Pielonefritis
Pielonefritis
Pielonefritis
Medicine, University of Miami Miller School of Medicine, University of Miami, Miami Florida; 3Department of Family and Community Medicine, University
of Maryland, Baltimore, Maryland, 4Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, and 5Department of Emergency Medicine and
Division of Infectious Diseases Olive View-UCLA Medical Center, Slymar, California; 6Deptartment of urology, Northwestern University, Chicago, Illinois; and
7Departments of Obstetrics and Gynecology and Medicine, Medical University of South Carolina, Charleston, South Carolina; 8Department of Internal
Medicine and Department of Medical Mirobiology University of Manitoba, Winnipeg, Canada; 9Technical University of Munich, Munich, Germany; 10Lund
University Hospital, Lund, Sweden; and 11Infectious Diseases Unit, Ha'Emek Medical Center, Afula, and Rappaport Faculty of Medicine, Technion, Haifa, Israel
A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in
collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the
1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include 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.
The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses
limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities
or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of
antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment
choices and thus are reflected in the rankings of recommendations.
EXECUTIVE SUMMARY
Yes
Fluoroquinolones
Can one of the recommended antimicrobials* (resistance prevalence high in
No
below be used considering: some areas)
Availability
Allergy history OR
Tolerance
-lactams
Nitrofurantoin monohydrate/macrocrystals 100 (avoid ampicillin or amoxicillin
mg bid X 5 days alone; lower efficacy than other
(avoid if early pyelonephritis suspected)
Trimethoprim-sulfamethoxazole 160/800 mg
(one DS tablet) bid X 3 days
(avoid if resistance prevalence is known to
exceed 20 or if used for UTI in previous 3
months)
OR
Yes
Figure 1. Approach to choosing an optimal antimicrobial agent for empirical treatment of acute uncomplicated cystitis. DS, double-strength; UTI,
urinary tract infection.
the ecological adverse effects of antimicrobial therapy (collateral considered by some experts to have uncomplicated urinary
damage) has increased, newer agents and different durations of tract infection (UTI), but a discussion of specific management
therapy have been studied, and clinical outcomes have in- of these groups is outside the scope of this guideline. In ad-
creasingly been reported. In addition, women with uropath- dition, management of recurrent cystitis and of UTI in
ogens resistant to the treatment drug have been included in pregnant women, prevention of UTI, and diagnosis of UTI are
some studies, allowing for estimations of expected response rates all important issues that are not addressed in this guideline.
in a ‘‘real-life’’ clinical setting in which empirical therapy is The issues of in vitro resistance prevalence and the potential
prescribed either without a urine culture and susceptibility for collateral damage were considered as important factors in
testing or before such results are known. In light of these de- making optimal treatment choices and thus are reflected in
velopments, an update of the guidelines was warranted. the rankings of recommendations.
The focus of this guideline is treatment of women with acute Summarized below are the recommendations made in the
uncomplicated cystitis and pyelonephritis, diagnoses limited 2010 guideline update. The Panel followed a process used in the
in these guidelines to premenopausal, nonpregnant women development of other IDSA guidelines which included a sys-
with no known urological abnormalities or comorbidities. It tematic weighting of the quality of the evidence and the grade of
should be noted that women who are postmenopausal or have recommendation [32] (Table 1). A detailed description of the
well-controlled diabetes without urological sequelae may be methods, background, and evidence summaries that support
Category/grade Definition
Strength of recommendation
A Good evidence to support a recommendation for or against use
B Moderate evidence to support a recommendation for or against use
C Poor evidence to support a recommendation
Quality of evidence
I Evidence from >1 properly randomized, controlled trial
II Evidence from >1 well-designed clinical trial, without randomization; from cohort or case-
controlled analytic studies (preferably from .1 center); from multiple time-series; or from
dramatic results from uncontrolled experiments
III Evidence from opinions of respected authorities, based on clinical experience, descriptive
studies, or reports of expert committees
management of patients with cystitis and pyelonephritis. A It should be emphasized that, as is true with any treatment
specific effort was made to include representatives from diverse guideline, an assessment of the literature for a given agent’s
geographic areas and a wide breadth of specialties, including clinical efficacy is limited by the comparators studied. For ex-
urology, obstetrics and gynecology, emergency medicine, family ample, amoxicillin-clavulanate has been shown to be statistically
medicine, internal medicine, and infectious diseases, with a goal significantly inferior to ciprofloxacin in a randomized trial re-
of improving the generalizability and acceptance of the recom- cently published. On the other hand, in the only published
mendations and subsequent incorporation into clinical practice. randomized study of cefpodoxime, its clinical efficacy appears to
Process Overview be comparable to that of trimethoprim-sulfamethoxazole. It is
The evaluation of evidence for each antimicrobial class used in not clear how amoxicillin-clavulanate would compare with
treatment of cystitis and pyelonephritis was performed by 2 cefpodoxime or to trimethoprim-sulfamethoxazole.
