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. 2017 Dec 15;114(50):866–873. doi: 10.3238/arztebl.2017.0866

eTabelle 1. Effektstärken der verschiedenen empfohlenen Antibiotika.

Reference Level of evidence & Risk of
Bias*
Outcome Intervention
& number of patients
Dosage Duration Comparison &
number of patients
Dosage Duration
Randomized controlled trials
Ciprofloxacin
Bleidorn
2010
(e28)
Ib


Random sequence generation -
Allocation concealment -
Blinding of participants and
personal -
Blinding of outcome data assessment -
Incomplete outcome data -
Selective outcome reporting -
Other bias -
Uncomplicated lower UTI


Primary outcomes:
Symptom resolution on day 4: Ibuprofen: 58.3%
Ciprofloxacin: 51.5%, p=0.744

Secondary outcomes:
Symptom burden day 4:
Ibuprofen: mean 0.97, SD 1.42
Ciprofloxacin: mean 1.3, SD 1.9

Symptom burden day 7:
Ibuprofen: mean 0.67, SD 1.26
Ciprofloxacin: mean 0.61, SD 0.86
Symptom resolution day 7:
Ibuprofen: 75%
Ciprofloxacin: 60.6%, p=0.306

Frequency of relapse (secondary antibiotic treatment day 0 to 9; per
protocol analysis):
Ibuprofen: 33.3%
Ciprofloxacin: 18.2%, p=0.247
Ibuprofen


N=40
3 × 400 mg 3 days Ciprofloxacin


N=39
2 x 250mg (+1 placebo) 3 days
Ceran
2010
(e29)
IIb

Random sequence generation -
Allocation concealment -
Blinding of participants and
personal +
Blinding of outcome data assessment +
Incomplete outcome data +
Selective outcome reporting ?
Other bias ?
Uncomplicated lower UTI

Clinical effects (clinical response= disappearance of signs and
symptoms):
FMT 83.1%
Ciprofloxacin 81%, p>0.05

Bacteriological effects (antibiotic sensitivity):
FMT 83.1%
Ciprofloxacin 78.4%, p>0.05

Improvement of urinary findings:
FMT 80.5%
Fosfomycin
trometamol (FMT)

N=77
1 x 3g 1 day Ciprofloxacin

N=65
2 x 500mg 5 days
Ciprofloxacin 80%
Hooton
2012
(e30)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal -
Blinding of outcome data assessment ?
Incomplete outcome data -
Selective outcome reporting -
Other bias ?
Women with acute uncomplicated cystitis

Primary outcomes:
Overall clinical cure: 11% difference, CI95% [3; 8]

Secondary outcomes:
Early clinical cure (at first followup visit):
5% difference, CI95% [1; 12]

Early microbiological cure (at first followup visit):
15% difference, CI95% [8; 23]
Ciprofloxacin

N=150
2 x 250mg 3 days Cefpodoxime

N=150
2 x 100mg 3 days
Palou
2013
(e31)
Ib

Random sequence generation ?
Allocation concealment ?
Blinding of participants and
personal -
Blinding of outcome data assessment ?
Incomplete outcome data -
Selective outcome reporting +
Other bias ?
Women post-menopause with lower UTI

Eradication:
FMT, N, %: 23, 62.16 Cipro, N, %: 23, 58.97

Persistence:
FMT, N, %: 10, 27.03
Cipro, N, %: 9, 23.08

New infection:
FMT, N, %: 4, 10.81
Cipro, N, %: 7, 17.95

Clinical cure:
FMT, N, %: 32, 86.49
Cipro, N, %: 32, 82.05
Clinical improvement:
FMT, N, %: 1, 2.7
Cipro, N, %: 2, 5.13
Clinical failure:
FMT, N, %: 4, 10.81
Cipro, N, %: 4, 10.26

relapse:
FMT, N, %: 0, 0
Cipro, N, %: 1, 2.56
Fosfomycin
trometamol
N=59
2 x 3g 2 doses
separated
by 72hrs
Ciprofloxacin

N=59
2 x 250mg 3 days
Peterson Ib Complicated UTI and acute pyelonephritis Levofloxacin 1 x 750mg IV or orally 5 days Ciprofloxacin 2 x 400mg IV and/or 10
2008
(e32)

Random sequence generation -
Allocation concealment -
Blinding of participants and
personal -
Blinding of outcome data assessment +
Incomplete outcome data -
Selective outcome reporting -
Other bias?

