International Journal of Urology (2010) 17, 450–456 doi: 10.1111/j.1442-2042.2010.02500.

Review Article iju_2500 450..456

Current therapy of acute uncomplicated cystitis

Shingo Yamamoto, Yoshihide Higuchi and Michio Nojima
Department of Urology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

Abstract: Acute uncomplicated cystitis (AUC) is one of the most common bacterial urinary tract infections. AUC fre-
quently occurs in young sexually active, as well as postmenopausal, women. According to the guidelines published by the
Infectious Diseases Society of America in 1999, the standard antimicrobial regimen for treatment of AUC is 3 days with
trimethoprim–sulfamethoxazole (TMP/SMX); however, today the most popular antibiotics are the fluoroquinolones
because of the emergence of uropathogens that are resistant to TMP/SMX. Fluoroquinolone resistance is also increasing
worldwide, although the resistance rates have not been as high as those for TMP/SMX. Extended-spectrum b-lactamase
(ESBL)-producing strains are another problem because most nosocomial ESBL producers are also resistant to non-b-
lactams, such as the fluoroquinolones. Under such circumstances, 3 days of therapy with fluoroquinolones or 7 days with
b-lactams is recommended for empirical therapy, although these regimens should be re-evaluated in the next decade.
Low-dose fluoroquinolones should no longer be used because of the potential for emergence of resistance.
Key words: acute uncomplicated cystitis, 3-day therapy, fluoroquinolone, guidelines, treatment.

Introduction tigated widely,7 some fluoroquinolones such as ofloxacin

Acute uncomplicated cystitis (AUC) is one of the most
common bacterial urinary tract infections (UTI). A previous
cohort study has shown that the incidence of AUC accounts
for 0.5–0.7 per person-year among sexually active young
women.1 Another study has reported that 50–60% of women
experience at least one UTI in their lifetime.2 AUC is a
common condition that is diagnosed and treated by all kinds
of physicians including urologists, gynecologists and other
medical and health care providers. Therefore, appropriate
guidelines for diagnosis and treatment of AUC should be
provided by a review of epidemiological, pharmacological
and clinical investigations.
According to the guidelines published by the Infectious
Diseases Society of America (IDSA) in 1999,3 the standard
antimicrobial regimen for treatment of AUC is 3 days with
trimethoprim–sulfamethoxazole (TMP/SMX); however, the
emergence of uropathogens that are resistant to TMP/SMX
has led to a shift in the prescribing pattern to fluoroquino-
lones.4 Thus, today the most popular antibiotics might be
fluoroquinolones, which are recommended by several guide-
lines and reviews for treatment of AUC.3,5,6
For treatment of AUC, a variety of fluoroquinolones are
administered by different regimens with different doses,
schedules and durations. Although 3-day regimens using
fluoroquinolones administered twice daily have been inves-
Correspondence: Shingo Yamamoto MD PhD, 1-1
Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan. Email:
shingoy@hyo-med.ac.jp
Received 24 December 2009; accepted 22 January 2010.
Online publication 10 March 2010
and gatifloxacin could be administered once daily for 3 days
for treatment of AUC.8,9 Furthermore, other fluoroquinolo-
nes with a prolonged half-life, such as pefloxacin and
rufloxacin, are possible candidates for single-dose therapy.3
Epidemiology and pathophysiology
Escherichia coli is isolated most frequently in approximately
80% of episodes of AUC, while other enterobacteria such as
Enterococcus faecalis, Klebsiella pneumoniae, Proteus
mirabilis and Staphylococcus saprophyticus are also impor-
tant pathogens.10,11 In our recent study, E. coli was found in
88.2% of 102 AUC cases, as a single causative pathogen in
74.5% and as one of several pathogens in 13.7% (Fig. 1).12
The fecal–perineal–urethral hypothesis has been recog-
nized widely to explain the cause of ascending UTI; uro-
pathogenic organisms reside in the individual rectal flora
and serve as a reservoir for UTI. Several studies have shown
that E. coli isolates that cause UTI have the same genotypes,
serotypes and pulse-field gel electrophoresis patterns as
those discovered predominantly among the rectal flora in
each subject.13,14 Recent studies have reported that uropatho-
genic E. coli isolated from women with UTI can form intra-
cellular bacterial communities in a mouse model of cystitis.
This suggests that organisms that persist within uroepithelial
cells in the bladder are a reservoir for recurrent infection,15
although these observations have not been repeated in
humans.
As several studies have reported , AUC frequently occurs
in young sexually active women.1,2 In a multivariate model,
independent risk factors for recurrent UTI included recent

