Methods

Prospective RCT at a tertiary care centre.
No central randomisation.
Opaque envelopes blindly selected from bin, clinicians blinded.

Participants

INCLUSION CRITERIA
Number: 34 (group 1), 35 (group 2).
Gender (F/total): 32/34 (group 1), 30/35 (group 2).
Age: 6 months to 12 years.
Fever > 38.0°C, history and physical examination suggesting UTI and positive urine culture from catheter specimen or MSU.

EXCLUSION CRITERIA
Abnormality of urinary tract, already taking antibiotics, allergy to study medication.

Interventions

TREATMENT GROUP 1
Single shot IM /oral therapy.
Ceftriaxone IM 50 mg/kg once initially followed by oral trimethoprim 10 mg/kg/d for 10 days.

TREATMENT GROUP 2
Oral therapy.
Trimethoprim 10 mg/kg/d for 10 days.

Outcomes

1. Clinical and bacteriological cure after 48 hours.
2. Bacteriological cure rate after 48 hours.
3. Reinfection after interval of 1 month (n, %)
4. Relapse rate after interval of 1 month (n, %).
5. Adverse events rate (n, %).

Notes

Of 95 patients who met the inclusion criteria, 87 were enrolled (6 gave no consent, 2 were not petitioned).
Fourteen patients were excluded after randomisation because urine culture was negative.
Three (group 1) and 1 (group 2) were lost to follow‐up.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective RCT.
Computer‐generated randomisation.
No ITT.

Participants

INCLUSION CRITERIA
Number: 19 (group 1), 21 (group 2).
Gender (M/F): unknown.
Age: > 18 years.
Clinical symptoms of severe UTI requiring parenteral antibiotic therapy and a positive urine culture.

EXCLUSION CRITERIA
Cases of allergy, severe underlying disease, renal impairment, pregnancy, urinary tract obstruction, catheterization.

Interventions

GROUP 1
IV switch therapy.
Ciprofloxacin 200 mg twice daily IV for 2 to 5 days, followed by 500 mg twice daily orally for up to 14 days.

GROUP 2
IV therapy.
Ceftazidime 500 mg thrice daily for 4 to 9 days.

Outcomes

1. Clinical cure rate at end of therapy (clinical cure or improvement at end of therapy, bacteriologic eradication 5 to 9 days after therapy end).
2. Bacteriological cure rate at end of therapy (clinical cure or improvement at end of therapy, bacteriologic eradication 5 to 9 days after therapy end).
3. Reinfection rate at end of therapy.

Notes

Of 63 patients enrolled, 23 were excluded from evaluation because of missing/sterile urine culture before or after therapy (20), pathogen resistant to study drug (2) or renal impairment (1).
Two patients in each group had acute prostatitis, 1 patient in IV group had epididymitis.
Fifteen patients in each group were classified as having complicated UTI.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective RCT.
Randomisation table.
No information whether ITT.

Participants

INCLUSION CRITERIA
Number: 10 (group 1), 10 (group 2).
Age: children, age not stated.
Gender (F/total): 8/10 (group 1), 7/10 (group 2).
Less than 1 year with fever > 38.5°C, pyuria, bacteriuria, positive urine culture, ESR > 35 mm/h, elevated CRP and orosomucoid.

EXCLUSION CRITERIA
Beta lactam allergy, antibiotic therapy 72 hours before study inclusion, impaired renal function or post‐op infection.

Interventions

GROUP 1
IV switch therapy.
amoxicillin/clavulanate acid 100 mg/kg/d IV for 7 days followed by 50 mg/kg/d po for 7 days.

GROUP 2
IV therapy.
Cefotaxime 100 mg/kg/d IV for 14 days.

Outcomes

1. Number of patients with fever > 48 hours.
2. Number of patients with bacteriological cure after 48 hours.
3. Number of patients with reinfection after interval (7 days after end of therapy).
4. Number of patients with relapse after interval (7 days after end of therapy).
5. Number of patients with adverse events.
6. Lab parameter.
7. No treatment failure rate.
8. No clinical cure rate.

Notes

No patient flow diagram.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Prospective, multicentre RCT.
Randomisation per telephone call (Minitel) at day 4.
No ITT.

Participants

INCLUSION CRITERIA
Number: 63 (group 1), 65 (group 2).
Age: 6 months to 10 years.
Gender (F/total): 57/63 (group 1), 57/65 (group 2).
Fever > 38.0°C, elevated CRP, pyuria, bacteriuria, positive urine culture with germ sensitive to ceftriaxon, netilmicin and cefixime.

EXCLUSION CRITERIA
Allergy to antibiotics, catheterization, complicated UTI, immune deficiency, kidney failure, urine culture not sterile after 48 hours of treatment.

Interventions

GROUP 1
IV switch therapy.
Ceftriaxon 50 mg/kg/d IV and netilmicin 6 to 7.5 mg/kg/d IV for 4 days followed by cefixime 8 mg/kg/d PO for 6 days.

GROUP 2
IV/IM therapy.
Ceftriaxon/netilmicin for 4 days followed by ceftriaxon 50 mg/kg/d IM or IV for 6 days.

CO INTERVENTIONS
Both groups received antibiotic prophylaxis for 20 days (nitroxoline).

Outcomes

1. Cure rate defined as no clinical signs and bacteriological eradication 48 hours after end of treatment (n, %) and after interval of 20 to 30 days.
2. Reinfection rate after interval (20 to 30 days) (n, %).
3. Adverse events rate (n, %).

Notes

Of 169 patients who met the inclusion criteria, 147 were randomised.
Seven (group 1) and 12 (group 2) were excluded from analyses because there was no evaluable result.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective RCT at Paediatric University Hospital.
No information on method of randomisation or type of analysis (ITT?)

Participants

INCLUSION CRITERIA
Number: 25 (group 1), 29 (group 2).
Age: 2 to 13 years, mean age 6.6 ± 3.3 years.
Gender (F/total): 20/25 (group 1) 24/29 (group 2).
Symptoms of UTI and pyuria, bacteriuria and positive urine culture (clean catch urine) without antibiotic prophylaxis.

Interventions

GROUP 1
Oral therapy.
Cefixime 8 mg/kg/d for 10 days.

GROUP 2
IM switch therapy.
Ceftizoxime IM 50 mg/kg twice daily for 2 days followed by oral cefixime for 8 days.

Outcomes

1. Cure rate: defined as resolution of all signs and symptoms and eradication of pathogen at end of treatment and after 3 weeks.
2. Reinfection rate: defined as development of new or worsened signs or symptoms and infection with a new pathogen in patients who had been cured at end of treatment and after 3 weeks.
3. Relapse: defined as eradication of baseline pathogen with reappearance of same pathogen at end of treatment and after 3 weeks.

Notes

Symptoms of UTI not further specified.
No patient flow diagram.
Adverse events: one patient developed diarrhoea caused by cefixime, but no information to which group this patient belonged.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Prospective, multicentre RCT.
Computer‐generated randomisation list.
Stratification based on age and duration of fever.
ITT.

Participants

INCLUSION CRITERIA
Number: 153 in each group.
Gender (F/total): 137/153 (group 1), 136/153 (group 2)
Age: 1 to 24 months.
Fever > 38.3°C, pyuria, bacteriuria and positive urine culture from catheter specimen.

EXCLUSION CRITERIA
Unequivocal source for fever, history of UTI or abnormality of urinary tract.

Interventions

GROUP 1
IV switch therapy.
Cefotaxime IV 200 mg/kg/d for 3 days or until afebrile > 24 hours, followed by oral cefixime 8 mg/kg/d for 14 days.

GROUP 2
Oral therapy.
Cefixime 16 mg/kg/d initially followed by 8 mg/kg/d for 14 days.

Outcomes

1. Cessation of fever (hours, mean ± SD).
2. Cure rate defined as resolution of clinical signs and symptoms and sterilization of urine (obtained in 291/306 children) after 24 hours.
3. Reinfection rate after interval of 6 months (n, %).
4. DMSA renal scan after 0.5 year.

Notes

Three children were not randomised because they were deemed too sick.
One child in the oral group was unable to tolerate oral drugs and was given IV drugs.
Children between 4 to 8 weeks of age and children who needed IV drip were kept at hospital, but treated orally according to protocol.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective RCT at University hospital.
Random number table used to create sealed, opaque envelopes, randomisation in blocks of 6, envelopes kept separately.
ITT.