Eradication rate end of therapy:
Levofloxacin (N, %): 253, 79.8
Ciprofloxacin (N, %): 234, 77.5

Clinical success rate end of therapy:
Levofloxacin (N, %): 262, 82.6
Ciprofloxacin (N, %): 210, 87.1

N=543

N=559
2 x 500mg orally days
Fosfomycin
Ceran
2010
(e29)
IIb

Random sequence generation -
Allocation concealment -
Blinding of participants and
personal +
Blinding of outcome data assessment +
Incomplete outcome data +
Selective outcome reporting ?
Other bias ?
Uncomplicated lower UTI

Clinical effects (clinical response= disappearance of signs and
symptoms):
FMT 83.1%
Ciprofloxacin 81%, p>0.05

Bacteriological effects (antibiotic sensitivity):
FMT 83.1%
Ciprofloxacin 78.4%, p>0,05

Improvement of urinary findings:
FMT 80.5%
Ciprofloxacin 80%
Fosfomycin
trometamol (FMT)
N=77
1 x 3g 1 day Ciprofloxacin

N=65
2 x 500mg 5 days
Palou
2013
(e31)
Ib

Random sequence generation ?
Allocation concealment ?
Blinding of participants and personal -
Blinding of outcome data assessment ?
Incomplete outcome data -
Selective outcome reporting +
Other bias ?
Women post-menopause with lower UTI

Eradication:
FMT, N, %: 23, 62.16
Ciprofloxacin, N, %: 23, 58.97

Persistence:
FMT, N, %: 10, 27.03
Ciprofloxacin, N, %: 9, 23.08

New infection:
FMT, N, %: 4, 10.81
Ciprofloxacin, N, %: 7, 17.95

Clinical cure:
FMT, N %: 32, 86.49
Ciprofloxacin, N, %: 32, 82.05
Fosfomycin
trometamol

N=59
2 x 3g 2 doses
separated
by 72
hours
Ciprofloxacin

N=59
2 x 250mg 3 days
Clinical improvement:
FMT, N, %: 1, 2.7
Ciprofloaxin, N, %: 2, 5.13

Clinical failure:
FMT, N, %: 4, 10.81
Ciprofloaxin, N, %: 4, 10.26
relapse:
FMT, N, %: 0, 0
Ciprofloxacin, N, %: 1, 2.56
Estebanez
2009
(e33)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal +
Blinding of outcome data assessment +
Incomplete outcome data -
Selective outcome reporting -
Other bias ?
Pregnant women

Eradication rate (primary outcome):
Similar in both groups, over 80%
RR=1.195, CI95% [0.451; 3.165], p=0.720

Reinfection:
Lower with fosfomycin
RR=0.13, CI95% [0.02; 0.81], p=0.045

Adverse effects:
Lower with fosfomycin
RR=0.10, CI95% [0.01; 0.72], p=0.008

Persistence:
RR=2.64, CI95% [0.59; 11.79], p=0.39

Development of symptomatic UTI:
p=0.319

Recurrences:
RR=1.06, CI95% [0.11; 10.12], p=0.96
Fosfomycin

N=53
1 x 3g 1 day Amoxicillin–clavulanate

N=56
3 x 500mg/125mg 7 days
Gágyor
2015
(26)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal -
Blinding of outcome data assessment -
Incomplete outcome data -
Selective outcome reporting -
UTI in women

Primary outcomes:
Total number of courses of antibiotics for UTIs days 0-28 during
followup (N, %):
Ibuprofen: 75, 31
Fosfomycin: 30, 12
mean difference: 18.8, CI95% [11.6; 25.9]
Symptom burden day 0-7 (mean, SD):
Ibuprofen: 17.3, 11.0
Fosfomycin: 12.1, 8.2
Fosfomycin

