Duration of antibacte rial treatment for uncomplicated
urinary tract infection in women (Review)
Milo G, Katchman EA, Paul M, Christiaens T, Baerheim A, Leibov ici L
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2007, Issue 1
http://www.thecochranelibrary.com
1Duration of antibacterial treatment for uncomplicated urinary tract infection in women (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
T A B L E O F C O N T E N T S
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW . . . . . . . . . . . . . . . . . .
3SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . . .
3METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4DESCRIPTION OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . .
8ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
29Characteristics of excluded studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
30ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
30Table 01. Electronic search strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . .
32ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
32Comparison 01. Three days versus 5-10 day antibiotic therapy . . . . . . . . . . . . . . . . . . .
33INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33COVER SHEET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
35GRAPHS AND OTHER TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
35Figure 01. Funnel plot - symptomatic failure . . . . . . . . . . . . . . . . . . . . . . . . .
36Figure 02. Funnel plot - bacteriologic failure . . . . . . . . . . . . . . . . . . . . . . . . .
37Analysis 01.01. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 01 Short-term symptomatic
failure (2-15 days from end of treatment) . . . . . . . . . . . . . . . . . . . . . . . .
38Analysis 01.02. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 02 Short-term symptomatic
failure - ITT (2-15 days from e nd of treatment) . . . . . . . . . . . . . . . . . . . . . .
40Analysis 01.03. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 03 Long-term symptomatic
failure (4-10 weeks from end of treatment) . . . . . . . . . . . . . . . . . . . . . . . .
41Analysis 01.04. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 04 Long-term symptomatic
failure - ITT (4-10 weeks from end of treatment) . . . . . . . . . . . . . . . . . . . . .
42Analysis 01.05. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 05 Short-term bacteriologic
failure (2-15 days from end of treatment) . . . . . . . . . . . . . . . . . . . . . . . .
44Analysis 01.06. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 06 Short-term bacteriological
failure by antiboitic class (same drug) (2-15 days from end of treatment) . . . . . . . . . . . . .
45Analysis 01.07. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 07 Short-term bacteriological
failure - ITT (2-15 days from e nd of treatment) . . . . . . . . . . . . . . . . . . . . . .
47Analysis 01.08. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 08 Long-term bacteriological
failure (4-10 weeks from end of treatment) . . . . . . . . . . . . . . . . . . . . . . . .
48Analysis 01.09. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 09 Long-term bacteriological
failure by antibiotic class (same drug) (4-10 weeks from end of treatment) . . . . . . . . . . . . .
49Analysis 01.10. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 10 Long-term bacteriological
failure - ITT (4-10 weeks from end of treatment) . . . . . . . . . . . . . . . . . . . . .
50Analysis 01.11. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 11 Long-term bacteriological
failure - ITT by antibiotic class (same drug) (4-10 weeks from end of treatment) . . . . . . . . . . .
iDuration of antibacterial treatment for uncomplicated urinary tract infection in women (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
52Analysis 01.12. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 12 Patients with any adverse
effects during treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
53Analysis 01.13. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 13 Patients developed
pyelonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
54Analysis 01.14. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 14 Adverse eff ects requiring
therapy discontinuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
56Analysis 01.15. Comparison 01 Three days versus 5-10 day antibiotic ther apy, Outcome 15 Gastrointestinal adverse
effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
57Analysis 01.16. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 16 Skin adverse effects . .
59Analysis 01.17. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 17 CNS adverse effects . .
60Analysis 01.18. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 18 Vaginal discharge as an
adverse effect of therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
61Analysis 01.19. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 19 Other adverse effects .
