Fusidic acid for the treatment of bone and joint infections caused by meticillin-resistant Staphylococcus aureus.

Contents

lists

available

at

SciVerse

ScienceDirect

International

Journal

of

Antimicrobial

Agents

j o u

r n

a l

h

o m

e p a

g e :

h

t t p : / / w w w . e l s e v i e r . c o m / l o c a t e / i j a n t i m i c a g

Review

Fusidic

acid

for

the

treatment

of

bone

and

joint

infections

caused

by

meticillin-resistant

Staphylococcus

aureus

Jiun-Ling

Wang

a

_,

_Hung-Jen

_Tang

b

_,

_Pang-Hsin

_Hsieh

c

_,

_Fang-Yao

_Chiu

d

_,

_Yen-Hsu

_Chen

e

,

f

_,

Ming-Chau

Chang

d

_,

_Ching-Tai

_Huang

g

_,

_Chang-Pan

_Liu

h

_,

_Yeu-Jun

_Lau

i

_,

_Kao-Pin

_Hwang

j

_,

_Wen-Chien

_Ko

k

_,

Chen-Ti

Wang

l

_{, Cheng-Yi}

_Liu

m

_{, Chien-Lin}

_Liu

d

_,

_Po-Ren

_Hsueh

n

,

∗

a_{DepartmentofInternalMedicine,E-DaHospital/I-ShouUniversity,Kaohsiung,Taiwan}

b_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,ChiMeiMedicalCenterandDepartmentofHealthandNutrition,ChiaNanUniversityofPharmacyandScience,}

Tainan,Taiwan

c_{DivisionofJointReconstruction,DepartmentofOrthopaedicSurgery,ChangGungMemorialHospitalatLinkou,Taiwan}

d_{DepartmentofOrthopaedicSurgery,TaipeiVeteransGeneralHospital,NationalYangMingUniversity,Taipei,Taiwan}

e_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,KaohsiungMedicalUniversityHospital,Kaohsiung,Taiwan}

f_{GraduateInstituteofMedicine,TropicalMedicineResearchCenter,CollegeofMedicine,KaohsiungMedicalUniversity,Kaohsiung,Taiwan}

g_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,ChangGungUniversityandMemorialHospitalatLinkou,Taiwan}

h_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,MackayMemorialHospital,Taipei,Taiwan}

i_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,ShowChwanMemorialHospital,Changhua,Taiwan}

j_{DivisionofInfectiousDiseases,DepartmentofPediatrics,ChinaMedicalUniversityHospital,ChinaMedicalUniversitySchoolofMedicine,Taichung,Taiwan}

k_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,NationalChengKungUniversityHospital,Tainan,Taiwan}

l_{DepartmentofOrthopaedicSurgery,NationalTaiwanUniversityHospitalandNationalTaiwanUniversityCollegeofMedicine,Taipei,Taiwan}

m_{DivisionofInfectiousDiseases,DepartmentofInternalMedicine,TaipeiVeteransGeneralHospital,Taipei,Taiwan}

n_{DepartmentsofLaboratoryMedicineandInternalMedicine,NationalTaiwanUniversityHospital,NationalTaiwanUniversityCollegeofMedicine,No.7Chung-ShanS.Road,Taipei}

100,Taiwan

a

r

t

i

c

l

e

i

n

f

o

Keywords:

Fusidicacid

Meticillin-resistantStaphylococcusaureus

(MRSA)

Boneandjointinfection

Rifampicin

Combinationtherapy

a

b

s

t

r

a

c

t

Thereisalackofsurveillancedataonresistancetofusidicacid(FA)inAsia,andnoreviews ofFA usageforthetreatmentoforthopaedicinfectionshavebeenconductedsincetheyear2000.Inthis study,wepresentasystemicliteraturereviewofFAresistanceinAsiaandtheclinicaluseofFAfor thetreatmentofboneandjointinfections(BJIs).TheinvitroactivityofFAagainstmeticillin-resistant Staphylococcusaureus(MRSA)isolatesremainsgood,withlow(<10%)resistanceratesinmostAsian countries.FAinAsiaappearstobeabetteroralanti-MRSAagentthantrimethoprim/sulfamethoxazole andclindamycin.Morethan80casesofFAuseforBJIhavebeenreportedsince2000andthe recur-renceorfailurerateis<10%.ThereismuchevidencesupportingtheuseofFAincombinationwith otherantibiotics(e.g.rifampicin)asanoraltreatmentfollowingintravenousglycopeptidetreatmentfor BJIs.

© 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

1.

Introduction

There

is

a

need

for

safe,

oral

antibiotics

against

meticillin-resistant

Staphylococcus

aureus

(MRSA)

for

effective

step-down

therapy

after

hospitalisation

or

for

initial

therapy

for

community-acquired

infections

[1]

.

Fusidic

acid

(FA),

manufactured

by

Leo

Pharmaceuticals,

has

been

widely

used

in

Europe,

Canada,

Australia

and

some

Asian

countries

for

decades.

Although

FA

has

not

been

approved

for

use

in

the

USA

by

the

US

Food

and

Drug

Administra-tion

(FDA),

Cempra

Pharmaceuticals

has

designed

a

dosing

regimen

∗ Correspondingauthor.

E-mailaddress:hsporen@ntu.edu.tw(P.-R.Hsueh).

for

the

use

of

FA

as

monotherapy

if

and

when

it

is

approved

for

use

in

the

USA

[1,2]

.

A

number

of

review

papers

on

FA

were

published

in

the

Inter-national

Journal

of

Antimicrobial

Agents

in

the

1990s

[3–7]

and,

in

2010,

Schöfer

and

Simonsen

reviewed

the

clinical

efficacy

of

FA

for

skin

and

soft-tissue

infections

(SSTIs)

[8]

.

The

evidence

provided

in

those

review

papers

showed

that

FA

is

an

effective

treatment

for

SSTIs,

acute

osteomyelitis,

chronic

osteomyelitis,

vertebral

infection,

septic

arthritis,

and

prosthetic

and

other

device-related

infections

due

to

meticillin-susceptible

S.

aureus

(MSSA).

There

are

few

oral

antibiotics

listed

in

the

treatment

guidelines

for

treatment

of

MRSA

infections

[3–8]

.

The

therapeutic

guidelines

in

Australia

list

the

combination

of

rifampicin

(RIF)

and

FA

as

a

treat-ment

option

for

recurrent

staphylococcal

skin

infections

(including

0924-8579/$–seefrontmatter © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

MRSA-positive

infections)

and

MRSA

osteomyelitis

involving

the

bone

or

joint

prostheses,

both

in

adult

and

paediatric

patients

[9]

.

Treatment

guidelines

in

the

UK

recommend

FA

and

RIF

for

bone

and

joint

infections

(BJIs)

[10]

.

In

several

reviews

on

BJIs,

FA

is

listed

as

the

treatment

of

choice

[11–15]

.

Here

we

provide

a

review

of

FA

resistance

patterns

in

Asia

and

focus

on

the

use

of

FA

for

the

treatment

of

BJIs

due

to

MRSA

after

the

year

2000.

Comprehensive

searches

were

conducted

of

Medline,

PubMed,

Google

Scholar,

CINAHL,

EMBASE

and

the

CNKI

(Chinese

National

Knowledge

Infrastructure)

database

as

well

as

reference

lists

of

retrieved

articles.

Search

terms

were

‘fusidic

acid’,

‘Staphy-lococcus

aureus’,

‘MRSA’,

‘osteomyelitis’,

‘septic

arthritis’

and

‘bone

and

joint

infection’,

with

each

of

the

target

country

names

in

turn.

Studies

with

a

percentage

of

FA

resistance

in

MRSA

in

Chinese

arti-cles

are

included.

2.

