Ertapenem for the Treatment of Osteomyelitis: A Retrospective Analysis

sadhospitalΜηχανική

22 Φεβ 2014 (πριν από 3 χρόνια και 7 μήνες)

115 εμφανίσεις

Ertapenem for the Treatment of
Osteomyelitis: A Retrospective
Analysis

of the
Bone And Joint Infection Organization (BAJIO)
Database.


Medina
Stella
MD¹,
Gnoni Martin
MD¹,
Mariko Cheick
CRC¹,
Harting Julie
PharmD¹,³,
Newman David
PharmD²,
Kelley Robert
PhD¹,Christensen Diana MD¹,²,
and Julio Ramirez
MD¹².

¹Division
of Infectious Diseases, University of Louisville,
²Robley
Rex Veterans Affairs Medical Center,
³Sullivan
College of Pharmacy all in Louisville,
Kentucky. Bone
And Joint Infection
Organization (BAJIO)
Group.

ABSTRACT




Background
:

There

is

limited

data

regarding

ertapenem

in

the

treatment

of

osteomyelitis
.

The

objective

of

this

study

was

to

analyze

data

from

patients

receiving

ertapenem

for

the

treatment

of

osteomyelitis

to

further

characterize

clinical

outcomes

and

adverse

effects

associated

with

ertapenem
-
prolonged

therapy
.

Methods
:

This

was

a

retrospective

study

of

adult

patients

with

diagnosis

of

osteomyelitis

treated

with

ertapenem

at

the

UofL

Hospital

and

the

VA

Hospital

in

Louisville,

KY
.

All

patients

from

December

2010

to

February

2013

with

diagnosis

of

osteomyelitis

treated

with

ertapenem

for



2

weeks

were

reviewed
.

The

diagnosis

of

osteomyelitis

was

confirmed

using

radiographic

or

histopathologic

criteria,

or

positive

bone

culture
.

The

microbiological

diagnosis

was

confirmed

with

positive

bone

culture,

deep

tissue

culture,

or

blood

culture
.

A

patient

was

a

candidate

for

ertapenem

if

the

osteomyelitis

was

polymicrobial
.

Results
:

A

total

of

33

patients

were

reviewed

(
79
%

males)
.

Nine

diabetic

foot

infections,

19

other

locations,

3

PJI

and

2

Septic

arthritis
.

Median

ertapenem

days

were

40

(
18
-
76
)
.

Median

follow

up

was

114

days

(
20
-
547
)
.

Seventeen

and

16

patients

received

2

grams

Q
24

and

1

gram

Q
24

respectively
.

The

success

rate

was

85
%
.

Minor

adverse

effects

were

seen

in

33
%

and

were

not

related

with

the

dose
.

Conclusion
:

e
rtapenem

appears

to

be

effective

in

the

treatment

of

osteomyelitis
.

It

possesses

a

favorable

safety

profile

even

with

high

doses
.

These

findings

warrant

further

research

describing

ertapenem

use

in

bone

infections
.

INTRODUCTION

MATERIALS AND METHODS

REFERENCES

RESULTS

Study

Design
:



This

was

a

secondary

analysis

of

the

BAJIO

database

examining

osteomyelitis

cases

treated

with

ertapenem
.



The

database

included

patients

from

the

University

of

Louisville

Hospital

and

the

Robley

Rex

Veterans

Affairs

Medical

Center

both

in

Louisville,

Kentucky
.



Inclusion

Criteria
:





18

years

of

age



Confirmed

osteomyelitis
:


1.
Osteomyelitis

confirmed

by

x
-
rays,

computed

tomography,

magnetic

resonance

imaging,

and/or

nuclear

medicine

studies
.


1.
Suggestive

radiologic

indices

augmented

by

histologic

evaluation

of

bone

and/or

positive

cultures

for

bacteria

in

bone

biopsy

specimens
.



A

patient

was

a

candidate

for

ertapenem

if

the

osteomyelitis

was

polymicrobial

either

by

culture

or

clinical

suspicion
.


