Diagnostic value of BHI-V4 for heterogeneous and vancomycin-intermediate Staphylococcus aureus isolates: a systematic review and meta-analysis

Background Brain-heart infusion agar supplemented with 4 µg/mL of vancomycin (BHI-V4) was commonly used for the detection of heterogeneous (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA). However, its diagnostic value remains unclear. This study aims to compare the diagnostic accuracy of BHI-V4 with population analysis profiling with area under the curve (PAP-AUC) in hVISA/VISA. Methods The protocol of this study was registered in INPLASY (INPLASY2023120069). The PubMed and Cochrane Library databases were searched from inception to October 2023. Review Manager 5.4 was used for data visualization in the quality assessment, and STATA17.0 (MP) was used for statistical analysis. Results In total, eight publications including 2153 strains were incorporated into the meta-analysis. Significant heterogeneity was evident although a threshold effect was not detected across the eight studies. The summary receiver operating characteristic (SROC) was 0.77 (95% confidence interval [CI], 0.74–0.81). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic score and diagnostic odds ratio were 0.59 (95% CI: 0.46–0.71), 0.96 (95%CI: 0.83–0.99), 14.0 (95% CI, 3.4–57.1), 0.43 (95%CI, 0.32–0.57), 3.48(95%CI, 2.12–4.85) and 32.62 (95%CI, 8.31-128.36), respectively. Conclusion Our study showed that BHI-V4 had moderate diagnostic accuracy for diagnosing hVISA/VISA. However, more high-quality studies are needed to assess the clinical utility of BHI-V4. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-024-09274-4.


A. Risk of Bias
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 Could the conduct or interpretation of the index test have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Low concern
Reference Standard

A. Risk of Bias
Target condition and reference standard(s) 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 Could the reference standard, its conduct, or its interpretation have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the target condition as defined by the reference standard does not match the question?

Low concern
Flow and Timing

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 Could the patient flow have introduced bias?Low risk

Riederer2011
Patient Selection

Patient characteristics and setting
Are there concerns that the included patients and setting do not match the review question?

Index Test
Index tests

A. Risk of Bias
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 Could the conduct or interpretation of the index test have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Low concern
Reference Standard

A. Risk of Bias
Target condition and reference standard(s) 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 Could the reference standard, its conduct, or its interpretation have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the target condition as defined by the reference standard does not match the question?

Low concern
Flow and Timing

Patient characteristics and setting
Are there concerns that the included patients and setting do not match the review question?

Low concern
Index Test

Index tests
All tests

A. Risk of Bias
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 Could the conduct or interpretation of the index test have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Reference Standard
A. Risk of Bias Target condition and reference standard(s) 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 Could the reference standard, its conduct, or its interpretation have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the target condition as defined by the reference standard does not match the question?

Low concern
Flow and Timing

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?No

Patient characteristics and setting
Are there concerns that the included patients and setting do not match the review question?

Index Test
Index tests

A. Risk of Bias
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 Could the conduct or interpretation of the index test have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Low concern
Reference Standard

A. Risk of Bias
Target condition and reference standard(s) 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 Could the reference standard, its conduct, or its interpretation have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the target condition as defined by the reference standard does not match the question?

Low concern
Flow and Timing

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

Patient characteristics and setting
Are there concerns that the included patients and setting do not match the review question?

Low concern
Index Test

A. Risk of Bias
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 Could the conduct or interpretation of the index test have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Low concern
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 Could the reference standard, its conduct, or its interpretation have introduced bias?Low risk

B. Concerns regarding applicability
Are there concerns that the target condition as defined by the reference standard does not match the question?

Low concern
Flow and Timing Could the patient flow have introduced bias? or random sample of patients enrolled?Unclear Was a case-control design avoided?No Did the study avoid inappropriate exclusions?Unclear Could the selection of patients have introduced bias?Unclear risk appropriate interval between index test and reference standard?Unclear Did all patients receive the same reference standard?NoWere all patients included in the analysis?YesCould the patient flow have introduced bias?
Is the reference standards likely to correctly classify the target condition?YesWere the reference standard results interpreted without knowledge of the results of the index tests?Yes A. Risk of BiasTarget condition and reference standard(s)