Skip to main content

Short time to positivity of blood culture predicts mortality and septic shock in bacteremic patients: a systematic review and meta-analysis

Abstract

Background

The value of time to positivity (TTP) on diagnosis for catheter-related bloodstream infection and distinguishment on bacteria group and infection source has been investigated. However, the relationship between TTP and patient outcome requires verification, and we performed a systematic review and meta-analysis.

Methods

We searched PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science for publications associated with the topic. We included studies that researched the TTP on predicting patient mortality and septic shock. Quality assessment is performed with Critical Appraisal Skills Programme (CASP). The analysis is performed using Review Manager Version 5.0.24. on articles available for data extraction on the exact population of each outcome group. The existence of publication bias was assessed by funnel plots. Statistical heterogeneity was evaluated using the Cochran Q and \({I}^{2}\) statistics. The outcome is reported as an odds ratio. PROSPERO registration: CRD42021272286.

Results

Twenty-four eligible studies were included in our study. Twenty-four in the mortality group and six in the septic shock group. Mortality is significantly associated with the short time to positivity group with an odds ratio of 2.98 (95% CI: 2.25–3.96, p-value < 0.001). The odds ratio for developing septic shock in the short TTP group is 4.06 (95% CI: 2.41–6.84, p-value < 0.001). Subgroup analysis revealed short TTP as a significant predictor of mortality and septic shock in Gram's positive and Gram's negative related bloodstream infections. TTP is not associated with mortality among patients with candidaemia.

Conclusions

Short time to positivity is a reliable marker for patient outcome in certain bacterial species. Studies concerning confounding factors such as the delay in bottle loading and other confounding factors are needed to enhance external validity.

Peer Review reports

Background

Time to bacterial culture positivity, or time to positivity (TTP), is defined as the time from the start of incubation to the preliminary positive result of blood culture. The value of TTP provides indirect information of bacteremia load in the blood sample and is perceived as a new method for physicians to identify or evaluate the treatment or prognosis of the patient [1, 2]. Initially, the utility of TTP is focused on recognizing the bacteria genre or infection source. TTP was then reported to be helpful with differential diagnosis of catheter-related bloodstream infections (CRBSIs) [3], salvaging central venous catheters [4], and prognosis prediction for infective endocarditis [5]. Short TTP had also been acknowledged to be associated with mortality [5,6,7,8,9].

Though an increasing number of TTP-associated articles were published in the past decade, there is still a notable knowledge gap on the outcome prediction of TTP. Despite many articles had analyzed the correlation of TTP and patient outcome, the application of TTP requires further study. Most of the studies faced limitations such as small study populations, uncontrolled confounders, and differentiation between centers [10]. These hurdles make the implementation of TTP impractical. Thus, we aim to clarify the relationship between TTP and patient outcome, test the robustness of TTP as a predictor in patient outcome, and overcome the limitation of population size in current articles by performing a systemic review and meta-analysis.

Methods

Search strategy and study selection

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to conduct this systematic review. [11] We searched PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science through August 13, 2021. The search was done with Medical Subject Headings (MeSH), and appropriate adjustments were made according to different databases. The index terms included time to positivity, time to blood culture positivity, mortality, septic shock, and prognosis, Supplementary Material Table gives the retrieval strategy in detail. We included prospective and retrospective observational studies that addressed: 1) Association of the length of TTP and patient prognosis (mortality and septic shock) or 2) Cut-off value of TTP for patient prognosis prediction. The search incorporated a limitation for articles available in English after 2000 and studies involving humans. Case reports and reviews were excluded. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO) as record number CRD42021272286.

Two authors assessed the titles and abstracts of the studies to eliminate those not relevant to the inclusion criteria. Eligible studies include those focused on patient's blood culture TTP's impact on patient outcome (mortality and septic shock). Articles discussing TTP after antibiotic usage were excluded.

Data extraction

Two independent reviewers (YC Hsieh and TC Chen) extracted the data using a standardized protocol and PICO (Patient, Intervention, Comparison, and Outcome). Disagreement on specific studies between the two reviewers was resolved through discussion or consultation with the third reviewer (SY Lin). Quality assessment is performed with the Critical Appraisal Skills Programme (CASP). The titles and abstracts were screened for relevance. After a review of the full-text articles, the following data were extracted from each study: the year of the publication, patient characteristic, study design, TTP characteristic, the proportion of death and survival in both short and long TTP groups, and the proportion of patients developing septic shock in short and long TTP groups. Short TTP and long TTP are defined through the cut-off value in each article. TTP shorter than the cut-off value defined in each study is classified into short TTP group, vice versa. The classification of septic shock was defined according to the criteria previously published in The Journal of the American Medical Association (JAMA). [12] Only articles using this criterion for septic shock were included in our analysis.

Statistical analysis

The exact number of mortality events and septic shock events in both short TTP and long TTP groups extracted from each study were combined using a Mantel–Haenszel statistical method with random-effects model, which assumes that individual studies are estimating different treatment effects, rather than the fixed-effect model, which is based on the mathematical assumption that a single common effect underlies every study in the meta-analysis. We performed the statistical analysis and subgroup analyses based on Gram’s stain and Candida spp. on mortality and septic shock, respectively. In order to eradicate the bias effect contributed from the variation of cut-off value defined in each article included in the mortality group, we conducted another statistical analysis based on studies with defined TTP cut-off values shorter than the median in the mortality group, which is 12 h. Dichotomous data were reported as an odds ratio with corresponding 95% CI p-value < 0.05 is considered to be significant. Statistical heterogeneity was evaluated using the Cochran Q and \({I}^{2}\) statistics. '\({I}^{2}\)' denotes the percentage of total variation across the studies that are the result of heterogeneity rather than chance. We assessed for the presence of publication bias using a funnel plot. The meta-analysis was performed using Review Manager Version 5.0.24.

Results

The initial database search identified 230 articles. We screened titles and abstracts of a total of 145 non-duplicate records and excluded 99 articles not relevant to the topic. A total of forty-six full-text articles were reviewed for eligibility, and twenty-four studies that met our search criteria with eligible quality were included in the analysis. Twenty-four studies with complete data (twenty-four for patient mortality and six for patients developing septic shock) were included in the final meta-analysis (Table 1). All studies included in our analysis are based on bacteremia. Detailed results of our search are presented in Fig. 1 as a PRISMA flowchart.

Table 1 Table of included studies
Fig. 1
figure 1

Flow diagram of the study selection

Mortality is significantly associated with the short TTP group with an odds ratio of 2.98 (95% CI: 2.25–3.96, p-value < 0.001; Fig. 2). Moderate heterogenicity was found among our studies included in the mortality analysis group (\({I}^{2}\)=62%; Cochrane’s Q < 0.1). In sub-group analysis, short TTP is significantly correlated with mortality in Gram's positive and Gram’s negative bacterial group (Fig. 3), with an odds ratio of 3.11(95% CI: 1.72–5.62, p-value < 0.001), and 3.31(95% CI: 2.45–4.48, p-value < 0.001). However, in the Candida species group, mortality was not significantly correlated with short TTP (OR 1.27, 95% CI: 0.37–4.35, p-value = 0.7). In studies with a cut-off value shorter than the median, the odds ratio is 3.49 (95% CI: 2.57–4.74, p-value < 0.001; Fig. 4) with low heterogenicity (\({I}^{2}\)=30%; Cochrane’s Q = 0.14).

Fig. 2
figure 2

Forest plot showing the association between short TTP and patient mortality using the random-effects model. Events, population of mortality in both TTP groups; total, total population in both TTP groups

Fig. 3
figure 3

Forest plot showing the association between short TTP and patient mortality in Gram’s stain and Candida spp. subgroups. Events, population of mortality in both TTP groups; total, total population in both TTP groups

Fig. 4
figure 4

Forest plot showing the association between short TTP and patient mortality in studies with TTP cut-off value shorter than the median (12 h) using the random-effects model

The odds ratio for developing septic shock in the short TTP group is 4.06 (95% CI: 2.41–6.84, p-value < 0.001; Fig. 5), and the heterogenicity is low (\({I}^{2}\)=41%; Cochrane’s Q = 0.13). Sub-group analysis (Fig. 6) showed a significant correlation of septic shock incidence rate with short TTP in both Gram's positive (OR 3.32, 95% CI: 1.24–8.84, p-value = 0.02) and Gram's negative (OR 5.17, 95% CI: 2.87–9.33, p-value < 0.001) bacterial group.

Fig. 5
figure 5

Forest plot showing the association between short TTP and septic shock in patients using the random-effects model. Events, population of septic shock in both TTP groups; total, total population in both TTP groups

Fig. 6
figure 6

Forest plot showing the association between short TTP and septic shock in patients in Gram’s stain. subgroups. Events, population of mortality in both TTP groups; total, total population in both TTP groups

Funnel plot analysis for the mortality group and the septic shock group showed grossly symmetrical with poor narrowing on large population studies (Figs. 7 and 8), which might represent publication bias and small sample size bias.

Fig. 7
figure 7

Funnel plot of studies included in the meta-analysis between short TTP and mortality

Fig. 8
figure 8

Funnel plot of studies included in the meta-analysis between short TTP and septic shock

Discussion

In this study, we collected numerous studies about the correlation between TTP and patient outcomes. Populations on mortality and septic shock in both TTP shorter and longer than the cut-off value defined in the article were extracted if available. Meta-analysis revealed a 2.98-fold higher mortality risk and a 4.06-fold higher risk for developing septic shock in the short TTP group. Sub-group analysis also showed short TTP to be an effective predictor of mortality and septic shock in different bacterial groups except for Candida species in mortality.

The utility of TTP has been investigated in several different aspects. Work has been done on the effectiveness of TTP for distinguishing bacterial species, differentiating the infection source, and predicting patient outcomes. TTP is proved to be an independent predictor of mortality and other categories of outcome in several studies [5,6,7,8,9]. Most of the previous studies reported a significant relationship between short TTP and mortality. This corresponds to the hypothesis that short TTP might be correlated to higher bacterial load [1, 9, 33], which results in higher mortality. Interestingly, mortality risk isn't always correlated with short TTP. In a retrospective study included in our analysis, mortality is associated with the long TTP group [8]. Six hundred eighty-four patients consisting of adult and pediatric S. aureus bacteremia revealed that TTP > 48 h was associated with higher 30-day mortality. The possible explanation might be because bacteria load in pediatric bacteremia is different in adult bacteremia, so merging two groups of S. aureus bacteremia might not be appropriate [34, 35]. Three recent articles reported a non-significant relationship between TTP and mortality, but the final result of the analysis was not affected. In a cohort enrolled 87 patients with S. aureus bacteremia, TTP of < 12 h was not significantly associated with mortality [13]. Only patients with bacteremia persisting for more than 48 h were included, and patients who died within 48 h were excluded, which might contribute to the phenomenon. The other two studies that showed TTP to be unpredictable for mortality might be because of the small population size included in their analyses. One study of 68 patients with nontyphoidal Salmonella bacteremia [22], and another is a prospective observational study about Gram-negative bacilli bacteremia with 63 patients enrolled in the final analysis [28].

Most bacterial groups we analyzed revealed a significant relationship among the subgroup analysis of short TTP and mortality. However, our analysis reported a non-significant result (p-value = 0.7) in the Candida species group. We included two studies in Candida species subgroup analysis. One is a retrospective study including 152 patients [25]. In this article, short TTP is independently associated with an increased 6-week mortality rate in patients with candidaemia. Another is a separate cohort study including 89 adult patients with C. Albicans bacteremia infection [24]. Interestingly, this study showed that the longer the TTP, the higher the mortality risk. The result could be the etiology of candidaemia, general patient health included in this study, or the volume inoculated into the blood culture bottles. To our knowledge, these two articles are the only articles discussing TTP and patient outcome in candidaemia and having available data for us to extract and analyze. Other articles about candidaemia and TTP mainly discuss the relationship between TTP and different Candida species or different culture sites.

The predictive capability of short TTP for septic shock events is also evaluated in our study. Our analysis revealed that short TTP could indicate septic shock, which is in line with previous studies. The result of our subgroup analysis is also consistent with previous reports.

We conducted another statistical analysis, including studies with cut-off values shorter than the median of cut-off values in our study to eradicate the effect of the varied cut-off values and the heterogenicity noticed among the articles in the mortality group. The correlation remains significant with short TTP with a higher odds ratio (3.49, 95% CI: 2.57–4.74, p-value < 0.001) compared with the original analysis (2.98, 95% CI: 2.25–3.96, p-value < 0.001) but with lower heterogenicity in the latter analysis. This result emphasizes the correlation between short TTP and mortality.