Exclusion

Criteria

for

Primary

Outcome
:



Those

not

receiving


2

continuous

weeks

of

ertapenem



Study

D
efinitions

and

Outcomes
:



1
-

Primary

outcome
:

-

Clinical

success

=

resolution

of

disease

measured

clinically

and

with

decreased

ESR

and

CRP,

without

need

for

alteration

in

antibiotic

therapy

or

repeat

surgical

intervention



2
-

Secondary

outcomes
:

-

Adverse

events

=

enumerated

and

compared

by

dosing

strategy

(
1
g

daily

versus

2

g

daily)

=

side

effects

or

laboratory

aberrations

in

patients

on

ertapenem



Statistics
:



Fisher’s

exact

test

or

Chi
-
squared

test,

as

appropriate,

for

comparisons

between

e
rtapenem

dosing

groups




Clinical

success

was

described

as

the

number

(
%
)

of

those

clinically

evaluable

who

were

coded

as

successes
.




Microsoft

Excel™

2010

was

used

for

all

calculations
.




P
-
values


0
.
05

were

considered

significant
.



CONCLUSIONS

[1]
http://
www.invanz.com/ertapenem_sodium/invanz/hcp/index.xhtml


[2] Goswami ND, et al. Ertapenem for the treatment
of osteomyelitis. BMC Research
Notes 2011,
4:478.
http
://
www.biomedcentral.com/1756
-
0500/4/478


[3]
Ramos A, Berbari E, Huddleston P. Diagnosis and treatment of Fusobacterium
nucleatum discitis and vertebral osteomyelitis: case report and review of the literature.
Spine
.
2013 Jan 15; 38(2
).


[4]
Lee CH, Su LH, Lin WC, Tang YF, Liu JW. Refractory vertebral osteomyelitis due to
CTX
-
M
-
14
-
producing Escherichia coli at ertapenem treatment in a patient with a
coexisting urinary tract infection caused by the same pathogen. Int J Infect Dis. 2010
Sept; 14 (3).


[5] M
.
Chen, A et al. Comparative
Pharmacokinetics and Pharmacodynamic Target

Attainment of Ertapenem in Normal
-
Weight,
Obese, and
Extremely Obese
Adults.

A
ntimicrobial agents and chemotherapy,
Apr. 2006, p.
1222

1227.



For

the

primary

endpoint

of

clinical

success,

27
/
30

evaluable

patients

(
90
%
)

achieved

success,

3

patients

were

lost

to

follow
-
up
.




A

total

of

33

patients

were

evaluated

for

adverse

events

and

discontinuations

of

e
rtapenem



Dosing

regimens

for

e
rtapenem

were

1
g

administered

once

daily

(
n

=

16
),

or

2
g

administered

once

daily

(
n

=

17
)
.

Mean

l engt h

of

treatment

was

39
.
3

days

(
18
-
76
)
.



Approximately

27
%

experienced

some

adverse

event
.

Nausea

and

vomiting

3

(
8
%
),

eosinophilia

3

(
8
%
),

neutropenia

1
(
3
%
),

hyperbilirubinemia

1

(
3
%
),

and

diarrhea

1

(
3
%
)
.




The

incidence

of

adverse

events

between

the

1
g

and

2
g

dosing

strategies

did

not

differ

statistically
.



Ertapenem

was

discontinued

in

5

patients

due

to

an

adverse

event
.

Discontinuations

between

the

1
g

and

2
g

groups

did

not

differ

statistically
.


RESULTS (Cont’d)


Ertapenem is FDA approved for the treatment of complicated
intra
-
abdominal infections, complicated skin/skin structure infections,
including diabetic foot infections without
osteomyelitis,
community
-
acquired pneumonia, complicated urinary tract
infections (including
pyelonephritis), acute
pelvic
infections (including
postpartum
endomyometritis),
septic abortion, and postsurgical gynecologic
infections and prophylaxis of surgical site infection following elective
colorectal
surgery. [1]



Ertapenem is a broad
-
spectrum carbapenem with a long


half
-
life
permitting once
-
daily dosing.