450 © 2010 The Japanese Urological Association


Multiple pathogens
2 species (n = 12)
E.coli+Enterococcus faecalis
E.coli+CNS
E.coli+Enterococcus sp.
E.coli+K.pneumoniae
E.coli+Streptococcus agalactiae
3 species (n = 2)
E.coli+E.faecalis+K.pneumoniae
E.coli+E.faecalis+
Corynebacterium sp.
Fig. 1 Pathogens isolated from 102
patients with uncomplicated cystitis
in Japan.12 CNS, coagulase negative
staphylococci.
1-month intercourse frequency, 12 months spermicide use
and a new sexual partner during the past year. This study has
suggested that age <15 years at first UTI and a history of
UTI in the mother are risk factors for recurrent UTI.16
Physiological changes associated with menopause, such
as decreased vaginal glycogen and increased pH, are also
considered to be risk factors for UTI. It has been reported
that the intravaginal administration of estriol prevents recur-
rent UTI in postmenopausal women, and is associated with
reappearance of lactobacilli in the vaginal flora.17 Another
study has reported that, among postmenopausal women,
insulin-treated diabetes and a lifetime history of UTI are risk
factors for AUC, whereas AUC is not associated with sexual
activity, urinary incontinence, parity, postcoital urination,
vaginal dryness, use of cranberry juice, vaginal bacterial
flora and postvoid residual bladder volume.18
Antibiotic resistance and
antibiotic selection
The IDSA guidelines recommend TMP/SMX as the first
choice for empirical treatment when the resistance rate
among uropathogens that cause AUC is <10–20% in the
community.3 Although TMP/SMX might be less expensive
than fluoroquinolones, it has been shown that empirical
fluoroquinolone therapy could become less costly than
TMP/SMX when TMP/SMX resistance exceeds 22% in the
community, because of treatment failure, repeated visits to
physicians and associated laboratory testing.19 Another
similar analysis has reported that the threshold of TMP/
SMX resistance at which fluoroquinolone therapy becomes
less expensive was 19–21%, which supports the findings of
the previous study.20
© 2010 The Japanese Urological Association
Treatment of acute uncomplicated cystitis
Single pathogen; other than E. coli (n = 12)
CNS 3
8
K.pneumoniae 2
1
Proteus mirabilis 2
1
1 Enterococcus faecalis 1
1 Enterobacteriaceae sp. 1
Citrobacter koseri 1
Citrobacter sp. 2
1
1
Single pathogen; E. coli (n = 76)
Several studies have shown that TMP/SMX resistance has
indeed increased in many countries (Table 1).21–25 In Israel,
for patients with uncomplicated UTI, 29% of cultures grew
TMP/SMX-resistant organisms and microbiological cure
was achieved in 86% of patients with TMP/SMX-
susceptible organisms, but only in 42% of those with TMP/
SMX-resistant organisms.26 In a prospective cohort study in
the United Kingdom, among patients with uncomplicated
UTI, TMP resistance was present in 13.9% of isolates.
Patients with resistant isolates had a longer median time to
symptom resolution (7 vs 4 days, P = 0.0002), greater
reconsultation with the practice (39% vs 6% in the first
week, P < 0.0001), more subsequent antibiotics (36% vs 4%
in the first week, P < 0.0001) and higher rates of significant
bacteriuria at 1 month (42% vs 20% with susceptible iso-
lates, P = 0.04).27 In recent studies from the United States,
TMP/SMX resistance rates have accounted for 15–23% of
isolates from patients with AUC.28,29 In our recent study,
17% of isolates from patients with AUC showed TMP/SMX
resistance, which indicated that TMP/SMX might no longer
be a candidate for first-line therapy of AUC in Japan.12
In contrast, fluoroquinolone resistance is also increasing
worldwide, although its rate has not been as high as that of
TMP/SMX (Table 1). In the Mediterranean region, about
one-third of the strains that display reduced susceptibility to
ciprofloxacin and cause uncomplicated UTI belong to two
clonal groups: O15:H1 and O25:H4. This suggests that
strains that belong to these two clonal groups play a major
role in determining the high rate of fluoroquinolone-
resistant E. coli strains observed in the community.30 In
Japan, it has been reported that fluoroquinolone-resistant E.
coli accounted for 8% of isolates from patients with uncom-
plicated UTI in 2001,31 and this resistance rate was similar to
451
S YAMAMOTO ET AL.