Pharmacology

FA

inhibits

polypeptide

chain

elongation

by

binding

to

the

ribo-some

elongation

factor

G

(EF-G)–GDP

complex.

FA

has

good

oral

bioavailability

and

is

metabolised

and

excreted

by

the

liver

[16]

.

This

bacteriostatic

agent

is

highly

protein-bound

and

has

been

shown

to

have

good

concentrations

in

soft

tissue,

bone

and

syn-ovial

fluid

[3,17,18]

.

FA

is

active

against

several

Staphylococcus

spp.,

including

MSSA

and

MRSA,

but

has

poor

activity

against

Streptococcus

pyogenes

[4]

.

Rates

of

resistance

to

FA

are

higher

among

coagulase-negative

staphylococci

(CoNS)

than

among

S.

aureus

[4,19–21]

.

The

recommended

dose

of

FA

is

250–500

mg

every

8–12

h;

however,

new

pharmacokinetic

data

show

that

front-loaded

dosing

[

_≥1200

mg

every

12

h

(q12h)

_{× 2}

doses

followed

by

≥600

mg

q12

h]

has

better

activity

against

MRSA

and

S.

pyogenes

than

non-front-loaded

dosing

(600

mg

q12

h)

[2]

.

3.

In

vitro

activity

of

fusidic

acid

in

combination

with

other

antibiotics

Most

in

vitro

and

in

vivo

studies

on

FA

combinations

have

concentrated

on

the

effects

of

FA

with

RIF.

Other

common

oral

com-binations

with

FA

include

minocycline,

linezolid

and

fosfomycin.

Checkerboard

dilution

and

time–kill

methods

have

revealed

that

FA

combined

with

RIF

had

partial

synergistic

effects

[22–26]

.

A

combi-nation

of

FA

and

minocycline

has

been

reported

for

the

treatment

of

vancomycin-intermediate

S.

aureus

(VISA)

infection,

but

there

is

a

lack

of

in

vitro

data

[27]

.

FA

combined

with

linezolid

has

been

suc-cessful

in

the

treatment

of

VISA

infection

and

endocarditis

[28–30]

.

When

combined

with

FA,

linezolid

was

shown

to

prevent

selec-tion

of

resistant

mutants

but

showed

no

synergy

in

one

study

[31]

.

Saginur

et

al.

found

that

RIF

and

FA,

plus

either

ciprofloxacin

or

vancomycin,

were

consistently

bactericidal

against

MRSA

biofilms

[32]

.

Another

study

in

China

showed

88%

synergism

when

FA

was

combined

with

fosfomycin

[33]

.

Tang

et

al.

found

that

the

in

vitro

killing

effects

of

fosfomycin

combined

with

FA

were

better

than

the

killing

effects

of

RIF

combined

with

FA

[34]

.

4.

Fusidic

acid

resistance

in

North

America

and

Europe

The

prevalence

of

resistance

to

FA

in

S.

aureus

remained

low

well

into

the

1990s.

In

staphylococci,

high-level

FA

resistance

is

usually

caused

by

mutations

in

fusA,

the

gene

encoding

EF-G,

and

low-level

resistance

is

generally

caused

by

the

horizontally

trans-ferable

genes

fusB

and

fusC

[35–37]

.

FusB-type

proteins

bind

to

EF-G

on

the

ribosome,

which

allows

the

ribosomes

to

resume

transla-tion.

There

is

also

a

concern

that

recent

exposure

to

topical

FA

is

correlated

with

the

presence

of

FA-resistant

S.

aureus

[38–40]

.

In

addition,

there

is

also

a

significant

trend

towards

increased

FA

resistance

among

S.

aureus

with

increased

duration

of

use

[40,41]

.

Updated

surveillance

data

on

FA

resistance

in

MRSA

have

been

reported

in

studies

from

North

America,

Australia

and

Europe

[20,21,41,42,36]

.

Staphylococcus

aureus

resistance

rates

are

very

low

in

the

USA

(0.3%)

and

are

relatively

high

in

Canada

and

Australia

(ca.

7.0%)

[20,21]

.

In

Canada,

the

occurrence

of

fusB

and

fusC

is

sim-ilar

among

S.

aureus,

whereas

in

Australia

S.

aureus

isolates

tend

to

be

fusC-positive

[20,21]

.

The

increase

in

FA

resistance

in

Europe

appears

to

be

due

to

clonal

expansion

of

a

strain

called

the

epidemic

European

FA-resistant

impetigo

clone.

This

clone

has

been

reported

in

the

UK,

France

and

other

European

countries

[43–45]

.

In

an

updated

surveillance

report

on

FA

resistance

in

13

European

countries,

10.7%

of

S.

aureus

isolates

displayed

FA

minimum

inhibitory

concentra-tions

(MICs)

≥2

mg/L

[41]

.

Israel,

Italy,

Poland,

Spain

and

Sweden

had

low

rates

(1.4–3.1%)

of

FA

resistance

[41]

.

Greece

(62.4%)

and

Ireland

(19.9%)

had

the

highest

resistance

rates.

Many

of

the

FA-resistant

S.

aureus

isolates

in

Greece

and

Ireland

were

spread

clonally

and

showed

high

fusidic

MIC

values

(

≥512

mg/L),

espe-cially

among

isolates

that

carried

the

fusA

L461

K

mutation

[41]

.

It

is

unclear

whether

the

emerging

FA

resistance

patterns

seen

in

some

European

countries

are

also

present

in

Asia

[37,41,42]

,

mainly

because

there

is

an

overall

lack

of

surveillance

data

in

Asian

coun-tries.

5.

Fusidic

acid

resistance

in

Asia

Resistance

rates

to

FA

in

Asian

countries

are

shown

in

Table

1

(

references

S1–S31

in

Supplementary

data

).

Resistance

rates

from

2000

to

the

present

are

available

for

13

Asian

countries,

namely

China,

Japan,

South

Korea,

Taiwan,

Hong

Kong,

Singapore,

Malaysia,

Thailand,

Cambodia,

Kuwait,

Iran,

Saudi

Arabia

and

Pakistan.

Resis-tance

was

determined

by

the

disk

diffusion

method

in

most

of

those

studies.

In

most

Asian

countries,

with

the

exception

of

Kuwait,

Pakistan

and

South

Korea,

resistance

rates

are

relatively

low

(<10%).

In

general,

clindamycin

resistance

is

high

in

Asia

(>60%).

Although

most

isolates

are

more

susceptible

to

trimethoprim

than

to

clin-damycin,

the

rates

of

resistance

to

these

two

antimicrobial

agents

are

higher

than

those

to

FA.

Few

studies

have

provided

data

on

resistance

to

doxycycline

and

minocycline

(data

not

shown).

In

Kuwait,

most

MRSA

isolates

have

high

FA

MICs

(>256

mg/L),

possibly

because

of

the

circulation

of

epidemic

clones.

Transmis-sion

of

these

clones

and

their

maintenance

in

different

hospitals

may

explain

their

high

prevalence

in

Kuwaiti

hospitals.

The

cir-culating

strains

with

sequence

type

(ST)

80

commonly

isolated

from

patients

with

community-acquired

(CA)

MRSA

in

Kuwait

are

not

seen

in

other

Asian

countries.

In

contrast,

ST59

is

the

most

common

CA-MRSA

strain,

and

ST239

is

the

most

common

noso-comial

MRSA

strain

in

most

Asian

countries.

In

contrast

to

other

CA-MRSA

clones,

the

ST80

clone

commonly

carries

the

fusB

gene,

which

appears

to

confer

reduced

susceptibility

to

FA.

Studies

from

Greece

and

Kuwait

have

reported

a

high

incidence

of

ST80

among

CA-MRSA

isolates

and

high

rates

of

FA

resistance

[46,47]

.

Accord-ing

to

recent

data

gathered

by

the

Asian

Network

for

Surveillance

of

Resistant

Pathogens

(ANSORP),

which

is

a

prospective,

multina-tional

surveillance

study,

ST80

has

not

been

isolated

in

any

Asian

country

[48]

.

ST80

is

common

in

the

Mediterranean

and

Balkan

regions

as

well

as

in

the

Middle

East.

The

reason

for

the

relatively

high

prevalence

of

FA

resistance

in

Pakistan

and

South

Korea

is

not

known.

FA

resistance

among

MSSA

is

also

high

in

South

Korea

[49,50]

.

In

Kuwait,

the

rate

of

FA

resistance

increased

dramatically

from

22%

in

1994

to

92%

in

2004

[51]

.

In

Malaysia,

the

rate

of

resis-tance

to

FA

among

MRSA

isolates

increased

from

3–5%

during

the

Table1

Resistanceprofilesoffusidicacid(FA)inAsiancountries.

Country Referencea _{Studyyear Susceptibilitytestingmethod No.ofisolatestested %ofresistantisolates}

FA CLI SXT RIF

HighFAresistance

SouthKorea Leeetal.[S1] 1996 DDM 90 12.2 86.7 N/A N/A

SouthKorea Kimetal.[S2] 1999–2001 DDM 439 14.1 84.3 8.9 18.0

SouthKorea Kimetal.[S3] 2008 ADM 40 52.5 50 10 17.5

Kuwait Udoetal.[S4] 2004 DDM 930 92 N/A 27 4.7

Kuwait Udoetal.[S5] 2005 DDM 588 84 N/A 81 1

Pakistan Idreesetal.[S6] 2005–2007 DDM 501 9 79 59 50

Pakistan Zafaretal.[S7] 2006–2007 DDM 126 18 N/A 43 N/A

Pakistan Shabiretal.[S8] 2010 DDM 60 20 N/A N/A 52

LowFAresistance

Cambodia Chhengetal.[S9] 2006–2007 DDM 17 0 77 88 N/A

Chinab _{Chenetal.[S10] 2001–2003 DDM 50 2.0 N/A 36 14}

Chinab _{Ni[S11] 2002 DDM 57 1.7 95.9 23.5 22.7}

Chinab _{Chang[S12] 2002–2003 DDM 280 1.7 95.9 23.5 22.7}

Chinab _{Pan[S13] 2002–2003 DDM 50 12 100 40 10}

China Liuetal.[S14] 2003–2007 ADM 11 0 90.9 N/A N/A

Chinab _{Huetal.[S15] 2006–2007 DDM 56 1.8 92.8 25.0 N/A}

China Liuetal.[S16] 2008–2009 DDM 66 3 N/A N/A N/A

HongKong Ipetal.[S17] 2000–2001 DDM 200 1 67.5 6 N/A

Iran Askarianetal.[S18] 2006 DDM 32 0 69 N/A 3

Iran Japonietal.[S19] 2008–2009 Etest 156 0 76 69 11

Japan Takizawaetal.[S20] 2003 ADM 54 0 N/A N/A 0

Japan Nakaminamietal.[S21] 2006 DDM 76 1.3 35.5 N/A N/A

Malaysia Norazahetal.[S22] 1997–1999 DDM 640 5 N/A N/A 5

Malaysia Thongetal.[S23] 2003–2007 DDM 66 11 19 N/A 12

Taiwan Chenetal.[S24] 1995–2006 ADM 257 0 88 75.8 N/A

Taiwan Linetal.[S25] 2003–2007 DDM 94 1.1 85.6 4.8 N/A

Taiwan Loetal.[S26] 2004–2006 DDM 131 0 88.5 0 0

Taiwan Loetal.[S26] 2007–2009 DDM 240 0 89.6 2.9 1.3

Thailand Hortiwakuletal.[S27] 2000–2001 Etest 100 0 N/A N/A N/A

Thailand Mekviwattanawongetal.[S28] 2005 DDM 184 6.1 91.4 85.9 53.8

Thailand Nickersonetal.[S29] 2006–2007 DDM 23 13 65 96 35

SaudiArabia Baddouretal.[S30] 2004–2005 Etest 512 4.3 N/A 33.8 N/A

Singapore Hsuetal.[S31] 2005 DDM 197 <5 N/A N/A <5

CLI,clindamycin;SXT,trimethoprim/sulfamethoxazole;RIF,rifampicin;DDM,diskdiffusionmethod;N/A,notavailable;ADM,agardilutionmethod.

a_{ReferencesaregivenintheSupplementarydata.}

b_{ArticleinChinese.}

period

1992–1996

to

11%

in

2009

[52]

.

In

Singapore,

the

rate

of

FA

resistance

was

<5%

during

1997–2004

[53]

.

Data

from

one

medical

centre

in

Taiwan

revealed

that

FA

usage

remained

stable

from

2002

to

2009

and

that

the

prevalence

of

FA-resistant

Gram-positive

bac-teria

causing

healthcare-associated

infections

also

remained

stable

(ca.

3–7%)

[54]

.

Only

three

papers

have

been

published

on

FA

resistance

gene

determinants

in

Asia.

In

one

study

from

central

Taiwan,

the

most

common

FA

resistance

determinant

in

34

isolates

was

fusC

(74%)

[55]

.

In

northern

Taiwan,

Chen

et

al.

found

that

84%

of

45

FA-resistant

MRSA

isolates

had

fusA

mutations

[56]

.

A

small

study

in

China

showed

that

fusB

and

fusC

were

the

main

resistance

determinants

in

four

FA-resistant

clinical

isolates

[57]

.

6.

Fusidic

acid

in

bone

and

joint

infections

caused

by

meticillin-resistant

Staphylococcus

aureus

No

randomised

controlled

trials

of

FA

as

treatment

for

BJIs

due

to

MRSA

have

been

conducted.

Trampuz

and

Zimmerli

recom-mended

a

2-week

regimen

of

vancomycin

and

RIF

followed

by

FA

for

treatment

of

prosthetic

joint

infections

due

to

MRSA

[13]

.

Oral

antimicrobial

therapy

for

osteomyelitis

is

important

given

the

associated

costs

and

potential

morbidity

of

prolonged

courses

of

intravenous

(i.v.)

therapy

[14]

.

Unfortunately,

the

only

oral

antibi-otics

that

are

active

against

MRSA

include

pristinamycin,

linezolid,

trimethoprim/sulfamethoxazole

(SXT),

doxycycline

and

FA.

Table

2

presents

the

results

of

the

literature

search

for

reviews

of

treatment

of

osteomyelitis

and

septic

arthritis

[30,58–70]

.

The

three

large

series

of

FA

use

for

BJIs

involved

prosthetic

joint

infec-tions

with

or

without

implant

removal

[63,67,69]

.

In

most

cases,

FA

was

administered

along

with

RIF

following

administration

of

i.v.

glycopeptides.

Other

oral

antibiotics

that

are

used

in

combina-tion

with

FA

for

the

treatment

of

osteomyelitis

and

septic

arthritis

with

or

without

removal

of

the

prosthesis

include

chlorampheni-col,

doxycycline,

linezolid

and

pristinamycin.

In

general,

oral

FA

is

appropriate

for

long-term

use.

In

more

than

80

reported

cases

of

infections

treated

with

FA,

only

7

patients

(<10%)

had

treatment

failure

or

recurrence.

In

one

study

of

a

two-stage

revision

in

total

knee

arthroplasty

infected

with

MRSA

(89%)

or

meticillin-resistant

CoNS

(11%)

in

Taiwan

[69]

,

i.v.

vancomycin

or

teicoplanin

was

used

for

≥2

weeks

or

until

clinical

infection

control

was

observed

and

C-reactive

protein

(CRP)

had

decreased

to

<2.0

mg/dL.

Oral

sodium

fusidate

tablets

were

then

administered

for

≥4

weeks

until

the

CRP

value

returned

to

normal.

The

criteria

for

re-implantation

were

CRP

<

1.0

mg/dL

and

no

clinical

signs

of

infection

2

weeks

after

dis-continuing

the

oral

regimen.

In

that

series,

there

were

only

three

cases

of

recurrent

infection

[69]

.

In

a

retrospective

cohort

study

of

patients

with

MRSA

orthopaedic

device-related

infections

between

2000

and

2008

at

Geneva

University

Hospital

(Switzerland),

none

of

the

patients

who

received

RIF

plus

FA

(n

=

12)

experienced

treatment

failure

[67]

.

In

a

large

series

from

Australia

involving

patients

with

MRSA

prosthetic

joint

infections

treated

with

surgi-cal

debridement

and

prosthesis

retention,

RIF

combined

with

FA

was

administered

for

a

mean

duration

of

12

months

(range

6–33

months)

and

only

1

of

11

MRSA

infections

recurred

[63]

.

Other

case

reports

of

FA

use

for

the

treatment

of

BJIs

caused

by

MRSA

after

2000

are

listed

in

Table

2

[30,58–70]

.

Table2

Literaturereviewoffusidicaciduseforthemanagementofboneandjointinfectionscausedbymeticillin-resistantStaphylococcusaureus.

Reference Publication year

Country No.ofpatients Prosthetic device Durationofi.v. antibiotic treatment Oralantibioticin combination

No.ofpatientswith treatmentfailureor recurrence Howdenetal.[30] 2004 Australia 4 Yes N/R RIF,CHL 1

NgandGosbell[58] 2005 Australia 4 No N/R PRI 0

Natheretal.[59] 2005 Singapore 3 No 6–8weeks CLI 0

Chiangetal.[60] 2005 Taiwan 1 No 4weeks None 0

Donaldsonetal.[61] 2006 Australia 2 No 7weeks RIF 2

Inverarityetal.[62] 2006 UK 1 No 6weeks DOX 0

Aboltinsetal.[63] 2007 Australia 11 Yes 1–4weeks RIF 1

ApisarnthanarakandMundy[64] 2007 Thailand 1 No 2weeks RIF 0

Murrayetal.[65] 2008 Australia 7 No N/R RIF 0

AhamedPuthiyaveetil[66] 2009 Australia 1 No N/R RIF 0

Ferryetal.[67] 2010 Switzerland12 Yes N/R RIF 0

O’Neilletal.[68] 2011 Ireland 1 No 2weeks LZD 0

Chiangetal.[69] 2011 Taiwan 39 Yes 2–4weeks N/R 3

Wolfe[70] 2011 USA 1 No 10weeks None 0

i.v.,intravenous;N/R,notreported;RIF,rifampicin;CHL,chloramphenicol;PRI,pristinamycin;CLI,clindamycin;DOX,doxycycline;LZD,linezolid.

7.

Conclusions

The

in

vitro

activity

of

FA

in

Asia

is

good

and

most

countries,

with

the

exception

of

Kuwait,

South

Korea

and

Pakistan,

have

low

resis-tance

rates

(<10%).

FA

appears

to

be

a

better

oral

anti-MRSA

agent

than

SXT,

doxycycline/minocycline

and

linezolid.

For

the

treatment

of

MRSA

BJIs,

most

studies

support

the

use

of

FA

in

combination

with

other

antibiotics

(e.g.

RIF)

as

step-down

oral

antibiotic

regi-mens

following

administration

of

i.v.

glycopeptides.

Funding:

No

funding

sources.

Competing

interests:

None

declared.

Ethical

approval:

Not

required.

Appendix

A.

Supplementary

data

Supplementary

data

associated

with

this

article

can

be

found,

in

the

online

version,

at

http://dx.doi.org/10.1016/

j.ijantimicag.2012.03.010

.

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