16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis

PLOS ONE, Dec 2019

Objective We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis. Methods A computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software. Results Twenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.85–0.89), 0.94 (95% CI, 0.93–0.95), 12.65 (95% CI, 8.04–19.90), 0.14 (95% CI, 0.08–0.24), and 116.76 (95% CI, 52.02–262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect. Conclusion Existing data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future.

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16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis

May 16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis Guoming Su 0 1 2 Zhuqing Fu 0 1 2 Liren Hu 0 1 2 Yueying Wang 0 1 2 Zuguo Zhao 0 1 2 Weiqing Yang 0 1 2 0 1 Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical College , Dongguan , China , 2 Department of Microbiology and Immunology, Guangdong Medical College , Zhanjiang , China , 3 Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical College , Zhanjiang , China 1 Received: January 4 , 2015 2 Academic Editor: Cordula M. Stover, University of Leicester , UNITED KINGDOM - Competing Interests: The authors have declared that no competing interests exist. We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis. A computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software. Twenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.850.89), 0.94 (95% CI, 0.930.95), 12.65 (95% CI, 8.0419.90), 0.14 (95% CI, 0.080.24), and 116.76 (95% CI, 52.02262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect. Existing data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future. Bloodstream infections (BSIs) remain a major cause of morbidity and mortality especially in the Intensive Care Unit [15]. Moreover, inadequate antibiotic therapy is associated with higher mortality rates. Early microbiological diagnosis is of paramount importance for appropriate antibiotic treatment which increases the survival rate of patients [4]. Therefore, it is evident that a rapid, sensitive and specific diagnosis of BSIs is urgently needed. Conventional identification methods have several limitations such as lack of rapidity and sensitivity. Blood cultures followed by conventional identification methods are currently the reference method for the detection of pathogens in blood. This well-established method can detect a wide range of microorganisms. However, disadvantages do exist, as the time to detection is often too long. After the detection of bacteria by conventional blood culture, identification and assessment of antibiotic sensitivity take at least a further 24 h [6, 7]. The sensitivity is also unacceptably low in the detection of pathogenic bacteria in cases of low-grade bacteremia, in cases where blood cultures are inoculated without adequate sample volume, and in cases where antibiotics are used before blood samples are taken [8, 9]. If blood cultures were negative, repetition of sampling would been required, while positive cases need further identification of the isolated microorganism using different culture media and biochemical tests [9]. For these reasons, development of detection methods that provide more rapid results and higher sensitivity is expected to optimize use of antibiotics. An ideal diagnostic tool for BSIs should be rapid, sensitive and unaffected by antibiotic therapy. In recent years, polymerase chain reaction (PCR) assay using the 16S ribosomal ribonucleic acid (rRNA) gene has been used as a diagnostic tool in many setting [1, 9, 10]. This test is based on the rationale that 16S rRNA gene of bacteria comprises both conserved and variable regions [11]the conserved regions are targeted by universal primers for identification of bacterial infection and the variable regions by genus or species-specific assays [2]. Amplified target regions may then be subjected to downstream applications such as sequence analysis and microarray hybridization [5, 9, 11, 12]. In addition, the PCR test has the advantages of amplifying minute amounts of DNA, even from nonviable bacteria [13], and costing less money than blood cultures in both negative and positive cases [9]. However, the resu (...truncated)


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Guoming Su, Zhuqing Fu, Liren Hu, Yueying Wang, Zuguo Zhao, Weiqing Yang. 16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis, PLOS ONE, 2015, 5, DOI: 10.1371/journal.pone.0127195