© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
45
Diagnosis and management of simple and complicated urinary tract infections (UTIs)
Antimicrobial susceptibility and resistance
As with many other infectious diseases, antibiotic-
resistant pathogens have become more prevalent
as a cause of UTIs in both outpatient and inpatient
settings.
18-20
However, the prevalence of reported
antimicrobial resistance varies widely depending on
the patient population, geographic location, hospital,
patient ward/unit, patients’ prior antibiotic use,
and other factors.
19-22
Some studies of antimicrobial
resistance have included men and children.
21
Others
have looked at outpatient populations.
23
Yet others
have used test results from routine urine specimens
submitted for culture without information about age,
sex, type of infection, or prior antibiotic exposure.
24,25
Given that a large proportion of patients are treated
empirically without results from a urine culture, data
based on routine urine specimens submitted for culture
in the clinical settingmay not accurately reflect the true
incidence of antibiotic-resistant organisms associated
with UTIs.
14,26,27
However, despite the limitations
of currently available data, knowledge of local
antimicrobial susceptibility and resistance rates for
common uropathogens should always be considered
when making treatment decisions.
In Canada, resistance of
E. coli
to TMP-SMX has
been estimated to be as low as 10.8%
28
and as high
as 18.9% for the same time period.
23
More recently, a
study of Canadian tertiary care centers, which included
both males and females as well as inpatients and
outpatients, reported that 22.1% of
E. coli
infections
were resistant to TMP-SMX.
25
A higher rate of ciprofloxacin-resistant
E. coli
has
been reported in British Columbia.
29
In addition,
a 2010 report from the British Columbia Centre for
Disease Control found that between 1998 and 2010,
ciprofloxacin-resistant
E. coli
increased 10-fold.
30
However, these estimates were based on routine urine
specimens submitted for culture, without clinical
information regarding the patient’s sex or age, or the
clinical reason for obtaining the specimen.
Nitrofurantoin- resistance rates remain low in
isolates of
E. coli
from women with acute cystitis in
Canada.
28,29
However, resistance to this agent may be
increasing in organisms other than
E. coli
.
18,25
A growing concern has been the emergence of
extended-spectrum beta-lactamase (ESBL)-producing
gram-negative bacteria including
E. coli
and
Klebsiella
species that are multidrug resistant. These organisms
tend to be resistant not only to all generations of
cephalosporins but also to the fluoroquinolones and
beta-lactam/beta-lactamase inhibitor combinations
(
e.g., piperacillin/tazobactam), possibly leaving the
carbapenems as the only current alternatives for
therapy of all UTIs. Arecent cross-Canada study found
that most ESBLcaseswere fromUTIs in the community,
but it was not clear whether these were isolated only
fromwomen with uncomplicated cystitis or also from
other patients with UTIs.
31
An international study of
urinary tract isolates of
E. coli
from inpatients found
that 17.9% were ESBL positive.
20
This study included
both males and females, ranging from newborns to
patients older than 65 years. Susceptibility to other
agents in the ESBL-positive
E. coli
isolates was ≥ 98%
for the carbapenems (imipenem and ertapenem),
87.1%
for amikacin, 84.4% for piperacillin-tazobactam,
and only 15.3% for ciprofloxacin. As knowledge of
the epidemiology of ESBL-producing organisms in
community and hospital settings continues to evolve,
treatment choices will be significantly impacted,
including treatments for womenwith acute cystitis.
32,33
Antimicrobial treatment
Uncomplicated UTIs
Recent guidelines published by the Infectious Diseases
Society of America (IDSA) and endorsed by Canadian
and European organizations,
14
recommend that twice-
daily, double-strength TMP-SMX for 3 days remains the
empiric drug anddosage of choice for first-line treatment
of uncomplicated cystitis in premenopausal women,
unless the prevalence of TMP-SMX-resistant
E. coli
in a
given region or setting exceeds 20%.
7,14
The presence of
a resistant organism in a patient with acute cystitis has
been associatedwith lower rates of microbiologic cure,
34
longer time to symptomresolution,
35
and higher rates of
repeat consultations.
36
Although the prevalence of TMP-
SMX-resistant
E. coli
causing acute cystitis in women in
Canada remains below 20% nationally, it may exceed
this level in premenopausal women depending on
geographical location and prior antimicrobial exposure.
These observations suggest that TMP-SMX may no
longer have a role as a first-line, empirical antibiotic
treatment for acute cystitis in premenopausal women
in Canada as recommended by the IDSA guideline.
14
Alternatives to TMP-SMX in the outpatient
setting include nitrofurantoin twice daily for 5 days;
amoxicillin-clavulanic acid; a cephalosporin (e.g.,
cefdinir, cefixime, etc.) for 5 to 7 days; or single-
dose fosfomycin. Although the fluoroquinolones
(
ofloxacin, ciprofloxacin and levofloxacin) given for 3
days are effective, their use should be limited in acute,
uncomplicated cystitis. As with other agents, their
overuse is associated with increasing antimicrobial
resistance, and this may limit their use not only for
UTIs but also for a variety of other indications.
