Drugs 2008; 68 (9): Supplementary Material

0012-6667/08/0009-0001/$53.45/0REVIEW ARTICLE © 2008 Adis Data Information BV. All rights reserved.

Contemporary Management of Uncomplicated Urinary Tract Infections David R.P. Guay Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

Supplementary Material This supplementary material contains the table referred to in the full version of this article, which can be found at http://drugs.adisonline.com.

Epi

dem

iolo

gy o

f an

tim

icro

bial

s re

sist

ance

in u

ncom

plic

ated

uri

nary

trac

t inf

ecti

on (

uUT

I)

St

udy

Loc

atio

n #

(T

imef

ram

e)

isol

ates

D

etai

ls

G

upta

et a

l.[21]

U

SA

43

42

Res

ista

nce

rate

s:

(1

999)

(1

992-

6)

(all

18-5

0 y.

o.

Am

p 26

%-3

4%a (

E. c

oli,

N =

373

4),

29%

-38%

a (ov

eral

l, N

= 4

342)

fe

mal

e C

ipro

0-0

.2%

0.

2%-1

%

sour

ces)

N

itro

0.2%

-2%

6%

-9%

TM

P-S

MX

9%

-18%

a 8%

-16%

a

TM

P 9

%-1

8%a

9%-1

6%a

Kar

low

sky

et a

l.[22]

U

SA

51

3 R

esis

tanc

e ra

tes

for

E. c

oli:

(2

000)

(1

/00-

5/00

) (u

rina

ry is

olat

es

Am

p 39

.4/4

6.8%

(F/

M),

40

.1/3

7.4%

(18

-65/

>65

),

40.8

/40.

1%(i

npt./

outp

t.)

of E

. col

i fro

m

TM

P-S

MX

22.

5/31

.6%

24

.8/2

3.5%

22

.5/4

.3%

TR

UST

C

ipro

3.2

/12.

7%

3.7/

7%

7.1/

3.6%

surv

eilla

nce.

L

evo

3.2/

12.7

%

3.7/

7%

7.1/

3.6%

ty

pes

of U

TIs

w

ere

unkn

own)

G

upta

et a

l.[23]

U

SA

10

3223

R

esis

tanc

e ra

tes

wer

e si

gn. h

ighe

r in

> 5

0 ye

ar o

lds

vs. 1

5-50

yea

r ol

ds f

or

(200

1)

(199

8)

(out

patie

nt

Kle

bsie

lla

spp.

, Pro

teus

spp

., P

. aer

ugin

osa,

oth

er g

ram

-neg

ativ

e ro

ds,

fem

ales

≥

ente

roco

cci,

othe

r ba

cter

ia (

all p

< 0

.001

). R

esis

tanc

e ra

tes

wer

e si

gn. l

ower

15

yea

rs o

ld

in >

50

year

old

s vs

. 15-

50 y

ear

olds

for

E. c

oli a

nd S

. sap

roph

ytic

us

from

the

TSN

(b

oth

p <

0.0

01).

da

taba

se)

Res

ista

nce

rate

s fo

r E

. col

i (N

= 6

3196

):

A

mp

40/3

3% (

15-5

0/ >

50)

Nitr

o 1/

2%

C

ipro

1/2

%

Lev

o 1/

3%

T

MX

-SM

X 1

8/16

%

R

esis

tanc

e ra

tes

for

non-

E. c

oli (

N =

316

02):

Am

p 49

/49%

(15

-50/

> 5

0)

N

itro

40/3

9%

C

ipro

10/

22%

L

evo

5/21

%

T

MX

-SM

X 6

/11%

Res

ista

nce

rate

s ov

eral

l (N

= 9

4798

):

A

mp

42/3

9% (

15-5

0/ >

50)

Nitr

o 9/

16%

Cip

ro 2

/10%

L

evo

12/1

1%

T

MX

-SM

X 1

6/14

%

In

term

s of

E. c

oli s

usce

ptib

ilit

y by

reg

ion,

ther

e w

as n

o si

gn. a

ge-r

elat

ed

va

riat

ion

in r

esis

tanc

e ra

tes

wit

hin

regi

ons

for

Am

p or

TM

P-S

MX

. How

ever

,

ther

e w

as s

ign.

inte

r-re

gion

var

iatio

n in

res

ista

nce

rate

s fo

r bo

th a

gent

s w

ithi

n

bo

th a

ge s

trat

a (p

< 0

.001

). I

n ge

nera

l, re

sist

ance

rat

es w

ere

high

est i

n th

e

W

est a

nd S

outh

Cen

tral

reg

ions

, int

erm

edia

te in

the

Mid

wes

t and

Sou

thea

st

re

gion

s, a

nd lo

wes

t in

the

Nor

thea

st r

egio

n. T

he E

. col

i res

ista

nce

rate

s fo

r

N

itro

and

the

quin

olon

es d

id n

ot v

ary

by r

egio

n.

