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine have endorsed the 2010 IDSA-ESCMID guidelines. The IDSA and ESCMID plan to evaluate the need for revisions to the 2010 guidelines based on an annual review of the current literature.

HM Takeaways

The 2010 IDSA-ESCMID guidelines are a resource available to hospitalists treating acute uncomplicated cystitis and pyelonephritis. As important differences exist between the target population and the hospitalist’s patient population, there are some key points to consider for clinicians treating cystitis or pyelonephritis in hospitalized patients.

Importantly, while nitrofurantoin is favored as a first-line antimicrobial agent for cystitis in the 2010 IDSA-ESCMID guidelines, it might be problematic in hospitalized patients for several reasons:

it is not approved or recommended for the treatment of pyelonephritis;

it is contraindicated in patients with creatinine clearance <60 ml/min; and

it is generally not recommended for use in patients >65 years old because of the risk of renal impairment (Beers Criteria).⁵

Additionally, the treatment of acute cystitis in men requires special consideration. Notably, nitrofurantoin is not recommended in men because of poor prostatic tissue penetration, and although studies are limited, some sources recommend a longer treatment duration of at least 7 days.⁶ Finally, hospitalized patients commonly have other conditions, such as urological abnormalities, indwelling Foley catheters, recent urinary tract instrumentation, recent use of antibiotics, risk for multi-drug resistant organisms, potential interactions with other medications, and immunosuppression. The presence of any of these factors will influence the choice of empiric therapy and may warrant treatment for complicated cystitis or pyelonephritis, which are not addressed by these guidelines.

Drs. Tarvin and Sponsler are academic hospitalists at Vanderbilt University School of Medicine in Nashville, Tenn.

References

Huang ES, Stafford RS. National patterns in the treatment of urinary tract infections in women by ambulatory care physicians. Arch Intern Med. 2006;166:635-639.

Kahan NR, Chinitz DP, Kahan E. Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money. J Clin Pharm Therap. 2004;29:59-63.

Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Inf Dis. 2011;52(5):e103-20.

Warren JW, Abrutyn E, Hebel JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America. Clin Inf Dis. 1999;29(4):745-58.

Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a U.S. consensus panel of experts. Arch Intern Med. 2003;163(22):2716-2724.

Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. A Fam Phys. 2005;72(3):451-456.

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.

Although nitrofurantoin is favored as a first-line antimicrobial agent for cystitis in the 2010 IDSA-ESCMID guidelines, it might be problematic in hospitalized patients for several additional reasons.

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.

The American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine have endorsed the 2010 IDSA-ESCMID guidelines. The IDSA and ESCMID plan to evaluate the need for revisions to the 2010 guidelines based on an annual review of the current literature.

HM Takeaways

The 2010 IDSA-ESCMID guidelines are a resource available to hospitalists treating acute uncomplicated cystitis and pyelonephritis. As important differences exist between the target population and the hospitalist’s patient population, there are some key points to consider for clinicians treating cystitis or pyelonephritis in hospitalized patients.

Importantly, while nitrofurantoin is favored as a first-line antimicrobial agent for cystitis in the 2010 IDSA-ESCMID guidelines, it might be problematic in hospitalized patients for several reasons:

it is not approved or recommended for the treatment of pyelonephritis;

it is contraindicated in patients with creatinine clearance <60 ml/min; and

it is generally not recommended for use in patients >65 years old because of the risk of renal impairment (Beers Criteria).⁵

Additionally, the treatment of acute cystitis in men requires special consideration. Notably, nitrofurantoin is not recommended in men because of poor prostatic tissue penetration, and although studies are limited, some sources recommend a longer treatment duration of at least 7 days.⁶ Finally, hospitalized patients commonly have other conditions, such as urological abnormalities, indwelling Foley catheters, recent urinary tract instrumentation, recent use of antibiotics, risk for multi-drug resistant organisms, potential interactions with other medications, and immunosuppression. The presence of any of these factors will influence the choice of empiric therapy and may warrant treatment for complicated cystitis or pyelonephritis, which are not addressed by these guidelines.

Drs. Tarvin and Sponsler are academic hospitalists at Vanderbilt University School of Medicine in Nashville, Tenn.