members of the panel. Each member was assigned at least one
Literature Review and Analysis
antimicrobial class to review. The process for evaluating the
For the update, the Expert Panel completed a review and analysis
evidence was based on the IDSA Handbook on Clinical Practice
of data published since 1998. Computerized literature searches
Guideline Development and involved a systematic weighting of
of the Pubmed database were performed. The searches of the
the quality of the evidence and the grade of recommendation
English-language literature from 1998 thru 2008, using the
(Table 1) [32]. This scale had been modified from the one used
terms, cystitis or pyelonephritis with MESH terms of ‘‘acute
in the 1999 guideline.
uncomplicated UTI,’’ ‘‘women,’’ and specific antimicrobials and
The level of evidence rating (I, II, or III) for recommendations
or classes of antimicrobials. To be included, the study had to be
in this guideline refers to evidence of the antimicrobial’s efficacy
an open-label or randomized, clinical trial of treatment of
in randomized clinical trials. The strength of the recommen-
women with symptoms of acute uncomplicated cystitis or py-
dation (A, B, or C) refers to the panel’s level of comfort in
elonephritis. At least 1 follow-up visit assessing microbiological
recommending the antimicrobial for the treatment of un-
or clinical response was required. Studies including .10% men
complicated UTI and is based on the drug’s efficacy in clinical
or patients with complicated UTI were excluded. Non–English-
trials, rates of in vitro resistance among urinary pathogens, and
language studies were excluded because they could not be re-
the drug’s propensity to cause collateral damage and adverse
liably reviewed by panel members.
effects. For example, the panel felt that fosfomycin and piv-
Outcomes of interest included early (first visit after treatment,
mecillinam should be listed as agents recommended for treat-
typically occurring at 0–7 days after the last dose of the anti-
ment of uncomplicated cystitis, along with nitrofurantoin and
microbial) clinical and microbiological cure, late (last visit after
trimethoprim-sulfamethoxazole, even though they appear to be
treatment, typically occurring 30–45 days after the last dose of
less efficacious clinically, because they do not appear to cause
the antimicrobial) clinical cure, and adverse effects.
collateral damage. On the other hand, the panel was less en-
thusiastic about strongly recommending fluoroquinolones for Guidelines and Conflict of Interest
acute cystitis, even though they have high clinical efficacy, be- All members of the Expert Panel complied with the IDSA policy
cause of concerns about collateral damage and the subsequent on conflicts of interest, which requires disclosure of any financial
threat to the usefulness of fluoroquinolones for the treatment of or other interest that might be construed as constituting an actual,
other more serious infections, including pyelonephritis. potential, or apparent conflict. Members of the Expert Panel were
Figure 2. Meta-analysis of studies comparing trimethoprim-sulfamethoxazole (TMP-SMX) with nitrofurantoin (NTF) for acute uncomplicated cystitis. CI,
confidence interval.
NOTE. Data are proportion of subjects (%), unless otherwise indicated. Efficacy rates refer to cure rates on the visit closest to a 5–9-day period following
treatment. NA, not available; TMP-SMX, trimethoprim-sulfamethoxazole.
