- Preferred antibiotics for acute cystitis are nitrofurantoin, or trimethoprim-sulfamethoxazole (TMP-SMX) if local resistance rates are < 20%.
- In patients suspected of pyelonephritis, a urine culture and susceptibility testing should always be performed.
- Preferred antibiotics for outpatient pyelonephritis are a fluoroquinolone or TMP-SMX. Consider an initial single-dose IV ceftriaxone or an aminoglycoside if community resistance is > 10% or, for TMP-SMX, if susceptibility unknown.
- Women with pyelonephritis requiring hospitalization should be initially treated with an IV antimicrobial regimen such as a fluoroquinolone, an aminoglycoside with or without ampicillin, an extended-spectrum cephalosporin or extended-spectrum penicillin with or without an aminoglycoside, or a carbapenem.
Selecting a Treatment Regimen
Acute Uncomplicated Cystitis
- Nitrofurantoin monohydrate/macrocrystals 100 mg bid for 5 days is an appropriate choice for therapy due to minimal resistance and propensity for collateral damage; efficacy is comparable to 3 days of TMP-SMX (A-I).
- TMP-SMX DS bid for 3 days is an appropriate choice for therapy, given its efficacy as assessed in numerous clinical trials, if local resistance rates of uropathogens causing acute uncomplicated cystitis do not exceed 20% or if the infecting strain is known to be susceptible (A-I).
- Notes: The threshold of 20% as the resistance prevalence at which the agent is no longer recommended for empiric treatment of acute cystitis is based on expert opinion derived from clinical, in vitro, and mathematical modeling studies (B-III).
- In some countries and regions, trimethoprim 100 mg bid for 3 days is the preferred agent and is considered equivalent to TMP-SMX based on data presented in the original guideline (A-III).
- Data are insufficient to make a recommendation for other cystitis antimicrobials as to what resistance prevalence should be used to preclude their use for empiric treatment of acute cystitis.
- Fosfomycin tromethamine 3 g single-dose is an appropriate choice for therapy where it is available due to minimal resistance and propensity for collateral damage, but it appears to have inferior efficacy compared with standard short-course regimens according to submitted data (A-I).
- Pivmecillinam 400 mg bid for 3 to 7 days is an appropriate choice for therapy in regions where it is available (availability limited to some European countries; not licensed and/or available for use in North America), due to minimal resistance and propensity for collateral damage, but it may have inferior efficacy compared with other available therapies (A-I).
- The fluoroquinolones ofloxacin, ciprofloxacin, and levofloxacin in 3-day regimens are highly efficacious (A-I) but have a propensity for collateral damage and should be reserved for important uses other than acute cystitis. They should thus be considered alternative antimicrobials for acute cystitis (A-III).
- β-Lactam agents including amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime-proxetil in 3- to 7-day regimens are appropriate choices for therapy when other recommended agents cannot be used (B-I). Other β-lactams, such as cephalexin, are less well studied but may also be appropriate in certain settings (B-III). The β-lactams generally have inferior efficacy and more adverse effects compared to other urinary tract infection (UTI) antimicrobials (B-I). For these reasons, β-lactams other than pivmecillinam should be used with caution for uncomplicated cystitis.
- Amoxicillin or ampicillin should NOT be used for empiric treatment given their relatively poor efficacy and the very high prevalence of antimicrobial resistance to these agents worldwide (A-III).
- In patients suspected of pyelonephritis, a urine culture and susceptibility testing should always be performed, and initial empiric therapy should be tailored appropriately based on the infecting uropathogen (A-III).
- Oral ciprofloxacin 500 mg bid for 7 days with or without an initial 400 mg dose of IV ciprofloxacin is an appropriate choice for therapy in patients not requiring hospitalization where the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10% (A-I).
- If an initial one-time IV agent is utilized, a long-acting antimicrobial such as 1 g ceftriaxone or a consolidated
24-hour dose of an aminoglycoside could be used in lieu of
an IV fluoroquinolone (B-III).