63Analysis 01.20. Comparison 01 Three days versus 5-10 day antibiotic therapy, Outcome 20 Patients with any adverse
effects during treatment by antibiotic class (same drug) . . . . . . . . . . . . . . . . . . .
iiDuration of antibacterial treatment for uncomplicated urinary tract infection in women (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Duration of antibacte rial treatme nt for uncomplicated
urinary tract infection in women (Review)
Milo G, Katchman EA, Paul M , Christiaens T, Baerheim A, Leibovici L
This record should be cited as:
Milo G, Katchman EA, Paul M, Ch ristiaens T, Baerheim A, Leibovici L. Duration of antibacterial treatment for uncompli-
cated urinary tract infection in women. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD004682. DOI:
10.1002/14651858.CD004682.pub2.
This version first published online: 20 April 2005 in Issue 2, 2005.
Date of most recent substantive amendment: 22 February 2005
A B S T R A C T
Background
Uncomplicated urinary tract infection (UTI) is a common disease, occurring frequently in young sexually active women. In the past,
seven day antibiotic therapy was recommended while the current practice is to treat uncomplicated UTI for th ree days.
Objectives
TO compare the efficacy and safety of three-day antibiotic therapy to multi-day therapy (five days or longer) on relief of symptoms
and bacteriuria at short-term and long-term follow-up.
Search strategy
The Cochrane Library (Issue 1, 2004), the Cochrane Renal Group’s Register of trials (Jul y 2003), EMBASE (January 1980 to August
2003), and MEDLINE (January 1966 to August 2003) were searched. We scanned references of all included studies and contacted the
first or corresponding author of included trials and the pharmaceutical companies.
Selection criteria
Randomised controlled trials comparing three-days oral antibiotic therapy with multi-day therapy (five days and longer) for uncom-
plicated cystitis in 18 to 65 years old non-pregnant women without signs of upper UTI.
Data coll ection and analysis
Data concerning bacteriological and symptomatic failure rates, occurrence of pyelonephritis and adverse effects were extracted inde-
pendently by two reviewers. Relative risk (RR) and their 95% confidence intervals (CI) were e stimated. Outcomes were also extracted
by intention-to-treat analysis whenever possible.
Main results
Thirty-two trials (9605 patients) were included. For symptomatic failure rates, no difference between three-day and 5-10 day antibiotic
regimen was se en short-term (RR 1.06, 95% CI 0.88 to 1.28) and long-term follow-up (RR 1.09, 95% CI 0.94 to 1.27). Comparison
of the bacteriological failure rates showed that three-day therapy was less effective than 5-10 day therapy for the short-term follow-
up, however this difference was observed only in the subgroup of trials that used the same antibiotic in the two treatment arms (RR
1.37, 95% CI 1.07 to 1.74, P = 0.01). This difference was more significant at long-term follow-up (RR 1.43, 95% CI 1.19 to 1.73,
P = 0.0002). Adverse effects were significantly more common in the 5-10 day treatment group (RR 0.83, 95% CI 0.74 to 0.93, P =
0.0010). Results were consistent for subgroup and sensitivity analyses.
Authors’ conclusions
Three days of antibiotic therapy is similar to 5-10 days in achieving symptomatic cure during uncomplicated UTI treatment, while
the longer treatment is more ef fective in obtaining bacteriological cure. In spite of the higher rate of adverse effects, treatment for 5-10
days could be considered for treatment of women in whom eradication of bacteriuria is important.
1Duration of antibacterial treatment for uncomplicated urinary tract infection in women (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
P L A I N L A N G U A G E S U M M A R Y
Uncomplicated urinary tract infection (UTI) is a common disease occurring frequently in young women. It is caused by bacteria
multiplying in urine, and the patient usually complains of urgency and burning pain while urinating. The present practice is to treat
the patient with antibiotics for three days. In this review we included all studies that compared three-day therapy with longer treatment
(five days or more). Three days of treatment were adequate to achieve symptomatic relief for most patients, but it appears that longer
therapy is better in terms of bacteria elimination from the urine, no matter what antibiotic is used. Longer therapy for UTI is related to
higher rate of adverse reactions to the antibiotics used. Pending fur ther research, it could be considered for women in whom er adication
of bacteria in the urine is important.
