Study characteristics

Patient sampling

Participant sampling not clearly described.

Patient characteristics and setting

Newborns > 3 days old with suspected sepsis. No information on participant demographics or study period.

Index tests

PCR using universal candida DNA sequence.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood samples drawn at the same time.

Comparative

Notes

Data from conference abstract only. No information on participant demographics or study period.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Unclear

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Unclear

Unclear

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Participants were recruited consecutively.

Patient characteristics and setting

Preterm infants < 37 weeks and > 72 hours old with signs and symptoms of sepsis requiring antibiotic treatment. Interquartile range of age reported suggests some infants may have been > 28 days of age. Study period: March 2006 to June 2008 (28 months).

Index tests

Real‐time PCR using universal primers and Gram‐specific probes.

Target condition and reference standard(s)

Neonatal sepsis and blood, peritoneal fluid and CSF cultures.

Flow and timing

Index test and the reference standard performed at the same time.

Comparative

Notes

15 samples were excluded due to insufficient amount of sample (n = 9) and mistakenly left in the refrigerator for > 72 hours (n = 6). Excluded samples not included in the analysis. Cycle threshold cut‐off values for positive PCR were defined. Interquartile range of age reported suggests some infants may have been > 28 days of age.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Study did not classify whether participants were enrolled randomly or consecutively. Negative controls (n = 30) were not included in the analysis.

Patient characteristics and setting

Infants with suspected sepsis, admitted to the neonatal department and the intensive care unit of the Zhejiang University Children's University in China. It was unclear how many infants were < 28 days old as no participant demographics are available. Study period: September 2007 to June 2008.

Index tests

Broad‐range 16S rRNA‐based real‐time fluorescent PCR.

Target condition and reference standard(s)

Suspected sepsis and the reference standard were cultures of blood and CSF.

Flow and timing

Both index test and reference standard samples were drawn simultaneously.

Comparative

Notes

No participant demographics available and unclear if some infants were > 28 days of age.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

All neonates with suspected sepsis admitted during the period of May 2012 to August 2012 were enrolled.

Patient characteristics and setting

Neonates with suspected sepsis admitted to the NICU of Ain Shams University Hospitals. Study period: May 2012 to August 2012. Age range reported was 0 to 50 days.

Index tests

Broad‐range 16S rDNA PCR.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood sample for culture and PCR were collected concurrently using standard sterile procedures.

Comparative

Notes

Participants were referred to as neonates although the age range reported was 0 to 50 days. Participants included both preterm and full‐term infants.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Not clearly reported.

Patient characteristics and setting

Neonates with suspected sepsis admitted to Level III NICU. Study period not mentioned.

Index tests

Broad‐range conventional PCR after 5‐hour preamplification culture.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood samples for culture and PCR were drawn simultaneously. Reason for exclusion of participants were reported.

Comparative

Notes

Of the 64 participants that were excluded, 34 had malformations, 15 had < 12‐hour life expectancy and the remaining 15 had contaminated blood cultures. Study period not mentioned.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Infants were enrolled if they met the inclusion criteria during the study period. Controls (n = 50) were not included in the analysis.

Patient characteristics and setting

Newborn participants with signs and history suggestive of sepsis admitted in the NICU at Kobe Hospital University from June 2005 to September 2006.

Index tests

Multiplex PCR targeting 8 common pathogens.

Target condition and reference standard(s)

Neonatal sepsis and bacterial culture of blood, skin, bronchoalveolar lavage, mucus, CSF, urine and ascitic fluid.

Flow and timing

Only 77 samples with paired specimen culture and PCR were included in the 2 × 2 table. Samples for culture and PCR were drawn simultaneously.

Comparative

Notes

Of the 6 specimens that were positive for PCR but negative for culture, 1 culture was positive for normal flora and was considered negative.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Infants were enrolled if they met the inclusion criteria during the study period.

Patient characteristics and setting

Newborns < 7 days old with suspected sepsis or meningitis diagnosed at a participating hospital from November 2005 to January 2007.

Index tests

RT‐PCR targeting the 16S rRNA.

Target condition and reference standard(s)

Suspected early‐onset neonatal sepsis and blood and CSF cultures.

Flow and timing

Sample for PCR and culture were drawn concurrently. Samples for PCR were stored until DNA extraction.

Comparative

Notes

Analyzed only EOS in neonates and included 83 neonates.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Unclear

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Neonates were enrolled if they met inclusion criteria during the study period.

Patient characteristics and setting

Neonates admitted to the NICU of Jutendo University Hospital or Jutendo Shizuoka Hospital from February to August 2009. Mean (SD) gestational age was 34.8 ± 5.8 weeks. There were 36 participants with 39 episodes of sepsis.

Index tests

RT‐PCR targeting 16S rRNA.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Whole blood collected concurrently for PCR and culture.

Comparative

Notes

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Neonates were enrolled if they met inclusion criteria during the study period.

Patient characteristics and setting

Neonates up to 28 days old admitted to the NICU from August 2005 to July 2006.

Index tests

Broad‐range PCR.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Index test and reference standard sampling performed simultaneously.

Comparative

Notes

Only blood culture‐positive samples were included in the analysis.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

No

Did the study avoid inappropriate exclusions?

Yes

High

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Unclear

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Participants who met the inclusion criteria were enrolled prospectively.

Patient characteristics and setting

Neonates with suspected clinical sepsis admitted to the Central South Hospital of Petroleos Mexicanos, the Gynecological‐Obstetrics Hospital number 4 of the Mexican Institute of Social Security, the Dalinde Hospital and the Monterrey Nuevo Leon University Hospital and National Institute of Perinatology. Study period not mentioned.

Index tests

LightCycler SeptiFast Test.

Target condition and reference standard(s)

Suspected neonatal sepsis and blood culture.

Flow and timing

Samples for blood culture and LightCycler SeptiFast were drawn concurrently.

Comparative

Notes

Study period not mentioned in the report.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

All infants admitted to the NICU for sepsis evaluation.

Patient characteristics and setting

All infants admitted to the NICU for sepsis evaluation. No participant demographics available.

Index tests

Broad‐range conventional PCR and DNA dot‐blot hybridization.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Index test and reference standard were performed simultaneously.

Comparative

Notes

This was a feasibility study and blood sample for PCR was from discarded or unused sample sent to evaluate CBCs. It was not clear whether blood drawn for CBC was also done with the same aseptic technique as blood culture. Study period not mentioned.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

High

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Unclear

Study characteristics

Patient sampling

Infants were enrolled if they met inclusion criteria.

Patient characteristics and setting

Infant admitted to the NICU for sepsis evaluation that included at least blood culture and CBC. No demographic information or study period details available.

Index tests

Real‐time 16S rRNA PCR.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood sample used for PCR was from discarded or unused samples sent for evaluation of CBC. Unclear whether blood drawn for CBC was done in an aseptic manner.

Comparative

Notes

Study was done to design a sample preparation protocol that would eliminate tryptic soy broth pre‐enrichment step and to convert conventional PCR assay to a real‐time PCR platform. The methodology here is real‐time PCR from whole blood without enrichment. So a different methodology fromJordan 2000paper and overlap is very unlikely.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

High

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Unclear

Study characteristics

Patient sampling

All NICU admissions during the period of study were screened for eligibility.

Patient characteristics and setting

Infants > 34 weeks admitted to the NICU for suspected EOS from 1 September 2000 to 1 April 2004.

Index tests

Broad‐range conventional PCR followed by pyrosequencing.

Target condition and reference standard(s)

EOS in near‐term infants and blood culture.

Flow and timing

Samples for the index test and reference standard were collected simultaneously but PCR was evaluated from sample sent for CBC. Concerns about aseptic technique remain.

Comparative

Notes

Blood samples for PCR were from unused portion of the sample sent to evaluate CBC and were collected by venous, arteria or heel stick. The PCR was conventional PCR with enrichment with Trypticose soy before PCR just like the paperJordan 2000. The study period here was stated to be from September 2000.Jordan 2000paper was submitted for publication in 1999 as per the title page of the article and hence overlap ofJordan 2000andJordan 2006unlikely.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

High

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Unclear

Study characteristics

Patient sampling

Neonates who met inclusion criteria were enrolled on admission.

Patient characteristics and setting

VLBW infants > 72 hours old. Participant demographics or study period not available.

Index tests

Multiplex real‐time PCR using Roche LightCycler SeptiFast MGRADE system.