N=246
1x 3 g 1 day Ibuprofen

N=248
3x400mg 3 days
Other bias - mean difference: 5.3, CI95% [3.5; 7.0]

secondary outcomes:
adverse events (patient reported, N, %):
Ibuprofen: 42, 17
Fosfomycin: 57, 24
mean difference: -6.0, CI95% [-13.2; 1.1]

recurrence days 15-28, rated by GP (N, %):
Ibuprofen: 14, 6
Fosfomycin: 27, 11
mean difference: -5.3, CI95% [-10.2; 0.4]

Symptom free at day 7:
Ibuprofen: 163/232, 70
Fosfomycin: 186/227, 82
mean difference: -11.7, CI95% [-19.4; -4.0]
Pivmecillinam
Monsen
2014
(e34)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal +
Blinding of outcome data assessment +
Incomplete outcome data -
Selective outcome reporting -
Other bias ?
Symptomatic UTI

Symptom free at last follow-up (day 35-49 post inclusion):
PIV (total): 68%
Placebo: 54%, p<0.01
Pivmecillinam

N=855
3 x 200mg 7 days Pivmecillinam
or Pivmecillinam
or Placebo
N=288
2 x 200mg

2 x 400mg
7 days

3 days
Bjerrum
2009
(e35)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal +
Blinding of outcome data assessment +
Incomplete outcome data -
Selective outcome reporting -
Other bias -
Uncomplicated cystitis

Primary Outcomes:
Drug efficacy (clinical cure at follow-up visit 7-10 days):
Pivmecillinam: 68.8%
Sulfamethizole: 77.9% (difference -9.2%, CI95% [-24.7; 6.3].

Secondary Outcomes:
Bacteriological Cure (<10 hoch 3 cfu/ml):
Pivmecillinam: 68.8% Sulfamethizole: 77.9%
(difference 9.2%, CI95% [24.7; 6.3].
Pivmecillinam

N=89
3 x 400mg 3 days Sulfamethizole

N=86
2 x 1g 3 days
Recurrence within 6 months (GP survey data):
Pivmecilliam: 26.8%
Sulfamethizole: 18.4%
(difference 8.4%, CI95% [-4.5; 21.4%]
Kazemier
2015
(28)

Prospective cohort
with embedded
RCT
Ib-IIb
Random sequence generation -
Allocation concealment -
Blinding of participants and personal -
Blinding of outcome data assessment -
Incomplete outcome data -
Selective outcome reporting -
Other bias -
Asymptomatic pregnant women

Primary outcomes:
Composite (Pyelonephritis +delivery):
Risk difference -0.4, CI95% [-3.6; 9.4]

Pyelonephritis:
Risk difference -2.4, CI95% [-19.2; 14.5]

Delivery <34 weeks:
Risk difference -1.5, CI95% [-15.3; 18.5]
Nitrofurantoin

N=40
2x 100mg 5 days Placebo

N=45

Comparison is made with N=208, which is placebo or untreated (from cohort study).
2x 5 days
Lumbiganon
2009
(e36)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal -
Blinding of outcome data assessment ?
Incomplete outcome data ?
Selective outcome reporting ?
Other bias ?
Asymptomatic bacteriuria in pregnancy

Primary outcomes:
Bacterial cure on day 14:
Cure rate difference: -10.5, CI95% [-16.1; -4.9]
Cure rate ratio: 0.88, CI95% [0.82; 0.94]

Secondary outcomes:
Different Adverse effects.
Different pregnancy outcomes.
Nitrofurantoin

N=386
2 x 100mg 1 day Nitrofurantoin

N=392
2 x 100mg 7 days
Other
Little
2010
(e37)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal +
Blinding of outcome data assessment +
Incomplete outcome data -
Selective outcome reporting -
Women with uncomplicated UTI

Effectiveness:
Frequency symptom severity (mean difference, SD):
Immediate: 2.15, 1.18
Midstream urine: 2.08, -0.07
Dipstick: 1.74, -0.40
Symptom score: 1.77, -0.38
Delayed antibiotics: 2.11, -0.04, p=0.177

Duration of moderately bad symptoms in days (incidence ratio):
Immediate
antibiotics
Midstream urine or

Dipstick or

Symptom score or

Delayed antibiotics
Other bias ? Immediate: 1
Midstream urine: 1.21
Dipstick: 0.91
Symptom score: 1.11
Delayed antibiotics: 1.12, p=0.369

