Hémoculture | Clinique Omicron Québec
Sampling technique, culture systems, and limitations
- Sampling technique — optimal reliability conditions: time of sampling: ideally just before a febrile peak (shivering = transient bacteremia) → in practice impossible to anticipate → sample as soon as clinical suspicion arises + before any antibiotic therapy → if patient already on antibiotics : collect anyway (modification of antibiotic therapy possible if a germ is detected) + during shivering if possible → never delay treatment beyond 1h to wait for blood cultures in septic shock (Surviving Sepsis Campaign 2021 - Evans + SSC); number and volume - critical determinants of sensitivity: minimum 2 series of 2 vials (1 aerobic + 1 anaerobic per series) → collect from 2 different venous sites (different arms + time different by a few minutes) → volume per vial: 8-10 mL of blood → total volume per series: 20 mL → total volume recommended: 40-60 mL (2-3 series) → blood culture sensitivity is directly proportional to the volume of blood seeded: volume of 2-5 mL per vial → sensitivity 30-40 % → volume of 10 mL per vial → sensitivity 70-80 % → Mermel 1993 - Journal of Clinical Microbiology: each additional mL of blood → increase in sensitivity of 3 % → under-volume = main cause of false negatives → bacteremia is often intermittent and of low density (0.1-10 CFU/mL in most community-acquired bacteremias); rigorous asepsis - preventing contamination: 2-stage skin disinfection: isopropyl alcohol 70 % × 30 s → then iodinated antiseptic (povidone iodine 10 % or alcoholic chlorhexidine 0,5 %) × 30 s + allow to dry completely before puncturing (≥30 s) → never palpate the site after disinfection → also disinfect vial stoppers (isopropyl alcohol) → use sterile gloves → direct puncture technique (without transfer) = less risk of contamination → fill aerobic vial first (air bubble in aerobic vial not a problem → anaerobic vial must be filled without air) → acceptable contamination rate: <3 % des hémocultures prélevées (clsi standard) → taux>3 % → review sampling technique → most frequent sources of contamination : Staphylococcus epidermidis + Cutibacterium acnes (Propionibacterium acnes) + Bacillus spp. + Corynebacterium spp. + viridans streptococci (except in the context of endocarditis); access routes: peripheral vein preferable (less contamination than central routes) → if central venous catheter (CVC) suspect: sample simultaneously from CVC and peripheral vein → compare positivity times: if CVC positive ≥2h before peripheral vein → catheter infection likely (DTP - Differential Time to Positivity - Blot criterion) → Blot 2004 - Lancet Infectious Diseases: DTP >2h → sensitivity 89 % + specificity 87 % for catheter infection; automated culture systems - current technologies: continuous detection systems (BACTEC BD + BacT/ALERT bioMérieux + VersaTREK Thermo Scientific): flasks containing enriched liquid culture medium + CO₂ or fluorescent sensor → continuous reading every 10 min → positive signal if growth → median time to positivity: 12-24h for fast-growing bacteria (staphylococci + enterobacteria + pneumococci) → 24-72h for fastidious bacteria (Streptococcus bovis + Haemophilus + HACEK) → >5 days for Brucella + some fungi → pediatric vials (BACTEC Peds Plus + BacT/ALERT PF): suitable for low blood volumes (1-3 mL) → seed as a priority if volume is limited → special vials: vial for slow bacteria (mycobacteremia - BACTEC Myco/F + MB/BacT): incubation 42 days → vial for fungi (Candida + Cryptococcus + Histoplasma): standard aerobic vials - Candida is detected in 24-72h → vial with resins (antibiotic neutralization - BD BACTEC Plus Aerobic/F): useful if patient on antibiotics → improves sensitivity by 15-20 % (Reimer 1991 - Journal of Clinical Microbiology)
- Rapid Identification and Antibiogram — From Positivity to Therapeutic Orientation: as soon as a vial is reported positive: direct examination (Gram) as a matter of urgency → immediate orientation of empirical antibiotic therapy → results within 30 min → Gram-positive cocci in clusters → Staphylococcus → Gram-positive cocci in chains → Streptococcus / Enterococcus → Gram-negative bacilli → Enterobacteriaceae or Pseudomonas → Gram-positive yeasts → Candida → definitive identification by MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight) mass spectrometry : time: 15-60 min after visible colony on agar → accuracy: >99 % for species-level identification → replaced conventional biochemical identification (API strips - 24-48h) → Van Veen 2010 - Journal of Clinical Microbiology: MALDI-TOF → rapid identification → reduced antibiotic de-escalation time of 24-48h → antibiogram (MIC - Minimal Inhibitory Concentration): methods: broth dilution (reference) + diffusion discs (Kirby-Bauer + EUCAST) + gradient (E-test) → delay: 18-24h after identification → Bauer 1966 - American Journal of Clinical Pathology: standardization of the disc method → rapid resistance detection tests (directly on the positive vial without waiting for the colony): multiplex PCR on whole blood (SeptiFast Roche → 25 targets in 6h - replaced by more powerful panels) → Biofire FilmArray Blood Culture Identification panel (BCID + BCID2) on positive culture broth → identification of >20 microorganisms + resistance markers (mecA → MRSA + vanA/vanB → VRE + CTX-M → ESBL + KPC + NDM → carbapenemases) → results in 1h → Banerjee 2015 - JAMA Internal Medicine: BCID + active medical notification → 17h reduction in time to appropriate antibiotic therapy + reduced mortality → extended antibiogram if necessary: ESBL + carbapenemases (KPC + NDM + OXA-48 + VIM + IMP) + MRSA + VRE + fluconazole-resistant Candida
Indications, interpretation, and management
| Domain | Data, criteria and procedures | Key studies and recommendations |
|---|---|---|
| Clinical indications for blood cultures Sepsis — fever — chills — endocarditis — catheter-related infection — fungemia — immunocompromised — neutropenia |
Formal indications for blood cultures - always collect before antibiotic therapy: sepsis and septic shock (Surviving Sepsis Campaign 2021 + SSC 2016 - Rhodes): fever ≥38.3°C or hypothermia <36°C + suspected organ dysfunction → systematic blood cultures × 2 sets before antibiotic therapy → never delay antibio beyond 1h in septic shock for blood cultures → in septic shock: mortality increases by 7-10 % per hour of delay in antibiotic therapy (Kumar 2006 - Critical Care Medicine) → suspected infective endocarditis (IE): Duke criteria → IE protocol: 3 series of 2 vials collected in 30-60 min from 3 different sites → if emergency: 2 series + immediate antibio → 90 % of IE: 3 positive series → blood cultures are the major microbiological criterion of Duke criteria + central venous catheter (CVC) bacteremia: collect simultaneously from CVC and peripheral vein + calculate DTP (Blot 2004 - Lancet ID) → fever + severe chills → probable bacteremia → chills = pathognomonic sign of active bacteremia → febrile neutropenia (PNN 72h → deep focus + AE → workup escalation (ETT/ETO + PET-CT if available) + Candida bacteremia: daily blood cultures until negativation → systematic fundus (hematogenous chorioretinitis) + Streptococcus bovis (S. gallolyticus) bacteremia: colonoscopy mandatory (association with colorectal cancer in 25-50 % of cases - Boleij 2011 - Cancer Epidemiology) + Enterococcus bacteremia: ETT/ETO if risk factors for IE + persistent or recurrent bacteremia despite appropriate antibiotic therapy: deep undrained focus + IE + infected prosthesis | Fundamental data on indications and mortality: Kumar 2006 - Critical Care Medicine (n=2,731 patients in septic shock): each hour of delay in antibiotic therapy → increase in mortality of 7-10 % → basis for recommendation of antibiotic therapy within one hour → SSC 2021 (Evans - Intensive Care Medicine): bundle sepsis 1h → blood cultures + lactate + antibiotic therapy + filling → implementation → mortality reduction → Mermel 1993 - Journal of Clinical Microbiology: blood volume = main determinant of sensitivity → each additional mL → +3 % sensitivity → Blot 2004 - Lancet Infectious Diseases: DTP >2h on CVC → sens. 89 % + spec. 87 % for catheter infection → diagnosis without CVC removal → Banerjee 2015 - JAMA Internal Medicine: BCID + medical notification → -17h delay appropriate antibiotic therapy → reduced mortality + Boleij 2011 - Cancer Epidemiology: S. gallolyticus bacteremia → colonoscopy → colorectal cancer in 25-50 % → any S. gallolyticus bacteremia requires colonoscopy + Velasco 2003 - Emergency Medicine Journal: blood cultures in simple pyelonephritis → 15-20 % positive but do not alter management → not systematic if no sepsis |
| Interpretation of Positive Blood Cultures — True Bacteremia vs. Contamination Common contaminants — true pathogens — number of bottles — time to positivity — clinical context — interpretation rules |
Fundamental principles of interpretation: a positive blood culture does not automatically mean true bacteremia → 15-25 % of positive blood cultures are contaminations (skin flora introduced during sampling) → interpretation depends on 5 factors: the micro-organism identified + the number of positive vials + the time to positivity (TTP) + the number of series taken + the clinical context (heart valves + prostheses + immunodepression + central catheter); micro-organisms always significant (true pathogens): Staphylococcus aureus: a single positive series = significant bacteremia → immediate assessment (ETT/ETO + control blood cultures) → never contamination in a credible clinical context → AE in 25-30 % of S. aureus bacteremias → Streptococcus pyogenes (group A) + Streptococcus agalactiae (group B) → Streptococcus pneumoniae → enterobacteria (E. coli + Klebsiella + Proteus + Enterobacter + Serratia) → Pseudomonas aeruginosa → Neisseria meningitidis + Haemophilus influenzae → Candida spp. (always significant → complete fungemia workup + fundus + ETT + CVC removal) → Listeria monocytogenes → Bacteroides fragilis + other strict anaerobes (if correct sampling) → Salmonella typhi + paratyphi; frequent contaminants - significant only if particular context: Staphylococcus epidermidis (and other coagulase-negative staphylococci - SCN): most frequent contaminant (50-80 % of SCN positivities are contaminations) → significant if: 2/2 positive series + patient with valve prosthesis + CVC + dialysis catheter + neutropenic patient → short TTP (<12h) → identical phenotype on the 2 series → Cutibacterium acnes (Propionibacterium acnes): very often contaminant → rare context of AE on valve prosthesis after cardiac surgery + Bacillus cereus (excluding immunocompromised + CVC + IV drug addiction) → Corynebacterium spp. : almost constant contaminant except Corynebacterium jeikeium in the immunocompromised → viridans streptococci (S. mitis + S. sanguinis + S. mutans) : often contaminants → but significant if IE suspected (Duke's minor microbiological criterion) + immunocompromised patient + Micrococcus spp. → constant contaminant; practical rules of interpretation depending on number of positive vials and organism: SCN in 1/4 vials → very probable contamination → SCN in 2/4 or 4/4 vials → probable bacteremia if favorable context → S. aureus in 1/4 vials → true bacteremia → treat systematically → enterobacteria in 1/4 vials → true bacteremia (exceptional contamination) → treat → Candida in 1 vial → true fungemia → treat → time to positivity (TTP): short TTP (48h) → low load → indolent or contaminating bacteremia → significance depending on context endocarditis and implants: any positive SCN in 2+ series in a patient with a prosthetic valve or implantable cardiac electronic device (ICED) → AE on prosthesis until proven otherwise → ETT + ETO + PET-CT; polymicrobial bacteremias (several different germs in blood cultures): abdominal source (peritonitis) + bacteremia on CVC (polymicrobial colonization) + rarely endocarditis (exceptionally polymicrobial AE) → contaminated samples ??? → compare series → prime clinic | Interpretation rules - reference data: Weinstein 1997 - Clinical Infectious Diseases: meta-analysis of blood culture performance → sensitivity 40-65 % in community sepsis → blood volume = factor most correlated with sensitivity + Hall 2006 - Journal of Clinical Microbiology: median positivity time for the main germs: S. aureus: 15h + E. coli: 12h + Candida: 30h + SCN: 24h + Streptococcus spp. : 12h → short TTP = high bacterial load = severity → Bosshard 2006 - Journal of Clinical Microbiology: MALDI-TOF on colony → correct identification >99 % of cases + Kaygusuz 2006 - Diagnostic Microbiology and Infectious Disease: SCN positive in 1/4 vials → contamination in 90 % of cases → 2/4 vials → significant bacteremia in 70 % of cases → The rule «two or more positive series = more credible» is clinically validated + Kirby 2015 - Journal of Clinical Microbiology: BCID2 (FilmArray) → identification in 1h directly on positive broth → 97 % concordance with conventional methods + 20 resistance markers → Mermel 2009 - Clinical Infectious Diseases (IDSA Guidelines for catheter infections): DTP + quantitative blood cultures + comparative peripheral blood cultures → diagnosis of catheter infection without systematic removal |
| Empirical antibiotic therapy and adaptation based on results Empirical antibiotic therapy — de-escalation — MRSA — ESBL — carbapenemases — duration — secondary locus — endocarditis |
Empirical antibiotic therapy before results - choice according to context: principle: empirical antibiotic therapy must cover the most likely pathogens according to the suspected outbreak + local resistance + terrain (immunodepression + previous exposure to antibiotics + known MRSA or ESBL colonization); community-acquired sepsis without identified outbreak: ceftriaxone 2 g/d IV (covers enterobacteria + pneumococcus + Streptococcus spp.) → if resistant BGN suspected (recent hospitalization + ECBU with previous ESBL + travel): piperacillin-tazobactam 4.5 g × 4/d or meropenem 1 g × 3/d → if S. aureus infection (catheter + skin + bone infection) → if MRSA risk (dialysis + EHPAD + prolonged hospitalization + contact with carrier): add vancomycin → if MRSA unlikely: cloxacillin + or cefazolin (better for bacteremia with meti-sensitive S. aureus - Rybak 2020 - ASHP/IDSA guidelines) → if febrile neutropenia: cefepime 2 g × 3/d + or meropenem if high risk of resistant germs → if AE suspected before results (native valve): ampicillin + cloxacillin + gentamicin (streptococcus + enterococcus + S. aureus) → or ampicillin + ceftriaxone (if MRSA unlikely - Fernández-Hidalgo 2013 - Annals of Internal Medicine: ampicillin + ceftriaxone = ampicillin + gentamicin equivalent with less nephrotoxicity in enterococcal IE); antibiotic de-escalation according to susceptibility test results : key principle of reasoned antibiotic therapy → as soon as identified + antibiogram → adjust to the narrowest possible spectrum → reduce selection pressure + preserve the microbiome + reduce adverse effects → examples of de-escalation: S. aureus meti-susceptible → switch from vancomycin to cloxacillin or cefazolin (cefazolin: non-inferior to nafcillin in SAMS bacteremia - Bai 2015 - JAMA Internal Medicine) → E. coli susceptible to ceftriaxone → switch from meropenem to ceftriaxone → Streptococcus pneumoniae susceptible to penicillin G → switch to penicillin G IV → Klebsiella ESBL → maintain meropenem (effective) or use cefepime + avibactam if available according to phenotypic tests → Bacteroides fragilis → metronidazole (anaerobic narrow spectrum); germ-specific bacteremias - recommended durations: S. aureus uncomplicated bacteremia (no IE + no septic metastasis + focus removed + negative blood cultures at 72h): 14 days IV minimum (Fowler 2006 - JAMA: 14 days for simple bacteremia → 42 days for IE) → S. aureus complicated bacteremia (IE + spondylodiscitis + septic arthritis): 4-6 weeks → Enterococcus bacteremia without IE: 14 days + enterococcal IE: 4-6 weeks → ampicillin + ceftriaxone (if E. faecalis) or ampicillin + gentamicin (if susceptible) → Candida bacteremia: echinocandin (caspofungin + micafungin + anidulafungin) as 1st line → no fluconazole if instability or recent exposure → treatment up to 14 days after last negative blood culture + normal fundus (IDSA Pappas 2016 - Clinical Infectious Diseases) → BGN uncomplicated bacteremia: 7-14 days depending on focus + susceptibility + source (e.g. urinary: 7-10 days); source control - parallel to antibiotic therapy: drein any accessible abscess → remove catheter if catheter infection → surgery if necessary (IE with destroyed valve + perivalvular abscess) → pleural drain if empyema → debride if necrotizing fasciitis → without source control → antibiotic therapy alone is insufficient → persistent bacteremia | Fundamental data on antibiotic therapy and de-escalation: Kumar 2006 - Critical Care Medicine: antibiotic delay in septic shock → +7-10 % mortality per hour of delay → Bai 2015 - JAMA Internal Medicine: cefazolin vs nafcillin for SAMS bacteremia → non-inferiority + less toxicity + simpler administration → change of practice in many centers + Rybak 2020 - ASHP/IDSA vancomycin guidelines: AUC/CMI >400-600 as pharmacodynamic target → insufficient residual rate alone + Fowler 2006 - JAMA (SABR - Staphylococcus aureus Bacteremia Research): 14 days for uncomplicated S. aureus bacteremia + definition of criteria for «uncomplicated bacteremia» → IDSA Pappas 2016 - Clinical Infectious Diseases (Candida Guidelines): echinocandin 1st line + treatment 14 days after last negative blood culture + fundus + ETT + Fernández-Hidalgo 2013 - Annals of Internal Medicine (ENTIV trial): ampicillin + ceftriaxone = ampicillin + gentamicin equivalent in E. faecalis + better nephrotoxicity profile → change in practice + Banerjee 2015 - JAMA Internal Medicine: FilmArray BCID + active notification → -17h delay appropriate antibiotic therapy → -reduction in mortality + Evans 2021 - Intensive Care Medicine (SSC bundle hour-1): blood cultures + lactate + antibiotic therapy + filling within the 1st hour → reduction in 28-day mortality of 24.4 % vs 33.5 % → NNT = 11 to prevent 1 death |
| Sensitivity, causes of false negatives, and special blood cultures Overall sensitivity — false negatives — slow-growing bacteria — HACEK — Brucella — Coxiella — intracellular pathogens — multiplex PCR |
Sensitivity of blood cultures - important limitations: overall sensitivity: 40-65 % in community-acquired sepsis → 50-70 % in intensive care → blood cultures cannot rule out bacteremia if negative → main causes of false negatives: prior antibiotic therapy: sensitivity reduced by 20-30 % → use vials with neutralizing resins if antibiotic therapy in progress + insufficient volume: under-volume = 1st preventable cause → rigorous sampling technique + slow-growing or demanding germs: HACEK (Haemophilus aphrophilus + Aggregatibacter + Cardiobacterium + Eikenella + Kingella): require 7-21 days → prolonged blood cultures if AE and negative blood cultures at D5 + Brucella spp. : time to positivity 7-21 days + BSL-3 risk (alert laboratory) + Bartonella henselae (cat scratch disease + culture-negative AE): serology + PCR + culture in specific medium (Hemin + reference lab) → Coxiella burnetii (Q fever): strict intracellular germ → DOES NOT grow in conventional blood culture → serology + PCR on blood → culture-negative IE → Tropheryma whipplei (Whipple's disease) → PCR → Mycobacterium tuberculosis: mycobacterial blood cultures (BACTEC Myco/F) → PCR on blood → Aspergillus and molds: almost never grow in blood cultures (fungemia by angioinvasive route without circulating bacteremia) → serum galactomannan + beta-D-glucan + chest CT + fever after blood culture collection: bacteremia may be intermittent → peak of bacteremia just before febrile peak → collect during chills if possible; alternatives to blood cultures when they are negative and suspicion remains strong: serologies (Coxiella + Bartonella + Brucella + Chlamydophila) + multiplex PCR on whole blood (SeptiMax + SeptID → 20-40 target panels): detects non-cultivable germs or those on antibiotic therapy → 3-6h delay → variable sensitivity depending on panel + NEBEBd-glucan (1,3-β-D-glucan): marker of invasive fungemia (Candida + Pneumocystis + Aspergillus) → sensitivity 76 % + specificity 85 % (Karageorgopoulos 2011 - Clinical Infectious Diseases) → useful for culture-negative fungemia → serum galactomannan + BAL (Aspergillus) → procalcitonin (PCT): PCT ≥0.5 ng/mL → sensitivity 80 % + specificity 72 % for bacteremia (Lam 2019 - European Journal of Emergency Medicine - meta-analysis) → aids sampling decision + but does not replace blood cultures → ¹⁸F-FDG PET-CT: localization of a deep focus of infection if blood cultures positive without obvious focus (spondylodiscitis + IE + deep abscess) → Vos 2012 - Clinical Infectious Diseases: PET-CT + S. aureus bacteremia → unsuspected focus detected in 30 % of cases → guides duration of treatment; direct molecular methods on whole blood without blood culture: T2 Biosystems (T2Bacteria + T2Candida): direct detection by nanomagnetic MRI without culture → 5 Candida species detected in 3-5h → sensitivity 91 % + specificity 98 % (Mylonakis 2015 - Clinical Infectious Diseases) → useful if antibiotic therapy in progress + SepsiTest (Molzym) + IRIDICA (Abbott PCR + ESI-MS) → 6h delay → variable availability in Quebec → use reserved for tertiary centers → Metagenomics next-generation sequencing (mNGS) on blood: theoretical detection of all infectious agents without culture → turnaround time: 6-24h → high cost → false positives due to contamination of background DNA → currently experimental/research use. | Fundamental data on sensitivity and alternatives: Weinstein 1997 - Clinical Infectious Diseases: sensitivity 40-65 % in community sepsis → blood volume = main determinant → Reimer 1991 - Journal of Clinical Microbiology: vials with resins → sensitivity improvement of 15-20 % if antibiotic therapy in progress → Karageorgopoulos 2011 - Clinical Infectious Diseases (meta-analysis): beta-D-glucan → sensitivity 76 % + specificity 85 % for invasive fungemias → useful in addition to blood cultures + Lam 2019 - European Journal of Emergency Medicine (meta-analysis): PCT ≥0.5 ng/mL → sensitivity 80 % + specificity 72 % for bacteremia → Vos 2012 - Clinical Infectious Diseases: PET-CT + S. aureus bacteremia → deep focus detected in 30 % of unsuspected cases + Mylonakis 2015 - Clinical Infectious Diseases (T2Candida trial): T2Candida → sensitivity 91 % + specificity 98 % for the 5 major Candida species → time 3-5h vs 24-72h cultures → benefit if patient on antifungals + Banerjee 2015 - JAMA Internal Medicine: FilmArray BCID + antimicrobial stewardship notification → -17h delay appropriate antibiotic therapy → reduced mortality + change in practice in many centers; Van Veen 2010 - Journal of Clinical Microbiology: MALDI-TOF → reduced identification time by 24-48h + reduced hospitalization costs → transformation of clinical microbiology |
High fever or hypothermia + intense chills + hypotension or tachycardia + altered consciousness or vital functions → severe sepsis or septic shock → call 911 → blood cultures × 2 sets immediately (within 15 min) → IV broad-spectrum antibiotics within the first hour, without waiting for results → vascular filling → never delay antibiotic therapy beyond 1 hour for blood cultures in septic shock.
Blood culture positive for Staphylococcus aureus in an outpatient or hospitalized patient → infectious disease emergency → hospitalization if outpatient → TTE/TEE (echocardiography) to rule out IE → control blood cultures at 48–72h → IV antibiotic therapy (cloxacillin if MSSA + vancomycin or daptomycin if MRSA) → CT scan or PET-CT if secondary focus suspected → minimum duration 14 days IV even in the absence of IE.
Positive blood culture for Candida spp. in a patient on parenteral nutrition or with a CVC → fungemia → emergency → CVC removal ASAP + IV echinocandin → emergency funduscopy (chorioretinitis) → TTE + daily blood cultures until negative → treatment for 14 days after the last negative blood culture and normalization of funduscopy.
Blood culture positive for carbapenemase-producing Enterobacteriaceae (KPC + NDM + OXA-48) or for multidrug-resistant Pseudomonas aeruginosa detected by the FilmArray panel → Bacteremia with extremely resistant organism → Infectious emergency → Immediate infectious disease consultation → Meropenem-vaborbactam + ceftazidime-avibactam + imipenem-cilastatin-relebactam according to resistance profile → Contact precautions → Mandatory reporting (IORAs - osteoarticular infections with particular risks - depending on context and province).
Consult at Clinique Omicron
Clinique Omicron physicians order blood cultures in appropriate clinical situations (sepsis, fever with rigors, suspected bacteremia), refer patients requiring urgent management to emergency or infectious disease services, and manage uncomplicated bacteremia results as outpatients when clinically appropriate. Consultations are available at several service points in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not substitute for the advice of a physician or infectious disease specialist. Any positive blood culture or clinical presentation suggestive of sepsis constitutes a medical emergency requiring immediate hospital evaluation.
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