IDSA-2011
Evaluation of Cefepime 1 Gram every 6 hours for Treatment of Gram-Negative Bacteremia
#302
1 Department
Results: 89 patients were identified, 21 and 68 in the novel and
standard dosing groups, respectively. Baseline characteristics were
similar between groups; however, more patients receiving novel dosing
were in the ICU (67% v. 41%, p = 0.04). The most common organisms
isolated were P. aeruginosa (27%), E. coli (22%), E. cloacae (14%), and
K. pneumoniae (11%). FEP MICs (µg/mL) were ≤ 1 (76%), 2 (14%), 4
(7%), and 8 (6%). Comparing novel to standard dosing, no differences
in time (hours) to first antibiotic dose, (8.9 [4.9-13.9] v. 6.0 [0.6-15], p =
0.3) or total days of antibiotic therapy (11.8 [8-13.7] v. 12.1 [6.9-14.3], p
= 0.8) were observed. Clinical success (81% v. 82%, p = 1), mortality
(5% v. 10%, p = 0.7), and IR-LOS (10.5 [8.8-14.1] v. 10.6 [7.0-15.6]
days, p = 0.7) were also similar. Subgroup analysis of novel dosing
compared to 2g IV every 8h (n = 24) showed no differences in clinical
success (81% v. 88%, p = 0.7), mortality (4.8% v. 4.2%, p = 1), or IRLOS (10.5 [8.8-14.1] v. 10.9 [7.1-15.7] days, p = 0.9).
Conclusions: FEP 1g IV every 6h demonstrated similar efficacy to
standard doses and represents a cost-effective treatment strategy for
bacteremic patients compared to 2g IV every 8h.
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Clinical success
•
Mortality
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
Gram-negative organisms are a common source of bloodstream
infections (BSIs) in the United States.
Monte Carlo simulation has demonstrated comparable free time
above MIC when cefepime 1g every 6h and 2g every 8h have
been compared; thus, 1g every 6 h may represent a costeffective alternative to 2g every 8h.
The lack of data regarding treatment outcomes prompted a
formal evaluation.
Infection-related length of stay (IR-LOS)
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Retrospective cohort study from January 2008 to December
2010 in adult patients ≥ 18 years of age
Novel
Standard
(n = 21)
(n = 68)
64 ± 14
62 ± 17
Male
12 (57)
38 (56)
Primary service
TABLE 3. Clinical outcomes compared to 2g every 8 hours
p-value
0.87
0.92
0.51
Medicine
15 (72)
45 (66)
Heme/Onc
3 (14)
17 (25)
Surgery
3 (14)
6 (9)
1.1 (0.8 - 2.0)
1.0 (0.7 - 1.4)
Baseline SCr**
Comparison groups
FIGURE 2. Cefepime MIC distribution among identified organisms
TABLE 1. Patient demographics (N = 89)
Age*
Study design
Dosing Regimens
Novel
1g IV every 6 hours
Standard
• 2g IV every 12 hours
• 2g IV every 8 hours
• 1g IV every 8 hours
Inclusion criteria
•
•
Received cefepime for at least 72 hours
Exclusion criteria
•
•
86
74
1 g every 6 h
80
n = 21
n = 24
Clinical success
17 (81)
21 (88)
0.7
Hospital mortality
1 (5)
1 (4)
1
10.5 [8.8-14.1]
10.9 [7.1-15.7]
0.9
1st antibiotic dose, hrs
8.9 [4.9-13.9]
6.0 [1.4 - 14.7]
0.45
1st cefepime dose, hrs
13.8 [6.1 - 66.8]
11.4 [5.5 - 21.8]
0.47
Total antibiotic, days
11.8 [8.0 - 13.7]
13.3 [10.9 - 15.2]
0.34
Total cefepime, days
7.2 [5.0 - 12.1]
8.9 [4.0 - 13.6]
0.76
p-value
60
40
14
12
20
8
0
Infection-related LOS
6
0
Time from index to:
≤1
2
4
8
6 (29)
21 (31)
0.38
CVD
8 (38)
19 (28)
0.38
Non-Dialysis CKD
2 (10)
8 (12)
1
Immunosuppression
8 (38)
31 (46)
0.55
Liver Disease
1 (5)
4 (6)
1
ICU on index
10 (48)
18 (27)
0.07
ICU during admission
14 (67)
28 (41)
0.04
Clinical success
17 (81)
56 (82)
1
APACHE II*
21 ± 9
18 ± 8
0.22
Hospital mortality
1 (5)
7 (10)
0.67
10.5 [8.8 - 14.1]
10.6 [7.0 - 15.6]
0.7
SCr- Serum creatinine
CVD- Cardiovascular disease
CKD- Chronic Kidney Disease
2g IV every 8 h
Standard dosing
Diabetes mellitus
*Mean ± standard deviation
** Median (Inter-quartile range)
n (%), unless otherwise specified
APACHE- Acute Physiology and
Chronic Health Evaluation
1g IV every 6 h
Outcome
0
Gram-negative bacteremia
Received appropriate empiric therapy within 24 hours of
positive blood culture collection
100
0.20
Comorbidities
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[email protected]
RESULTS
Characteristic
METHODS
•
INTRODUCTION
Altamonte Springs, FL 32714
OBJECTIVE
Compare the following outcomes based on novel cefepime dosing
(1g every 6h) versus standard dosing regimens:
5021 Sweet Leaf Ct.
of Pharmacy; 2 Division of Infectious Diseases; Orlando Health, Orlando, FL
Percent of cases (%)
ABSTRACT
Methods: Inpatients at Orlando Health from 2008 to 2010 who received
FEP for ≥ 72h for Gram-negative bacteremia due to a susceptible (FEP
MIC ≤ 8 µg/mL) microorganism were retrospectively evaluated. Patients
with concomitant Gram-positive bacteremia or fungemia were excluded.
Clinical success, mortality, and infection-related length of stay (IR-LOS)
were compared based on novel (1g every 6h) v. standard (1g every 8h,
2g every 12h, or 2g every 8h) dosing.
Current Affiliation:
Optimer Pharmaceuticals
Matthew R. Helgeson1, Deba S. Rihani1, Robert A. Waite 1, Mark R. Wallace2, C. Andrew DeRyke 1,2
Background: Cefepime (FEP) dosing of 1 gram (g) IV every 6 hours (h)
is used commonly at our institution to maximize the free time above the
MIC. We report the outcomes of patients treated at our large
community-teaching hospital using this novel regimen.
C. Andrew DeRyke
Minimum Inhibitory Concentration (µg/mL)
TABLE 2. Clinical outcomes for entire cohort
Outcome
Infection-related LOS
Duration of therapy:
Novel
Standard†
(n = 21)
(n = 68)
p-value
n (%) or median [Inter-quartile range]
LOS = length of stay (days)
CONCLUSIONS
Time from index to:
Concomitant Gram-positive bacteremia and/or fungemia
Isolation of organisms in which cefepime is not routinely
effective (e.g., Acinetobacter spp., Stenotrophomonas
maltophilia, ESBL positive Enterobacteriaceae)
End-stage renal disease requiring dialysis prior to
admission
FIGURE 1. Organisms isolated
11%
8%
Index date: calendar date the first Gram-negative
organism isolated
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Clinical Success: Resolution of signs & symptoms of
infection such that no further antibiotic therapy was
required
8.9 [4.9-13.9]
6.0 [0.59 - 15.0]
0.29
1st cefepime dose, hrs
13.8 [6.1 - 66.8]
13.9 [5.5 - 23.6]
0.53

Patients treated with the novel cefepime dosing regimen of 1 gram IV every 6 hours
experienced no difference in clinical outcomes, mortality, or infection-related length of
stay

Cefepime 1 gram IV every 6 hours showed no difference in outcomes in comparison to 2
grams IV every 8 hours, and may represent a more cost-effective dosing strategy

Failure to find a difference in outcomes may be due to the low MIC’s among the infecting
organisms

Further prospective studies are needed to assess the validity of this novel dosing
strategy in patients with other documented sources of infection (i.e. pneumonia)
27%
Duration of therapy:
14%
Total antibiotic, days
Definitions
•
1st antibiotic dose, hrs
18%
Pseudomonas aeruginosa
Other
Klebsiella pneumoniae
11.8 [8.0 - 13.7]
12.1 [6.9 - 14.3]
0.78
22%
Total cefepime, days
Escherichia coli
Enterobacter cloacae
Serratia marcescens
7.2 [5.0 - 12.1]
6.7 [4.3 - 11.1]
n (%) or median [Inter-quartile range]
† 2g every 12 h (n = 7), 2g every 8 h (n = 24), 1g every 8 h (n = 37)
LOS = length of stay (days)
0.5