Women with an uropathogen resistant to either study drug women in the nitrofurantoin arm, with a nonsignificant dif-
(4 of 82 women in the trimethoprim-sulfamethoxazole arm ference of -5%. Rates were also equivalent (predefined as
and 0 of 81 women in the cefpodoxime arm) were excluded. a 610% difference between agents) at 5-9 days after therapy,
Clinical cure was achieved in 100% of the 70 women in the with clinical cure of 90% in each arm and bacterial cure of 91%
trimethoprim-sulfamethoxazole arm, compared with 62 in the trimethoprim-sulfamethoxazole arm and 92% in the ni-
(98%) of 63 women in the cefpodoxime arm. The microbio- trofurantoin arm. There was a significantly higher clinical cure
logical cure rates were the same as the clinical cure rates in rate among women in the trimethoprim-sulfamethoxazole
each arm. Adverse effects were reported in 1 patient in the arm who had a trimethoprim-sulfamethoxazole–susceptible
trimethoprim-sulfamethoxazole arm and 2 patients in the uropathogen, compared with those who had a trimethoprim-
cefpodoxime arm. sulfamethoxazole–resistant uropathogen (84% vs 41%,
The fourth study compared a 3-day course of trimethoprim- respectively;1 P , .001).
sulfamethoxazole (160/800 mg twice daily) with a 5-day The fifth study used a prospective observational trial design
course of nitrofurantoin monohydrate–macrocrystals (100 mg to compare clinical and bacterial outcomes among women
twice daily) and included women with uropathogens resistant with acute cystitis with a trimethoprim-sulfamethoxazole–
to the study drugs [36]. The primary end point, overall clinical susceptible or –resistant uropathogen [21]. All women were
cure rate at 30 days, was 79% among the 148 women in the treated with a 5-day course of trimethoprim-sulfamethox-
trimethoprim-sulfamethoxazole arm and 84% among the 160 azole (160/800 mg twice daily). The microbiological cure rates
Table 3. Results from Included Studies of Nitrofurantoin for Treatment of Acute Uncomplicated Cystitis
Study Regimen
Iravani et al (1999) [37] Nitrofurantoin monohydrate/ TMP-SMX, 160/800 Ciprofloxacin, 100 mg
macrocrystals, 100 mg twice mg twice daily for 7 days twice daily for 3 days
daily for 7 days
Early clinical cure 166/179 (93) 165/174 (95) 160/168 (95)
Early bacterial cure 153/177 (86) 161/174 (93) 148/168 (88)
Late clinical cure 135/151 (89) 137/153 (90) 132/147 (90)
Adverse events, % 34 38 28
Stein et al (1999) [39] Nitrofurantoin monohydrate/ Fosfomycin trometamol,
macrocrystals, 100 mg twice single 3-gdose
daily for 7 days
Early clinical cure 232/245 (95) 240/263 (90)
Early bacterial cure 189/219 (86) 192/246 (78)
Late clinical cure 168/180 (93) 189/202 (94)
Adverse events, % 5.6 5.3
Christiaens et al (2002) [28] Nitrofurantoin macrocrystals, Placebo, 4 times
100 mg 4 times daily for 3 days daily for 3 days
Early clinical cure 21/24 (88) 13/23 (54)
Early bacterial cure 17/23 (74) 9/22 (41)
Late clinical cure NA NA
Adverse events, % 23 26
Gupta et al (2007) [36] Nitrofurantoin monohydrate/ TMP-SMX, 160/800
macrocrystals, 100 mg twice mg twice daily for 3 days
daily for 5 days
Early clinical cure 144/160 (90) 133/148 (90)
Early bacterial cure 141/154 (92) 131/144 (91)
Late clinical cure 134/160 (84) 117/148 (79)
Adverse events, % 28 31
NOTE. Data are proportion of subjects (%), unless otherwise indicated. Efficacy rates refer to cure rates on the visit closest to a 5–9-day period following
treatment. NA, not available; TMP-SMX, trimethoprim-sulfamethoxazole.
Table 4. Treatment Regimens and Expected Early Efficacy Rates for Acute Uncomplicated Cystitis
trimethoprim-sulfamethoxazole would not be effective when the antimicrobial use and resistance in women with sporadic
uropathogen is susceptible, and additional studies of short-course uncomplicated UTI.