PROSPERO International prospective register of systematic reviews

Structured summary 2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.


simply do not tolerate medications.
This systematic review is aiming to summarise the main reasons why prophylaxis is failed for non-HIV immunocompromised patients looking at prospective studies done on this topic.
The objectives of this study are to review and analyse literature to determine which factors might contribute to failure of prophylaxis of opportunistic infections in transplant recipients.
The potential factors for failure are drug-drug interactions, microbiological susceptibility, drug pharmacokinetics, the dose of the medication, route of administration, transplant (specific organ or allogenic stem cell), status of the immunocompromised patient and medication compliance.

Searches
This systematic review will include prospective randomized controlled trials and prospective single-arm studies. There are no restrictions for the setting or language. Studies published from 1.01.2010 to present will be included to the systematic review.
To identify studies for this systematic review these databases will be searched: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed. Prophylaxis for opportunistic infections in transplant recipients.

Participants/population
The study will include adult patients (16 years and older) who have received: • allogeneic stem cell transplant

Types of study to be included
This systematic review will include prospective randomized controlled trials and prospective single-arm studies.

Context
There are no restrictions for the setting.

Primary outcome(s)
Primary outcomes: • adverse effects leading to stopping of treatment or switching medication or dose reduction • resistance to antimicrobials/antifungals/antivirals • death

Data extraction (selection and coding)
The literature search and data extraction for inclusion and eligibility for this systematic review will be done according to the inclusion criteria by two authors independently. If there are discrepancies between the results these will be discussed and resolved with a third author.
If there is data missing or additional questions from the selected studies then the authors of these studies will be contacted directly.
A form will be developed to document the characteristics and quality of the included studies.

Risk of bias (quality) assessment
Risk of bias in individual studies will be assessed independently by the two researchers who did the study selection and data extraction. For assessing bias in individual studies Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) will be used for RCTs and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) will be used for prospective single-arm studies If there are discrepancies between the authors these will be discussed and resolved with a third author.

Strategy for data synthesis
The criteria how the data will be quantitatively synthesised and if and how subgroup analysis will be done can be determined after the data is available.
The possibility of performing a meta-analysis and summary measures can also be determined after literature search and when we have done the data extraction.
After the preliminary searches we expect that there will not be sufficient data to conduct a meta-analysis.

Analysis of subgroups or subsets
The possibility and method for subgroup analysis can be determined after the data is available and

Rationale
3 Describe the rationale for the review in the context of what is already known. 3 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
3 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

4
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

4
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

4, 46-47
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

4
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

4-5
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

5
Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means).

5
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.

NA
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Section/topic # Checklist item Reported on page #
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

5
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

23
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

27-31
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

7, 35-36
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

33-36
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

NA
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

7-10
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

9-10
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.