There are some limitations to our analysis. First, there might be some notable bias in our study. Although the funnel plot in our analysis is symmetrical, the narrowing is insufficient among the large population studies, which might represent possible publication bias or reporting bias. Second, heterogenicity is noted in mortality analyses. Cochrane's Q value < 0.1 and an \({I}^{2}\) value of 62% were noted is mortality rate analysis. This could be attributable to the variation of cut-off values in each study. Each article we included reported an individual cut-off value for TTP. Meaning every short/long TTP group is defined under different cut-off value, which could cause underlying bias and poor utility of the result of our analysis. Thus, a cut-off value would be crucial for TTP to be clinically applicable, although the prediction with short TTP on patient mortality and septic shock is confirmed. However, we offset a part of the bias by performing another analysis including studies with cut-off values shorter than the median. The heterogenicity is lesser and the odds ratio is larger in this analysis. Third, merging pediatric and adult patients in our study might also contribute since children and adults have different bacterial loads and different blood culture volumes inoculated into the blood culture bottle [36, 37]. Fourth, there are notable confounders in our studies. Most of them are not included in our analysis due to the small number of articles discussing the association of these factors with TTP. All of our studies did not exclude the effect of confounding factors such as the delay of bottle loading, the difference between each blood culture system, administered antimicrobials, site of infection, time to start of antimicrobials, and the volume of blood cultured [10], which might lead to hampered external validity and difficulties for TTP application in respective centers. Thus, further analyses with studies considering more confounder effects and more articles included would be necessary. Fifth, the meta-regression analysis we performed revealed no significant result; this might be because of the small number of articles performing multivariate analysis with TTP and patient outcome. Last but not least, a systemic review on if a short time to positivity is associated with high markers of inflammation is necessary for our article to prove that hyper-inflammation is the explanation of unfavorable outcomes. Only few articles discuss the correlation between inflammation marker and TTP.

Conclusion

In conclusion, this meta-analysis confirmed that a short TTP might be predictive for patient mortality and septic shock. Possible infection etiology and bacteria genre should take into concern while trying to apply this result clinically.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BSI:

Bloodstream infection

CI:

Confidence interval

CASP:

Critical appraisal skills programme

CO2:

Carbon dioxide

CoNS:

Coagulase-negative staphylococcus

CRBSI:

Catheter-related bloodstream infections

GNB:

Gram’s negative bacteria

GNB:

Gram’s negative bacilli

IE:

Infective endocarditis

MeSH:

Medical subject headings

NTS:

Nontyphoidal Salmonella

OR:

Odds ratio

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

TTP:

Time to positivity

VCUMC:

Virginia Commonwealth University Medical Center

References

  1. Haimi-Cohen Y, Vellozzi EM, Rubin LG. Initial concentration of Staphylococcus epidermidis in simulated pediatric blood cultures correlates with time to positive results with the automated, continuously monitored BACTEC blood culture system. J Clin Microbiol. 2002;40(3):898–901.

    Article  Google Scholar 

  2. Blot F, Schmidt E, Tancrède C, Leclercq B, Laplanche A, et al. Earlier positivity of central-venous-versus peripheral-blood cultures is highly predictive of catheter-related sepsis. J Clin Microbiol. 1998;36(1):105–9.

    Article  CAS  Google Scholar 

  3. Blot F, Nitenberg G, Chachaty E, Raynard B, Germann N, Antoun S, et al. Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet. 1999;354(9184):1071–7.

    Article  CAS  Google Scholar 

  4. Mandolfo S, Anesi A, Maggio M, Rognoni V, Galli F, Forneris G. High success rate in salvage of catheter-related bloodstream infections due to Staphylococcus aureus, on behalf of project group of Italian society of nephrology. J Vasc Access. 2020;21(3):336–41.

    Article  Google Scholar 

  5. Siméon S, Le Moing V, Tubiana S, Duval X, Fournier D, Lavigne JP, et al. Time to blood culture positivity: an independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia. Clin Microbiol Infect. 2019;25(4):481–8.

    Article  Google Scholar 

  6. Martínez JA, Pozo L, Almela M, Marco F, Soriano A, López F, et al. Microbial and clinical determinants of time-to-positivity in patients with bacteraemia. Clin Microbiol Infect. 2007;13(7):709–16.

    Article  Google Scholar 

  7. Cillóniz C, Ceccato A, de la Calle C, Gabarrús A, Garcia-Vidal C, Almela M, et al. Time to blood culture positivity as a predictor of clinical outcomes and severity in adults with bacteremic pneumococcal pneumonia. PLoS ONE. 2017;12(8):e0182436.

    Article  Google Scholar 

  8. Kim J, Gregson DB, Ross T, Laupland KB. Time to blood culture positivity in Staphylococcus aureus bacteremia: association with 30-day mortality. J Infect. 2010;61(3):197–204.

    Article  Google Scholar 

  9. Willmann M, Kuebart I, Vogel W, Flesch I, Markert U, Marschal M, et al. Time to positivity as prognostic tool in patients with Pseudomonas aeruginosa bloodstream infection. J Infect. 2013;67(5):416–23.

    Article  Google Scholar 

  10. Lamy B. Blood culture time-to-positivity: making use of the hidden information. Clin Microbiol Infect. 2019;25(3):268–71.

    Article  CAS  Google Scholar 

  11. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1.

    Article  Google Scholar 

  12. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.

    Article  CAS  Google Scholar 

  13. Marra AR, Edmond MB, Forbes BA, Wenzel RP, Bearman GM. Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection. J Clin Microbiol. 2006;44(4):1342–6.

    Article  Google Scholar 

  14. Hsu MS, Huang YT, Hsu HS, Liao CH. Sequential time to positivity of blood cultures can be a predictor of prognosis of patients with persistent Staphylococcus aureus bacteraemia. Clin Microbiol Infect. 2014;20(9):892–8.

    Article  Google Scholar 

  15. Li Y, Li Q, Zhang G, Ma H, Wu Y, Yi Q, et al. Time to positivity of blood culture is a risk factor for clinical outcomes in Staphylococcus aureus bacteremia children: a retrospective study. BMC Infect Dis. 2019;19(1):437.

    Article  Google Scholar 

  16. Martínez JA, Soto S, Fabrega A, Almela M, Mensa J, Soriano A, et al. Relationship of phylogenetic background, biofilm production, and time to detection of growth in blood culture vials with clinical variables and prognosis associated with Escherichia coli bacteremia. J Clin Microbiol. 2006;44(4):1468–74.

    Article  Google Scholar 

  17. Peralta G, Roiz MP, Sánchez MB, Garrido JC, Ceballos B, Rodríguez-Lera MJ, et al. Time-to-positivity in patients with Escherichia coli bacteraemia. Clin Microbiol Infect. 2007;13(11):1077–82.

    Article  CAS  Google Scholar 

  18. Álvarez R, Viñas-Castillo L, Lepe-Jiménez JA, García-Cabrera E, Cisneros-Herreros JM. Time to positivity of blood culture association with clinical presentation, prognosis and ESBL-production in Escherichia coli bacteremia. Eur J Clin Microbiol Infect Dis. 2012;31(9):2191–5.

    Article  Google Scholar 

  19. Chen Y, Huang X, Wu A, Lin X, Zhou P, Liu Y, et al. Prognostic roles of time to positivity of blood cultures in patients with Escherichia coli bacteremia. Epidemiol Infect. 2020;148:e101.

    Article  Google Scholar 

  20. Tang PC, Lee CC, Li CW, Li MC, Ko WC, Lee NY. Time-to-positivity of blood culture: an independent prognostic factor of monomicrobial Pseudomonas aeruginosa bacteremia. J Microbiol Immunol Infect. 2017;50(4):486–93.

    Article  Google Scholar 

  21. Xu H, Cheng J, Yu Q, Li Q, Yi Q, et al. Prognostic role of time to positivity of blood culture in children with Pseudomonas aeruginosa bacteremia. BMC Infect Dis. 2020;20(1):665.

    Article  Google Scholar 

  22. Lin HW, Hsu HS, Huang YT, Yang CJ, Hsu MS, Liao CH. Time to positivity in blood cultures of adults with nontyphoidal Salmonella bacteremia. J Microbiol Immunol Infect. 2016;49(3):417–23.

    Article  Google Scholar 

  23. Chen SY, Weng TH, Tseng WP, Fu CM, Lin HW, Liao CH, et al. Value of blood culture time to positivity in identifying complicated nontyphoidal Salmonella bacteremia. Diagn Microbiol Infect Dis. 2018;91(3):210–6.

    Article  Google Scholar 

  24. Nunes CZ, Marra AR, Edmond MB, da Silva VE, Pereira CA. Time to blood culture positivity as a predictor of clinical outcome in patients with Candida albicans bloodstream infection. BMC Infect Dis. 2013;13:486.

    Article  Google Scholar 

  25. Kim SH, Yoon YK, Kim MJ, Sohn JW. Clinical impact of time to positivity for Candida species on mortality in patients with candidaemia. J Antimicrob Chemother. 2013;68(12):2890–7.

    Article  CAS  Google Scholar 

  26. Niu X, Xiaohui S, Qi-feng L. Differences in clinical characteristics of bloodstream infections caused by Escherichia coli and Acinetobacter baumannii. Int J Clin Exp Med. 2019;12(4):4330–8.

    CAS  Google Scholar 

  27. Zhang Q, Li D, Bai C, Zhang W, Zheng S, Zhang P, et al. Clinical prognostic factors for time to positivity in cancer patients with bloodstream infections. Infection. 2016;44(5):583–8.

    Article  Google Scholar 

  28. Palmer HR, Palavecino EL, Johnson JW, Ohl CA, Williamson JC. Clinical and microbiological implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia. Eur J Clin Microbiol Infect Dis. 2013;32(7):955–9.

    Article  CAS  Google Scholar 

  29. Savithri MB, Iyer V, Jones M, Yarwood T, Looke D, Kruger PS, et al. Epidemiology and significance of coagulase-negative staphylococci isolated in blood cultures from critically ill adult patients. Crit Care Resusc. 2011;13(2):103–7.

    PubMed  Google Scholar 

  30. Li Q, Li Y, Yi Q, Suo F, Tang Y, Luo S, et al. Prognostic roles of time to positivity of blood culture in children with Streptococcus pneumoniae bacteremia. Eur J Clin Microbiol Infect Dis. 2019;38(3):457–65.

    Article  Google Scholar 

  31. Michelson K, Löffler B, Höring S. Time to positivity as a prognostic factor in bloodstream infections with Enterococcus spp. Diagn Microbiol Infect Dis. 2021;101(3):115396.

    Article  CAS  Google Scholar 

  32. Liao CH, Lai CC, Hsu MS, Huang YT, Chu FY, Hsu HS, et al. Correlation between time to positivity of blood cultures with clinical presentation and outcomes in patients with Klebsiella pneumoniae bacteraemia: prospective cohort study. Clin Microbiol Infect. 2009;15(12):1119–25.

    Article  Google Scholar 

  33. Morata L, Cobos-Trigueros N, Martínez JA, Soriano A, Almela M, Marco F, et al. Influence of multidrug resistance and appropriate empirical therapy on the 30 day mortality rate of Pseudomonas aeruginosa bacteremia. Antimicrob Agents Chemother. 2012;56(9):4833–7.

    Article  CAS  Google Scholar 

  34. McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures: time to positivity. Pediatrics. 2000;106(2 Pt 1):251–5.

    Article  CAS  Google Scholar 

  35. Choi SH, Chung JW. Time to positivity of follow-up blood cultures in patients with persistent Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis. 2012;31(11):2963–7.

    Article  CAS  Google Scholar 

  36. Connell TG, Rele M, Cowley D, Buttery JP, Curtis N. How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children’s hospital. Pediatrics. 2007;119(5):891–6.

    Article  Google Scholar 

  37. Lin HH, Liu YF, Tien N, Ho CM, Hsu LN, Lu JJ. Evaluation of the blood volume effect on the diagnosis of bacteremia in automated blood culture systems. J Microbiol Immunol Infect. 2013;46(1):48–52.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Not applicable.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Funding

This work was supported by Kaohsiung Medical University Hospital (KMUH-96-6G60, KMUH-98-8G13) and Kaohsiung Municipal Ta-Tung Hospital (kmtth-104-019, kmtth-107-045, kmtth-109-001, kmtth-109-030).

Author information

Authors and Affiliations

Authors

Contributions

YCH and TCC designed the study, performed the systematic review, ran the statistical analysis, and drafted the manuscript. SYL, PLL, and HLC assessed the eligibility of the articles and performed the quality assessment, involved the interpretation of the data, and helped critical revision of the manuscript. We ensure that all authors contributed to manuscript revisions and have read and approved the final version for publication.

Corresponding author

Correspondence to Tun-Chieh Chen.

Ethics declarations

Ethics approval and consent to participate

This study is a systematic review. The primary studies evaluated included a statement on ethics approval and consent.

Consent to for publication

Not applicable.

Competing interests

The authors declare that there are no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

Search terms and connectors (AND/OR) for literature search.

Additional file 2.

CASP quality assessment.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hsieh, YC., Chen, HL., Lin, SY. et al. Short time to positivity of blood culture predicts mortality and septic shock in bacteremic patients: a systematic review and meta-analysis. BMC Infect Dis 22, 142 (2022). https://doi.org/10.1186/s12879-022-07098-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-022-07098-8

Keywords

  • Time to positivity
  • Patient outcome
  • Mortality
  • Septic shock