- If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial one-time IV dose of a long-acting parenteral antimicrobial such as 1 g ceftriaxone (B-III) or a consolidated 24-hour dose of an aminoglycoside is recommended (B-III).
- Note: Data are insufficient to make a recommendation about what fluoroquinolone resistance level requires an alternative agent in conjunction with or to replace a fluoroquinolone for treatment of pyelonephritis.
- A once-daily oral fluoroquinolone, including ciprofloxacin
1000 mg extended release for 7 days or levofloxacin 750 mg for 5 days, is an appropriate choice for therapy in patients not requiring hospitalization where the prevalence of resistance of community uropathogens is not known to exceed 10% (B-II).
- TMP-SMX DS bid for 14 days is an appropriate choice for therapy if the uropathogen is known to be susceptible (A-I). If TMP-SMX is used when the susceptibility is not known, an initial IV dose of a long-acting parenteral antimicrobial such as 1 g ceftriaxone (B-II) or a consolidated 24-hour dose of an aminoglycoside is recommended (B-III).
- Oral β-lactam agents are less effective than other available agents for treatment of pyelonephritis (B-III). If an oral β-lactam agent is used, an initial IV dose of a long-acting parenteral antimicrobial such as 1 g ceftriaxone (B-II) or a consolidated 24-hour dose of an aminoglycoside is recommended (B-III).
- Note: Data are insufficient to modify the previous guideline recommendation
for a duration of therapy of 10-14 days for treatment of pyelonephritis with a β-lactam agent.
- Women with pyelonephritis requiring hospitalization should be initially treated with an IV antimicrobial regimen such as a fluoroquinolone, an aminoglycoside with or without ampicillin, an extended-spectrum cephalosporin or extended-spectrum penicillin with or without an aminoglycoside, or a carbapenem. The choice between these agents should be based on local resistance data, and the regimen should be tailored based on susceptibility results (B-III).
Table 1. Antibiotics for Acute Uncomplicated Cystitis
|Drug and Dose||Estimated|
|Common Side Effects|
100 mg bid for 5-7 days
|93% (84%-95%)||88% (86%-92%)||Nausea, headache|
|Trimethoprim-sulfamethoxazole 160/800 mg|
(TMP-SMX DS) bid for 3 days
|93% (90%-100%)||94% (91%-100%)||Rash, urticaria, nausea,|
|Fosfomycin tromethamine (Monurol®)|
3 g single-dose sachet
|91%||80% (78%-83%)||Diarrhea, nausea, headache|
|Fluoroquinolones (dose varies by agent)|
3-day regimenc, e
|90% (85%-98%)||91% (81%-98%)||Nausea/vomiting, diarrhea,|
headache, drowsiness, insomnia
|β-lactams (dose varies by agent)|
3-5 day regimend, e
|89% (79%-98%)||82% (74%-98%)||Diarrhea, nausea,|
vomiting, rash, urticaria
|a Efficacy rates refer to cure rates on the visit closest to a 5-9 day period after treatment and are averages or ranges calculated from clinical trials discussed in the text.|
b Estimated clinical efficacy and microbiological efficacy rates should not necessarily be compared across agents since study design, efficacy definition, therapy duration, and other factors are heterogeneous. Studies represent clinical trials published since publication of the 1999 Infectious Diseases Society of America guidelines so as to represent efficacy rates that account for contemporary prevalence of antibiotic-resistant uropathogens. Note that efficacy rates may vary geographically depending on local patterns of antimicrobial resistance among uropathogens.
c Fluoroquinolones data are compiled from regimens of ofloxacin, norfloxacin, and ciprofloxacin from the referenced clinical trials and not other fluoroquinolones that are no longer commercially available.
d β-Lactams data cited are derived from clinical trials examining second- and third-generation cephalosporins and amoxicillin/clavulanate.
e See full text guidelines for details. http://cid.oxfordjournals.org/content/52/5/e103.full.pdf+html