Target condition and reference standard(s)

Neonates with suspected LOS and blood culture.

Flow and timing

Blood sample for PCR was collected during routine sepsis work‐up and before antibiotics.

Comparative

Notes

Participant demographics or study period not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Neonates were enrolled if they met inclusion criteria during the study period.

Patient characteristics and setting

Newborn at risk for EOS from January to September 1996. Predefined major and minor criteria were used to classify participants "at risk" for sepsis.

Index tests

Broad‐range conventional PCR

Target condition and reference standard(s)

Neonatal EOS and blood culture.

Flow and timing

Blood samples for analyses were drawn concurrently.

Comparative

Notes

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Neonates were enrolled if they met inclusion criteria during the study period.

Patient characteristics and setting

Neonates with suspected sepsis during the period of December 2004 to June 2005. Participant demographics not available.

Index tests

Real‐time PCR using universal primers.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn concurrently.

Comparative

Notes

Recalculated sensitivity, specificity, PPV, and NPV as samples positive for PCR were also positive for human DNA and not bacterial DNA. Participant demographics not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Unclear

Unclear

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

All neonates with suspected sepsis and had blood samples drawn for concomitant culture, CBC and CRP assay were included in the study.

Patient characteristics and setting

Neonates with suspected sepsis admitted to the NICU of the Women and Children's Hospital, the Children's Hospital and Tongji Hospital in Hubei Province from 1 September 2011 to 31 December 2011. Participants were from 4 hour to 28 days old.

Index tests

16S rRNA gene PCR.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Additional 0.5 mL to 1 mL EDTA blood sample was collected for PCR at the time of sepsis workup.

Comparative

Notes

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Prospective enrollment of infants that met inclusion criteria during a 12‐month period.

Patient characteristics and setting

Neonates aged > 3 days, admitted to the NICU with suspected LOS. Gestational age range 24 to 42 weeks and range of age at enrollment was 4 to 96 days. Study period not mentioned although reported over 12 months.

Index tests

Staphylococcal 16S rRNA PCR (both Staphylococcus aureus and coagulase‐negative Staphylococcus).

Target condition and reference standard(s)

Neonatal LOS and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn concurrently.

Comparative

Notes

There were 32 culture‐positive samples for bacteria and fungi but only 13 were positive for staphylococci and this was incorporated into the analysis.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Prospective enrollment of neonates that met the criteria for suspected LOS.

Patient characteristics and setting

Neonates aged > 3 days with suspected LOS. The age range of infants included were 4 to 105 days. Study period not available.

Index tests

Staphylococcal 16S rRNA PCR (both Staphylococcus aureus and coagulase‐negative Staphylococci).

Target condition and reference standard(s)

Neonates with suspected LOS and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn concurrently.

Comparative

Notes

The article mentioned 148 events of LOS but on further scrutiny there were on 146 events which were incorporated into the analysis.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

No

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Unclear

Low

Study characteristics

Patient sampling

Newborn infant that met inclusion criteria for EOS and LOS admitted to the NICU during the period of 1999 to 2005.

Patient characteristics and setting

Newborn infants < 28 days old with suspected EOS or LOS admitted to Öbrero University from 1999 to 2005.

Index tests

Real‐time PCR targeting 16S rRNA.

Target condition and reference standard(s)

Neonates with suspected EOS or LOS and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn simultaneously.

Comparative

Notes

PCR results from 1 sample that was positive for culture and PCR was considered uninterpretable as PCR result showed double sequence.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

All infants that met inclusion criteria were enrolled prospectively.

Patient characteristics and setting

All infants aged < 3 months who underwent sepsis evaluation and admitted to the NICU at 2 Swedish University Hospitals between October 2007 and November 2009. Of the participants enrolled in the study, 34 infants were > 28 days old.

Index tests

Broad‐range 16S real‐time PCR.

Target condition and reference standard(s)

Suspected sepsis and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn simultaneously.

Comparative

Notes

16 participants were excluded due to lack of consent, 7 for being older than 3 months and 10 participants whose blood sample for PCR and culture were not drawn concurrently. Excluded participants were not included in the analysis.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

High

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

34 newborns with LOS were enrolled in the study.

Patient characteristics and setting

Newborns > 3 days old with suspected LOS. Age of participants at enrollment and study period not available.