Mean unwell symptom severity (mean difference, SD):
Immediate: 1.60, 1.30
Midstream urine: 1.66, 0.05
Dipstick: 1.32, -0.28
Symptom score: 1.26, -0.35
Delayed antibiotics: 1.43, -0.18, p=0.392

Odds ratio for antibiotic use:
Immediate: 97%
Midstream urine: 0.15, CI95% [0.03; 0.73]
Dipstick: 0.13, CI95% [0.03; 0.63]
Symptom score: 0.29, CI95% [0.06; 1.55]
Delayed antibiotics: 0.12, CI95% [0.03; 0.59],
p=0.011

Time to reconsultation (hazard ratio):
Immediate: 1
Midstream urine: 0.81, CI95% [0.47; 1.39]
Dipstick: 0.98, CI95% [0.58; 1.65]
Symptom score: 0.73, CI95% [0.43; 1.22]
Delayed antibiotics: 0.60, CI95% [0.35; 1.05]
p=0.345
Monmaturap
oj 2012
(e38)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal -
Blinding of outcome data
assessment +
Incomplete outcome data -
Selective outcome reporting -
Other bias ?
Acute pyelonephritis

All patients were given 2g ceftriaxone (IV) over 30min 1x daily as an
initial antibiotic agent.
After day 3, patients who satisfied the inclusion criteria and the
criteria for switch therapy were enrolled and randomized to either the
control or study group regimens.

Clinical cure (N, %):
Group B: 41, 100
Group A: 39, 95.1

Symptom improvement (N, %):
Group B: 0
Group A: 1, 2.4

Treatment failure (N, %):
Group B: 0
Group B:

Placebo (IV) +
Cefditoren pivoxil

N=41
4x 100mg + placebo (IV) 10 days Group A:

ceftraxione (IV) + oral
placebo 4 tablets

N=41
4 x 100mg + 2g
ceftriaxone (IV)
10 days
Group A: 1, 2.4

Bacteriological eradication (N, %):
Group B: 24, 60
Group A: 26, 63.4
Shaheen
2015
(e39)
IIb
Random sequence generation +
Allocation concealment +
Blinding of participants and personal +
Blinding of outcome data assessment ?
Incomplete outcome data ?
Selective outcome reporting ?
Other bias ?
Urinary tract infections

Improved:
CranAdvantage (N, %): 23, 35.38
Urixin (N, %): 15, 23.07

Not improved:
CranAdvantage (N, %): 42, 64.61
Urixin (N, %): 50, 76.92
CranAdvantage

N=65
2 x 500mg 2-3 weeks Urixin

N= 65
2 x 400mg 2-3 weeks
Stein
2011
(e40)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal +
Blinding of outcome data assessment +
Incomplete outcome data ?
Selective outcome reporting ?
Other bias ?
Women with suspected UTI Computer –
expedited
management group

N=61
Usual care

N=42
Turner
2010
(e41)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and
personal +
Blinding of outcome data assessment +
Incomplete outcome data +
Selective outcome reporting -
Other bias ?
Women with UTI

Cost-effectiveness analysis
Immediate
antibiotics

N=56
Midstream urine
N= 46

Dipstick
N=42

Symptom scores
N=60

Delayed antibiotics
N=53
Drozdov
2015
(e42)

RCT
Ib
Random sequence generation -
Allocation concealment ?
Blinding of participants and personal +
Blinding of outcome data assessment +
Incomplete outcome data ?
Selective outcome reporting -
Other bias ?
Uncomplicated UTI

Primary outcome:
Overall antibiotic exposure within 90 days:
Intervention: Median 7.0, IQR 5.0 to 14.0,
control: Median 10.0, IQR 7.0 to 16.0,
p=0.011

Secondary outcome: no differences found.
(Duration of therapy; Persistant infection 7 days and 30 days after;
Recurrence; Hospitalization within 90 days)
Dif. Antibiotics,
administrationbased on algorithm

N=63
Dif. Antibiotics,
administration based
on standard guideline

N=66
Wagenlehner
2015
(e44)
Ib

Random sequence generation -
Allocation concealment -
Blinding of participants and personal -
Blinding of outcome data assessment -
Incomplete outcome data -
Selective outcome reporting -
Other bias -
Complicated UTI and pyelonephritis