Table 1 Resistant rate of E. coli isolated from patients with community acquired infections (%)
Italy21 Spain22 USA23 UK24 China25 Japan†
Ampicillin 49 65 – 54 – –
Amoxicillin/clavulanate 8 37 12 12 29 2
Pipellacillin 30 – – – – –
Pipellacillin/tazobactam 1 58 – – 7
Nitrofurantoin 9 7 3 5 – 1
TMP – – – 39 – –
TMP/SMX 27 37 20 – – 10
Ciprofloxacin 19 22 5 9 51 8
Gentamicin 6 10 – 5 39 2
Cefalexin – – – 8 – –
Cephazolin 7 – – – – –
Cefpodoxime – – 2 6 – 5
Cefuroxime – 13 24 – – –
Cefprozil – – 3 – – –
Cefotaxime – 4 – – 14 –
Ceftazidime – – – – 3 –
Ceftriaxone 2 – – – – –
Cefdinir – – 2 – – 5
Cefoperazone – – – – 17 –
Cefoperazone/sulbactam – – – – 5 –
Cefepime – 3 – – 8 –

†Data from the Japanese Society of UTI Cooperative Study Group (Chairman; Tetsuro Matsumoto) (2004). TMP/SMX,
trimethoprim–sulfamethoxazole.

that in our previous study in 2008.12 However, in South
Korea, it has been shown that the resistance rates of E. coli
isolated from AUC to ciprofloxacin increased from 15.2% in
2002 to 23.4% in 2006, which indicates that re-evaluation of
the guidelines for empirical therapy for AUC is required.32
The study from South Korea has shown the increasing
number of isolates of not only fluoroquinolone-resistant
pathogens, but also extended-spectrum b-lactamase
(ESBL)-producing strains.32 This is a serious clinical
problem because most nosocomial ESBL producers are also
resistant to non-b-lactams, such as the fluoroquinolones,
fosfomycin and co-trimoxazole.31 A study in Turkey has
shown that ciprofloxacin used more than once in the past
year was one of the risk factors for ciprofloxacin resistance,
and that detection of strains of E. coli that produce ESBL
was twice as common in patients who received ciprofloxacin
than in those who did not (15% vs 7.4%).33
Single-dose therapy, 3-day therapy
and prolonged therapy
A number of studies and meta-analyses have compared
single-dose therapy, 3-day therapy and longer duration of
antibiotic treatment using TMP/SMX, fluoroquinolones and
b-lactams for AUC.3,34,35
Single-dose therapy with b-lactams was significantly less
effective than longer duration therapy in terms of the eradi-
cation rate.3 However, for cefadroxil and pivmecillinam,
many studies have shown similar eradication rates for 3-day
and 5–10-day therapy, and fewer adverse effects but higher
rates of recurrence of bacteriuria were noted in 3-day
therapy groups.3,34 Similarly, 3-day therapy with these
b-lactams has excellent eradication rates, which are similar
to those with 3-day therapy with TMP/SMX or fluoroqui-
nolones. However, most studies have shown that these
b-lactams are inferior to TMP/SMX or fluoroquinolones in
terms of bacterial recurrence rate.3,34 Some Japanese studies
have investigated the effect of 3-day therapy using other,
third-generation b-lactams, although these studies were of
limited value because of the small numbers of subjects and
lack of long-term observation for bacteriological failure.
Fluoroquinolones have been more actively researched for
treatment of AUC. Several trials using fluoroquinolones
such as norfloxacin, ciprofloxacin and fleroxacin, have been
conducted to treat AUC by single-dose therapy, and lower
eradication rates have been reported when compared with
longer duration therapy. In this regard , pefloxacin and
rufloxacin, which have longer half-lives, have been shown
to be effective and useful for 5–7-day treatment in terms of
the eradication rate, recurrence rate and adverse effects,