Index tests

Commercial real‐time PCR using LightCycler SeptiFast system (multiplex PCR).

Target condition and reference standard(s)

Neonatal LOS and blood culture.

Flow and timing

Blood samples for LightCycler SeptiFast and culture were simultaneously.

Comparative

Notes

Age of participants at enrollment and study period not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Prospective, non‐randomized enrollment of participants that met inclusion criteria.

Patient characteristics and setting

Infants with birth weight > 1000 g admitted to the NICU at Akershus University Hospital with suspected sepsis during the first week of life. Age at study enrollment and study period not mentioned.

Index tests

Broad‐range 16S rRNA PCR followed by sequencing.

Target condition and reference standard(s)

Suspected neonatal sepsis and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn concurrently.

Comparative

Notes

PCR samples were stored until analysis. 4 infants were excluded from the study with 3 having incomplete registration and 1 with missing sample. 1 infant in the final analysis ended up with a diagnosis of asphyxia rather than sepsis. Age at study enrollment and study period not mentioned.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Neonates with clinically suspected sepsis.

Patient characteristics and setting

Neonates with suspected sepsis. The gestational age ranged from 26 to 39 weeks but age at enrollment not mentioned. Study period: October 2010 to December 2012.

Index tests

16S rDNA PCR.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood samples for blood culture and PCR were done simultaneously.

Comparative

Notes

Age at enrollment not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Unclear

Unclear

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Unclear

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

All infants that met inclusion criteria during a specified period of time. Controls were excluded from analysis.

Patient characteristics and setting

All neonates > 3 days old admitted to the neonatal ward or NICU who developed clinical signs of LOS during the period of 1 January 2004 to June 30, 2004. Other participant demographics not available.

Index tests

Broad‐range 16S rRNA PCR followed by microarray hybridization.

Target condition and reference standard(s)

Suspected neonatal LOS and blood culture.

Flow and timing

Unclear whether blood samples for PCR and blood culture were drawn simultaneously.

Comparative

Notes

Participant demographics not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Unclear

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Consecutive enrollment of infants (24 were neonates) with signs of systemic inflammatory response syndrome and risk factors for candidemia.

Patient characteristics and setting

Infants who were admitted to the ICU of 2 pediatric hospital in Sao Paulo State, Brazil over an 18‐month period. Study period (month and year) or participant demographics not available. Author provided results for the 24 neonates.

Index tests

Multiplex nested PCR with specific primers designed to identify 7 Candida species

Target condition and reference standard(s)

Candidemia and blood culture.

Flow and timing

Blood sample for both culture and PCR were done concurrently.

Comparative

Notes

Data based on email communication with Dr. Del Negro.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

All infants with suspected sepsis in the NICU and PICU during the study period were considered for inclusion in the study.

Patient characteristics and setting

Infants admitted in the NICU (n = 46) and PICU (n = 17) with suspected sepsis during the period from November 1999 to November 2000. PCR and blood culture data separately for neonates not available.

Index tests

Fungal conventional PCR targeting 18S rRNA.

Target condition and reference standard(s)

Suspected sepsis and blood culture.

Flow and timing

Excess blood used for culture was used for PCR.

Comparative

Notes

PCR and blood culture data separately for neonates not available. It was unclear how many of the infants admitted in the PICU were neonates hence, not all infants may have met the target condition of neonatal sepsis defined in this study. PCR products were analyzed by 2 independent observers blinded to blood culture results and participant information.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

High

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

High

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Study data derived from conference abstract only and hence limited.

Patient characteristics and setting

Neonates with suspected sepsis. No participant demographics or study period details available.

Index tests

16S rRNA‐based PCR followed by hybridization to chips with 18 probes.

Target condition and reference standard(s)

Infants with suspected sepsis and blood culture.

Flow and timing

Possible simultaneous sampling for index test and reference standard.

Comparative

Notes

Limited information from abstract. No participant demographics or study period details available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Unclear

Unclear

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Unclear

Unclear

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Unclear

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Participants who met inclusion criteria were admitted consecutively.

Patient characteristics and setting

Infants with febrile episodes admitted to the NICU at the Hospital Universitario Virgen de las Nieves. Study period: April 2007 to April 2009. Participants enrolled in the study were both preterm and term infants; however, age of participants at the time of enrollment range from 0 to 151 days old.

