Neutropenic Fever:
Challenges and Treatment
Dong-Gun Lee
Div. of Infectious Diseases,
Dept. of Internal Medicine,
The Cath...
Contents
• Epidemiology Focus in Asia
; Etiologic microorganisms & Resistance
• ESBL producing Enterobacteriaceae
; Empiri...
Question (1)
What is the most common pathogen
during neutropenia in your institution in
these days?
1. Pseudomonas aerugin...
Clin Infect Dis 2005;40:S240-5
Epidemiology, EU
Clin Infect Dis 2003;36:1103-10
Epidemiology, US [SCOPE] Project
Epidemiology, Malaysia (2004)
Int J Infect Dis
2007;11:513-7
Epidemiology, Taiwan (‘99-02)
Chemotherapy
2005;51:147-53
Epidemiology, Taiwan (‘02-06)
Epidemiol Infect 2010;138:1044;51
Korean J Intern Med 2011;26:220-52
Infect Chemother 2011;43:285-321
NA09-013
초기 항균요법 (2)
No. (%)
Reference Rho et al. Rhee et al. Choi et al. Kim et al. Park et al.
Period (year) 1996-2001 1996-2003 ...
Catholic HSCT Center (Pre-engraftment)
  ’83 ~ ’88 ’89 ~ ’92 ’93 ~ ’96 ’98 ~ ’99 ’01 ~ ’02
No. of isolates
13
14 8 24 25
G...
’83 ~ ’
88 ’89 ~ ’
92 ’93 ~ ’
96 ’98 ~ ’
99 ’01 ~ ’
02
Others
Enterobacter spp.
K. pneumoniae
E. coli
P. aeruginosa
0
10
2...
Catholic HSCT Center (Pre-engraftment)
’83 ~ ’88
’89 ~ ’92
’93 ~ ’96
’98 ~ ’99
’01 ~ ’02
Enterococcus spp.
Streptococcus s...
Organisms (n=243) Ward A Ward B Total (%) P value
Gram (+) (n=122) (n=108) (n=14)
S. aureus 9 2 11 (4.5) 0.649
CoNS 14 0 1...
Pathogens
(No. of isolates)
No. of isolates resistant to antibiotics/no. of isolates tested
PCV OXAC CLM EM CFTX CFPM GM
C...
Pathogens
(No. of isolates)
No. of isolates resistant to antibiotics/no. of isolates tested
ESBL AMC PIPC GM TOB CAZ LVX S...
Antibiotics
(susceptibility)
Adults
(≥ 20 years old)
(n=140)
Children
(< 20 years old)
(n=61)
Penicillin 57 (40.7) 22 (36....
초기 항균요법 (1)
 In contrast to western countries, Gram-negative bacteria are the
prevailing etiological agents of infections...
Question (2)
What is your strategy for the empirical
Tx in 1st
onset of neutropenic fever?
1. Broad spectrum Cephalosporin...
Question (3)
Do you think ESBL producing
organisms show higher mortality?
1. YES
2. NO
J Antimicrob Chemother 2012;67:1311-20
Mortality: ESBL vs. Non-ESBL BSI
Ann Hematol 2013; [in press]
ESBL vs. Non-ESBL BSI in NF
No. (%)
E. coli K. pneumoniae
ESBL
(n=15)
Non-ESBL
(n=72)
ESBL
(n...
Ann Hematol 2013; [in press]
Susceptibility
Characteristics
Unadjusted OR (95% CI) p-
value
Adjusted OR (95%
CI)
p-
value
Disease status, non-remitted
3.569 (1.375-9....
No. (%)
E. coli K. pneumoniae
ESBL
(n=15)
Non-
ESBL
(n=72)
P
ESBL
(n=11)
Non-ESBL
(n=3)
P
Early response (72hr)
CR
PR
Trea...
Factors associated with Mortality
Characteristics Unadjusted OR (95% CI) p-value Adjusted OR (95% CI) *
p-value
ESBL produ...
EJC Suppl 2007;5:13-22 [ECIL-1]
Role of Aminoglycoside in NF (1)
Role of Aminoglycoside in NF (2)
Ann Hematol 2012;91:1161-74
[DGHO]
Role of Aminoglycoside in NF (3)
 While the addition of an aminoglycoside has not been shown to
be of clinical advantage ...
초기 항균요법 (1)
 We may still use the beta-lactam + aminoglycoside combination
strategy for empirical therapy of NF. When ESB...
Question (4)
What do you use mainly
for MRSA bacteremia in NF?
1. Vancomycin
2. Teicoplanin
3. Arbekacin
4. Linezolid
5. F...
PKs in Neutropenia
 Reduced serum, tissue, and body fluid concentrations of
antibacterial agents have been reported in ne...
Lancet Infect Dis 2008;8:612-20
PK of Glycopeptides in
Neutropenia
What can we learn from studies
comparing Linezolid with
Vancomycin in neutropenic patients
when vancomycin doses are not
o...
Vancomycin TDM Consensus
Am J Health Syst Pharm 2009;66:82-98
Antimicrob Agents Chemother 2001;45:2460-7
Continuous vs. Intermittent
Infusion of Vancomycin in
Severe Staphylococcal
Inf...
Empirical Teicoplanin in Neutropenic
Fever in Korea: Comments
TPV 400 mg qd and then 200 mg qd
; is that enough?
1. Only o...
J Antimicrob Chemother 2003;51:971-5
Loading Dose of Teicoplanin
Teicoplanin Dose in Acute Leukemia
and Febrile Neutropenia
Clin Pharmacokinet 2004;43:405-15
H : q12h, 800-400-600-400-400...
Yonsei Med J 2011;52:616-23
초기 항균요법 (1)
 PK of glycopeptides in neutropenic patients is different with that of
normal volunteers. We need their PK da...
Summary
Etiology of NF is different according to the area, time, even the
wards in the same hospital.  We need to contin...
Thank You for
Your Attention
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Breakthroughs in the treatment of acute promyelocytic leukemia: curable disease with retinoic and ARSENIC-2

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  • 따라서 , 이번연구에서는 ESBL production 이 mortality 에는 관련이 없었다 . 아마도 aminoglycoside combination 때문이 아닐까 ??
  • Breakthroughs in the treatment of acute promyelocytic leukemia: curable disease with retinoic and ARSENIC-2

    1. 1. Neutropenic Fever: Challenges and Treatment Dong-Gun Lee Div. of Infectious Diseases, Dept. of Internal Medicine, The Catholic Univ. of Korea
    2. 2. Contents • Epidemiology Focus in Asia ; Etiologic microorganisms & Resistance • ESBL producing Enterobacteriaceae ; Empirical therapy as 1st onset of NF • When using Glycopeptides…
    3. 3. Question (1) What is the most common pathogen during neutropenia in your institution in these days? 1. Pseudomonas aeruginosa 2. Escherichia coli 3. Staphylococcus aureus 4. Coagulase negative Staphylococci 5. viridans streptococci 6. fungi
    4. 4. Clin Infect Dis 2005;40:S240-5 Epidemiology, EU
    5. 5. Clin Infect Dis 2003;36:1103-10 Epidemiology, US [SCOPE] Project
    6. 6. Epidemiology, Malaysia (2004) Int J Infect Dis 2007;11:513-7
    7. 7. Epidemiology, Taiwan (‘99-02) Chemotherapy 2005;51:147-53
    8. 8. Epidemiology, Taiwan (‘02-06) Epidemiol Infect 2010;138:1044;51
    9. 9. Korean J Intern Med 2011;26:220-52 Infect Chemother 2011;43:285-321 NA09-013
    10. 10. 초기 항균요법 (2) No. (%) Reference Rho et al. Rhee et al. Choi et al. Kim et al. Park et al. Period (year) 1996-2001 1996-2003 1998-1999 1999-2000 2001-2002 Hospital A B C D C Patients leukemia allo-HSCT acute leukemia cancer HSCT Prophylaxis NA Cotrimazole Nystatin gargle Ciprofloxacin, roxithromycin, fluconazole NA Ciprofloxacin, fluconazole/ itraconazole, TMP/SMX No. of MDI 27 (100) 78 (100) 158 (100) 42 (100) 72 (100) Gram (+) bacteria 11 (40.7) 36 (46.2) 75 (47.5) 11 (26.2) 25 (34.7) Streptococcus 1 (3.7) - 24 (15.2) 2 (4.8) 9 (12.5) CoNS 4 (14.8) 15 (19.2) 20 (12.7) 4 (9.5) 7 (9.7) Staphylococcus aureus 4 (14.8) - 13 (8.2) 3 (7.1) 2 (2.8) Enterococcus 2 (7.4) - 14 (8.9) 2 (4.8) 6 (8.3) Gram (-) bacteria 16 (59.3) 42 (53.8) 83 (52.5) 31 (73.8) 47 (65.3) Escherichia coli 4 (14.8) - 43 (27.2) 2 (4.8) 32 (44.4) Pseudomonas aeruginosa 1 (3.7) - 12 (7.6) 5 (11.9) 4 (5.6) Klebsiella pneumoniae 6 (22.2) - 12 (7.6) 8 (19.0) 4 (5.6) Enterobacter - - 5 (3.2) 4 (9.5) 3 (4.2) Acinetobacter baumanii 2 (7.4) - - 2 (4.8) 2 (2.8) Aeromonas hydrophila 1 (3.7) - 6 (3.8) - - Citrobacter freundii - - - 2 (4.8) 1 (1.4) Salmonella - - - 4 (9.5) - Epidemiology, Korea
    11. 11. Catholic HSCT Center (Pre-engraftment)   ’83 ~ ’88 ’89 ~ ’92 ’93 ~ ’96 ’98 ~ ’99 ’01 ~ ’02 No. of isolates 13 14 8 24 25 G (+)   CNS (6) CNS (6) S. aureus (4) S. epidermidis (10) Streptococcus (9) S. aureus (2) S. aureus (3) S. epidermidis (3) Streptococcus (5) CNS (7) Enterococcus (3) Enterococcus (2) E. faecalis (1) Staphylococcus (3) S.aureus (2) Streptococcus (2) Streptococcus (3)   E. faecium (4) E. faccium (4)       E. faecalis (2) E. faecalis (2)         Micrococcus (1) 15 12 24 40 47 G (-) P. aeruginosa (11) P. aeruginosa (8) P. aeruginosa (6) E. coli (32) E. coli (32) Klebsiella (2) Klebsiella (1) E. coli (5) Klebsiella (3) K. pneumoniae (4) E. coli (1) E. coli (1) Enterobacter (5) Enterobacter (2) P. aeruginosa (4) Other (1) Others (2) Klebsiella (3) P. aeruginosa (1) Enterobacter (3)     Others (5) Others (2) A. baumanii (2) Epidemiology, Catholic BMT Center (Pre-engraftment Period) J Korean Med Sci 2006;21:199-207
    12. 12. ’83 ~ ’ 88 ’89 ~ ’ 92 ’93 ~ ’ 96 ’98 ~ ’ 99 ’01 ~ ’ 02 Others Enterobacter spp. K. pneumoniae E. coli P. aeruginosa 0 10 20 30 40 50 60 70 80 GNB Catholic HSCT Center (Pre-engraftment) Epidemiology, Catholic BMT Center
    13. 13. Catholic HSCT Center (Pre-engraftment) ’83 ~ ’88 ’89 ~ ’92 ’93 ~ ’96 ’98 ~ ’99 ’01 ~ ’02 Enterococcus spp. Streptococcus spp. S. aureus CNS 0 10 20 30 40 50 GPC Epidemiology, Catholic BMT Center
    14. 14. Organisms (n=243) Ward A Ward B Total (%) P value Gram (+) (n=122) (n=108) (n=14) S. aureus 9 2 11 (4.5) 0.649 CoNS 14 0 14 (5.8) 0.227 Viridans streptococci 39 (18.6) 5 (15.2) 44 (18.1) 0.635 S. pneumonia 2 0 2 (0.8) Rothia mucilaginosa 5 0 5 (2.1) Enterococcus spp. 27 7 34 (14.0) 0.198 Corynebacterium spp. 4 0 4 (1.6) Bacillus spp. 3 0 3 (1.2) Others† 5 0 5 (2.1) Gram (-) (n=119) (n=100) (n=17) E. coli 58 (27.6) 14 (42.4) 72 (29.6) 0.083 K. pneumonia 28 (13.3) 3 (9.1) 31 (12.8) Pseudomonas spp. 5 1 6 (2.5) Enterobacter spp. 3 1 4 (1.6) Stenotrophomonas maltophilia 4 0 4 (1.6) Others* 2 0 2 (0.8) Fungus (n=2) Candida tropicalis 1 0 1 (0.4) No. of microorganims Epidemiology, Catholic BMT Center (‘09-’10)
    15. 15. Pathogens (No. of isolates) No. of isolates resistant to antibiotics/no. of isolates tested PCV OXAC CLM EM CFTX CFPM GM CPFX or LVX VAN IMPM AMP S. aureus (11) 11/11 7/11 5/11 5/11 - - 4/11 6/11 0/11 - - CoNS (14) 14/14 12/1 3 8/14 9/14 - - 10/14 13/14 0/14 - - Streptococci other than pneumococcus (46) 24/46 - 11/45 21/46 4/45 17/45 - 0/1 0/45 - 0/2 S. pneumonia (2) 0/2 - - 2/2 0/2 - - 0/2 0/2 - - Enterococcus faecium (19) 19/19 - 19/19 17/19 - - - 19/19 7/19 19/19 19/19 Enterococcus faecalis (15) 6/15 - 15/15 12/15 - - - 14/15 0/15 0/15 5/15 Gamella mibiliform (1) 1/1 - 0/1 0/1 0/1 0/1 - - 0/1 - - Total no. of G (+) 75/10 8 19/24 58/105 66/108 4/48 17/46 14/25 52/62 7/107 19/34 24/36 % of resistance 69.4 79.2 55.2 61.1 8.3 37.0 56.0 83.9 6.5 55.9 66.7 Resistance Patterns (GPC) Resistance Pattern, GPC
    16. 16. Pathogens (No. of isolates) No. of isolates resistant to antibiotics/no. of isolates tested ESBL AMC PIPC GM TOB CAZ LVX SXT AZTN IMPM MRPN E. coli (72) 22/63 64/72 64/72 30/72 33/72 24/72 65/70 40/72 23/72 0/72 0/72 K. pneumoniae (31) 22/31 31/31 27/31 18/31 21/31 22/31 24/29 20/31 22/31 0/31 0/31 Pseudomonas spp. (6) - - 0/6 0/6 0/5 2/6 3/5 4/4 2/6 4/6 0/6 Enterobacter spp. (4) - 4/4 4/4 0/4 0/4 1/4 1/4 3/4 1/4 0/4 0/4 S. maltophilia (4) - - - - - - 0/4 0/4 - - - B. cepacia (1) - - - - - 0/1 0/1 0/1 - - 0/1 C. indologenes (1) - - 1/1 1/1 1/1 1/1 1/1 0/1 1/1 1/1 1/1 Total no. of G (-) 44/94 99/107 96/114 49/114 55/113 50/115 94/114 67/117 49/114 5/114 1/115 % of resistance 46.8 92.5 84.2 43.0 48.7 43.5 82.3 57.3 43.0 4.4 0.9 Resistance Pattern, GNB
    17. 17. Antibiotics (susceptibility) Adults (≥ 20 years old) (n=140) Children (< 20 years old) (n=61) Penicillin 57 (40.7) 22 (36.1) 0.535 Cefotaxime 127 (90.7) 39 (65.0) < 0.001 Cefepime 120 (85.7) 39 (66.1) 0.002 Vancomycin 140 (100.0) 61 (100.0) NA Linezolid 140 (100.0) 60 (98.4) 0.303 Clindamycin 121 (86.4) 51 (83.6) 0.601 Erythromycin 78 (55.7) 21 (34.4) 0.006 Data from Catholic BMT Center [in press] Viridans Streptococci Bacteremia in NF
    18. 18. 초기 항균요법 (1)  In contrast to western countries, Gram-negative bacteria are the prevailing etiological agents of infections in neutropenic fever patients in Asia.  Because of the reported etiologic bacteria and their antimicrobial resistance rates causing neutropenic fever vary widely by times, area, even wards, every hospital should continue to monitor the changing patterns of etiology and adjustment of empirical antibiotics may be necessary. What is the major etiologic agents of neutropenic feverWhat is the major etiologic agents of neutropenic fever in Asia?in Asia?
