Bacteremia, Fungemia, and Blood Cultures

1
Bacteremia, Fungemia, and Blood Cultures

• Dr. John R. Warren
• Department of Pathology
• Northwestern University
• Feinberg School of Medicine
• June 2007

2
Essential Elements of Blood Cultures

• Pathophysiology of bacteremia and fungemia
• Microbiology of bacteremia and fungemia
• Determinants of mortality in bacteremia and
  fungemia
• Clinical signs and symptoms of septicemia
  (predictors)

3
Essential Elements of Blood Cultures

• Technical variables in the collection of blood
  cultures
• Incubation conditions
• Blood culture systems
• Quality management monitors

4
Pathophysiology of Bacteremia and Fungemia

• Bacteria and fungi normally cleared from blood by
  the mononuclear phagocyte system (MPS)
  (reticuloendothelial system)
• If entry of bacteria or fungi into the
  circulation exceeds MPS clearance capacity,
  bacteremia or fungemia results

5
Pathophysiology of Bacteremia and Fungemia

• Encapsulated bacteria and yeast poorly cleared
  from the circulation by fixed macrophages of the
  MPS (parasite factor) especially in the absence
  of opsonizing antibody (host factor)
• Diminished numbers of neutrophils impedes ability
  of the host to contain encapsulated bacteria and
  yeast at sites of tissue infection

6
Pathophysiology of Bacteremia and Fungemia

• Bacteremia or fungemia represents a failure of
  host defenses to localize an infection at its
  primary tissue site
• Bacteremia or fungemia also reflects a failure of
  a physician to remove, drain, or otherwise
  sterilize sites of infection
• Clinical patterns of bacteremia or fungemia
  transient, intermittent, and continuous

7
Pathophysiology of Bacteremia and Fungemia

• Transient bacteremia or fungemia lasts minutes to
  a few hours, is the most common type, and occurs
  after manipulation of infected tissue (abscesses,
  furuncles, cellulitis), instrumentation of
  colonized mucosal surfaces (dental procedures,
  cystoscopy, sigmoidoscopy), and surgery in
  contaminated areas (prostate resection,
  debridement of infected burns, vaginal
  hyterectomy), reflecting release of organisms
  into the circulation secondary to tissue trauma
  resulting from medical procedures

8
Pathophysiology of Bacteremia and Fungemia

• Transient bacteremia or fungemia also occurs
  early in acute bacterial infection including
  pneumonia, meningitis, septic arthritis, and
  hematogenous osteomyelitis, reflecting release of
  organisms through lymphatics draining infected
  tissue into the circulation
• Intermittent bacteremia or fungemia occurs,
  clears, then recurs with the same organism, and
  develops with undrained closed-space abscesses
  (intra-abdominal, pelvic, perinephric, hepatic,
  prostatic), and also focal infections that fail
  to resolve (pneumonia, osteomyelitis),
  reflecting irregular cycles of release into and
  clearance from the circulation of organisms
  infecting tissue

9
Pathophysiology of Bacteremia and Fungemia

• Continuous bacteremia or fungemia is a cardinal
  feature of endocarditis and other types of
  endovascular infections (suppurative
  thrombophlebitis, infected aneurysms), reflecting
  continuous shedding of organims from endovascular
  foci into the circulation
• Continuous bacteremia also occurs early (initial
  few weeks) in typhoid fever and brucellosis

10
Microbiology of Bacteremia and Fungemia

• Etiological Significance of Gram-Negative
  Bacteria
• Escherichia coli 142/143 (99.3)
• Klebsiella pneumoniae 65/65 (100)
• Enterobacter cloacae 25/25 (100)
• Serratia marcescens 22/22 (100)
• Proteus mirabilis 16/16 (100)
• Other Enterobacteriaceae 41/45 (91)
• Pseudomonas aeruginosa 53/55 (96)
• Acinetobacter baumannii 13/16 (81)
• Stenotrophomonas maltophilia 5/7 (71)
• Weinstein et al, 1997