Ertapenem has activity against the
most invasive bacterial pathogens
except for
methicillin
-
resistant
Staphylococcus aureus
(MRSA
),
Enterococci
,
Pseudomonas aeruginosa
, and
Acinetobacter baumannii
.
[2]



A prior
study
has shown 12 cases of osteomyelitis treated with
ertapenem as the primary antimicrobial with a success rate of 50%
among patients who received an average of six weeks of
ertapenem
.
[2]



There
are few
case reports
with ertapenem for the treatment of
osteomyelitis.[3,4]



A study of obese patients with
vertebral osteomyelitis
suggests
that 1gr
q 24 hs is suboptimal/sub therapeutic.[5]



There
are limited
data regarding ertapenem in the treatment of
osteomyelitis
.



The
objective

of this study was to analyze data from patients receiving
ertapenem for osteomyelitis to further characterize clinical outcomes
and adverse effects associated with ertapenem
-
prolonged therapy.

Table
1: Demographic
and laboratory data for
33
cases of
osteomyelitis treated
with Ertapenem

_________________________________________________________________________________________________________________________

Variable






No
./%
ª








(n
=
33)

_________________________________________________________________________________________________________________________

Demographic
data



Age
, mean (SD)




49.6 (33)



Male
sex




26 (79%)


Caucasian





25 (76%)


African
-
American





8 (24%)


Comorbidities


Hypertension




18
(
55%)


Current smoker




12 (36
%)



Diabetes





11 (33%)


Orthopedic hardware



10 (30%)



Peripheral
neuropathy





8 (24%)


Peripheral arterial disease



6 (18%)


Chronic
renal disease




2 (6%)


Current
alcohol use




3 (9%)



Coronary
artery
disease



3 (9%)



Current
steroid use




3 (9%)



Cirrhosis






1 (3%)

Site
of Infection/Surgical intervention


Diabetic
foot





9 (27%)


Other
site





19 (57%)







Mandible




9 (27%)



PJI 3 (9%)



S
eptic arthritis 2 (6%)

Laboratory
data upon
diagnosis

WBC
(cells/mm³), Median (IQR)


11.6 (3.5
-
21.9.)

ESR
(mm/hr), Median (IQR)



62.82 (0
-
140)

CRP
(mg/dl), Median (IQR)



8.91 (0.09
-
32.59)

Procalcitonin,
Median (IQR
) 0.77 (0.05
-
3.7)

---------------------------------------------------------------------------------

SD
: standard deviation; WBC: white blood cell count; IQR: interquartile range; ESR:
erythrocyte sedimentation rate; CRP: C
-
reactive protein.

ªAll values are given as No. (% of total patients) unless otherwise specified.





Ertapenem
appeared to be
efficacious
for the
treatment of polymicrobial
osteomyelitis.



Ertapenem possesses
a favorable safety
profile,
even with high doses
.




These
findings warrant further research describing ertapenem use
in
bone infections.

Table 2: Pathogenic
isolates from clinically evaluable patients with
osteomyelitis
.

___________________________________________________________________________________________________________________________

Organism (s)







No.
(%)










(
n

=
36)

___________________________________________________________________________________________________________________________

Enterobacteriaceae







13/36 (36%)


Enterobacter

cloacae






5


Escherichia
coli







3



Klebsiella 2


Serratia

marcescens






1


Citrobacter







1



Proteus mirabilis 1




Staphylococcus
aureus






4/36 (
11%
)


Methicillin
-
resistant






3


Methicillin
-
susceptible 1


Staphylococcus coagulase negative





5/36 (14%)


Streptococcus

species






7/36 (20%)


Streptococcus
viridans






2


Streptococcus anginosus

group




1


Other streptococcal species





4


Anaerobic
bacteria


1/36 (3%)




Bacteroides
fragilis

group




1



Enterococcus
faecalis






3/36 (8%)


Vancomycin resistant






0








Other

GNR


3/36 (8%)

ªAll values are given as No. of a given isolate (% of total bacterial isolates).