    19. 19. Question (2) What is your strategy for the empirical Tx in 1st onset of neutropenic fever? 1. Broad spectrum Cephalosporin monotherapy 2. Broad spectrum Penicillin monotherapy 3. Carbapenem monotherapy 4. Beta-lactam + Aminoglycoside 5. Beta-lactam + Quinolone 6. Double Beta-lactams
    20. 20. Question (3) Do you think ESBL producing organisms show higher mortality? 1. YES 2. NO
    21. 21. J Antimicrob Chemother 2012;67:1311-20 Mortality: ESBL vs. Non-ESBL BSI
    22. 22. Ann Hematol 2013; [in press] ESBL vs. Non-ESBL BSI in NF No. (%) E. coli K. pneumoniae ESBL (n=15) Non-ESBL (n=72) ESBL (n=11) Non-ESBL (n=3) Age, median (range), yr 44 (15-64) 42 (17-74) 39 (16-59) 31 (23-42) Sex, M:F 9:6 39:33 6:5 3:0 Underlying disease AML ALL MM Others* 10 (66.7) 2 (13.3) 1 (6.7) 2 (13.3) 33 (45.8) 31 (43.1) 4 (5.6) 4 (5.6) 5 (45.5) 4 (36.4) 0 (0.0) 2 (18.1) 1 (33.3) 0 (0.0) 0 (0.0) 2 (66.6) Undergoing therapy Chemotherapy HSCT 10 (66.7) 5 (33.3) 59 (81.9) 13 (18.1) 8 (72.7) 3 (27.3) 3 (100.0) 0 (0.0) 1st set fever† 13 (86.7) 72 (100.0) 4 (36.3) 3 (100.0) Empirical therapy 3rd generation cephalosporin Cefepime Piperacillin-tazobactam Carbapenem Aminoglycoside combination 13 (87.0) 2 (13.0) 0 (0.0) 0 (0.0) 14 (93.3) 60 (83.0) 3 (4.0) 8 (11.1) 1 (1.4) 71 (98.6) 4 (36.0) 1 (9.0) 0 (0.0) 6 (54.5) 5 (45.5) 1 (33.3) 0 (0.0) 1 (33.3) 1 (33.3) 3 (100.0)
    23. 23. Ann Hematol 2013; [in press] Susceptibility
    24. 24. Characteristics Unadjusted OR (95% CI) p- value Adjusted OR (95% CI) p- value Disease status, non-remitted 3.569 (1.375-9.263) 0.009 - 0.110 History of ICU admission within prior 3 months 13.455 (1.429-126.686) 0.023 - 0.162 Hospital stay for >2 weeks within the preceding 3 months 7.874 (2.177-28.475) 0.002 5.887 (1.572-22.041) 0.008 Previous antibiotics use within the preceding 4 weeks         Broad-spectrum cephalosporins 9.397 (2.584-34.179) 0.001 6.186 (1.616-23.683) 0.008 β-lactam/β-lactamase inhibitors 4.226 (1.040-17.173) 0.044 - 0.083 Aminoglycosides 6.088 (1.906-19.447) 0.002 - 0.565 Glycopeptides 8.690 (1.572-48.056) 0.013 - 0.436 Factors associated with ESBL BSI Ann Hematol 2013; [in press]
    25. 25. No. (%) E. coli K. pneumoniae ESBL (n=15) Non- ESBL (n=72) P ESBL (n=11) Non-ESBL (n=3) P Early response (72hr) CR PR Treatment failure 5 (33.3) 9 (60.0) 1 (6.7) 29 (40.3) 41 (56.9) 2 (2.8) NS 2 (18.2) 6 (54.5) 3 (27.3) 1 (33.3) 2 (66.7) 0 (0.0) NS Mortality Overall at 7 day at 30 day Bacteremia attributable 0 (0.0) 1 (6.7) 1 (6.7) 1 (1.4) 3 (4.2) 3 (4.2) NS NS NS 0 (0.0) 2 (20.0) 2 (22.0) 0 (0.0) 1 (33.3) 0 (0.0) NS NS SAnn Hematol 2013; [in press] Factors associated with Mortality
    26. 26. Factors associated with Mortality Characteristics Unadjusted OR (95% CI) p-value Adjusted OR (95% CI) * p-value ESBL production 3.227 (0.745-13.982) 0.117 0.735 (0.231-2.338) 0.602 Inappropriate empirical antimicrobial therapy 4.286 (0.393-46.785) 0.233 1.401 (0.254-7.722) 0.699 Disease status, non-remitted 4.843 (1.131-20.735)* 0.034 1.990 (0.534-7.416) 0.305 Duration of neutropenia >3 weeks 7.731 (1.465-40.787) 0.016 1.757 (0.675-4.570) 0.248 Septic shock at presentation 43.500 (7.180-263.552) <0.001 2.946 (1.075-8.073) 0.036 Infecting organism, Klebsiella pneumoniae 8.300 (1.791-38.459) 0.007 3.593 (1.023-12.628) 0.046 Copathogen 7.731 (1.465-40.787) 0.016 1.335 (0.513-3.471) 0.554 Ann Hematol 2013; [in press]
    27. 27. EJC Suppl 2007;5:13-22 [ECIL-1] Role of Aminoglycoside in NF (1)
    28. 28. Role of Aminoglycoside in NF (2) Ann Hematol 2012;91:1161-74 [DGHO]
    29. 29. Role of Aminoglycoside in NF (3)  While the addition of an aminoglycoside has not been shown to be of clinical advantage compared with beta-lactam monotherapy in systematic reviews, there are particular circumstances where the choice of aminoglycoside may be important. These include severe sepsis where there is a risk of resistance in Gram-negative bacilli and in Pseudomonas infection. Intern Med 2011;41:90-101 [Australian Guideline]