Participants

INCLUSION CRITERIA
Number: 60 pregnant women in each group.
Gestational week < 24 weeks, with fever > 38.4°C, flank pain, pyuria.

EXCLUSION CRITERIA
Sepsis, respiratory insufficiency, fever > 39.8°C, RR < 90/50 mm Hg, creatinine > 1.4 mg/dL, allergy to cephalosporins, inability to tolerate oral intake, serious medical illness, known renal or urologic problems, antibiotic therapy during 2 preceding weeks.

Interventions

GROUP 1
Single shot IM/oral therapy.
Ceftriaxone 1 g IM twice within 18 to 36 hours, followed by cephalexin 500 mg PO 4 times/d for 10 days.

GROUP 2
IV switch therapy.
Cefazolin 1 g three times/d until afebrile for 48 hours, followed by cephalexin 500 mg PO 4 times/d for 10 days.

CO INTERVENTIONS
All patients received oral prophylaxis with nitrofurantoin till 6 weeks postpartum.

Outcomes

1. Clinical cure during first 3 days.
2. Bacterial cure at end of therapy.
3. Adverse events rate (minor and major combined).

Notes

Of 120 patients enrolled, 1 patient each group had negative urine culture at beginning, 9 patients had no urine culture at beginning, 2 patients of Group 1 were given IV therapy because of sepsis, but all were analysed according to randomisation nevertheless (ITT).
Seven (group 1) and 3 (group 2) had no urine culture at end of therapy (of those, 3 were clinically doing well).
Number of patients with clinical cure at end of therapy not clearly presented.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective, multicentre RCT at 4 community care centres.
Randomisation at each centre by sealed envelopes/code list.
No ITT.

Participants

INCLUSION CRITERIA
Number: 72 (group 1), 69 (group 2).
Gender (F/total): (44/72 (group 1), 39/69 (group 2).
Age: >18 years.
Fever > 37.5°C, pyuria, bacteriuria, leukocytosis and signs of UTI or complicating urologic conditions. Included also if culture was negative because of recent antibiotic treatment (2 in each group) or contaminated with mixed flora superimposed on one pathogen having at least 100,000 CFU (4 (group 1), 2 (group 2)).

EXCLUSION CRITERIA
Ciprofloxacin allergy, inability to take oral medicine, severe sepsis, elevated creatinine levels, renal obstruction, pregnancy, high‐risk condition (e.g. agranulocytosis).

Interventions

GROUP 1
IV switch therapy.
Ciprofloxacin IV 400 mg/d for 72 hours or until afebrile for 24 hours followed by ciprofloxacin PO 1,000 mg/d.

GROUP 2
Oral therapy.
Ciprofloxacin 400 mg/d.

Outcomes

1. Cessation of fever (days, mean, CI).
2. Combined clinical and bacteriological cure rate under therapy (after 3 to 5 days of therapy).
3. Adverse events rate.

Notes

Of 163 enrolled, 22 patients (11/group) were excluded from analysis. Of those, 19 patients did not fulfil inclusion criteria retrospectively, 2 had incomplete outcome data, 1 withdrew consent. 2 patients of each group had received other antibiotics within 24 hours before study begin and had negative urine culture at inclusion.
SD calculated based on 95% CI.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective multicentre RCT.
Computer generated randomisation list with stratification for hospital, sex and age, block randomisation.
No information whether ITT.

Participants

INCLUSION CRITERIA
Number: 185 (group 1), 202 (group 2).
Gender: 244 females.
Age: 2 months to 6 years with normal kidney function.
First UTI defined as fever, 2 consecutive positive urinalysis, 2 positive urine cultures, high blood inflammation indices.

EXCLUSION CRITERIA
Excluded in case of urinary tract malformation, serious illness, hypersensitivity to antibiotics.

Interventions

GROUP 1
Oral therapy.
amoxicillin/clavulanic acid 50 mg/kg/d for 10 days.

GROUP 2
IV switch therapy.
Ceftriaxon 50 mg/kg/d until cessation of fever followed by amoxicillin/clavulanic acid.