11
Microbiology of Bacteremia and Fungemia

• Etiological Significance of Gram-Positive
  Bacteria
• Staphylococcus aureus 178/204 (87)
• Coagulase T Staphylococcus 87/703 (12)
• Streptococcus pneumoniae 34/34 (100)
• Group A Streptococcus 3/3 (100)
• Group B Streptococcus 10/15 (67)
• Enterococcus 65/93 (70)
• Viridans streptococci 27/71 (38)
• Bacillus 1/12 (8)
• Corynebacterium 1/53 (2)
• Lactobacillus 6/11 (55)
• Weinstein et al., 1997

12
Microbiology of Bacteremia and Fungemia

• Etiological Significance of Anaerobic Bacteria
• Bacteroides fragilis group 16/18 (89)
• Other gram-negatives 2/5 (40)
• Clostridium perfringens 3/13 (23)
• Clostridium species 12/15 (80)
• Propionibacterium 0/48 (0)
• Other gram-positives 4/7 (57)
• Weinstein et al., 1997

13
Microbiology of Bacteremia and Fungemia

• Etiological Significance of Yeast
• Candida albicans 27/30 (90)
• Candida glabrata 14/15 (93)
• Other Candida species 15/15 (100)
• Cryptococcus neoformans 8/8 (100)
• Weinstein et al., 1997

14
Microbiology of Bacteremia and Fungemia

• Blood Culture Contaminants1
• Propionibacterium (0)
• Corynebacterium (2)
• Bacillus (8)
• Coagulase-negative Staphylococcus (12)
• Viridans streptococci2 (38)
• 1In order of decreasing probability of being a
  contaminant of blood isolates considered
  etiological in parentheses (Weinstein et al.,
  1997)
• 2Excluding Streptococcus pneumoniae

15
Microbiology of Bacteremia and Fungemia

• Association of Organisms with Neutropenia1
• lt1,000 gt1,000
• S. aureus 9 (6) 169 (21)
• Yeasts 17 (12) 48 (6)
• Polymicrobial 24 (30) 55 (13)
• 1No. () of blood culture isolates from patients
  with indicated neutrophil count. Only
  differences statistically significant (plt.05) by
  ?2 are included (Weinstein et al., 1997).

16
Microbiology of Bacteremia and Fungemia

• Association of Organisms with Shock1
• Hypotensive Normotensive
• Polymicrobial2 16 (14) 63 (9)
• 1No. () of blood culture isolates from
  hypotensive and normotensive patients (Weinstein
  et al., 1977).
• 2plt.05 (?2). Significant differences not
  observed with individual organisms, nor for
  unimicrobial bacteremia and fungemia.

17
Microbiology of Bacteremia and Fungemia

• Sources of Bacteremia and Fungemia
• No. of episodes of total episodes1
• Unknown 216 26
• Vascular Catheter 161 19
• Genitourinary Tract 147 18
• Respiratory Tract 104 12
• Abdominal2 102 12
• Other3 113 13
• 1Total no. of episodes 843 (Weinstein et al.,
  1997) in which source confirmed by culture and/or
  clinical evidence
• 2Bowel and peritoneum, biliary tract,
  intra-abdominal abscess
• 3Skin, bone and joint, surgical wound, and other

18
Microbiology of Bacteremia and Fungemia

• Sources of Gram-Positive Bacteremia1
• Source No. () of Episodes2
• S. aureus (159) IV56 (35)
• Skin19 (12)
• Respiratory18 (11)
• Bone/joint10 (6)
• Coagulase T Staph (73) IV59 (81)
• Skin5 (7)
• Strep. pneumoniae (34) Respiratory26 (76)
• Enterococcus (38) GU15 (39)
• IV3 (8)
• 1Numbers in parentheses indicate bacteremic
  episodes for each organism. Weinstein et al.,
  1997
• 2() of the indicated source for the organism

