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Антибиотики при бессимптомной бактериурии у реципиентов почечного трансплантата

Appendices

Appendix 1. Electronic search strategies

Database

Search terms

CENTRAL

  1. MeSH descriptor: [Urinary Tract Infections] this term only

  2. MeSH descriptor: [Bacteriuria] this term only

  3. "urinary tract infection*":ti,ab,kw (Word variations have been searched)

  4. uti or utis:ti,ab,kw (Word variations have been searched)

  5. bacteriuria or asymptomatic or covert:ti,ab,kw (Word variations have been searched)

  6. #1 or #2 or #3 or #4 or #5

  7. MeSH descriptor: [Kidney Transplantation] explode all trees

  8. kidney transplant*:ti,ab,kw (Word variations have been searched)

  9. #7 or #8

  10. #6 and #9

MEDLINE

  1. Kidney Transplantation/

  2. Urinary Tract Infections/

  3. Bacteriuria/

  4. uti.tw.

  5. (bacteriuria and (asymptomatic or covert)).tw.

  6. or/2‐5

  7. and/1,6

EMBASE

  1. urinary tract infection/

  2. asymptomatic bacteriuria/

  3. urinary tract infection$.tw.

  4. uti.tw.

  5. (bacteriuria and (asymptomatic or covert)).tw.

  6. or/1‐5

  7. exp kidney transplantation/

  8. and/6‐7

Appendix 2. Risk of bias assessment tool

Potential source of bias

Assessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence

Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).

High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.

Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment

Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web‐based, and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).

High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study

Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors.

Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data.

Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.

High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.

Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting

Low risk of bias: The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).

High risk of bias: Not all of the study’s pre‐specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre‐specified; one or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table

Low risk of bias: The study appears to be free of other sources of bias.

High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data‐dependent process (including a formal‐stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.

Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.

Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Antibiotics versus no treatment, Outcome 1 Symptomatic urinary tract infection.
Figuras y tablas -
Analysis 1.1

Comparison 1 Antibiotics versus no treatment, Outcome 1 Symptomatic urinary tract infection.

Comparison 1 Antibiotics versus no treatment, Outcome 2 Antimicrobial resistance.
Figuras y tablas -
Analysis 1.2

Comparison 1 Antibiotics versus no treatment, Outcome 2 Antimicrobial resistance.

Comparison 1 Antibiotics versus no treatment, Outcome 3 Secondary dichotomous outcomes.
Figuras y tablas -
Analysis 1.3

Comparison 1 Antibiotics versus no treatment, Outcome 3 Secondary dichotomous outcomes.

Comparison 1 Antibiotics versus no treatment, Outcome 4 Graft function (creatinine at end of study).
Figuras y tablas -
Analysis 1.4

Comparison 1 Antibiotics versus no treatment, Outcome 4 Graft function (creatinine at end of study).

Summary of findings for the main comparison. Antibiotics versus no treatment for asymptomatic bacteriuria in kidney transplant recipients

Antibiotics versus no treatment for asymptomatic bacteriuria in kidney transplant recipients

Patient or population: adult kidney transplant recipients
Intervention: antibiotics1
Comparison: no treatment1

Outcomes

(follow‐up period)

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Risk with no treatment

Risk with antibiotics

Symptomatic UTI

Follow‐up: 12 to 22 months

240 per 1,000

207 per 1 000
(123 to 349)

RR 0.86 (0.51 to 1.45)

200 2 (2 studies)

Low 3

⊕⊕⊝⊝

Antimicrobial resistance

Mean follow‐up: 16.9 months

203 per 1,000

245 per 1,000
(123 to 490)

RR 1.21 (0.60 to 2.41)

112 (1 study)

Low 4

⊕⊕⊝⊝

All‐cause mortality

Mean follow‐up: 16.9 months

17 per 1,000

38 per 1,000
(4 to 404)

RR 2.23 (0.21, 23.86)

112 (1 study)

Low 5

⊕⊕⊝⊝

Graft loss

Mean follow‐up: 16.9 months

17 per 1,000

19 per 1,000
(1 to 294)

RR 1.11 (0.07 to 17.36)

112 (1 study)

Low 5

⊕⊕⊝⊝

Acute graft rejection

Mean follow‐up: 16.9 months

203 per 1,000

189 per 1,000
(89 to 401)

RR 0.93 (0.44 to 1.97)

112 (1 study)

Low 6

⊕⊕⊝⊝

Hospitalisation for UTI

Mean follow‐up: 16.9 months

51 per 1,000

38 per 1,000
(7 to 217)

RR 0.74 (0.13 to 4.27)

112 (1 study)

Low 5

⊕⊕⊝⊝

Graft function (creatinine at end of study)

Follow‐up: 12 to 22 months

Mean serum creatinine in the treatment group was 0.06 mg/dL lower (0.19 mg/dL lower to 0.08 mg/dL higher) than the control group

200 2 (2 studies)

Low 7, 8

⊕⊕⊝⊝

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RD: risk difference; RR: risk ratio; UTI: urinary tract infection

1 The two included studies compared antibiotics versus no treatment, with choice of antibiotics depending on antimicrobial susceptibility testing results. As participants could have had multiple episodes of asymptomatic bacteriuria during the follow‐up period, participants from the intervention group were retreated with antibiotics if asymptomatic bacteriuria recurred during the follow‐up period in both studies. Duration of antibiotics therapy ranged from 3 to 10 days for the first episode of asymptomatic bacteriuria.

2 212 participants included but data provided for 200 participants.

3 Neither study attempted to blind participants, personnel or data analysts. As symptoms of UTI are partly subjective, we anticipated this would put the results at risk of being biased in favour of antibiotic treatment.

4 Samples could be collected both in case of symptoms of UTI or as part of routine screening.

5 The confidence interval crosses the line of no effect but does not rule out a significant effect of antibiotics on mortality and/or graft loss.

6 No systematic graft biopsy performed during the study follow‐up. Not all episodes of allograft rejection were biopsy‐proven.

7 Graft function was evaluated using creatinine at end of study, despite different values between groups at time of inclusion. We were unable to pool the data for change in graft function from baseline to end of study (data missing for one study).

8 No significant effect of antibiotics on change in graft function from baseline to end of study in both studies.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Figuras y tablas -
Summary of findings for the main comparison. Antibiotics versus no treatment for asymptomatic bacteriuria in kidney transplant recipients
Comparison 1. Antibiotics versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Symptomatic urinary tract infection Show forest plot

2

200

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.51, 1.45]

2 Antimicrobial resistance Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3 Secondary dichotomous outcomes Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3.1 All‐cause mortality

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Graft loss

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.3 Acute rejection

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.4 Hospitalisation for UTI

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Graft function (creatinine at end of study) Show forest plot

2

200

Mean Difference (IV, Random, 95% CI)

‐0.08 [‐0.35, 0.18]

Figuras y tablas -
Comparison 1. Antibiotics versus no treatment