Microbiological eradication (N, %, CI95%):
Cefto.: 320, 80.4 [2.4-; 4.1]
Levo.: 290, 72.1
% difference: 8.3, CI95% [2.4; 14.1]

Clinical cure (N, %, CI95%):
Ceftolozane/tazobactam.: 366, 92.0
Levofloxacin.: 356, 88.6
% difference: 3.4, CI95% [-0.7, 7.6]
Ceftolozane-
tazobactam

N=543
3 x 1,5g iv 7 days Levofloxacin

N=540
1 x 750 mg iv 7 days
Systematic reviews and meta-analyses
Costelloe
2010
(e44) MA
IIa
High quality
Individuals prescribed antibiotics in primary care
Resistance (UTI only) at 0-12 months:
OR= 1.33, CI95% [1.15; 1.53]
Antibiotic use No antibiotic
Eliakim-Raz
2013
(e45)

MA
Ia

Acceptable quality
Acute Pyelonephritis and septic UTI

RCTs=8

Primary outcomes:
Clinical failure at end of treatment (at 10-14 days):
5 RCT, RR=0.63, CI95% [0.33; 1.18]
Secondary outcomes:
Different antibiotics <= 7 days Different antibiotics > 7 days
Clinical failure at end of followup:
7 RCT, RR=0.79, CI95% [0.56; 1.12]

Microbiological failure at end of treatment:
8 RCT, RR=0.60, CI95% [0.09; 3.86]

Microbiological failure at end of followup:
8 RCT, RR=1.16, CI95% [0.83; 1.62]

any adverse event:
7 RCTs, RR=0.93, CI95% [0.73; 1.18]
Falagas
2009
(e46)
MA
Ia

High quality
Patients with cystitis.
5 RCTs on non-pregnant, non-immunocompromised adult women
Clinical success (cure and non-cure but symptom relief):
Antibiotics superior
4 RCTs, 1062 patients, OR=4.81, CI95% [2.51; 9.21]

Clinical success (cure):
Antibiotics superior
4 RCTs, 967 patients, OR=4.67, CI95% [2.34; 9.35]

Microbiological eradication (at end of treatment):
Antibiotics superior
3 RCTs, 1062 patients, OR=10.67, CI95% [2.96; 38.43]

Microbiological eradication (after end of treatment):
Antibiotics superior
3 RCTs, 738 patients, OR=5.38, CI95% [1.63; 17.77]
Microbiological reinfection or relapse (after end of treatment):
Antibiotics superior
5 RCTs, 843 patients, OR=0.27, CI95% [0.13; 0.55]
No difference was found between the compared treatment arms regarding study withdrawals from adverse events, the development of pyelonephritis and emergence of resistance.
Different antibiotics placebo
Falagas
2010
(e47)
MA
Ia

High quality
Patients with cystitis.

27 trials (8 double-blind) included.

16/27 on non-pregnant female patients, 3 adult mixed populations of older age, 5 on pregnant patients, 3 on paediatric patients.
Clinical success (non-pregnant and mixed populations, complete cure and improvement of symptoms): no difference regarding all comparators combined [10 RCTs, 1657 patients, RR= 1.00, CI95% [0.98; 1.03]
Fosfomycin Other antibiotics
Insufficient relevant data for paediatric and pregnant patients.
No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection).
Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR=0.35, CI95% [0.12; 0.97]
Flower
2015
(e48)

Cochrane
MA
Ia

High quality
Women with recurrent UTIs

Effectiveness (CHM vs antibiotic):
3 RCT, RR 1.21, CI95% [1.11; 1.33]

Recurrence (CHM vs antibiotic):
3 RCT, RR 0.28, CI95% [0.09, 0.82]
Chinese herbal
medicine (CHM) only
Chinese herbal medicine combined with active placebo or conventional biomedical treatment
Guinto
2010
(e49)

Cochrane MA
Ia

High quality
Asymptomatic bacteriuria in pregnancy

Fosfomycin Trometamol versus Cefuroxime:
Persistent infection: RR, CI95%: 1.36, [0.24; 0.75]
Adverse event: RR, CI95%: 2.73, [0.11; 65.24]

Pivmecillinam versus Ampicillin (RR, CI95%:):
Persistent infection after 6 weeks: 0.67, [0.29-; 1.54]
Recurrences: 0.69, [0.12-; 0.85]

1-day Nitrofurantoin versus 7-day Nitrofurantoin (RR, CI95%):
Symptomatic infection at 2 weeks: 0.71, [0.23; 2.22]
Persistence: 1.76, [1.29; 2.46]
Preterm delivery: 1.24, [0.79; 1.94]

Pivampicillin/Pivmecillinam (Miraxid) versus Cephalexin (RR, CI95%):
Persistence: 5.75, [0.75; 44.15]
Recurrence: 0.77, [0.23; 2.5]

Cycloserine versus Sulphadimidine (RR, CI95%):
symptomatic infection: 0.62, [0.33; 1.16]
persistence: 0.70, [0.41; 1.21]
recurrence: 0.89, [0.47; 1.68]
Different antibiotics Different antibiotics
Gutiérrez-
Castrellón
2015
(e50)
MA
Ia

Acceptable quality
Acute and complicated UTIs
(results for acute UTI)

Primary outcomes:
Bacteriological eradication end of treatment:
RR=1.01, CI95% [0.99; 1.04]

Clinical cure end of treatment:
Ciprofloxacin Other antibiotics
RR=1.00, CI95% [0.98; 1.02]

Resistance:
RR=0.97, CI95% [0.67; 1.39]

Adverse events:
RR=0.88, CI95% [0.81; 0.96]
Jepson
2014
(e51)

Cochrane MA
Ia

High quality
Lower UTIs

24 studies

Canberry products vs placebo, water or no treatment
(RR 0.86, 95%CI [0.71; 1.04]

subgroups:
women with recurrent UTIs (RR 0.74, CI95% [0.42; 1.31];

older people (RR 0.75, CI95% [0.39; 1.44];

pregnant women (RR 1.04, CI95% [0.97; 1.17];

children with recurrent UTI (RR 0.48, CI95% [0.19; 1.22];

cancer patients (RR 1.15 CI95% [0.75; 1.77];

people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75
to 1.20)

gastrointestinal adverse effects cranberry product vs placebo/no
treatment (RR 0.83, 95% CI 0.31 to 2.27)
Cranberry juice or derivates Placebo or no treatment or any other treatment
Knottnerus
2012
(e52)

Network
MA
Ia

High quality
UTIs in females >12 yrs

Clinical cure (short term):
Ciprofloxacin (reference)
TMP/SMX 0.71, 0.14-1.49
Norfloxacin 0.63, 0.29-1.39
Nitrofurantoin 0.86, 0.31-2.34
Placebo 0.30, 0.70-1.35
Pivmecillinam 1.39, 0.30-6.46
Amoxicillin-Clavulante 0.07, 0.02-0.24
Gatifloxacin 0.93, 0.68-1.28
Fosfomycin –-

Bacteriological cure (short term):
Ciprofloxacin (reference)
TMP/SMX 0.36, 0.18-0.72
Norfloxacin 0.81, 0.35-1.89
Nitrofurantoin 0.27, 0.11-0.66
Placebo 0.03, 0.01-0.07
Pivmecillinam 0.40, 0.16-0.97
Ciprofloxacin TMP/SMX
Norfloxacin
Nitrofurantoin
Placebo
Pivmecillinam
Amoxicillin-Clavulante Gatifloxacin
Fosfomycin
Amoxicillin-Clavulante 0.17, 0.8-0.35
Gatifloxacin 1.06, 0.79-1.43
Fosfomycin 0.12, 0.03-0.42

Clinical cure (long term):
Ciprofloxacin (reference)
TMP/SMX 0.87, 0.40-1.89
Norfloxacin 0.91, 0.44-1.90
Nitrofurantoin 1.28, 0.49-3.32
Placebo –-
Pivmecillinam –-
Amoxicillin-Clavulante 0.31, 0.19-0.53
Gatifloxacin 0.93, 0.71-1.22
Fosfomycin –-

Bacteriological cure (long term):
Ciprofloxacin (reference)
TMP/SMX 0.87, 0.40-1.89
Norfloxacin 0.86, 0.42-1.77
Nitrofurantoin –-
Placebo 0,12, 0.05-0.27
Pivmecillinam 0.60, 0.27-1.35
Amoxicillin-Clavulante –-
Gatifloxacin 0.96, 0.75-1.22
Fosfomycin –-

Adverse effects (OR, CI95%):
Ciprofloxacin (reference)
TMP/SMX 1.42, [0.60; 3.35]
Norfloxacin 1.53, [0.54; 4.31]
Nitrofurantoin 1.07, [0.41; 2.78]
Placebo 1.24, [0.42; 3.66]
Pivmecillinam 1.36, [0.48; 3.89]
Amoxicillin-Clavulante 1.55, [0.92; 2.62]
Gatifloxacin 1.16, [0.90; 1.49]
Fosfomycin –-
Kyriakidou
2008
(e53)

MA
Ia

Acceptable quality
Pyelonephritis

Clinical success:
OR 1.27, CI95% [0.59; 2.70]

Bacterial efficacy
OR 0.80, CI95% [0.13; 4.94]

Relapse
OR 0.65, CI95% [0.08; 5.39]

Adverse events
OR 0.64, CI95% [0.33; 1.25]
Recurrence
Different antibiotics Short
course
Different antibiotics Long course
OR 1.39, CI95% [0.63; 3.06]
Lutters
2008
(e54)

Cochrane MA
Ia

High quality
Lower UTI in elderly

Single dose versus short-course treatment:
Persistent UTI short term: RR 2.01, CI95% [1.05; 3.84] (5 studies)
Persistent UTI long term: RR 1.18, CI95% [0.59; 2.32] (3 studies)

Single dose versus long-course treatment:
Persistent UTI short term: RR 1.93, CI95% [1.01; 3.70] (6 studies)
Persistent UTI long term: RR 1.28, CI95% [0.89; 1.84] (5 studies)
Adverse events: RR 0.80, CI95% [0.45; 1.41] (3 studies)

short-course versus long-course treatment:
Persistent UTI short term (trials comparing the same antibiotic): RR
1.00, CI95% [0.12; 8.57] (2 studies)
Persistent UTI long term (trials comparing the same antibiotic): RR
1.18, CI95% [0.50; 2.82] (2 studies)
Clinical failure (trials comparing the same antibiotic): RR 0.96, CI95%
[0.27; 3.47] (2 studies)

Single dose versus short-course or long-course treatment (3 to 14 days):
Persistent UTI short term (trials comparing the same antibiotic): RR
1.87, CI95% [0.91; 3.83] (4 studies)
Persistent UTI long term (trials comparing the same antibiotic): RR
1.06, CI95% [0.50; 2.24] (2 studies)
Adverse events: RR 0.80, CI95% [0.45; 1.41] (3 studies)
Different antibiotics Different antibiotics
with different
treatment duration
Naber
2014
(e55)

IPP MA
Ib Women with acute uncomplicated cystitis

Eradication of bacteriuria (per protocol):
Nitroxoline: 184/200 (92.0%)
Controls: 197/206 (95.6%)
OR: 0.47 CI95% [0.19; 1.14]

Clinical efficacy (symptom scoring) in the PP
Nitroxoline (n=193) controls (n= 203) (after treatment):
Dysuria: p= 0.223
Frequency: p=0.006
Urgency: p=0.030
Nycturia: p=0.254
Flank/back pain: p=0.330

Adverse events, total:
Nitroxoline: 23 (9,8%)
Controls: 18 (7.8%), p=0.360
Nitroxoline Cotrimoxazole or
Norfloxacin of other
dosage
Smail
2015
(e56)

Cochrane MA
Ia

High quality
Asymptomatic bacteriuria in pregnancy

14 studies (almost 2000 women)

Incidence of pyelonephritis:
Different antibiotics Placebo or no
treatment
Antibiotics reduced the risk: (RR) 0.23, 95%CI [0.13; 0.41]; 11 studies, 1932 women)
Incidence of low birthweight babies:
RR 0.64, 95% CI 0.45 to 0.93; six studies, 1437 babies) is lower with antibiotics
Preterm birth: (RR 0.27, CI95% [0.11; 0.62]; two
studies, 242 women) is lower in antibiotics
Persistent bacteriuria at the time of delivery
(RR 0.30, CI95% [0.18; 0.53]; four studies; 596 women) lower in antibiotics
Widmer
2015
(e57)
Cochrane MA
Ia
High quality
Asymptomatic bacteriuria in pregnant women

13 studies (1622 women)
All were comparisons of single-dose treatment with short-course (4- to 7-day) treatments.

Single dose vs short term (4-7 days) (comparing same agent, RR CI95%):

No cure:
1.34, [0.85; 2.12] (10 studies)

Recurrence:
1.12, [0.76; 1.66] (6 studies)

Pyelonephritis:
3.09, [0.54; 17.55] (2 studies)

Preterm delivery:
1.17, [0.77; 1.78] (3 studies)

Low birth weight:
1.65, [1.06; 2.57] (1 study)

Side effects:
0.77, [0.61; 0.97] (9 studies)
Different antibiotics Different antibiotics of different duration
Vazquez
2011
(e58)

Cochrane MA
Ia

High quality
UTI during pregnancy

IV + oral antibiotics versus IV only:
cure (RR, CI95%): 1.08, [0.93; 1.27]
recurrence (RR, CI95%): 0.47, [0.47; 6.32]

IV and oral Cephradine versus IV and oral Cefuroxime:
cure (RR, CI95%): 0.75, [0.57; 0.99]
recurrence (RR, CI95%): 1.93, [1.03; 3.60]

IV Cephazolin versus IV Ampicillin + Gentamicin:
Different antibiotics Different antibiotics
cure (RR, CI95%): 1.01, [0.93; 1.11]
recurrence (RR, CI95%): 1.52, [0.36; 6.47]
preterm delivery (RR, CI95%): 1.90, [0.48; 7.55]

Intramuscular Ceftriaxone versus IV Ampicillin + Gentamicin:
cure (RR, CI95%): 1.05, [0.98; 1.13]
recurrence (RR, CI95%): 1.10, [0.23; 5.19]
preterm delivery (RR, CI95%): 1.10, [0.23; 5.19]

Intramuscular Ceftriaxone versus IV Cephazolin:
cure (RR, CI95%): 1.04, [0.97; 1.11]
recurrence (RR, CI95%): 0.72, [0.17-; 3.06] preterm delivery (RR, CI95%):0.58, [0.15; 2.29]

Oral Ampicillin versus oral Nitrofurantoin:
cure (RR, CI95%): 0.97, [0.83; 1.13]
recurrence (RR, CI95%): 1.49, [0.55; 4.09]

Oral Fosfomycin Trometamol versus oral Ceftibuten:
cure (RR, CI95%): 1.06, [0.89; 1.26]

Outpatient versus inpatient antibiotics:
cure (RR, CI95%): 1.07, [1.00; 1.14]
recurrence (RR, CI95%): 1.13, [0.94; 1.35]
preterm delivery (RR, CI95%): 0.47, [0.22; 1.02]

Cephalosporins once-a-day versus multiple doses:
cure (RR, CI95%): 1.02, [0.96; 1.09]
recurrence (RR, CI95%): 0.73, [0.17; 3.11]
preterm delivery (RR, CI95%): 1.10, [0.44; 2.72]

Single versus multiple dose of Gentamicin:
cure rate: RR 0.97, CI95% [0.91; 1.03]
Zalmanovici
Trestioreanu
2010
(e59)

Cochrane
MA
Ia

High quality
Asymptomatic bacteriuria

9 studies (1614 participants)

Symptomatic UTI:
(RR 1.11, CI95% [0.51; 2.43]

Complications:
(RR 0.78, CI95% [0.35; 1.74]

Death:
(RR 0.99, CI95% [0.70; 1.41]

Bacteriological cure in favor of antibiotics:
(RR 2.67, CI95% [1.85; 3.85]
Adverse events higher with antibiotics
(RR 3.77, CI 95% [1.40; 10.15]
Different antibiotics Placebo or no
treatment
Minimal data were available on the emergence of resistant strains after antimicrobial treatment.

*Bias-assessment: RCTs via Cochrane Collaboration Tool, cohort studies via SIGN Tool. MA: meta-analysis, SR: systematic review, CI: confidence interval, RR: relative risk, OR: odds Ratio, UTI: urinary tract infections, GP: general practitioner, + high risk, - low risk, ? unclear risk, IV: intravenous.