PCR Using Blood for Diagnosis of Invasive Pneumococcal Disease: Systematic Review and Meta-Analysis

Abstract

The use of molecular-based methods for the diagnosis of bacterial infections in blood is appealing, but they have not yet passed the threshold for clinical practice. A systematic review of prospective and case-control studies assessing the diagnostic utility of PCR directly with blood samples for the diagnosis of invasive pneumococcal disease (IPD) was performed. A broad search was conducted to identify published and unpublished studies. Two reviewers independently extracted the data. Summary estimates for sensitivity and specificity with 95% confidence intervals (CIs) were calculated by using the hierarchical summary receiver operating characteristic method. The effects of sample processing, PCR type, the gene-specific primer, study design, the participants' age, and the source of infection on the diagnostic odds ratios were assessed through meta-regression. Twenty-nine studies published between 1993 and 2009 were included. By using pneumococcal bacteremia for case definition and healthy people or patients with bacteremia caused by other bacteria as controls (22 studies), the summary estimates for sensitivity and specificity were 57.1% (95% CI, 45.7 to 67.8%) and 98.6% (95% CI, 96.4 to 99.5%), respectively. When the controls were patients suspected of having IPD without pneumococcal bacteremia (26 studies), the respective values were 66.4% (95% CI, 55.9 to 75.6%) and 87.8% (95% CI, 79.5 to 93.1%). With lower degrees of proof for IPD (any culture or serology result and the clinical impression), the sensitivity of PCR decreased and the specificity increased. All analyses were highly heterogeneous. The use of nested PCR and being a child were associated with low specificity, while the use of a cohort study design was associated with a low sensitivity. The lack of an appropriate reference standard might have caused underestimation of the performance of the PCR. Currently available methods for PCR with blood samples for the diagnosis of IPD lack the sensitivity and specificity necessary for clinical practice.Identification of the pathogens responsible for sepsis and septic shock is of primary importance for therapeutic decision making. Survival is dramatically influenced by the early initiation of treatment with the appropriate antibiotics (17, 35). Unnecessary or superfluous antibiotic treatment is associated with side effects and leads to the induction of resistance without the provision of a benefit (19).Blood culture findings are classically used to define infections. However, they lack sensitivity for most types of infections, particularly following antibiotic treatment, and the results are delayed by the time required for pathogen growth. The case is especially noteworthy for community-acquired pneumonia (CAP), for which positivity rates are very low and blood cultures cannot be used to direct treatment (3). The results of sputum Gram stain and culture are positive for 31 to 68% and 28 to 86% of patients with pneumococcal pneumonia who can produce sputum, respectively (8,21,43,46,54), while the test for pneumo...

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema

“…Moreover, in the metaanalysis by Avni et al [17] the rate of diagnosis by positive PCR was also higher than the rate by positive blood culture in 16 of 25 studies.…”

“…al. [17] have published an accurate meta-analysis and found that the studies were highly heterogeneously including different type of PCR methods [18,19], different target genes [20], most used stored frozen [21] and different samples (i.e. whole blood or plasma) [22], as well as different patients' characteristics and different clinical syndromes [23,24].…”

Non-culture-based methods to diagnose bloodstream infection: Does it work?

“…In pneumococcal pneumonia, blood cultures often remain negative and polymerase chain reaction (PCR)-based detection of Streptococcus pneumoniae in patients with a clinical suspicion for pneumonia has been shown to be more sensitive than blood cultures in clinical studies [6,7]. However, in a recent meta-analysis of 29 studies, published between 1993 and 2009, the authors concluded that PCR from blood samples for the diagnosis of invasive S. pneumoniae infection lacks the sensitivity and specifi city necessary for clinical practice [8]. This meta-analysis highlights the problems associated with determining accuracy of a diagnostic test.…”

Invasive Pneumococcal Disease in Children: The Contribution of Real-Time PCR on Blood

“…Real-time PCR is theoretically useful for the diagnosis of IPD. However, these techniques are not in routine use for diagnosing pneumococcal infections and must be evaluated to ascertain their value among the tools used for clinical diagnoses especially when PCR is performed from blood samples [7]. PCR-based methods usually target the ply gene encoding pneumolysin and the lytA gene encoding autolysin.…”