N

otab

le r

esis

tanc

e pa

ttern

s (1

5-50

/ > 5

0):

A

mp

vs. S

. sap

roph

ytic

us

71/7

3%

A

mp

vs. S

. aur

eus

84/9

3%

C

ipro

vs.

ent

eroc

occi

33

/56%

Lev

o vs

. ent

eroc

occi

17

/44%

Am

p vs

. Ent

erob

acte

r sp

p.

97

/95%

Nitr

o vs

. Ent

erob

acte

r sp

p.

49

/45%

Am

p vs

. Kle

bsie

lla

spp.

99

/98%

Nitr

o vs

. Kle

bsie

lla

spp.

43

/42%

Cip

ro v

s. P

. aer

ugin

osa

26/2

9%

L

evo

vs. P

. aer

ugin

osa

28/2

9%

C

ipro

vs.

S. a

ureu

s 10

/62%

Lev

o vs

. S. a

ureu

s 5/

50%

Cli

nica

lly-

sign

. age

-rel

ated

var

iatio

ns in

res

ista

nce

rate

s ex

iste

d fo

r th

e

qu

inol

ones

vs.

S. a

ureu

s an

d th

e en

tero

cocc

i. T

MP

/SM

X p

erfo

rmed

bet

ter

agai

nst n

on-E

. col

i iso

late

s (6

-11%

res

ista

nt)

vs. E

. col

i iso

late

s (1

6-18

%

re

sist

ant)

. Am

ong

the

non-

E. c

oli i

sola

tes,

thos

e fr

om p

atie

nts

over

50

year

s

old

exhi

bite

d a

12-1

6% in

crea

se in

res

ista

nce

rate

s to

the

quin

olon

es c

ompa

red

wit

h th

ose

patie

nts

15-5

0 ye

ars

old.

In

the

over

all i

sola

te p

opul

atio

n, th

ose

from

pat

ient

s ov

er 5

0 ye

ars

old

exhi

bite

d an

8-9

% in

crea

se in

res

ista

nce

rate

s

to th

e qu

inol

ones

and

Nitr

o co

mpa

red

wit

h th

ose

from

pat

ient

s 15

-50

year

s

ol

d.

Lau

plan

d et

al.[7

] C

alga

ry, C

anad

a 31

270

Res

ista

nce

rate

s:

(200

7)

(200

4-20

05)

(am

bula

tory

T

MP

-SM

X

14%

su

bjec

ts o

f bo

th

Cip

ro

5%

gend

ers)

N

itro

6%

T

MP

-SM

X r

esis

tanc

e ra

te m

odes

tly

decl

ined

wit

h ad

vanc

ing

age

(15

→

12

.5%

) w

hile

Cip

ro a

nd N

itro

resi

stan

ce r

ates

ros

e (2

.5 →

10%

and

4 →

12.5

%, r

espe

ctiv

ely)

. In

nurs

ing

hom

e re

side

nts

(N =

390

7), T

MP

-SM

X,

C

ipro

, and

Nitr

o re

sist

ance

rat

es w

ere

15, 1

8, a

nd 2

1%, r

espe

ctiv

ely

(lat

ter

two,

p <

0.0

01 v

s. a

mbu

lato

ry p

atie

nts)

. K

arlo

wsk

y et

al.[2

4]

US

A +

Can

ada

1858

R

esis

tanc

e ra

tes

for

Cip

ro-r

esis

tant

E. c

oli:

(200

6)

(1/0

4-6/

05)

(Cip

ro-r

esis

tant

A

mp

79.8

%

E. c

oli f

rom

uri

ne

TM

P-S

MX

66

.5%

sp

ecim

ens

Nitr

o 4%

ob

tain

ed f

rom

N

itro

and

Am

p M

ICs

incr

ease

d as

Cip

ro M

ICs

incr

ease

d (b

oth

p <

0.0

1).

outp

atie

nts)

T

MP

-SM

X M

ICs

stay

ed th

e sa

me

as C

ipro

MIC

s in

crea

sed.

Qui

nolo

ne-r

esis

tant

uri

nary

E. c

oli i

sola

tes

wer

e fr

eque

ntly

mul

tires

ista

nt

(o

nly

11%

wer

e re

sist

ant t

o C

ipro

alo

ne).

K

iffe

r et

al.[2

5]

Sao

Pau

lo, B

razi

l 37

,261

R

esis

tanc

e ra

tes:

(2

007)

(2

000-

2003

)

(out

patie

nt

E

. col

i K

. pne

umon

iae

P. m

irab

ilis

is

olat

es f

rom

(N =

22,

679)

(N

= 2

059)

(N

= 1

944)

bo

th g

ende

rs;

Am

p 43

%

100%

19

%

GN

R, 3

2,53

0;

Cip

ro

12%

6%

4%

GP

C, 2

,570

) N

itro

3%

21%

10

0%

Nor

flox

12

%

9%

4%

T

MP

-SM

X

34%

18

%

22%

Res

ista

nce

rate

s si

gn. f

ell w

ith

incr

easi

ng a

ge f

or A

mp

and

TM

P-S

MX

(bo

th p

< 0

.000

1) a

nd r

ose

wit

h in

crea

sing

age

for

Cip

ro, N

itro,

and

Nor

flox

(al

l p <

0.00

01).

Wit

h re

spec

t to

resi

stan

ce r

ates

for

E. c

oli o

ver

tim

e, o

nly

cipr

o an

d

no

rflo

x ex

hibi

ted

a si

gn. c

hang

e (i

.e. i

ncre

ase)

ove

r ti

me

(bot

h p

< 0

.000

1).

Ric

hard

s et

al.[1

] N

ew Z

eala

nd

94

Res

ista

nce

rate

s:

(200

2)

(12

wk.

(a

ll 16

-50

y.o.

A

mox

29

% o

vera

ll (N

= 9

4),

34%

E. c

oli (

N =

59)

pe

riod

dur

ing

fe

mal

e so

urce

s)

Am

ox-C

lav

8%

10%

late

200

0 or

TM

P 9%

12

%

20

01)

T

MP

-SM

X

11%

15

%

N

itro

2%

0

Cip

ro

0 0

N

orfl

ox

0 0

T

he o

nly

resi

stan

ce n

oted

wit

h S.

sap

roph

ytic

us (

N =

19)

was

that

to A

mox

(21%

). T

MP

res

ista

nce

rate

was

hig

her

in 3

1-40

yea

r ol

ds (

22%

) co

mpa

red

to

th

ose

in th

e 16

-21,

22-

30, a

nd 4

1-50

yea

r ol

d ag

e gr

oups

. G

olds

tein

[26]

Fr

ance

11

60

Res

ista

nce

rate

s (i

n pa

tien

ts w

ith

neit

her

rece

nt p

rior

hos

pita

liza

tion

nor

(2

000)

(1

2/96

-3/9

7)

(adu

lt o

utpa

tien

ts

rece

ipt o

f an

tim

icro

bial

s):

wit

h U

TIs

[no

E. c

oli

Kle

bsie

lla

spp.

P

. mir

abil

is

nurs

ing

hom

e

(N =

588

) (N

= 2

5)

(N =

39)

re

side

nts]

) A

mox

31

%

8%

18%

Nor

flox

3%

0

5%

Ofl

ox

3%

0 8%

C

ipro

1%

0

5%

T

MP

-SM

X

16%

8%

13

%

Fo

sfo

1%

32%

13

%

T

here

wer

e no

sig

n. d

iffe

renc

es in

res

ista

nce

rate

s by

age

(≥

65 y

ear

olds

vs.

< 6

5 ye

ar o

lds)

or

by g

ende

r.

Hum

mer

s-P

radi

er

Ger

man

y 28

1 27

% h

ad c

ompl

icat

ing

fact

ors

and

33%

had

rec

urre

nt U

TIs

so

not a

pur

e uU

TI

et

al.[2

7] (2

006)

(1

1/00

-2/0

1)

(all

fem

ales

>

stud

y po

pula

tion

12

yea

rs o

ld

Res

ista

nce

rate

s:

wit

h sy

mpt

oms

E

. col

i P

rote

us s

pp.

c/w

UT

I)

(N

= 1

91)

(N =

27)

A

mox

39

%

33%

A

mox

-Cla

v 33

%

22%

Cip

ro

9%

11%

TM

P-S

MX

29

%

41%

T

MP

29%

48

%

Nitr

o 2%

−

Log

istic

Reg

ress

ion

Mod

elin

g of

Res

ista

nce

Ris

k Fa

ctor

s: E

. col

i res

ista

nce

rate

s in

crea

sed

wit

h in

crea

sing

age

for

Cip

ro (

OR

3.2

1), T

MP

(O

R 1

.73)

, and

TM

P-S

MX

(O

R 1

.82)

. E. c

oli r

esis

tanc

e ra

tes

wer

e re

duce

d in

pat

ient

s w

ith

com

plic

ated

vs.

uU

TIs

for

Am

ox-C

lav

(OR

2.2

0), C

efaz

(O

R

2.

12),

TM

P (O

R 2

.92)

, and

TM

P-S

MX

(O

R 3

.00)

. E. c

oli r

esis

tanc

e ra

tes

wer

e

incr

ease

d in

old

er (

> 7

0 ye

ars

old)

vs.

you

nger

(<

50

year

s ol

d) p

atie

nts

for

C

efaz

(O

R 2

.36)

, Cip

ro (

OR

6.5

2), T

MP

(O

R 4

.03)

, and

TM

P-S

MX

(O

R

4.

48).

All

of

thes

e as

soci

atio

ns w

ere

stat

isti

call

y-si

gnif

ican

t. U

nghe

ri e

t al.[2

8]

Ital

y 79

R

esis

tanc

e ra

tes

for

quin

olon

e-re

sist

ant E

. col

i: (2

002)

(N

A)

(sou

rce

NA

) Fo

sfo

0%

A

mox

63

%

T

MP

-SM

X

48%

Nitr

o 13

%

T

etra

84

%

C

hlor

o 58

%

Mar

ches

e et

al.[2

9]

Ital

y 42

6 R

esis

tanc

e ra

tes:

(2

003)

(N

A)

(sub

ject

s w

ith

E

. col

i P

. mir

abil

is

K. p

neum

onia

e

uU

TIs

)

(N =

387

) (N

= 2

4)

(N =

15)

Fo

sfo

1%

13%

47

%

A

mox

-Cla

v 11

%

0 7%

T

MP

-SM

X

24%

33

%

11%

C

ipro

12

%

4%

7%

N

orfl

ox

15%

8%

7%

Nitr

o 3%

−

21%

T

empe

ra e

t al.[3

0]

Ital

y 58

2 R

esis

tanc

e ra

tes:

(2

004)

(1

1/01

-2/0

2)

(sub

ject

s w

ith

Fosf

o 6.

2% o

vera

ll, (

N =

582

),

1.6%

E.c

oli (

N =

430

)

uU

TIs

) C

ipro

10

.7%

10

.0%

N

orfl

ox

10.8

%

10.5

%

Nitr

o 11

.7%

1.

6%

T

MP

-SM

X

18.9

%

15.4

%

A

mox

-Cla

v 12

.7%

5.

8%

Ges

u an

d M

arch

etti[3

1] It

aly

2486

55

.3%

of

isol

ates

wer

e E

. col

i.

(200

7)

(6 w

k. p

erio

d (a

dult

subj

ects

R

esis

tanc

e ra

tes

for

E. c

oli (

N =

137

5):

be

twee

n M

ay

atte

ndin

g A

mox

37

%

an

d O

ctob

er

non-

hosp

ital

TM

P-S

MX

19

.2%

2004

) la

bora

tori

es)

Fosf

o 5.

9%

N

itro

8.9%

Cip

ro

14.4

%

L

evo

14.6

%

N

alA

c 23

.2%

Alt

houg

h E

. col

i res

ista

nce

incr

ease

d in

inci

denc

e w

ith

incr

easi

ng a

ge a

nd

w

ith

mal

e as

com

pare

d to

fem

ale

gend

er, t

he d

ata

pres

enta

tion

was

prob

lem

atic

. SE

MIC

[32]

B

resc

ia, I

taly

56

3 (2

002)

R

esis

tanc

e ra

tes:

(2

007)

(2

002-

5)

936

(200

3)

E

. col

i K

. pne

umon

iae

Pro

teus

spp

.

11

14 (

2004

)

(N =

241

8)

(N =

217

) (N

= 1

01)

12

05 (

2005

) A

mp

49%

−

40%

Am

ox-C

lav

8%

2%

10%

T

MP

-SM

X

27%

8%

37

%

Cip

ro

19%

3%

19

%

N

itro

9%

− −

R

esis

tanc

e ra

tes

did

not c

hang

e si

gnif

ican

tly

for

any

gram

-neg

ativ

e or

-pos

itiv

e

ur

opat

hoge

n ov

er th

e st

udy

peri

od.

In

358

isol

ates

of

E. f

aeca

lis,

res

ista

nce

rate

s fo

r A

mp,

Cip

ro, N

orfl

ox, a

nd

N

itro

wer

e 1%

, 20%

, 39%

, and

6%

, res

pect

ivel

y.

Hry

niew

icz

et a

l.[33]

P

olan

d 37

7 R

esis

tanc

e ra

tes:

(2

001)

(7

/98-

5/99

) (s

ubje

cts

wit

h

E. c

oli (

N =

330

) O

ther

Ent

erob

acte

riac

eae

(N =

40)

uU

TIs

) A

mp

45%

58

%

Am

ox-C

lav

4%

15%

Cip

ro

4%

5%

N

orfl

ox

14%

0

N

itro

9%

90%

TM

P 26

%

43%

TM

P-S

MX

17

%

25%

Fo

sfo

3%

10%

Z

emko

va e

t al.[3

4]

Hra

dec

Kra

love

, 11

,856

E. c

oli

Fluo

roqu

inol

one

resi

stan

ce r

ates

am

ong

E. c

oli i

ncre

ased

fro

m 2

% →

10%

(2

007)

C

zech

oslo

vaki

a is

olat

es

(hos

pita

l iso

late

s) a

nd 1

% →

11%

(ou

tpat

ient

isol

ates

) fr

om 2

001

to 2

006

(2

001-

2006

) (i

npat

ient

s an

d (b

oth

p <

0.0

1). O

ver

the

sam

e ti

me

peri

od, f

luor

oqui

nolo

ne u

tili

zati

on

outp

atie

nts)

in

crea

sed

in th

e in

patie

nt s

etti

ng (

2.73

→ 4

.89

DB

D, p

< 0

.01)

and

in th

e

outp

atie

nt s

etti

ng (

0.29

→ 1

.15

DID

, p <

0.0

1). T

he d

evel

opm

ent o

f re

sist

ance

of E

. col

i to

fluo

roqu

inol

ones

cor

rela

ted

sign

. wit

h ut

iliza

tion

in b

oth

the

hosp

ital

(r

= 0

.996

, p =

0.0

05)

and

outp

atie

nt (

r =

0.8

78, p

= 0

.029

) se

ttin

gs.

Gob

erna

do e

t al.[3

5,36

] Spa

in

2230

R

esis

tanc

e ra

tes:

(2

007)

(1

1/03

-10/

04)

(E. c

oli i

sola

tes

Am

p 52

%

from

fem

ales

T

MP

-SM

X

26%

w

ith

Am

ox-C

lav

< 3

%

uUT

Is)

Fosf

o <

3%

Qui

nolo

nes

18%

Res

ista

nce

rate

s w

ere

sign

. hig

her

in th

e el

derl

y vs

. you

ng f

or C

ipro

(29

vs.

13%

, p <

0.0

01),

TM

P-S

MX

(32

vs.

23%

, p <

0.0

01),

and

Am

p (5

6 vs

. 50%

,

p =

0.0

2). S

ign.

cor

rela

tion

was

fou

nd b

etw

een

quin

olon

e co

nsum

ptio

n an

d

E

. col

i res

ista

nce

to C

ipro

(r

= 0.

5, p

= 0

.025

). T

here

wer

e al

so s

ign.

reg

iona

l

diff

eren

ces

in q

uino

lone

res

ista

nce

of E

. col

i (8%

in n

orth

vs.

17%

in s

outh

and

east

).

Gar

cia

et a

l.[37]

Sp

ain

2724

(20

02)

Res

ista

nce

rate

s:

(200

7)

(200

2, 2

004)

30

13 (

2004

)

E

. col

i

P

. mir

abil

is

(∼

80%

fro

m

20

02

2004

20

02

2004

w

omen

)

(N =

198

9)

(N =

210

8)

(N =

196

) (N

= 1

97)

A

mox

59

58

38

36

Am

ox-C

lav

9 8

6 2

T

MP

-SM

X

34

31

38

36

C

ipro

23

24

17

13

Nitr

o 6

4 96

98

Fosf

o 2

3 24

20

2.7%

of

gram

-neg

ativ

e or

gani

sms

in 2

004

wer

e E

SBL

pro

duce

rs.

D

rug-

resi

stan

t E. c

oli w

ere

sign

. mor

e fr

eque

nt in

men

(in

200

2, 3

3 vs

. 21%

,

p <

0.0

001)

and

in th

e el

derl

y (o

vera

ll an

d fo

r A

mox

, TM

P-S

MX

). T

here

wer

e

hi

gh c

o-re

sist

ance

rat

es b

etw

een

Am

ox, C

ipro

, and

TM

P-S

MX

. The

re w

ere

sign

. reg

iona

l dif

fere

nces

in r

esis

tanc

e ra

tes

in th

e 9

regi

ons.

St

orby

et a

l.[38]

S

wed

en

4671

D

ata

wer

e no

t str

atif

ied

for

isol

ates

fro

m u

ncom

plic

ated

vs.

com

plic

ated

(2

004)

(1

990-

2001

) (1

990-

1993

) U

TIs

. E. c

oli c

onst

itut

ed 6

5.5%

and

73.

7% o

f 19

90-1

993

and

1998

-200

1

4110

is

olat

es, r

espe

ctiv

ely.

Sig

n. li

near

tren

ds f

or in

crea

sing

res

ista

nce

over

tim

e

(1

998-

2001

) w

ere

seen

for

Am

p (p

= 0

.005

), T

MP

(p

= 0

.004

), a

nd th

e qu

inol

ones

(p

<

0.

001)

. No.

sig

n. c

hang

e ov

er ti

me

was

not

ed f

or P

ivm

ec (

rang

e 0-

3%)

and

N

itro

(≤ 1

%).

Res

ista

nce

fell

over

tim

e vs

. Cef

adro

x (p

< 0

.007

).

Ars

lan

et a

l.[39]

T

urke

y 32

1 E

. col

i con

stitu

ted

90%

of

isol

ates

. 5%

of

thes

e is

olat

es p

rodu

ced

ESB

L.

(200

5)

(1/0

4-6/

04)

(gra

m-n

egat

ive

Res

ista

nce

rate

s vs

. Cip

ro w

ere

17%

in u

UT

Is a

nd 3

8% in

pa

thog

ens

in

com

plic

ated

UT

Is.

uUT

I)

Res

ista

nce

rate

s fo

r E

. col

i:

A

mp

51%

A

mox

-Cla

v 26

%

Cef

az

22%

O

flox

17

%

N

alA

c 20

%

T

MP

-SM

X

36%

Nitr

o 4%

Fosf

o 0.

3%

R

isk

fact

ors

for

Cip

ro-r

esis

tant

E. c

oli (

univ

aria

te a

naly

ses)

: age

> 5

0 ye

ars

old

(p =

0.0

004)

, iso

late

s fr

om a

rur

al a

rea

(p =

0.0

39),

pre

senc

e of

com

plic

ated

UT

I (p

< 0

.001

), E

SBL

-pro

duci

ng s

trai

n (p

< 0

.001

), a

nd C

ipro

use

> o

nce

in p

revi

ous

year

(p

= 0

.001

).

R

isk

fact

ors

for

Cip

ro-r

esis

tant

E. c

oli (

mul

tiva

riat

e an

alys

es):

age

> 5

0 ye

ars

old

(OR

1.6

, p =

0.0

2), c

ipro

use

> o

nce

in p

revi

ous

year

(O

R 2

.8, p

= 0

.004

),

an

d pr

esen

ce o

f co

mpl

icat

ed U

TI

(OR

2.4

, p <

0.0

01).

ESB

L-p

rodu

cing

isol

ates

wer

e tw

ice

as c

omm

on in

Cip

ro r

ecip

ient

s (1

5%)

vs. n

on-C

ipro

reci

pien

ts (

7.4%

) R

ock

et a

l.[40]

N

orth

ern

Isra

el

6212

(19

95)

Res

ista

nce

rate

s fo

r E

. col

i (19

95/1

999/

2002

/200

5):

(200

7)

(199

5, 1

999,

200

2,

6519

(19

99)

Am

p 55

/56/

54/5

4%

20

05)

6272

(20

02)

Am

ox-C

lav

11/1

0/5/

4% (

p <

0.0

01 f

or tr

end)

63

68 (

2005

) C

ipro

6/

6/7/

11%

(p

< 0

.001

for

tren

d)

(out

patie

nt

TM

P-S

MX

29

/27/

25/2

8% (

p =

0.0

1 fo

r tr

end)

gr

am-n

egat

ive

Nitr

o 6/

5/3/

3% (

p <

0.00

1 fo

r tr

end)

is

olat

es)

Res

ista

nce

rate

s fo

r ot

her

GN

Rs

(199

5/19

99/2

002/

2005

):

A

mp

76/8

5/86

/81%

(p

< 0

.001

for

tren

d)

A

mox

-Cla

v 32

/25/

20/2

6% (

p <

0.0

01 f

or tr

end)

Cip

ro

8/4/

9/11

% (

p =

0.0

04 f

or tr

end)

TM

P-S

MX

19

/19/

14/2

0%

N

itro

56/6

2/49

/56%

Fro

m 2

000-

2006

, the

re w

ere

sign

. dec

reas

es in

the

util

izat

ion

of T

MP

-SM

X

an

d N

itro

(bot

h p

< 0

.001

) an

d a

sign

. inc

reas

e in

the

util

izat

ion

of A

mp

(p <

0.00

1) in

the

com

mun

ity

(bas

ed o

n D

DD

). T

hese

ant

imic

robi

al u

tili

zati

on

pa

tter

ns c

ould

not

exp

lain

the

chan

ges

seen

in a

ntim

icro

bial

res

ista

nce

pa

ttern

s.

Him

a-L

erib

le

Cen

tral

Afr

ican

31

3 R

esis

tanc

e ra

tes:

et

al.[4

1]

(200

3)

Rep

ublic

(o

utpa

tient

s E

. col

i (N

= 1

74)

Oth

er E

nter

obac

teri

acea

e (N

= 9

2)

(1

/00-

4/02

) w

ith

susp

ecte

d A

mox

80

%

96%

uUT

Is)

TM

P-S

MX

80

%

70%

C

ipro

8%

5%

Fosf

o 2%

10

%

N

alA

c 9%

9%

Am

ox-C

lav

28%

36

%

R

andr

iani

rain

a M

adag

asca

r 90

3 E

. col

i con

stitu

ted

67.2

% o

f is

olat

es.

et

al.[4

2] (

2007

) (1

/04-

4/06

) (o

utpa

tient

s R

esis

tanc

e ra

tes:

w

ith

susp

ecte

d

E. c

oli (

N =

607

) A

ll G

NR

(N

= 7

94)

uUT

Is)

Am

ox

74%

77

%

TM

P-S

MX

70

%

66%

C

ipro

16

%

16%

Nal

Ac

25%

26

%

Fo

sfo

0.2%

4.

6%

C

ipro

res

ista

nce

rate

s w

ere

sign

. inc

reas

ed in

isol

ates

fro

m o

lder

(≥

65 y

ears

old)

vs.

you

nger

pat

ient

s (<

65

year

s ol

d) (

p <

0.0

1).

Issa

ck e

t al.[4

3]

Mau

riti

us

260

Res

ista

nce

rate

s:

(2

007)

(1

/05-

4/05

) (o

utpa

tien

ts

E

nter

obac

teri

acea

e E

. col

i K

lebs

iell

a sp

p.

> 1

5 ye

ars

old

(N =

212

) (N

= 1

21)

(N =

36)

requ

irin

g U

C

Am

p 80

%

73%

10

0%

for

clin

ical

car

e)

TM

P-S

MX

50

%

54%

44

%

Nal

Ac

34%

31

%

47%

Cip

ro

26%

23

%

42%

M

ec

2%

3%

3%

Fo

sfo

0 0

0 N

abet

h et

al.[4

4]

Sene

gal

102

Res

ista

nce

rate

s:

(200

5)

(6/0

1-6/

03)

(qui

nolo

ne-

Am

p 93

%

resi

stan

t GN

R)

Am

ox-C

lav

78%

T

etra

78

%

SMX

78

%

Gen

t 31

%

M

ec

47%

Nitr

o 32

%

Fo

sfo

2%

Dro

mig

ny e

t al.[4

5]

Sene

gal

398

73%

of

isol

ates

wer

e fr

om u

UT

Is. O

nly

11%

of

isol

ates

wer

e (2

005)

(6

/01-

6/03

) (E

. col

i onl

y)

susc

eptib

le to

all

test

ed a

gent

s.

R

esis

tanc

e ra

tes:

Am

p 74

%

A

mox

-Cla

v 58

%

Nal

Ac

23%

Qui

nolo

nes

19%

TM

P-S

MX

68

%

R

esis

tanc

e ra

tes

rose

ove

r ti

me

wit

h A

mox

-Cla

v (5

0.4%

→64

%)

and

TM

P-S

MX

(64

.6%

→71

.1%

).

R

esis

tanc

e ph

enot

ype

rate

s w

ith

“top

5”

agen

ts:

A

mp

+ T

MP

-SM

X

60

%

A

mp

+ A

mox

-Cla

v +

TM

P-S

MX

47

%

A

mp

+ A

mox

-Cla

v +

TM

P-S

MX

+ N

alA

c 15

%

A

mp

+ A

mox

-Cla

v +

TM

P-S

MX

+ N

alA

c +

Qui

nolo

nes

12%

Ris

k fa

ctor

s fo

r re

sist

ance

:

Am

p:

gend

er (

men

> w

omen

, OR

2.1

), e

xpos

ure

duri

ng

prev

ious

6 m

o. (

OR

3.7

)

Am

ox-C

lav:

ex

posu

re d

urin

g pr

evio

us 6

mo.

(O

R 2

.5)

N

alA

c:

age

grea

ter

than

45

year

s ol

d (O

R 3

.1),

UT

I in

pre

viou

s

ye

ar (

OR

3.0

), e

xpos

ure

in p

revi

ous

6 m

o. (

OR

1.8

)

Qui

nolo

nes:

ag

e gr

eate

r th

an 4

5 ye

ars

old

(OR

3.5

), U

TI

in p

revi

ous

year

(O

R 4

.1)

T

MP

-SM

X:

expo

sure

in p

revi

ous

6 m

o. (

OR

2.4

) A

hmed

et a

l.[46]

Su

dan

362

Res

ista

nce

rate

s:

(200

0)

(NA

) (≥

5 y

ear

old

E

. col

i K

. pne

umon

iae

P. m

irab

ilis

in

patie

nts

and

(N

= 1

65)

(N =

60)

(N

= 2

7)

ou

tpat

ient

s)

TM

P-S

MX

67

%

68%

81

%

T

MP

74%

73

%

83%

N

alA

c 6%

18

%

7%

C

ipro

0

0 0

A

mox

72

%

85%

78

%

N

itro

10%

46

%

59%

For

E. c

oli,

58%

of

isol

ates

wer

e re

sist

ant t

o at

leas

t 4 o

f 10

age

nts

and

26%

wer

e re

sist

ant t

o 5

or m

ore

of 1

0 ag

ents

. For

K. p

neum

onia

e, th

e

co

rres

pond

ing

freq

uenc

ies

wer

e 70

% a

nd 5

2% w

hile

for

P. m

irab

ilis

, the

y

w

ere

82%

and

60%

(an

d, f

or th

e la

tter,

33%

wer

e re

sist

ant t

o 6

or m

ore

of

10

age

nts)

.

A

kram

et a

l.[47]

In

dia

100

36.5

% a

nd 1

6.7%

of

isol

ates

wer

e ob

tain

ed f

rom

ped

iatr

ic a

nd e

lder

ly

(200

7)

(08/

04-0

7/05

) (p

atie

nts

of a

ll

(≥ 5

0 ye

ars

old)

sub

ject

s, r

espe

ctiv

ely.

ag

es a

tten

ding

R

esis

tanc

e ra

tes:

th

e ho

spita

l

E. c

oli (

N =

61)

K

. pne

umon

iae

(N =

22)

ou

tpat

ient

T

MP

-SM

X

76%

53

%

cl

inic

) N

itro

80%

76

%

Cip

ro

69%

47

%

N

orfl

ox

69%

47

%

E

SBL

was

pro

duce

d by

34.

4% o

f E

. col

i and

27.

3% o

f K

. pne

umon

iae

isol

ates

. A

rya

and

Aga

rwal

[48]

Del

hi, I

ndia

22

76 (

inpa

tient

, A

ll bu

t 6 is

olat

es (

E. f

aeca

lis)

wer

e G

NR

s. R

esis

tanc

e ra

tes

for

outp

atie

nt/

(200

7)

(200

4-20

06)

474;

out

patie

nt,

inpa

tient

isol

ates

:

18

02)

Am

ox-C

lav

12/9

%

N

itro

2/1%

Am

ikac

in

7/8%

Net

ilm

icin

12

/11%

Res

ista

nce

rate

s ro

se s

ign.

fro

m 2

004

to 2

006

for

ceft

azid

ime

(11

→ 2

6%, p

=

0.

0007

) an

d fe

ll si

gn. f

or g

enta

mic

in (

36 →

27%

, p =

0.0

20).

K

ahlm

eter

[49]

17

cou

ntri

es

3278

E

. col

i rep

rese

nted

77%

of

isol

ates

. 42%

of

stra

ins

wer

e re

sist

ant t

o ≥

1 of

12

(200

3)

(EC

O-S

EN

S)

(out

patie

nt

test

ed a

gent

s. F

or E

. col

i, re

sist

ance

was

mos

t com

mon

ly n

oted

wit

h A

mp

(1/9

9-12

/00)

fe

mal

es ≤

65

(30%

), S

MX

(29

%),

TM

P (

15%

), T

MP

-SM

X (

14%

), a

nd N

alA

c (5

.4%

). I

n

year

s ol

d w

ith

cont

rast

, rat

es f

or A

mox

-Cla

v, M

ec, N

itro,

Fos

fo, G

ent,

and

Cip

ro w

ere

all

sym

ptom

s c/

w

< 3

%. R

ates

var

ied

as a

fun

ctio

n of

geo

grap

hy:

uUT

Is)

eg. E

. col

i vs.

A

mox

-Cla

v in

P

ortu

gal (

9% r

esis

tanc

e ra

te)

Nal

Ac

Por

tuga

l (12

%)

Cip

ro

Por

tuga

l (6%

)

N

alA

c Sp

ain

(27%

)

Cip

ro

Spai

n (1

5%)

P

. mir

abil

is (

4.4%

of

isol

ates

) ha

d a

low

er r

esis

tanc

e ra

te v

s. A

mp

(16.

1%)

but

hi

gher

rat

e vs

. TM

P (2

5.5%

) th

an E

. col

i. K

lebs

iell

a sp

p. (

2.2%

of

isol

ates

)

ha

d hi

gher

res

ista

nce

rate

s th

an E

. col

i vs.

Am

p (8

3.5%

) an

d Fo

sfo

(56.

7%).

Oth

er E

nter

obac

teri

acea

e (2

.7%

of

isol

ates

) ha

d hi

gher

rat

es, c

ompa

red

to

E

. col

i, vs

. Am

p (4

5.9%

), A

mox

-Cla

v (2

1.3%

), N

itro

(40.

2%)

and

Fosf

o

(1

5.6%

).

R

esis

tanc

e w

as r

are

for

S. s

apro

phyt

icus

(hi

ghes

t wit

h G

ent a

t 4.3

%-e

xpec

ted)

.

In g

ener

al, a

ntim

icro

bial

res

ista

nce

rate

s w

ere

low

est i

n th

e N

ordi

c co

untr

ies

and

high

est i

n S

pain

/Por

tuga

l. T

he e

mpi

ric

use

of T

MP

-SM

X m

ay n

o lo

nger

be a

ppro

pria

te in

Ger

man

y, I

rela

nd, S

pain

, and

Por

tuga

l (E

. col

i res

ista

nce

rate

s >

20%

for

all)

.

A

bbre

viat

ions

: A

mp

= a

mpi

cill

in, C

ipro

= c

ipro

flox

acin

, Nit

ro =

nitr

ofur

anto

in, T

MP

-SM

X =

trim

etho

prim

-sul

fam

etho

xazo

le, L

evo

= le

vofl

oxac

in, F

= f

emal

e, M

= m

ale,

MIC

= m

inim

um in

hibi

tory

co

ncen

trat

ion,

Am

ox =

am

oxic

illin

, Am

ox-C

lav

= a

mox

icill

in-c

lavu

lana

te, N

orfl

ox =

nor

flox

acin

, Ofl

ox =

ofl

oxac

in, F

osfo

= f

osfo

myc

in, O

R =

odd

s ra

tio, C

efaz

= c

efaz

olin

, Tet

ra =

te

trac

ycli

ne, C

hlor

o =

chl

oram

phen

icol

, Nal

Ac

= n

alid

ixic

aci

d, P

ivm

ec =

piv

mec

illi

nam

, ESB

L =

ext

ende

d-sp

ectr

um b

eta-

lact

amas

e, G

NR

= g

ram

-neg

ativ

e ro

ds, M

ec =

mec

illi

nam

, Gen

t =

gent

amic

in, C

efad

rox

= c

efad

roxi

l, T

RU

ST =

Tra

ckin

g R

esis

tanc

e in

the

Uni

ted

Stat

es T

oday

sur

veill

ance

stu

dy, N

A =

not

ava

ilabl

e, U

C =

uri

ne c

ultu

re, T

SN =

The

Sur

veil

lanc

e N

etw

ork,

D

BD

= d

efin

ed d

aily

dos

es p

er 1

00 b

eds-

days

, DID

= d

efin

ed d

aily

dos

es p

er 1

000

clie

nts

per

day,

GP

C =

gra

m-p

ositi

ve c

occi

. a si

gn. l

inea

r tr

end

(upw

ard)

ove

r ti

me

(all

p ≤

0.00

2).

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