Outcomes

1. Cessation of fever (hours mean, SD)

Notes

Abstract only plus information from www.clinicaltrials.gov.
At time of publication, 88% of required population was enrolled

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective multicentre RCT.
Computer generated randomisation list, sealed envelopes.
No ITT.

Participants

INCLUSION CRITERIA
Number: 78 (group 1), 72 (group 2).
Gender (F/M): unknown.
Age: 6 months to 16 years.
Fever > 38°C, CRP > 10 mg/L, positive urine culture (catheter urine) and positive DMSA scintigraphy at beginning (signs of pyelonephritis).

EXCLUSION CRITERIA
Normal scintigraphy, sepsis, complex urinary abnormalities.

Interventions

GROUP 1
Oral therapy.
Ceftibuten 9 mg/kg/d PO for 14 days.

GROUP 2
IV switch therapy.
Ceftriaxone 50 mg/kg IV for 3 days followed by ceftibuten for 11 days.

Outcomes

1. Number of patients with renal scarring (DMSA) after 6 months.
2. Adverse events rate.

Notes

Of 365 children initially enrolled and randomised, 346 had an acute DMSA scan.
Children excluded because of normal DMSA scan (127).
Follow‐up scan and included in analysis (152).

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A ‐ Adequate

Methods

Prospective RCT in a tertiary care centre.
Randomisation list kept with principal investigator.
No ITT.

Participants

INCLUSION CRITERIA
Number: 24 (group 1), 30 (group 2).
Gender (F/M): unknown.
Age: </= 10 years.
Fever, flank pain, pyuria and positive urine culture.

EXCLUSION CRITERIA
Severe allergy to study therapy, obstructive uropathy, renal abscess, immune‐compromising disease, acute hepatic failure, clinical signs of sepsis, requirement for dialysis.

Interventions

GROUP 1
IV switch therapy.
Ceftriaxone IV 50 mg/kg/d for 2 to 3 days, then cefixime 8 mg/kg/d for 8 to 12 days.

GROUP 2
IV therapy.
Amikacin 15 mg/kg/d or gentamicin 3 mg/kg/d with ampicillin 100 mg/kg/d for 7 to 10 days.

Outcomes

1. Combined clinical and microbiological cure rate at end of therapy.

Notes

Of 30/30 patients enrolled, only 24 (group 1) received switch therapy.
The other 6 were treated IV because of lack of cefixime. These patients were not added to analysis (personal communication of author)

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Prospective RCT.
Randomisation method: not stated.
ITT: unclear (not stated whether 100 patients were randomised, 18 excluded afterwards, or 100 patients assessed, 18 excluded and 82 randomised).

Participants

INCLUSION CRITERIA
Number: 18 (group 1), 20 (group 2).
Gender (F/total): 15/22 females in total study population.
Age: > 18 years.
Clinical symptoms of severe UTI/ pyelonephritis and positive urine culture (24/20 adults with mild UTI/cystitis, not included in review).

EXCLUSION CRITERIA
Hypersensitivity to drugs, pregnancy, breast feeding, severe liver or kidney disease. 78 (5% group 1, /75% group 2) had complicated pyelonephritis.

Interventions

GROUP 1
Oral therapy.
Norfloxacin 400 mg twice daily for 7 days.

GROUP 2
IM therapy.
Aztreonam 1 g IM twice daily for 7 days.

Outcomes

1. Bacteriological cure rate at end of treatment and after 4 week interval (n, %).
2. Other outcomes not differentiated in pyelonephritis and cystitis.

Notes

Of 100 enrolled, 18 patients were excluded before or after randomisation (unclear).
Only patients with pyelonephritis included in review (38), patients with cystitis (44) not included

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Prospective multicentre RCT.
Randomisation table in blocks of 4, stratification according to centre.
No ITT.

Participants

INCLUSION CRITERIA
Number: 47 (group 1), 48 (group 2).
Gender (F/total): unknown, but 4 times more females
Age: > 15 years.
Severe UTI defined as fever, bacteriuria, positive urine culture and pyuria or at least one clinical sign or 2 positive urine cultures.
Severity defined as either fever > 39°C, age > 65 years or pre‐existing nephro‐urological disease or positive haemoculture.