    30. 30. 초기 항균요법 (1)  We may still use the beta-lactam + aminoglycoside combination strategy for empirical therapy of NF. When ESBL is not proven, aminoglycoside is only used for 3-5 days.  Adjustment for inadequate empirical therapy can lead to a reduction of mortality. For example, combination therapy with aminoglycoside… in high incidence of ESBL producingin high incidence of ESBL producing Enterobacteriaceae area…Enterobacteriaceae area…
    31. 31. Question (4) What do you use mainly for MRSA bacteremia in NF? 1. Vancomycin 2. Teicoplanin 3. Arbekacin 4. Linezolid 5. Fusidic acid 6. Others
    32. 32. PKs in Neutropenia  Reduced serum, tissue, and body fluid concentrations of antibacterial agents have been reported in neutropenic patients and animal models, potentially reducing the bactericidal activities of these agents.  PK changes in neutropenic patients are probably not only related to neutropenia per se, but also to the severity of sepsis, as has been in ICU patients.  host defense mechanism… Lancet Infect Dis 2008;8:612-20
    33. 33. Lancet Infect Dis 2008;8:612-20 PK of Glycopeptides in Neutropenia
    34. 34. What can we learn from studies comparing Linezolid with Vancomycin in neutropenic patients when vancomycin doses are not optimized? Clin Infect Dis 2006;42:1813-4 1. PK of vancomycin therapy in neutropenic patients is different. ; 3-fold increases of initial Vd, shorted half-life (vs. healthy volunteer) 2. Achievement of trough serum conc. ≥15 mg/L? 3. T>MIC 100% 4. 1 g iv q12hrs fixed dose  30 mg/kg/day
    35. 35. Vancomycin TDM Consensus Am J Health Syst Pharm 2009;66:82-98
    36. 36. Antimicrob Agents Chemother 2001;45:2460-7 Continuous vs. Intermittent Infusion of Vancomycin in Severe Staphylococcal InfectionFrance, Prospective study, CIV (plateau 20-25 mg/L), IIV (trough 15-20 mg/L) N= 119, Hospital acquired infection, bacteremia 35%, pneumonia 45%
    37. 37. Empirical Teicoplanin in Neutropenic Fever in Korea: Comments TPV 400 mg qd and then 200 mg qd ; is that enough? 1. Only one strains of S. aureus, 2. CNS can be affected by catheter removal 3. Four out of 6 strains of E. faecium were vancomycin resistant. 4. Viridans streptococci would be susceptible with cefepime. Infect Chemother 2004;36:83-91
    38. 38. J Antimicrob Chemother 2003;51:971-5 Loading Dose of Teicoplanin
    39. 39. Teicoplanin Dose in Acute Leukemia and Febrile Neutropenia Clin Pharmacokinet 2004;43:405-15 H : q12h, 800-400-600-400-400-400 S : 400 mg q12hrs (×3), 400 mg q24h
    40. 40. Yonsei Med J 2011;52:616-23
    41. 41. 초기 항균요법 (1)  PK of glycopeptides in neutropenic patients is different with that of normal volunteers. We need their PK data!!! may need higher doses than usual  Vancomycin trough concentrations 15-20 mg/L or AUC/MIC >400 would be required in neutropenic fever as well as in severe staphylococcal infection.  Teicoplanin PK/PD magnitude for neutropenic fever is not established yet (trough >10 or 20 mg/L, AUC/MIC >345??). However, TDM would be needed for monitoring TAR. Teicoplanin dose would be needed more than we usually prescribe. When using glycopeptide to NF patients, Consider…When using glycopeptide to NF patients, Consider…
    42. 42. Summary Etiology of NF is different according to the area, time, even the wards in the same hospital.  We need to continue monitoring the changing patterns. ESBL producing organisms are common. High index of suspicion (prior use of beta-lactams, Hx of long hospital stay…) is important. For empirical Tx against ESBL organisms, consider the susceptibility patterns and adjust for inadequate antibiotics… PK of glycopeptides in neutropenic patients is different with that of normal volunteers.  We need their PK data!!! Population PK
    43. 43. Thank You for Your Attention

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