Infection is defined as:
1) Fever of unknown origin (FUO): New onset of fever without clear clinical or microbiological evidence; Fever is defined as: a single oral temperature of = 38.3°C or = 38.0° C, over at least 1 hour or twice within 12 hours without evident cause (Hughes, 2002).

2) Clinically documented infection (CDI): Fever in connection with unambiguous diagnostic signs of localized infection, e.g. pneumonia or skin/soft tissue inflammation without microbiological proof or if not accessible for examination.

3) Micro‐biologically documented infection (MDI): Fever with plausible pathogenic evidence (in the microbiological / time context) in addition to identified localized infection, or pathogenic agents found in blood culture without localized infection.

Fungaemia/ Proven Fungal infection is defined as:
1) Microbiological cultures of specimens from normally sterile but clinically abnormal sites with positive results from blood, sputum, urine, cerebrospinal fluid, bone or joint, peritoneum, bronchoalveolar lavage, sinus aspirate specimen or any other sterile body fluid samples.

2) Clinical criteria: findings from radiological or other imaging examination to distinguish between evidence of abnormality of an organ or organ system like ophthalmologic examination, ultrasound examination, HRCT scan of the lungs (Ascioglu, 2002).

Neutropenia is defined as:
Absolute Neutrophil Count (ANC) (the total white blood cell count multiplied by the combined percentage of segmented neutrophils and band cells) is < 0.5 x 109 /L for an episode of at least 7 days

Selection bias
Allocation concealment:
A.Adequate: Use of randomisation method that did not allow investigator and participant to know or influence the allocation of treatment before eligible participants entered the study.
B.Unclear: Randomisation stated but no information on method used in available.
C.Inadequate: Use of alternate medical record numbers or unsealed envelopes as randomisation method, and/or there is information in the study indicating that investigators or participants could have influenced the allocation of treatment.

Performance bias
Blinding of care providers: Yes/ No/ Unclear
Blinding of participants: Yes/ No/ Unclear
Care providers and patients are considered not blinded if the intervention group can be identified in >20% of participants because of side‐effects of treatment.

Detection bias
Blinding of outcome assessors: Yes/ No/ Unclear

Attrition bias
Intention to treat analysis:
A.Yes: All participants are analysed in the treatment group to which they were allocated, regardless of whether or not they received the allocated intervention.
B.No: Some participants (<5%, 5‐10%, 10‐20%, >20%) are not analysed in the treatment group to which they were randomised because they did not receive study intervention, they withdrew from the study, or because of protocol violation.
C.Unclear: Inability to determine if patients were analysed according to the intention to treat principle after contact with the authors.

Completeness of follow‐up
Percentage of participants excluded or lost to follow‐up for the different treatment groups for the primary and secondary outcomes (<5%, 5‐10%, 10‐20%, >20%).

NEWCASTLE ‐ OTTAWA QUALITY ASSESSMENT SCALE

Note: A study can be awarded a maximum of one star for each numbered item within the Selection and Outcome categories. A maximum of two stars can be given for Comparability

Selection
1. Representativeness of the exposed cohort
a)Truly representative of the average _______________ (describe) in the community
b)Somewhat representative of the average ______________ in the community
c)Selected group of users e.g. nurses, volunteers
d)No description of the derivation of the cohort

2. Selection of the non exposed cohort
a)Drawn from the same community as the exposed cohort
b)Drawn from a different source
c)No description of the derivation of the non exposed cohort

3. Ascertainment of exposure
a)Secure record (e.g. surgical records)
b)Structured interview
c)Written self report
d)No description

4. Demonstration that outcome of interest was not present at start of study
a)Yes
b)No

Comparability
1. Comparability of cohorts on the basis of the design or analysis
a)Study controls for _____________ (select the most important factor)
b)Study controls for any additional factor (This criteria could be modified to indicate specific control for a second important factor.)

Outcome
1. Assessment of outcome
a)Independent blind assessment
b)Record linkage
c)Self report
d)No description

2. Was follow‐up long enough for outcomes to occur
a)Yes (select an adequate follow up period for outcome of interest)
b)No

3. Adequacy of follow up of cohorts
a)Complete follow up ‐ all subjects accounted for
b)Subjects lost to follow up unlikely to introduce bias ‐ small number lost ‐ > ____ % (select an adequate %) follow up, or description provided of those lost)
c)Follow‐up rate < ____% (select an adequate %) and no description of those lost
d)No statement