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Bacteremia_ Fungemia_ and Blood Cultures

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									Bacteremia, Fungemia, and
     Blood Cultures
          Dr. John R. Warren
       Department of Pathology
        Northwestern University
      Feinberg School of Medicine
               June 2007
   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)
   Essential Elements of Blood
             Cultures
• Technical variables in the collection of
  blood cultures
• Incubation conditions
• Blood culture systems
• Quality management monitors
 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
 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
 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
 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
 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
 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
 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
 Microbiology of Bacteremia and
           Fungemia
         Etiological Significance of Gram-Positive Bacteria
Staphylococcus aureus                  178/204 (87%)
Coagulase Θ 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
 Microbiology of Bacteremia and
           Fungemia
    Etiological Significance of Anaerobic Bacteria
Bacteroides fragilis group      16/18 (89%)
Other gram-negative’s           2/5 (40%)
Clostridium perfringens         3/13 (23%)
Clostridium species             12/15 (80%)
Propionibacterium               0/48 (0%)
Other gram-positive’s           4/7 (57%)

Weinstein et al., 1997
 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
    Microbiology of Bacteremia and
              Fungemia
               Blood Culture Contaminants1
•   Propionibacterium (0%)
•   Corynebacterium (2%)
•   Bacillus (8%)
•   Coagulase-negative Staphylococcus (12%)
•   Viridans streptococci2 (38%)
1Inorder of decreasing probability of being a
  contaminant; % of blood isolates considered
  etiological in parentheses (Weinstein et al., 1997)
2Excluding Streptococcus pneumoniae
Microbiology of Bacteremia and
          Fungemia
 Association of Organisms with Neutropenia1
                    <1,000    >1,000
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 (p<.05) by
 χ2 are included (Weinstein et al., 1997).
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).
2p<.05 (χ2). Significant differences not

  observed with individual organisms, nor for
  unimicrobial bacteremia and fungemia.
 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
 Microbiology of Bacteremia and
           Fungemia
              Sources of Gram-Positive Bacteremia1
                                Source & No. (%) of Episodes2
S. aureus (159)                       IV=56 (35%)
                                      Skin=19 (12%)
                                      Respiratory=18 (11%)
                                      Bone/joint=10 (6%)
Coagulase Θ Staph (73)                IV=59 (81%)
                                      Skin=5 (7%)
Strep. pneumoniae (34)                Respiratory=26 (76%)
Enterococcus (38)                     GU=15 (39%)
                                      IV=3 (8%)
1Numbers in parentheses indicate bacteremic episodes for each
   organism. Weinstein et al., 1997
2(%)=% of the indicated source for the organism
 Microbiology of Bacteremia and
           Fungemia
              Sources of Bacteremia due to Enterobacteriaceae1
                              Source & No. (%) of Episodes2
E. coli (116)                              GU=67 (58%)
                                           Biliary=11 (9%)
                                           Peritoneal=10 (9%)
K. pneumoniae (48)                         Biliary=10 (21%)
                                           GU=8 (17%)
                                           Peritoneal=5 (10%)
S. marcescens (20)                         GU=4 (20%)
                                           Respiratory=4 (20%)
                                           IV=3 (15%)
Prot. mirabilis (13)                       GU=9 (69%)

1Numbers  in parentheses indicate bacteremic episodes for each
   organism. Weinstein et al., 1997
2(%)=% of the indicated source for the organism
 Microbiology of Bacteremia and
           Fungemia
    Sources due to Gram-Negative Non-Fermenters and Yeast1
                               Source & No. (%) of Episodes2
P. aeruginosa (48)                  Respiratory=19 (40%)
                                    GU=9 (19%)
A. baumannii (12)                   Respiratory=3 (25%)
C. albicans (21)                    IV=5 (24%)
                                    Peritoneal=2 (10%)
C. glabrata (12)                    GU=4 (33%)

1Numbers  in parentheses indicate bacteremic or fungemic
     episodes for each organism. Weinstein et al., 1997
2(%)=% of the indicated source for the organism
 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
CoagΘ 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
 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%)

1Onlydifferences statistically significant (p<.05) by χ2 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.
     Determinants of Mortality in
      Bacteremia and Fungemia
                                Multivariate Relative Risk
                           of Death (<.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 (>70 years)                            1.80
     Clinical Indicators of True
     Bacteremia or Fungemia1
• Peripheral leukocyte count >20,000 or
  <4,000
• Neutropenia (neutrophil count < 1,000)
• Hypotension
• Hypothermia (<36oC) or hyperthermia
  (>40oC)
1At the time of first positive blood culture