Index tests

LightCycler SeptiFast Assay.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Sample for blood culture and LightCycler SeptiFast assay were collected at the same time.

Comparative

Notes

Participants enrolled in the study were both preterm and term infants; however, age of participants at the time of enrollment range from 0 to 151 days old.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

High

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Unclear

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Only participants with probable candidiasis were included in the study.

Patient characteristics and setting

Neonates at high risk for invasive candidiasis from Jan 2009 to Dec 2010. No information on participant demographics available.

Index tests

Detection of fungal DNA directly from lysis‐centrifugation blood culture. Fungus‐specific universal primer ITS1 and ITS2 were used to amplify 18S rDNA, the adjacent ITS1 and a small portion of the 28S rDNA region.

Target condition and reference standard(s)

Suspected neonatal candidiasis and blood culture.

Flow and timing

Blood samples for PCR and culture came from the same Isolator 1.5 microbial tubes.

Comparative

Notes

No information on participant demographics available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Consecutive enrollment of preterm infants with suspected LOS.

Patient characteristics and setting

Preterm infants with suspected LOS admitted to the NICU. Participant demographics or study period not mentioned.

Index tests

Multiplex real‐time PCR assay.

Target condition and reference standard(s)

LOS in neonates and blood culture.

Flow and timing

Blood samples for culture and PCR were drawn concurrently.

Comparative

Notes

Participant demographics or study period not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Yes

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Limited information from abstract.

Patient characteristics and setting

Newborns aged > 3 days with suspected LOS. Participant demographics or study period data not available.

Index tests

Broad‐range 16S rRNA conventional PCR.

Target condition and reference standard(s)

Neonatal LOS and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn concurrently.

Comparative

Notes

Study data derived from abstract only. Participant demographics or study period data not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Unclear

Unclear

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Limited information from abstract. Controls not included in the analysis.

Patient characteristics and setting

Newborns with suspected sepsis admitted to the neonatal ward or NICU. Participant demographics or study period data not available.

Index tests

Real‐time PCR targeting 16S rRNA.

Target condition and reference standard(s)

Neonatal sepsis and blood culture.

Flow and timing

Blood samples were tested for routine culture and PCR separately. There was no mention if blood sample was drawn simultaneously.

Comparative

Notes

Abstract only. Participant demographics or study period data not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Unclear

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Unclear

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Neonates who met inclusion criteria during the study period were enrolled. Controls were not included in the analysis.

Patient characteristics and setting

Neonates aged 1 to 28 days with suspected sepsis admitted to the neonatal ward and NICU of Zhejiang University Children's Hospital from January 2005 to January 2007. 108 of the participants were preterm infants.

Index tests

Real‐time PCR with Gram‐specific probes followed by sequencing.

Target condition and reference standard(s)

Suspected neonatal EOS and LOS and blood culture.

Flow and timing

PCR and culture were done simultaneously. Unclear if samples were concurrently.

Comparative

Notes

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Yes

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Unclear

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low

Study characteristics

Patient sampling

Infants were enrolled if they met inclusion criteria.

Patient characteristics and setting

Infants < 7 days old with suspected sepsis admitted to a level II NICU. Study period details not available.

Index tests

Broad‐range 16S rRNA PCR.

Target condition and reference standard(s)

Suspected neonatal sepsis and blood culture.

Flow and timing

Blood samples for PCR and culture were drawn concurrently.

Comparative

Notes

Study period details not available.

Methodological quality

Item

Authors' judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection

Was a consecutive or random sample of patients enrolled?

Unclear

Was a case‐control design avoided?

Yes

Did the study avoid inappropriate exclusions?

Yes

Low

Low

DOMAIN 2: Index Test All tests

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

If a threshold was used, was it pre‐specified?

Yes

Low

Low

DOMAIN 3: Reference Standard

Is the reference standards likely to correctly classify the target condition?

Yes

Were the reference standard results interpreted without knowledge of the results of the index tests?

Unclear

Low

Low

DOMAIN 4: Flow and Timing

Was there an appropriate interval between index test and reference standard?

Yes

Did all patients receive the same reference standard?

Yes

Were all patients included in the analysis?

Yes

Low