19
Microbiology of Bacteremia and Fungemia

• Sources of Bacteremia due to Enterobacteriaceae1
• Source No. () of Episodes2
• E. coli (116) GU67 (58)
• Biliary11 (9)
• Peritoneal10 (9)
• K. pneumoniae (48) Biliary10 (21)
• GU8 (17)
• Peritoneal5 (10)
• S. marcescens (20) GU4 (20)
• Respiratory4 (20)
• IV3 (15)
• Prot. mirabilis (13) GU9 (69)
• 1Numbers in parentheses indicate bacteremic
  episodes for each organism. Weinstein et al.,
  1997
• 2() of the indicated source for the organism

20
Microbiology of Bacteremia and Fungemia

• Sources due to Gram-Negative Non-Fermenters and
  Yeast1
• Source No. () of
  Episodes2
• P. aeruginosa (48) Respiratory19 (40)
• GU9 (19)
• A. baumannii (12) Respiratory3 (25)
• C. albicans (21) IV5 (24)
• Peritoneal2 (10)
• C. glabrata (12) GU4 (33)
• 1Numbers in parentheses indicate bacteremic or
  fungemic episodes for each organism. Weinstein
  et al., 1997
• 2() of the indicated source for the organism

21
Microbiology of Bacteremia and Fungemia

• No. () deaths/ Relative risk
• No. episodes of death
• Yeast 19/53 (36) 6.54
• Polymicrobial 27/79 (34) 2.16
• Enterobacteriaceae2 31/125 (25) 4.53
• S. pneumoniae 6/34 (18) 3.22
• P. aeruginosa 8/48 (17) 3.04
• Unimicrobial 120/764 (16) 1.00
• Enterococccus 5/38 (13) 2.40
• E. coli 14/116 (12) 2.20
• Staph. aureus 19/159 (12) 2.18
• CoagT Staph. 4/73 (6) 1.00
• 1Associated mortality for individual organisms in
  unimicrobial bacteremia or fungemia, and
  unimicrobial vs. polymicrobial bacteremia.
  Weinstein et al, 1997
• 2Enterobacteriaceae other than E. coli

22
Microbiology of Bacteremia and Fungemia

• No. () deaths/ No. episodes1
• Hypotensive Normotensive
• Staph. aureus 5/18 (28) 14/141 (10)
• E. coli 4/13 (31) 10/103 (10)
• Enterobac. (other) 12/23 (52) 19/104 (18)
• P. aeruginosa 3/6 (50) 5/42 (12)
• Yeast 5/7 (71) 14/46 (30)
• Unimicrobial 35/96 (36) 85/668 (13)
• Polymicrobial 10/16 (63) 17/63 (27)
• 1Only differences statistically significant
  (plt.05) by ?2 are included (Weinstein et al.,
  1997). No significant differences in mortality
  were observed for coagulase-negative
  staphylococci, S. pneumoniae, other streptococci,
  Enterococcus, other gram-negative non-fermenters,
  and anaerobic bacteria.

23
Determinants of Mortality in Bacteremia and
Fungemia

• Multivariate Relative Risk
• of Death (lt.05, Weinstein et al, 1997)
• Respiratory tract, 2.86
• bowel, peritoneum,
• or unknown source
• Inappropriate antibiotic 2.72
• treatment
• Hypotension 2.29
• Enterobacteriaceae and 2.27
• yeast
• Absence of fever 2.04
• Malignancy, AIDS, or 1.98
• renal failure
• Age (gt70 years) 1.80

24
Clinical Indicators of True Bacteremia or
Fungemia1

• Peripheral leukocyte count gt20,000 or lt4,000
• Neutropenia (neutrophil count lt 1,000)
• Hypotension
• Hypothermia (lt36oC) or hyperthermia (gt40oC)
• 1At the time of first positive blood culture
  (Weinstein et al., 1997)

25
Clinical Manifestations of Bacteremia

• Significant Independent Multivariate Predictors
  of Positive Blood Culture Results1
• Variable OR (95 CI) P2
• Temp gt37.8oC 2.42 (1.41-4.14) .001
• WBC gt12,000 2.40 (1.41-4.10) .001
• Hospital gt10 d 2.02 (1.25-3.24) .004
• Age gt30 y 2.07 (1.19-3.60) .010
• Heart rate gt90 1.90 (1.13-3.17) .015
• Central venous lines 1.89 (1.02-3.50) .043
• 1Jaimes et al, 2004 n89 patients with positive
  blood cultures, and n411 patients with negative
  cultures
• 2Likelihood ratio statistic

26
Clinical Manifestations of Bacteremia

• Insignificant Predictors of Positive Blood
  Culture Results1
• Variable Negative Positive
  P2
• Comorbities2 159 (38.7) 32 (36)
  .630
• Chills 43 (10.4) 9 (10)
  .769
• Antibiotic use 210 (51.1) 45 (50.6)
  .785
• 1No. () of patients with negative blood cultures
  (n411) and positive blood cultures (n89)
  subjected to univariate analysis for each
  variable by Students t test (Jaimes et al.,
  2004)
• 2HIV infection, chronic renal failure, diabetes
  mellitus, immunosupressive chemotherapy, systemic
  cortico-steroid, and malignant disease

27
Technical Variables in the Collection of Blood
Cultures

• Skin antisepsis
• Volume of blood
• Ratio of blood to broth
• Number of blood cultures
• Sites of blood collection
• Blood culture sets

28
Skin antisepsis

• Preparation of skin with an agent bactericidal
  for surface bacterial commensals
• Commensals (especially coagulase-negative
  staphylococci) residing deep within sebaceous
  glands evade the bactericidal action of skin
  preparation agents
• Preparation agents include povidone-iodine (skin
  contact killing time of 1.5-2 min), tincture of
  iodine (contact killing time of 0.5 min), and
  recently chlorhexidine (ChloraPrep) (NMH
  application to skin venepuncture site for 30 sec
  by back and forth friction scrub, followed by 30
  sec drying time)
• Blood culture contamination rate reflects
  effectiveness of antisepsis with lowest rates
  obtained by laboratory phlebotomy teams

29
Volume of blood

• Bloodstream infections frequently caused by
  relative few organisms in a given volume of blood
  (lt1- 10 colony forming units/mL of blood)
• Sensitivity of blood cultures thus directly
  proportional to the volume of blood cultured
• Optimal volume for adults 20-30 mL of blood per
  culture set
• Blood volumes gt30 mL do not enhance the
  sensitivity of blood cultures for adults and
  contribute to nosocomial anemia
• Optimal volume for children (birth-15 y) 4 to
  4.5 of patients total blood volume (Kellogg et
  al., JCM 382181-2185, 2000)

30
Ratio of blood to broth

• Balance between dilutional effect of broth on
  antibiotics, complement, lysozyme, and phagocytic
  white cells on the one hand and inadequate volume
  of blood on the other
• Optimal dilution of blood to broth is 15 to 110
  (v/v)

31
Number of blood cultures

• Collection of multiple blood culture sets at
  different venipuncture sites
• Contamination by skin organism or environmental
  spores indicated if only one of multiple sets
  positive for coagulase-negative Staphylococcus,
  Bacillus, Corynebacterium, viridans streptococci,
  or Propionibacterium.
• Acute febrile episode 2 sets from separate sites
  within 10 minutes before antimicrobial
• Nonacute disease 2 or 3 sets from separate sites
  at gt 3 hr intervals within 24 hr before
  antimicrobial
• Acute endocarditis 3 sets from separate sites
  within 1-2 hr before antimicrobial
• Subacute endocarditis 3 sets from separate sites
  at gt1 hr intervals within 24 hr if these sets
  culture negative obtain 2-3 additional sets
• Fever of unknown origin 2 or 3 sets from
  separate sites at gt1 hr intervals within 24 hr
  if these sets culture negative, obtain 2-3
  additional sets

32
Optimal Testing Parameters for Blood Cultures1

• 37,568 blood cultures tested with automated
  BACTEC 9240 instrument at Mayo Medical Center
  June 1996-October 1997
• 20 mL blood inoculated in equal volumes to two
  culture bottles, first to BACTEC Plus Aerobic/F
  resin bottle, and then to BACTEC Lytic/10
  Anaerobic bottle
• 20 mL blood obtained separately for a total of 40
  mL within 30 min
• Blood cultures incubated 7 days on BACTEC 9240
  instrument
• 1Cockerill, III et al., Clin Inf Dis
  381724-1730, 2004

33
Optimal Testing Parameters for Blood Cultures1

• No. pathogens recovered
• 10 mL 20 mL 30 mL 40 mL
• S2 235 3053 3464 3715
• EC2 13 14 14 14
• 1Cockerill, III et al., Clin Inf Dis
  381724-1730, 2004
• 2S sepsis without endocarditis, E
  endocarditis
• 320 mL vs. 10 mL 29.8 increase in yield
• 430 mL vs. 20 mL 13.4 increase in yield
• 540 mL vs. 30 mL 7.2 increase in yield

34
Optimal Testing Parameters for Blood Cultures1,2

• Cons 1st 1st 1st 1st
• Cult3 gt1 gt2 gt3 gt4
• 615(81) 497(77)
  106(65) 62(61)
• 116(15) 116(18)
  25(15) 17(17)
• 3 25(3) 25(4) 25(15)
  15(15)
• 4 7(1) 7(1) 7(5)
  7(7)
• 5 - - - -
• - - - -
• 1Cockerill, III et al., Clin Inf Dis
  381724-1730, 2004.
• 2Pathogen recovery without endocarditis (n763)
  1st bottle
• indicated for patients with 1 or more, 2 or
  more, 3 or more, and 4
• or more (up to 6) collected.
• 3Consecutive blood culture drawn 1 culture
  (n118), 2 cultures (n482), 3
• cultures (n62), 4 cultures (n98), 5 cultures
  (n0), and 6 cultures (n3)
• drawn for the indicated number of patients.

35
Optimal Testing Parameters for Blood Cultures1

• 1st 1st 1st 1st
• gt1 gt2 gt3 gt4
• 37(93) 31(91) 16(89)
  9(82)
• 2(5) 2(6) 1(6)
  1(9)
• 3 0 0 0 0
• 4 1(3) 1(3) 1(6) 1(9)
• 5 - - - -
• - - - -
• 1Cockerill, III et al., Clin Inf Dis
  381724-1730, 2004
• 2Pathogen recovery with endocarditis (n40) and
  consecutive
• blood cultures (1-6) over 24 hours. 1st bottle
  indicated for
• patients with 1, 2, 3, or 4 or more bottles (up
  to 6) collected.

36
Optimal Testing Parameters for Blood Cultures1

• Twenty mL of blood inoculated in equal volumes to
  an aerobic and anaerobic broth bottle (one blood
  culture set)
• Second blood culture set inoculated immediately
  after the first from a different venipuncture
  site
• Two additional blood culture sets inoculated over
  remaining 24 hr if sepsis persist
• 1Cockerill, III et al., Clin Inf Dis
  381724-1730, 2004

37
Sites of blood collection

• Venipuncture at separate skin sites method of
  choice
• Blood should not be obtained from an indwelling
  intravenous or intra-arterial catheter unless
  catheter-related infection suspected, or skin
  venipuncture sites not available
• For the evaluation of catheter-associated
  bloodstream infection, a concomitantly drawn
  venipuncture specimen should be paired with a
  catheter specimen

38
Blood culture sets

• Two aerobic bottles versus a pair of aerobic and
  anaerobic bottles (?) (Decreased frequency of
  anaerobic bacteremia)
• Three bottle versus two bottle sets (?)
  (Increased sensitivity of automated continuously
  monitoring blood culture instruments)

39
Incubation conditions

• Without EC With EC
• 1d 2,052 (76.5) 144 (77.8)
• 2d 393 (91.2) 26 (91.9)
• 3d 123 (95.8) 8 (96.2)
• 4d 61 (98.1) 1 (96.8)
• 5d 35 (99.4) 2 (97.8)
• 6d 14 (99.9) 4 (100)
• 7d 3 (100) -------------
• 1Positivity of blood cultures for pathogens by
  incubation day (BACTEC 9240), ECendocarditis
• 2Cockerill, III et al., Clin Inf Dis
  381724-1730, 2004

40
Blood Culture Systems

• Manual
• Septi-Chek (Becton Dickinson)
• Isolator (Wampole)
• Semi-Automated
• BACTEC 460 (Becton Dickinson)
• Automated
• BacT/ALERT (bioMérieux)
• BACTEC 9000 System (Becton Dickinson)
• VersaTREK (formerly ESP System) (Trek)

41
Septi-Chek (Becton Dickinson)

• Aerobic broth bottle with attached plastic
  paddles containing agar medium (chocolate,
  MacConkey, malt)
• Inoculated broth bottle initially inverted to
  allow blood-broth mixture to flood the agars, and
  then each time bottle is inspected for growth
• Paddles are visually examined once or twice daily
  for colony formation, and broth for evidence of
  microbial growth (hemolysis, turbidity, gas
  production, chocolatization of blood, visible
  colonies or layer of growth on fluid meniscus)
• Separate anaerobic bottle without agar paddles
• Not practical for larger laboratories due to
  manual steps required for monitoring and
  processing

42
Isolator (Wampole)

• Isolator tube contains a blood cell lysing
  solution consisting of saponin and a fluorocarbon
  cushion that captures organisms during
  centrifugation
• Following centrifugation supernatants are
  discarded, and pellets resuspended for
  inoculation to solid medium appropriate for type
  of culture being performed (sheep blood,
  chocolate, MAC, CNA, BCYE, IMA, Middlebrook agar)
• Highly versatile and sensitive (except for
  anaerobic bacteria), but labor intensive for
  routine work
• Excellent system for isolation from blood of
  Mycobacterium avium or M. tuberculosis complex,
  dimorphic fungi, Bartonella, Legionella, and
  other fastidious pathogens

43
BACTEC 460 (Becton Dickinson)

• Blood culture broth medium (aerobic and
  anaerobic) contains 14C labeled carbohydrate
  substrate
• With microbial growth carbohydrate substrate
  metabolized and 14C labeled CO2 gas released into
  head space of bottles
• Needles perforate rubber septum of each bottle
  and headspace gas withdrawn for radiometric
  measurement of 14C labeled CO2
• Bottles reaching threshold 14C levels flagged as
  positive for Grams stain and subculture of broth
  to solid medium
• A semi-automated system that requires placement
  of racks with bottles on a shuttle of the BACTEC
  460 radiometer for testing
• Replaced in routine work by automated blood
  culture systems
• Remains an excellent system for recovery of
  mycobacteria from a wide variety of specimens,
  including sputum, where broth contains 14C
  labeled palmitic acid as substrate for cell wall
  mycolic acid synthesis, with release of 14C
  labeled CO2 into headspace of bottles containing
  Middlebrook broth

44
BacT/ALERT (bioMérieux)

• The first continuous-monitoring blood culture
  system (CMBCS), introduced in early 1990s
• Broth bottles monitored continuously (every 10-15
  min) for growth in self-contained modular units
  and bottles require no manipulation until flagged
  as positive for growth
• Growth monitored by a colorimetric CO2 sensor at
  the base of each bottle
• Computer algorithms interpret CO2 production as
  microbial growth when arbitrary thresholds
  exceeded, minimal linear increases of CO2 occur,
  or there is change in the rate of CO2 production

45
BACTEC 9000 System (Becton Dickinson)

• Three instruments in the BACTEC 9000 CMBCS
  series 9050 system (monitors 50 bottles), 9120
  system (120 bottles), and 9240 system (240
  bottles)
• Growth monitored by a fluorescent CO2 sensor at
  the base of each broth bottle
• Computer algorithms interpret CO2 production as
  microbial growth by linear increases in
  fluorescence, and an increase in the rate of
  flouorescence

46
VersaTREK (ESP System) (Trek)

• Third CMBCS introduced commercially
• Differs from BacT/ALERT and BACTEC 9000 series in
  that direct measurement of CO2 production not
  utilized to monitor microbial growth
• Bottles fitted with pressure transducers to
  monitor gas pressure changes within bottle
  headspaces
• Computer algorithms interpret the consumption
  and/or production of gas as microbial growth in
  which pressure changes are plotted against time
  to yield growth curves
• Positive cultures are signaled in accordance with
  these proprietary algorithms

47
Characteristics of CMBCSs

• Microbial growth detected 1-2 days earlier than
  with manual systems (total incubation time of 5
  days)
• Provides 24/7 service with prompt reporting of
  Grams stain results for positive blood cultures
• Decreases laboratory workload

48
Quality management monitors

• Contamination rate (should not exceed 3 of blood
  culture sets accessioned)
• Identification and susceptibility testing of
  coagulase-negative stapylococci (CNS) (should not
  exceed 12-30 of blood cultures sets positive for
  CNS)
• Blood volume (determined by broth bottles and
  blood culture systems utilized by the laboratory)

49
Probability of Same Contaminant in Two Blood
Culture Sets

• 0.03 X 0.03 0.0009 (lt1 per 1,000 sets)
• 36 episodes/40,000 culture sets
• 0.05 X 0.05 0.0025 (2-3 per 1,000 sets)
• 100 episodes/40,000 culture sets
• 0.10 X 0.10 0.01 (1 per 100 sets)
• 400 episodes/40,000 culture sets
• 0.15 X 0.15 0.02 (2 per 100 sets)
• 800 episodes/40,000 culture sets

50
CNS Algorithm

• Single blood culture for CNS, no other blood
  cultures collected /- 48 hr Evaluation of
  patient for sepsis
• Single blood culture for CNS, additional blood
  cultures collected /- 48 hr negative for CNS No
  ID or susceptibility unless physician request
• Single blood culture for CNS, additional blood
  cultures collected /- 48 hr positive for CNS
  Evaluation of patient for sepsis
• Richter et al. JCM 402437-2444, 2002.

51
CNS Algorithm

• If 2 or more blood cultures submitted and only
  one for CNS, reported as likely contaminant (no
  species ID, no susceptibility)
• If 1 of 1 blood culture submitted and is positive
  for CNS, reported as of indeterminate significant
  and physician advised to contact laboratory if ID
  and susceptibility needed
• If 2 or more blood cultures submitted for CNS,
  ID and susceptibility determined if both
  isolates same species, ID and susceptibility
  reported if different species, reported only as
  CNS without species and susceptibility
• Weinstein JCM 412275-2278, 2003.

52
References

• Weinstein et al. The clinical significance of
  positive blood cultures in the 1990s A
  prospective comprehensive evaluation of the
  microbiology, epidemiology, and outcome of
  bacteremia and fungemia in adults. Clin Inf Dis
  24584-602, 1997.
• Munson et al. Detection and treatment of
  bloodstream infection Laboratory reporting and
  antimicrobial management. J Clin Micro
  41495-497, 2003.
• Jaimes et al. Predicting bacteremia at the
  bedside. Clin Inf Dis 38357-362, 2004.
• Mohr et al. Manual and automated systems for
  detection and identification of microoranisms.
  Manual of Clinical Microbiology, Volume
  1185-191, 2003.
• Reimer et al. Update on detection of bacteremia
  and fungemia. Clin Micro Rev 10444-465.
• Weinstein. Current blood culture methods and
  systems Clinical concepts, technology, and
  interpretation of results. Clin Inf Dis
  2340-46, 1996.
• Dunne et al. Blood Cultures III. Cumitech 1B,
  1997.

53
References

• Kellogg et al. Frequency of low-level bacteremia
  in children from birth to fifteen years of age.
  J Clin Micro 382181-2185.
• Cockerill III et al. Optimal testing parameters
  for blood cultures. Clin Inf Dis 381724-1730.
• Weinstein et al. Remarks concerning testing
  parameters for blood cultures. Clin Inf Dis
  40202, 2005.
• Cockerill III. Reply to Weinstein and Reller.
  Clin Inf Dis 40202-203, 2005.
• Richter et al. Minimizing the workup of blood
  culture contaminants Implementation and
  evaluation of a laboratory-based algorithm. J
  Clin Micro 402437-2444, 2002.
• Weinstein. Blood culture contamination
  Persisting problems and partial progress. J Clin
  Micro 412275-2278, 2003.
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