  (Weinstein et al., 1997)
      Clinical Manifestations of
             Bacteremia
   Significant Independent Multivariate Predictors of
              Positive Blood Culture Results1
Variable                      OR (95% CI)            P2
Temp >37.8oC                2.42 (1.41-4.14)        .001
WBC >12,000                 2.40 (1.41-4.10)        .001
Hospital >10 d              2.02 (1.25-3.24)        .004
Age >30 y                   2.07 (1.19-3.60)        .010
Heart rate >90              1.90 (1.13-3.17)        .015
Central venous lines        1.89 (1.02-3.50)        .043
1Jaimes et al, 2004; n=89 patients with positive blood
   cultures, and n=411 patients with negative cultures
2Likelihood ratio statistic
      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
  (n=411) and positive blood cultures (n=89) subjected
  to univariate analysis for each variable by Student’s t
  test (Jaimes et al., 2004)
2HIV infection, chronic renal failure, diabetes mellitus,
  immunosupressive chemotherapy, systemic cortico-
  steroid, and malignant disease
      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
             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
            Volume of blood
• Bloodstream infections frequently caused by relative
  few organisms in a given volume of blood (<1- 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 >30 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
  patient’s total blood volume (Kellogg et al., JCM
  38:2181-2185, 2000)
     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 1:5
  to 1:10 (v/v)
     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 > 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 >1 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 >1
  hr intervals within 24 hr; if these sets culture negative, obtain 2-
  3 additional sets
 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 38:1724-1730, 2004
 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 38:1724-1730, 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
  Optimal Testing Parameters for
        Blood Cultures1,2
Cons     1st +           1st+             1st +             1st +
Cult3    >1              >2               >3                >4
1       615(81)         497(77)          106(65)           62(61)
2       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        -               -                -                 -
6       -                -                -                 -

1Cockerill, III et al., Clin Inf Dis 38:1724-1730, 2004.
2Pathogen recovery without endocarditis (n=763); 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 (n=118), 2 cultures (n=482), 3

 cultures (n=62), 4 cultures (n=98), 5 cultures (n=0), and 6 cultures (n=3)
 drawn for the indicated number of patients.
    Optimal Testing Parameters for
           Blood Cultures1
       1st +            1st+            1st +           1st +
       >1               >2              >3              >4
1      37(93)          31(91)          16(89)           9(82)
2      2(5)            2(6)            1(6)             1(9)
3      0               0               0                0
4      1(3)            1(3)            1(6)             1(9)
5      -                -               -               -
6      -                -               -               -

1Cockerill,III et al., Clin Inf Dis 38:1724-1730, 2004
2Pathogen recovery with endocarditis (n=40) 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.
 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 38:1724-1730,
  2004
    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
        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)
        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), EC=endocarditis
2Cockerill, III et al., Clin Inf Dis 38:1724-1730, 2004
     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)
  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
          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
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 CO gas released into head space of bottles
                 2
• 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
  Gram’s 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
      BacT/ALERT (bioMérieux)

• The first continuous-monitoring blood culture
  system (CMBCS), introduced in early 1990’s
• 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
  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
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
 Characteristics of CMBCS’s
• 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 Gram’s stain results for
  positive blood cultures
• Decreases laboratory workload
  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)
Probability of Same Contaminant
   in Two Blood Culture Sets
• 0.03 X 0.03 = 0.0009 (<1 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
              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 40:2437-2444, 2002.
              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 41:2275-2278, 2003.
                        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 24:584-602, 1997.
•   Munson et al. Detection and treatment of bloodstream infection:
    Laboratory reporting and antimicrobial management. J Clin Micro
    41:495-497, 2003.
•   Jaimes et al. Predicting bacteremia at the bedside. Clin Inf Dis
    38:357-362, 2004.
•   Mohr et al. Manual and automated systems for detection and
    identification of microoranisms. Manual of Clinical Microbiology,
    Volume 1:185-191, 2003.
•   Reimer et al. Update on detection of bacteremia and fungemia. Clin
    Micro Rev 10:444-465.
•   Weinstein. Current blood culture methods and systems: Clinical
    concepts, technology, and interpretation of results. Clin Inf Dis 23:40-
    46, 1996.
•   Dunne et al. Blood Cultures III. Cumitech 1B, 1997.
                        References
•   Kellogg et al. Frequency of low-level bacteremia in children from birth
    to fifteen years of age. J Clin Micro 38:2181-2185.
•   Cockerill III et al. Optimal testing parameters for blood cultures. Clin
    Inf Dis 38:1724-1730.
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