Importance of blood volume cultured in the detection of bacteremia

Arpi, Magnus; Bentzon, Michael Weis; Jensen, Jørgen Skov; Frederiksen, Wilhelm

doi:10.1007/bf02185857

Cited by 77 publications

(55 citation statements)

References 18 publications

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“…Numerous factors influence the likelihood of detecting bacteremia. These factors include the volume of blood specimens cultured and the number of blood cultures performed (1,8,10,11,17,21,25,27,29). The conventional practice has been to obtain blood specimens at or around the time of a temperature elevation as a means of enhancing the likelihood of documenting bacteremia (5,32).…”

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confidence: 99%

Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia

et al. 2008

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Bloodstream infections are an important cause of morbidity and mortality. Physician orders for blood cultures often specify that blood specimens be collected at or around the time of a temperature elevation, presumably as a means of enhancing the likelihood of detecting significant bacteremia. In a multicenter study, which utilized retrospective patient chart reviews as a means of collecting data, we evaluated the timing of blood culture collection in relation to temperature elevations in 1,436 patients with bacteremia and fungemia. The likelihood of documenting bloodstream infections was not significantly enhanced by collecting blood specimens for culture at the time that patients experienced temperature spikes. A subset analysis based on patient age, gender, white blood cell count and specific cause of bacteremia generally also failed to reveal any associations.Bloodstream infections (BSIs) occur more than 200,000 times annually in the United States, with associated mortality rates of 35 to 60% (20,33,34). Prompt administration of appropriate antimicrobial therapy plays an important role in reducing the mortality associated with this condition (9,12,14, 15,16,18,22,26,31). In patients with bacteremia, the optimization of therapy is ultimately predicated on rapid documentation of positive blood cultures, expeditious performance of in vitro antimicrobial susceptibility tests, and timely reporting of results (2,23,33). Numerous factors influence the likelihood of detecting bacteremia. These factors include the volume of blood specimens cultured and the number of blood cultures performed (1,8,10,11,17,21,25,27,29). The conventional practice has been to obtain blood specimens at or around the time of a temperature elevation as a means of enhancing the likelihood of documenting bacteremia (5, 32). This practice is based on the principle that the presence of organisms in the intravascular space leads to the elaboration of cytokines, which in turn causes body temperatures to rise.The value of attempting to time the collection of blood for culture around temperature elevations is complicated by the fact that many patients with bacteremia, especially those that are elderly, may be hypothermic at the time that they are bacteremic or may be unable to mount a febrile response to infection (7). Furthermore, there are numerous causes of fever other than bacteremia, e.g., ischemia, drug reactions, immunological conditions, and malignancy (4). This issue is further complicated by the observation made more than 50 years ago by Bennett and Beeson: bacteremia actually precedes temperature elevations by 1 or 2 h (3). These researchers noted that blood cultures were frequently negative at the time of the temperature spike and concluded that, ideally, blood cultures should be drawn some time prior to elevations in temperature. More recently, Jaimes et al. found that fever was not a useful independent predictor of bacteremia and needed to be considered in light of other factors, such as hypotension, white blood cell (WBC) counts, an...

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Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia

et al. 2008

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“…One of the most important factors influencing blood culture diagnostic yield is blood volume (71,191). Several studies of adults (4,17,30,84,126) and pediatric patients (82,86) confirmed that the rate of isolation from blood cultures increases with the quantity of blood submitted. This is particularly important for pediatric patients, for whom it is not always possible to draw a sufficient volume of blood.…”

Section: The Limits Of a Gold Standard: Factors Influencing Blood Culmentioning

confidence: 90%

The Era of Molecular and Other Non-Culture-Based Methods in Diagnosis of Sepsis

et al. 2010

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SUMMARY Sepsis, a leading cause of morbidity and mortality throughout the world, is a clinical syndrome with signs and symptoms relating to an infectious event and the consequent important inflammatory response. From a clinical point of view, sepsis is a continuous process ranging from systemic inflammatory response syndrome (SIRS) to multiple-organ-dysfunction syndrome (MODS). Blood cultures are the current “gold standard” for diagnosis, and they are based on the detection of viable microorganisms present in blood. However, on some occasions, blood cultures have intrinsic limitations in terms of sensitivity and rapidity, and it is not expected that these drawbacks will be overcome by significant improvements in the near future. For these principal reasons, other approaches are therefore needed in association with blood culture to improve the overall diagnostic yield for septic patients. These considerations have represented the rationale for the development of highly sensitive and fast laboratory methods. This review addresses non-culture-based techniques for the diagnosis of sepsis, including molecular and other non-culture-based methods. In particular, the potential clinical role for the sensitive and rapid detection of bacterial and fungal DNA in the development of new diagnostic algorithms is discussed.

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“…The reported detection limit for SeptiFast real-time PCR is 3-100 CFU/ml 29 which compares relatively favourably to the microbial burden often associated with adult sepsis (< 10 CFU/ml). 23,97 However, this varies considerably between species with some organisms including C. glabrata, being undetectable at 3 CFU/ml blood. A similar explanation could be proposed for the performance of the test in detecting CoNS.…”

Section: Discussionmentioning

confidence: 99%

“…The amplification of the pathogen signal during real-time PCR is crucially important owing to the low numbers of circulating bacteria [10 colony-forming units (CFUs) per ml] or fungi (1-10 CFU/ml) reported in adult sepsis. 23,24 The use of real-time PCR also facilitates detection of fastidious, difficult-to-culture organisms such as fungi. 25 Two basic approaches have been taken in the design of real-time PCR assays for sepsis pathogens, either (i) broad-range detection of bacterial or fungal DNA with universal primers followed by species identification using post-PCR techniques such as DNA sequencing, electrospray ionisation mass-spectrometry or high resolution melting analysis [26][27][28] or (ii) multiplex assays utilising a panel of species-specific hybridisation probes that provide direct confirmation that a particular species is present.…”

Section: Molecular Approaches To Diagnosis Of Health-care-associated mentioning

confidence: 99%

Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review

Warhurst

Dunn

Chadwick

et al. 2015

Health Technology Assessment

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BackgroundThere is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias.ObjectiveDetermine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture.DesignProspective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria.SettingCritical care departments within NHS hospitals in the north-west of England.ParticipantsAdult patients requiring blood culture (BC) when developing new signs of systemic inflammation.Main outcome measuresSeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard.ResultsOf 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4–16 days) of hospital care, had high levels of organ support activities and recent antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy.ConclusionSeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is prone to error.Study registrationThe systematic review is registered as PROSPERO CRD42011001289.FundingThe National Institute for Health Research Health Technology Assessment programme. Professor Daniel McAuley and Professor Gavin D Perkins contributed to the systematic review through their funded roles as codirectors of the Intensive Care Foundation (UK).

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Importance of blood volume cultured in the detection of bacteremia

Cited by 77 publications

References 18 publications

Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia

Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia

The Era of Molecular and Other Non-Culture-Based Methods in Diagnosis of Sepsis

Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review

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