452 © 2010 The Japanese Urological Association

 Table 2 Recommendations of current guidelines for treatment of acute uncomplicated cystitis

© 2010 The Japanese Urological Association

IDSA Europe Union Japan
Agent Dose Duration Agent Dose Duration Agent Dose Duration
First line TMP/SMX 160/800 mg b.i.d. 3 days TMP/SMX 160/800 mg b.i.d. 3 days Fluoroquinolones Intermediate 3 days
dose
Cefems (3rd Intermediate 7 days
generation) dose
Alternatives TMP 200 mg b.i.d. 3 days Cefpodoxime 100 mg b.i.d. 3 days Penicillins/BLI Intermediate 7 days
proxetil dose
Ofloxacin 200 mg once 3 days Ciproxacin 250–500 mg b.i.d. 3 days
Norfloxacin 400 mg b.i.d. 3 days Fosfomycin single dose
tromtamol
Ciproxacin 250–500 mg b.i.d. 3 days Levofloxacin 250–500 mg once 3 days
Norfloxacin 400 mg b.i.d. 3 days
Ofloxacin 200 mg once 3 days
Pivmecillinam 200 mg b.i.d. 7 days
TMP 200 mg b.i.d. 5–7 days
Others Fosfomycin tromtamol 3 g single dose Nitrofurantoin 50–100 mg q.i.d. 5–7 days
Nitrofurantoin 50–100 mg q.i.d. 7 days Pivmecillinam 400 mg b.i.d. 3 days
TMP 200 mg b.i.d. 3 days

b.i.d., twice daily; BLI, b-lactamase inhibitor; IDSA, Infectious Diseases Society of America; q.i.d., four times daily; TMP/SMX, trimethoprim–sulfamethoxazole.

453
Treatment of acute uncomplicated cystitis
S YAMAMOTO ET AL.

although these drugs are not available in some Asian coun-

tries, including Japan.3 A recent study has shown that single-
dose therapy with gatifloxacin is equivalent to 3-day therapy
with gatifloxacin and ciprofloxacin for AUC;9 however, this Cmax
agent has been removed from the market because of adverse

Concentration
effects in patients with diabetes. Therefore, no available
fluoroquinolone is marketed in Japan for single-dose
therapy.
Fluoroquinolones are currently accepted as standard
agents for short-term (3 days) therapy of AUC. Several
studies using fluoroquinolones such as spafloxacin, ciprof-
loxacin, norfloxacin, lomefloxacin, levofloxacin, ofloxacin
and fleroxacin have shown that there is no significant differ-
ence between 3-day and longer duration therapy in terms
of the eradication rate, recurrence rate and adverse
effects.3,34–36
In these studies, fluoroquinolones were administrated
once or twice daily (e.g. 250 mg levofloxacin once daily or
250 mg ciprofloxacin twice daily), which led to recommen-
dations of current guidelines for AUC in the United States or
the European Union (Table 2).6 However, these agents are
commonly prescribed for administration three times daily by
most physicians in Japan (e.g. 100 mg levofloxacin or
100 mg ciprofloxacin three times daily), probably to avoid
adverse effects. However, the current opinion is that low-
dose fluoroquinolones should no longer be used because of
the potential for emergence of resistance.37 Two or more
concurrent mutations cause fluoroquinolone resistance;38
therefore, to prevent the enrichment of resistant mutants, the
antibiotic concentration is required to exceed the mutant
selection window (MSW) when used clinically. Insufficient
antibiotic concentration could eradicate the susceptible
population, but further mutation is likely to be promoted in
single- or double-step mutants (Fig. 2). A study in an in vitro
kinetic model has indicated that ciprofloxacin 750 mg twice
daily is required to prevent the selection of single- and
double-resistant E. coli mutants because norfloxacin 200 mg
twice daily selected for single and double mutants, and
ciprofloxacin 250 mg twice daily and moxifloxacin 400 mg
once daily eradicated the single mutant but not the double
mutant.39 In this regard , 500 mg tablets of levofloxacin are
now available in Japan, and are recommended for once daily
administration for treatment of infections.40 Regimens for
other fluoroquinolones should be re-evaluated in the near
future.
Conclusion
AUC is of significant importance in the community because
of its high prevalence. Three-day therapy using fluoroqui-
nolones or 7-day therapy using b-lactams is recommended
for empirical therapy because resistance rates to these agents
are approximately 10%. Low-dose fluoroquinolones should
no longer be used. In the next decade, an increasing number
MPC
MSW
MIC
Time
Fig. 2 Concept to prevent resistant mutation. To eradicate
the susceptible population and block the growth of single- or
double-step mutants and the emergence of additional muta-
tions, the antibiotic concentration is required to surpass the
upper boundary of the mutant selection window (MSW). Cmax,
maximum drug concentration; MIC, minimum inhibitory con-
centration; MPC, mutant prevention concentration.
of isolates of fluoroquinolone-resistant pathogens, as well as
ESBL-producing strains, could be a serious clinical
problem, as shown by recent studies.31–33 In this respect,
low-dose fluoroquinolones should no longer be used
because of the potential for emergence of resistance. Single-
dose therapy could be attractive for improvement of patient
compliance, but it should be further assessed in terms of the
effectiveness and potential for emergence of resistance.
References
1 Hooton TM, Scholes D, Hughes JP et al. A prospective
study of risk factors for symptomatic urinary tract infection
in young women. N. Engl. J. Med. 1996; 335: 468–74.
2 Foxman B. Epidemiology of urinary tract infections:
incidence, morbidity, and economic costs. Am. J. Med.
2002; 113 (Suppl 1A): 5S–13S.
3 Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer
AJ, Stamm WE. Guidelines for antimicrobial treatment of
uncomplicated acute bacterial cystitis and acute
pyelonephritis in women. Infectious Diseases Society of
America (IDSA). Clin. Infect. Dis. 1999; 29: 745–58.
4 Gupta K, Stamm WE. Outcomes associated with
trimethoprim/sulphamethoxazole (TMP/SMX) therapy in
TMP/SMX resistant community-acquired UTI. Int. J.
Antimicrob. Agents 2002; 19: 554–6.
5 Naber KG, Bergman B, Bishop MC et al. EAU guidelines
for the management of urinary and male genital tract
infections. Urinary Tract Infection (UTI) Working Group of
the Health Care Office (HCO) of the European Association
of Urology (EAU). Eur. Urol. 2001; 40: 576–88.

454 © 2010 The Japanese Urological Association


6 Nicolle LE. Uncomplicated urinary tract infection in adults
including uncomplicated pyelonephritis. Urol. Clin. North
Am. 2008; 35: 1–12.
7 Tice AD. Short-course therapy of acute cystitis: a brief
review of therapeutic strategies. J. Antimicrob. Chemother.
1999; 43 (Suppl A): 85–93.
8 Hooton TM, Johnson C, Winter C et al. Single-dose and
three-day regimens of ofloxacin versus
trimethoprim-sulfamethoxazole for acute cystitis in women.
Antimicrob. Agents Chemother. 1991; 35: 1479–83.
9 Naber KG, Allin DM, Clarysse L et al. Gatifloxacin
400 mg as a single shot or 200 mg once daily for 3 days is
as effective as ciprofloxacin 250 mg twice daily for the
treatment of patients with uncomplicated urinary tract
infections. Int. J. Antimicrob. Agents 2004; 23: 596–605.
10 Kahlmeter G, ECO.SENS. An international survey of the
antimicrobial susceptibility of pathogens from
uncomplicated urinary tract infections: the ECO.SENS
Project. J. Antimicrob. Chemother. 2003; 51: 69–76.
11 Hooton TM. The current management strategies for
community-acquired urinary tract infection. Infect. Dis.
Clin. North Am. 2003; 17: 303–32.
12 Yamamoto S, Akiyama K, Yoshimoto T et al. Clinical
efficacy of oral administration of 200 mg gatifloxacin once
daily for 3 days for the treatment of patients with
uncomplicated cystitis. J. Infect. Chemother. 2009; 15:
104–7.
13 Yamamoto S, Tsukamoto T, Terai A, Kurazono H, Takeda
Y, Yoshida O. Genetic evidence supporting the
fecal-perineal-urethral hypothesis in cystitis caused by
Escherichia coli. J. Urol. 1997; 157: 1127–9.
14 Mitsumori K, Terai A, Yamamoto S, Yoshida O. Virulence
characteristics and DNA fingerprints of Escherichia coli
isolated from women with acute uncomplicated
pyelonephritis. J. Urol. 1997; 158: 2329–32.
15 Garofalo CK, Hooton TM, Martin SM et al. Escherichia
coli from urine of female patients with urinary tract
infections is competent for intracellular bacterial
community formation. Infect. Immun. 2007; 75: 52–60.
16 Scholes D, Hooton TM, Roberts PL, Stapleton AE, Gupta
K, Stamm WE. Risk factors for recurrent urinary tract
infection in young women. J. Infect. Dis. 2000; 182:
1177–82.
17 Raz R, Stamm WE. A controlled trial of intravaginal estriol
in postmenopausal women with recurrent urinary tract
infections. N. Engl. J. Med. 1993; 329: 753–6.
18 Jackson SL, Boyko EJ, Scholes D, Abraham L, Gupta K,
Fihn SD. Predictors of urinary tract infection after
menopause: a prospective study. Am. J. Med. 2004; 117:
903–11.
19 Le TP, Miller LG. Empirical therapy for uncomplicated
urinary tract infections in an era of increasing antimicrobial
resistance: a decision and cost analysis. Clin. Infect. Dis.
2001; 33: 615–21.
20 Perfetto EM, Gondek K. Escherichia coli resistance in
uncomplicated urinary tract infection: a model for
determining when to change first-line empirical antibiotic
choice. Manag. Care Interface 2002; 15: 35–42.
© 2010 The Japanese Urological Association
Treatment of acute uncomplicated cystitis
21 De Francesco MA, Ravizzola G, Peroni L, Negrini R,
Manca N. Urinary tract infections in Brescia, Italy: etiology
of uropathogens and antimicrobial resistance of common
uropathogens. Med. Sci. Monit. 2007; 13: BR136–44.
22 Daza R, Gutiérrez J, Piédrola G. Antibiotic susceptibility of
bacterial strains isolated from patients with
community-acquired urinary tract infections. Int. J.
Antimicrob. Agents 2001; 18: 211–15.
23 Sader HS, Biedenbach DJ, Streit JM, Jones RN. Cefdinir
activity against contemporary North American isolates from
community-acquired urinary tract infections. Int. J.
Antimicrob. Agents 2005; 25: 89–92.
24 Bean DC, Krahe D, Wareham DW. Antimicrobial
resistance in community and nosocomial Escherichia coli
urinary tract isolates, London 2005–2006. Ann. Clin.
Microbiol. Antimicrob. 2008; 7: 13.
25 Ling TK, Xiong J, Yu Y, Lee CC, Ye H, Hawkey PM.
Multicenter antimicrobial susceptibility survey of
gram-negative bacteria isolated from patients with
community-acquired infections in the People’s Republic of
China. Antimicrob. Agents Chemother. 2006; 50: 374–8.
26 Raz R, Chazan B, Kennes Y et al. Empiric use of
trimethoprim-sulfamethoxazole (TMP-SMX) in the
treatment of women with uncomplicated urinary tract
infections, in a geographical area with a high prevalence of
TMP-SMX-resistant uropathogens. Clin. Infect. Dis. 2002;
34: 1165–9.
27 McNulty CA, Richards J, Livermore DM et al. Clinical
relevance of laboratory-reported antibiotic resistance in
acute uncomplicated urinary tract infection in primary care.
J. Antimicrob. Chemother. 2006; 58: 1000–8.
28 Hames L, Rice CE. Antimicrobial resistance of urinary
tract isolates in acute uncomplicated cystitis among
college-aged women: choosing a first-line therapy. J. Am.
Coll. Health 2007; 56: 153–6.
29 Colgan R, Johnson JR, Kuskowski M, Gupta K. Risk
factors for rimethoprim-sulfamethoxazole resistance in
patients with acute uncomplicated cystitis. Antimicrob.
Agents Chemother. 2008; 52: 846–51.
30 Cagnacci S, Gualco L, Debbia E, Schito GC, Marchese A.
European emergence of ciprofloxacin-resistant Escherichia
coli clonal groups O25:H4-ST 131 and O15:K52:H1
causing community-acquired uncomplicated cystitis. J.
Clin. Microbiol. 2008; 46: 2605–12.
31 Muratani T, Matsumoto T. Urinary tract infection caused
by fluoroquinolone- and cephem-resistant
Enterobacteriaceae. Int. J. Antimicrob. Agents 2006; 28
(Suppl 1): S10–13.
32 Kim ME, Ha US, Cho YH. Prevalence of antimicrobial
resistance among uropathogens causing acute
uncomplicated cystitis in female outpatients in South
Korea: a multicentre study in 2006. Int. J. Antimicrob.
Agents 2008; 31 (Suppl 1): S15–18.
33 Arslan H, Azap OK, Ergönül O, Timurkaynak F, Urinary
Tract Infection Study Group. Risk factors for ciprofloxacin
resistance among Escherichia coli strains isolated from
community-acquired urinary tract infections in Turkey. J.
Antimicrob. Chemother. 2005; 56: 914–18.
455
S YAMAMOTO ET AL.
34 Katchman EA, Milo G, Paul M, Christiaens T, Baerheim
A, Leibovici L. Three-day vs longer duration of antibiotic
treatment for cystitis in women: systematic review and
meta-analysis. Am. J. Med. 2005; 118: 1196–207.
35 Rafalsky V, Andreeva I, Rjabkova E. Quinolones for
uncomplicated acute cystitis in women. Cochrane Database
Syst. Rev. 2006; (3): CD003597.
36 Nicolle LE. Short-term therapy for urinary tract infection:
success and failure. Int. J. Antimicrob. Agents 2008; 31
(Suppl 1): S40–5.
37 Wagenlehner FM, Naber KG. Antibiotic treatment for
urinary tract infections: pharmacokinetic/pharmacodynamic
principles. Expert. Rev. Anti. Infect. Ther. 2004; 2: 923–31.
38 Takahashi A, Muratani T, Yasuda M et al. Genetic profiles
of fluoroquinolone-resistant Escherichia coli isolates
456
obtained from patients with cystitis: phylogeny, virulence
factors, PAIusp subtypes, and mutation patterns. J. Clin.
Microbiol. 2009; 47: 791–5.
39 Olofsson SK, Marcusson LL, Strömbäck A, Hughes D,
Cars O. Dose-related selection of fluoroquinolone-resistant
Escherichia coli. J. Antimicrob. Chemother. 2007; 60:
795–801.
40 Zhang YY, Huang HH, Ren ZY et al. Clinical evaluation of
oral levofloxacin 500 mg once-daily dosage for treatment of
lower respiratory tract infections and urinary tract
infections: a prospective multicenter study in China. J.
Infect. Chemother. 2009; 15: 301–11.
© 2010 The Japanese Urological Association