B A C K G R O U N D
Uncomplicated urinary tract infection (UTI) is a common dis-
ease, occurring frequently in young sexually active women. In one
cohort study the incidence of the disease was estimated to be 0.5-
0.7/person-year (Hooton 1996). All over the world the most com-
mon pathogens of uncomplicated UTI are similar: 80-90% Es-
cherichia coli, 5-10% Staphylococcus saprophyticus, the remaining
infections being caused by Proteus spp., and other Gram-negative
rods. Most are bacteria from the gut that colonize the perineum
and then ascend through the urethra to infect the bladder mu-
cosa. The infection causes specific symptoms, mainly the triad
of dysuria (painful urination), urgency (the urgent need to void)
and frequency (very f requent urination). In randomised controlled
trials (RCTs) the diagnosis is based on positive urine cultures in
symptomatic subjects. In the past, the th reshold for diagnosis of
UTI was >10
5
colony forming units (CFU)/ml of voided mid-
stream urine (Stamm 1982). However two decades ago studies
have shown that in young symptomatic women with leucocyturia
even 100 CFU/ml voided midstream urine can establish the diag-
nosis (Stamm 1980; Stamm 1982; Kunin 1993).
A large range of antimicrobials with different rates of cure and side
effects are used in the treatment of UTI. It is thought that a short-
course therapy consisting of a three-day antibacterial regimen is
sufficient for uncomplicated urinary tract infection, as it is prob-
ably as effective as 7-10 days therapy, and may be associated with
less side e ffects and lower costs (Hooton 1997). Single dose ther-
apy has been advocated for years but about a decade ago reviews
have raised doubts as to its use because of a higher frequency of
bacteriological recurrence (Leibovici 1991; Norrby 1990), and it
is no longer common clinical practice. On the other hand, single-
dose treatment probably achieves symptomatic relief more rapidly
than seven days of treatment (Arav-Boger 1994).
In most clinical tr ials assessing effectiveness of therapy, cure was
defined as bacteriological cure, rather than symptomatic relief.
Uncomplicated UTI is not considered a serious disease. It is not
clear whether untreated UTI can progress to pyelonephritis, and
if so how often. Progression to pyelonephritis probably occurs at
a very low rate, while asymptomatic bacteriuria in young, healthy
and non-pregnant women is not associated with renal damage
(Stamm 1991).
Thus since our last systematic review on the l ength of treatment
of uncomplicated UTI in young women (Leibovici 1991), the
following questions arose:
1. What is the relative effectiveness of three days treatment com-
pared with multi-day treatment?
2. Is any diff erence modified by the antibiotic used (old versus
new) or CFU/ml count?
3. Do persistent positive cultures lead to persistent symptoms?
4. What is the relative effectiveness of single dose and three-day
treatment, compared with seven days treatment, when the out-
come of interest is symptomatic cure rather than bacteriological
one?
5. Does the duration of treatment influence the development of
resistant strains during treatment?
O B J E C T I V E S
The main objective of this review was to assess the evidence, as
found in RCTs for the relative effectiveness of different re gimens
of antibacterial treatments in acute, uncomplicated lower urinary
tract infection in otherwise healthy 16 to 65 years ol d females.
Specific objectives were:
1. To assess the evidence for the relative effectiveness as assessed in
RCT’s comparing three-day versus multi-day therapy on:
a. Relief of symptoms within two weeks after start of treatment (
mostly within seven days)
b. Re solution of bacteriuria within two weeks after start of treat-
ment (bacteriological cure)
c. Recurrence of symptoms or bacteriuria between cure and up-to
eight weeks after start of treatment
d. To assess the frequency of adverse events in the different regi-
mens
2. To assess the evidence for the relative effectiveness of the differ-
ent antibacterial drugs used in the RCTs.
3. To assess the evidence for development of resistance for different
durations of treatment with different drugs (comparing resistance
of grown bacteria before and after therapy).
2Duration of antibacterial treatment for uncomplicated urinary tract infection in women (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd