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Table 1 Table of included studies

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

Year, author

Country

Bacteria

Culturing method

Study design

Cut-off value (hrs)

Population

Patient Characteristic

2006, Alexandre R. Marra et el. [13]

USA

Staphylococcus aureus

Blood cultures were processed by the institution's clinical laboratory using the BacT/ALERT blood culture instrument. All the bottles were loaded into the instrument at any time of the day (24 h a day, 7 days a week) without delay

Historical cohort study

12

91

A total of 91 patients with monobacterial S. aureus BSIs with no antibiotics treatment were identified at VCUMC were retrospectively by use of the electronic medical microbiology record

2006, Jose A. Martı´nez et al. [16]

Spain

Escherichia coli

Blood cultures were processed by the BACTEC 9240 system. The volume of blood cultured was not verified. The exact time from the start of incubation to a positive reading was recorded, considering time to positivity to be that for the bottle in the processed set or sets that became positive first

Prospective study

7

177

During one year (2003), all 177 patients with 185 episodes of E.coli bloodstream infections were prospectively followed up from diagnosis to discharge

2007, G. Peralta et al. [17]

Spain

Escherichia coli

They took 20 mL of venous blood and inoculate it in equal parts into one aerobic blood culture bottle and one anaerobic blood culture bottle. Blood from a peripheral vein was sampled by nurses, three times at intervals of 30 min. On a 24-h basis, the blood culture bottles were sent to the microbiology laboratory, immediately loaded into the blood culture instrument (BacT/ALERT microbial detection system; bioMe´rieux), and cultured for 5 days. The BacT/ALERT system tests for CO2 production and records the time interval between the addition of each blood culture bottle to the system and the detection of microbial growth (defined as TTP). No antibiotic removal device was used for the blood cultures of patients treated previously with antibiotics. When multiple cultures were positive, the shortest TTP was selected for the analysis. Neither the volume of blood cultured nor the time interval between obtaining the blood for culture and incubation of the bottles was recorded

Retrospective study

10.25

459

459 cases of monomicrobial E. coli bloodstream infections with no undergoing antibiotics treatment from a single institution between 1997 and 2005 were reviewed

11.1

2009, C.-H. Liao et al. [32]

Taiwan

K. pneumoniae

At least two sets of blood samples, 10 mL each, were taken from separate locations, and inoculated into aerobic and anaerobic culture flasks, which were incubated using the BACTEC 9240 automated detection blood culture system. The BACTEC 9240 system continuously monitors CO2 production every 10 min, and indicates positivity by means of a fluorescent signal. All bottles with positive results were examined by Gram staining, and subcultured. TTP, defined as the time from the start of incubation to the start of the alert signal, was recorded for each bottle of positive blood cultures. For a patient with multiple sets of positive blood cultures at approximately the same time, the shortest TTP was used in the study

Prospective cohort study

7

231

Patients > 18y/o admitted with monomicrobial K. pneumoniae BSI

2010, J. Kim et al. [8]

Canada

Staphylococcus aureus

All blood cultures were obtained by use of a standardized sterile technique. Upon receipt, the blood culture bottles were placed in BacT/ALERT 3D blood culture system at any time of the day. Each blood culture set consisted of an aerobic and anaerobic bottle with a volume of 10 mL per bottle. Time to positivity was defined as the first bottle in a set to be flagged positive. If multiple sets were inoculated in the same 24-h period, the earliest time at which a bottle was flagged positive was used as the TTP

Retrospective study

48

684

All persons identified in the Calgary Health Region with first episode S. aureus bacteremia between July 1, 2006 and December 31, 2008 were included in the study

2011, Mahesh B Savithri et el. [29]

Australia

Coagulase-negative staphylococci

Blood samples were collected using aseptic technique. 20 millilitres of blood were collected and inoculated in two equal aliquots of 10 mL each into a BacT/ALERT aerobic bottle and an anaerobic bottle and incubated at 37 °C. Organisms isolated from blood culture bottles were identified by the automated BacT/ALERT system

Retrospective study

24

54

A retrospective chart audit in the intensive care unit of a tertiary hospital comprising all patients who had positive blood cultures for CoNS in 2009

2012, R. Álvarez et al. [18]

Spain

Escherichia coli

Following the hospital protocol, the blood culture bottles were sent to the microbiology laboratory and immediately loaded into the blood culture instrument (BACTEC FX system; Becton Dickinson), during the day (8 am to 9 pm) or stored during the night until 8 am. They were incubated for a maximum of five days and the TTP was defined as the exact time from the start of incubation to a positive reading

Retrospective study

8

226

All patients > 14y/o with E. coli bacteraemia with at least one positive blood culture were identified retrospectively from the clinical microbiology laboratory database. Only the first positive blood culture was considered, or those which were separated by at least 30 days from the previous one

2013, Cintia Zoya Nunes [24]

Brazil

Candida albican

Blood cultures were processed by the institution's clinical laboratory using the BACTEC 9240 blood culture instrument. Each blood culture set consisted of an FA aerobic bottle and an SN anaerobic bottle. All the samples of blood cultures were collected and submitted in a timely manner to the microbiology laboratory. All cultures were obtained via peripheral venipuncture and at least two bottles were obtained for each patient. The bottles were loaded into the instrument (24 h a day, 7 days a week) without delay at any time of the day. The time to positivity of the first bottle in a set to be flagged as positive was used to determine the time to positivity and was obtained by using the system's software

Historical cohort study

36

89

Patients with BSIs from 1 January 2002 through 31 July 2009 were identified retrospectively. Each patient was included only once, at the time of the first BSI. Patients less than 18 years old, those with polymicrobial infections, and those receiving antifungal therapy at the time of the BSI were excluded from the analysis

2013, H. R. Palmer et el. [28]

USA

GNB bacteremia

Blood cultures were processed using the VersaTREK automated blood culture system. This system requires 10 mL of blood to be split between aerobic and anaerobic 40-mL VersaTREK bottles. Inoculated bottles were transported to the microbiology laboratory and placed in the VersaTREK instrument. Bottles were incubated either until they were flagged as positive or for 5 days

Prospective observational study

11

63

Patients > 18 y/o with 1 blood cultures positive for GNB

2013, Matthias Willmann et al. [9]

Germany

Pseudomonas aeruginosa bloodstream infection

From all patients an approximate volume of 10 ml blood was inoculated into each aerobic and anaerobic BACTEC PLUS bottle and was promptly transported to the microbiological laboratory. Bottles with antibiotics were not used. We generally recommend the concomitant drawing of blood from at least three different peripheral punctures after disinfection. However, in practice we usually received two blood culture sets. Blood cultures were processed employing the Bactec 9240 blood culture instrument. The system monitors bacterial growth by measuring CO2 production through fluorescent sensor technology every 10 min. An automated alert signal indicates a positive blood culture. Time to positivity was documented by the system software and recorded for each bottle from an index culture. The final analysis was performed on the TTP from aerobic bottles since P. aeruginosa grew only in a limited number of anaerobic bottles. Blood culture bottles were usually processed between 8 am and 6 pm during the week and between 8 am and 2 pm during the weekends. Our laboratory provides an on-call service that processes samples during late hours. Thus, transport and storage of samples amounted to less than 12 h in most cases

Retrospective cohort study

15

74

From 2006 until 2012, 74 patients with monomicrobial Pseudomonas aeruginosa blood stream infection were studied in 3 hospitals in the region surrounding Tubingen, Germany

17

18

2013, Si-Hyun Kim et al. [25]

Korea

Candida albican

Blood cultures were performed in patients with signs or symptoms of infection as routine practice. In patients with a positive culture for yeast, blood cultures were usually repeated every 3 days until negative or when indicated clinically. At least two sets of blood samples were obtained for blood culture from separate venepunctures. If a central venous catheter was present, a blood culture set could be replaced by a blood sample drawn through the catheter. Each set of blood samples was inoculated into one aerobic and one anaerobic bottle and immediately loaded into a BacT/ALERTw 3D Microbial Detection System

Retrospective study

24

152

All consecutive patients 18 years of age with candidaemia between January 2006 and July 2012 were included

2014, Hui-Wen Lin et al. [22]

Taiwan

Nontyphoidal samonella

Two sets of blood samples (10 mL each) were generally taken from separate locations, inoculated into aerobic and anaerobic culture flasks, and then incubated using the BACTEC 9240 automated detection blood culture system. All bottles were loaded when they were received in the central laboratory. The BACTEC 9240 system continuously monitors carbon dioxide (CO2) production every 10 min, and indicates positivity by a fluorescent signal. The TTP, defined as the time from the start of incubation to the start of an alert signal, was recorded for each blood culture. When multiple cultures were positive, the shortest TTP was used for analysis

Retrospective study

10

66

From January 2010 to December 2012, 66 patients > 20y/o with NTS bacteremia were identified by central laboratory personnel. Included only at the time of the first bacteremia

2014, M-S. Hsu et el. [14]

Taiwan

Staphylococcus aureus

Blood samples (approximately 10 mL) were taken and inoculated into aerobic and anaerobic culture flasks, and incubated in the automated detection blood culture system. All samples were loaded into the machine upon arrival at the central laboratory. The BACTEC 9240 system monitors CO2 production continuously at 10-min intervals, and positivity is indicated by means of a fluorescent signal. The TTP is automatically recorded by the machine. TTP was recorded for each positive sample. For a patient with multiple sets of positive blood cultures, the shortest TTP was selected. Blood cultures collected from central venous catheters were not excluded

Retrospective study

12

87

From January 2007 to December 2011, we enrolled 87 consecutive patients who had S. aureus bacteraemia persisting for > 48 h at our institution, excluded patients who were aged < 18 years and had polymicrobial bacteraemia were excluded

2016, Qing Zhang et el. [27]

China

Enterobacteriaceae

Blood cultures containing 8–10 mL blood from patients were incubated using an automated blood culture system at 35 °C for at least 5 days. All isolates were identified using the Vitek 2 Compact automated microbiology system

Retrospective study

8

173

From September 2013 through March 2015, all hospitalized tumor patients (> 18 y/o) with at least one episode of BSI were included in the study

Nonfermenters

18

25

Staphylococci

18

49

2017, Catia Cillo' niz et al. [7]

Spain & Argentina

Pneumococcal

Blood cultures were processed by the BACTEC 9240 system, and vials were loaded into the machine around the clock. Volumes between 8 to 10 ml of blood samples were inoculated into aerobic and anaerobic vials. The incubation period was 5 days before being discarded as negative

Prospective observational study

9.2

278

Including 278 immuno-functioning adults consecutively admitted between 2003 to 2015 with a diagnosis of community-acquired pneumococcal pneumonia to the Hospital Clinic of Barcelona, Spain

2017, Poh-Chang Tang et al. [20]

Taiwan

Pseudomonas aeruginosa

Blood cultures were placed in an automated blood culture system. The automated microbiology growth and detection system detected microbial growth from blood specimens. TTP was routinely measured and automatically recorded by the machine

Retrospective cohort study

13

139

139 patients aged 18 years or older with the growth of P. aeruginosa in one or more blood cultures were included. When the bacteria grew in multiple blood cultures, the shortest TTP of blood cultures was recorded. Patients younger than 18 years, with polymicrobial bacteremia were excluded

2018, S. Simeon et al. [5]

France

Staphylococcus aureus

In each centre, approximately 10 mL of blood was inoculated into aerobic and anaerobic bottles by nurses using a standardized sterile technique. The BACTEC system (Becton Dickinson) was used in three sites, and BacT/Alert (bioMerieux) in one. TTP was defined as the time from the start of incubation to alert signal

Prospective cohort study

13.7

587

The VIRSTA prospective cohort study included 587 consecutive adult patients with SAB between April 2009 and October 2011 in eight tertiary-care university hospitals in France

2018, Shang-Yu Chen et al. [23]

Taiwan

Nontyphoidal salmonella

The standard practice of obtaining blood cultures in our hospital is to draw two sets of blood sample from separate limbs and inoculate into aerobic and anaerobic blood culture flasks (10 mL each, BD BACTECTM blood culture media). Blood samples were immediately sent to the microbiology laboratory and incubated in a BACTEC FX automated detection blood culture system. TTP refers to the time elapsed from the onset of incubation into the blood culture processor to the detection of bacterial growth, which was routinely reported to clinicians in our hospital. In patients with two or more sets of positive blood culture results, only the shortest TTP was used for analysis in this study

Retrospective study

10

206

206 patients > 20y/o with NTS bacteremia

2019, Niu, Xinrong et al. [26]

China

Escherichia coli and Acinetobacter baumannii

Isolation, identification, and sensitivity monitoring of microbiology were performed using the Vitek 2 automatic system (Meriere, France). Double-disc confirmation testing was used to detect ESBL + . E. coli ATCC 25,922 and A. baumannii ATCC 19,606 were used as controls

Retrospective study

7 days

89

A total of 118 patients, including 87 males and 31 females, with an average age of 52 ± 10.66, ranging from 25 to 78 years old, were collected

2019, Qinyuan Li [30]

China

Streptococcus pneumoniae

Approximately 3 ml of blood was inoculated into BACTEC plus aerobic bottles, which were then transported to the laboratory and incubated in an automated continuous monitoring system immediately. The Becton–Dickinson diagnostic systems were used for blood culture; it monitors CO2 production every 5 min by means of a fluorescent signal. Bottles with positive results were examined by Gram staining, and their contents were subcultured

Retrospective study

12

136

136 Children (< 18 y/o) with1 positive S. pneumoniae positive blood culture hospitalized in Children's Hospital of Chongqing Medical University from May 2011 to December 2017 were enrolled retrospectively

2019, Yuanyuan Li et el. [15]

China

Staphylococcus aureus bacteremia children

Approximately 3 mL of blood was inoculated into BACTEC plus aerobic bottles, which were then transported to the laboratory and immediately incubated in an automated continuous monitoring system. The BD diagnostic system was used for blood culture, which monitors CO2 production every 5 min by means of a fluorescent signal. Bottles with positive results were examined by Gram staining, and their contents were subcultured

Retrospective study

17

84

Children (< 18y/o) with 1S. aureus positive blood culture hospitalized in Children's Hospital of Chongqing Medical University between 29 January 2014 and 29 August 2017 were enrolled retrospectively

2020, Huiting Xu et al. [21]

China

Pseudomonas aeruginosa

An approximately 3–5 ml of venous blood (> 0.5 mL for neonate) was inoculated into aerobic each BACTEC PLUS bottle and transported to the microbiological laboratory at any time of the day (24 h a day, 7 days a week). Blood cultures were processed employing the Becton–Dickinson diagnostic systems, which automated measured bacterial growth by continuously monitoring CO2 production in every 5 min, through a fluorescent sensor technology. Those positive cultures were subsequently subcultured after Gram staining

Retrospective study

18

52

52 children (< 18y/o) with P. aeruginosa bacteremia were enrolled

2020, Yufang Chen et al. [19]

China

Escherichia coli

At least two sets of blood samples, 20 ml each, were taken from separate venous sites and inoculated into aerobic and anaerobic culture bottles. These were loaded on a BACTEC 9120 automated detection blood culture system. All bottles giving a positive signal were examined by Gram staining, subcultured to blood agar medium and incubated for 18–48 h. The TTP for each bottle was defined as the time period from the start of incubation to the alert signal as documented by the monitoring system

Retrospective study

11

167

Adult inpatients (18 years old) were considered eligible if they had a bloodstream infection with one or more blood culture positive for E.coli

2021, K. Michelson et al. [31]

Germany

E. faecalis

Blood cultures were drawn by medical professionals and sent to the Department of Microbiology, where they were incubated by Bactec FX automated incubation system. Bacterial growth was monitored via a fluorescent based detector measuring bacterial CO2 production. A positive blood culture was indicated by an automated alert signal. The shortest TTP of the first blood culture to be positive with Enterococcus spp. during one hospital stay was recorded. Every patient was only included once. Monomicrobial infections were defined as infection. that showed an exceeding majority of number of blood cultures with Enterococcus spp. For example, when three of four blood cultures were positive with Enterococcus spp. they were considered as monomicrobial. When two of four blood cultures were positive with Enterococcus spp. they were classified as polymicrobial and excluded from this analysis

Retrospective cohort study

4.35

54

477 patients were found to be positive for polymicrobial E-BSI. 244 patients with monomicrobial BSI and inappropriate antimicrobial therapy on the day of positive blood culture were analyzed

Vancomycin sensitive E. faecium

135

Vancomycin resistant E. faecium

55

  1. BSI Bloodstream infection, 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, NTS Nontyphoidal Salmonella, TTP Time to positivity, VCUMC Virginia Commonwealth University Medical Center