EXCLUSION CRITERIA
pregnancy, breast feeding, insufficient contraception, cephalosporin allergy, renal or hepatic failure, or other chronic disease, antibiotics within 48 hours.

Interventions

GROUP 1
IV switch therapy.
Ceftriaxone 2 g/d for 4 days IV followed by oral cefixime 200 mg twice daily for 11 days.

GROUP 2
Parenteral therapy.
IV ceftriaxone 2 g/d for 4 days followed by IM or IV ceftriaxone 1 g/d for 11 days.

Outcomes

1. Clinical cure rate at end of therapy.
2. Clinical and bacteriological cure rate at the end of treatment and after interval of 30 to 45 days.
3. Reinfection rate at end of treatment and after interval.
4. Relapse rate after interval.
5. Adverse events rate.

Notes

Of 97 patients enrolled, 2 patients of parenteral group were excluded from analysis because of negative urine culture at beginning.
No urine culture at the end of treatment in 11/12 patients (1/12 complete loss to follow‐up) and therefore exclusion from most of the outcomes.
8/6 patients lost to follow‐up after 30 to 45 days.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Prospective RCT at a tertiary care centre.
Randomisation based on computer generated numbers.
No ITT.

Participants

INCLUSION CRITERIA
Number: 51 (group 1), 54 (group 2).
Gender (F/M): all women.
Age: 18 to 75 years.
Diagnosis of UTI defined as fever > 38°C, flank pain and pyuria.

EXCLUSION CRITERIA
Pregnancy, catheterisation, preceding antibiotic treatment, complicated UTI, sterile urine culture at beginning, hypersensitivity to cephalosporins.

Interventions

GROUP 1
Single shot IV/oral therapy.
Ceftriaxone 1 g IV, then cefixime 400 mg or other oral antibiotic according to results of urine culture for 10 days.

GROUP 2
IV switch therapy.
Ceftriaxone 1 g/d IV until results of urine culture then oral antibiotics for a total of 10 days.

Outcomes

1. Clinical cure rate under therapy (after 3 days).
2. Clinical cure rate at end of therapy (after 10 days).
3. Bacterial cure rate under therapy (after 3 days).
4. Duration of fever (days).
5. Duration of clinical symptoms (days).
6. Adverse events rate.

Notes

Of 144 patients enrolled with clinical symptoms of UTI, 51 (group 1) and 54 (group 2) had a positive urine culture (others were excluded after randomisation).

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Prospective RCT at a tertiary care centre.
Randomised in blocks of 4, method not stated.
ITT.

Participants

INCLUSION CRITERIA
Number: 18 (group 1), 18 (group 2).
Gender (F/total): 9/18 (group 1) 8/18 (group 2).
Age: 1 month to 15 years.
Fever, > 38°C or subnormal temperatures in small infants, pyuria and/or bacteriuria and a positive urine culture from MSU or bag and a positive 99mTc‐DMSA scan proving pyelonephritis.

EXCLUSION CRITERIA
History of previous UTI, anatomic abnormalities, neurogenic bladder, kidney failure, allergy to cephalosporin or penicillin, systemic antibiotics within 48 hours, chronic disease.

Interventions

GROUP 1
IV switch therapy.
Ceftriaxon IV 75 mg/kg/d until afebrile > 24 to 48 hours, followed by oral ceftibuten 9 mg/kg/d for 10 days.

GROUP 2
IV therapy.
Ceftriaxone IV 75 mg/kg/d for 10 days.

Outcomes

1. Bacteriological cure rate at end of therapy (day 14).
2. Clinical cure rate after interval of 6 months.
3. Bacteriological cure rate after interval of 6 months.
4. Reinfection rate after 6 months (n, %).
5. DMSA renal scan after 0.5 year.

Notes

Of 100 patients, 64 were excluded before randomisation because of recurrent UTI (9), anatomical abnormalities (5), chronic disease (2), failure to notify (4), normal DMSA scan at beginning (18), negative urine culture (26).
Hospitalisation rate cannot be compared because only mean (no SD) is given.
Adverse events rate only given for IV switch group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear