nfgnr

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http://slidepdf.com/reader/full/nfgnr 1/10

Recentadvancesonthetreatment

ofNFGNBinfections

Li Guanghui MD PhD

Huashan Hospital, Fudan University

2

BAD BUG,NO DRUG,NO ESKAPEE EE E nterococcus nterococcus nterococcus nterococcus S SS S taphylococcustaphylococcustaphylococcustaphylococcusK KK K lebsiella lebsiella lebsiella lebsiella A AA Acinetobacter cinetobacter cinetobacter cinetobacter P PP P seudomonas seudomonas seudomonas seudomonas E EE E nterobacter nterobacter nterobacter nterobacter

3

Importance of non-fermenters Non-fermenting gram-negative bacilli (non-

fermenters) include: Pseudomonas aeruginosa

Acinetobacter spp.

Stenotrophomonas maltophilia

Alcaligenes spp.

Burkholderia spp

Flavobacterium (Chryseobaterium ) spp. , et al

Non-fermenters are highly resistant to commonlyused antimicrobials

The infections of non-fermenters are difficult totreat with high mortality

Percentage of non-fermenters in Gram-negative bacilli in Shanghai,1991-2008(Wang F, et al. Int J Antimicrob Agents 2003; 22: 444)

4

146 0 1 632 1215 1171 136 9 16 61 2028 3028 327 5 3005 5242 565 6 48 18 58 19 5 665 6616YearYear

26262626

25252525

26262626

23232323

28282828

3030303 0 3 0303030

32323232

3434343 4 3 43434343535353 5 3 5353535

33333333

3434343435353535

33333333

34343434

36363636

20202020

22222222

24242424

26262626

28282828

30303030

32323232

34343434

36363636

38383838

1 9 9 1

1 9 9 1

1 9 9 1

1 9 9 1

1 9 9 2

1 9 9 2

1 9 9 2

1 9 9 2

1 9 9 3

1 9 9 3

1 9 9 3

1 9 9 3

1 9 9 4

1 9 9 4

1 9 9 4

1 9 9 4

1 9 9 5

1 9 9 5

1 9 9 5

1 9 9 5

1 9 9 6

1 9 9 6

1 9 9 6

1 9 9 6

1 9 9 7

1 9 9 7

1 9 9 7

1 9 9 7

1 9 9 8

1 9 9 8

1 9 9 8

1 9 9 8

1 9 9 9

1 9 9 9

1 9 9 9

1 9 9 9

2 0 0 0

2 0 0 0

2 0 0 0

2 0 0 0

2 0 0 1

2 0 0 1

2 0 0 1

2 0 0 1

2 0 0 2

2 0 0 2

2 0 0 2

2 0 0 2

2 0 0 3

2 0 0 3

2 0 0 3

2 0 0 3

2 0 0 4

2 0 0 4

2 0 0 4

2 0 0 4

2 0 0 5

2 0 0 5

2 0 0 5

2 0 0 5

2 0 0 6

2 0 0 6

2 0 0 6

2 0 0 6

2 0 0 7

2 0 0 7

2 0 0 7

2 0 0 7

2 0 0 8

2 0 0 8

2 0 0 8

2 0 0 8

P e r c e n t a g e ( % )




上海地区糖非发酵菌中3个主要菌种的构成比变迁

5351

48

42

47

39 40

43

38

36

4042

41

28

21

29 2928

26 27 27

34

31

33

35 35

3

7 7 8 8

11 11

9 1 0 10

12 12 12

0

10

20

30

40

50

60

1 9 9 61 9 9 61 9 9 61 99 6 1 99 71 9 9 71 9 9 71 99 7 1 99 81 9 9 81 9 9 81 99 8 1 99 91 9 9 91 9 9 91 99 9 2 00 02 0 0 02 0 0 02 00 0 2 00 12 0 0 12 0 0 12 00 1 2 00 22 0 0 22 0 0 22 00 2 2 00 32 0 0 32 0 0 32 00 3 2 00 42 0 0 42 0 0 42 00 4 2 00 52 0 0 52 0 0 52 00 5 2 00 62 0 0 62 0 0 62 00 6 2 00 72 0 0 72 0 0 72 00 7 2 00 82 0 0 82 0 0 82 0 0 8

铜绿假单胞菌铜绿假单胞菌铜绿假单胞菌铜绿假单胞菌不动杆菌属不动杆菌属不动杆菌属不动杆菌属嗜麦芽窄食单胞菌嗜麦芽窄食单胞菌嗜麦芽窄食单胞菌嗜麦芽窄食单胞菌

铜绿假单胞菌呈下降趋势铜绿假单胞菌呈下降趋势铜绿假单胞菌呈下降趋势铜绿假单胞菌呈下降趋势

不动杆菌属呈上升趋势不动杆菌属呈上升趋势不动杆菌属呈上升趋势不动杆菌属呈上升趋势

嗜麦芽窄食单胞菌趋于稳定嗜麦芽窄食单胞菌趋于稳定嗜麦芽窄食单胞菌趋于稳定嗜麦芽窄食单胞菌趋于稳定

6

High incidence of non-fermentersin Gram-negative bacilli

45% (6686/15244) of GNB were non-fermenters

in CHINET (Resistance surveillance network in

China) surveillance program in China in 2005

(Wang F. Chin J Infect Chemother 2006; 6: 289)

Non-fermenters increased from 41% in 1999 to

48% in 2001 in ICU clinical isolates of GNB inNPRS (Nosocomial Pathogens Resistance

Surveillance) study program in China(Wang H, Chen MJ. Natl Med J China 2003; 83:385)

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华山医院2009年4588株细菌分布情况

7 8

Major Trends in Susceptibility

Pseudomonas: Substantial losses of

imipenem and ciprofloxacin susceptibilityinternationally

Acinetobacter: Carbapenem resistantorganisms now endemic in many ICUs (butvirulence generally not high)

Resistance to ceftazidime and imipenem among P. aeruginosaisolates collected in association with ICU-acquiredinfections,1986-2004.

9Clinical Infectious Diseases 2005; 41:848–54

SENTRY Program data for MDR P.aeruginosafrom bloodstream isolates (1997–2001).

10International Journal of Antimicrobial Agents 29 Suppl. 3 (2007) S33–S41

11

BSAC bacteraemia surveillance data for Pseudomonas

aeruginosa, 2002–2005 for the UK and Republic of Ireland.

12

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13

Resistance in P. aeruginosa, Shanghai 2000-2007(%)

0000

5555

10101010

15151515

20202020

25252525

30303030

35353535

2000200020002 00 0 2 00 1200120012 00 1 2 00 2200220022 00 2 2 00 3200320032 00 3 2 00 4200420042 00 4 2 00 5200520052 00 5 2 00 6200620062 00 6 2 00 7200720072007

Cefoperazone/sulbactamCefoperazone/sulbactamCefoperazone/sulbactamCefoperazone/sulbactam CeftazidimeCeftazidimeCeftazidimeCeftazidime ImipenemImipenemImipenemImipenem pip/tazopip/tazopip/tazopip/tazo

14.8

18.2 19.7 20.3

23.9 24.1 25.2

29.9 30.5

41.1

0

10

20

30

40

50

60

A m i k a c i n

A m i k a c i n

A m i k a c i n

A m i k a c i n

C P Z / S U L

C P Z / S U L

C P Z / S U L

C P Z / S U L

C e f e p i m e

C e f e p i m e

C e f e p i m e

C e f e p i m e

C e f t a z i m e

C e f t a z i m e

C e f t a z i m e

C e f t a z i m e

C i p r o f l o x a c i n




P I P / T A Z

P I P / T A Z

P I P / T A Z

P I P / T A Z

M e r o p e n e m

M e r o p e n e m

M e r o p e n e m

M e r o p e n e m

A z t r e o n a m

A z t r e o n a m

A z t r e o n a m

A z t r e o n a m

I m i p e n e m

I m i p e n e m

I m i p e n e m

I m i p e n e m

T C / C L

T C / C L

T C / C L

T C / C L

R e s i s t a n c e

R e s i s t a n c e

R e s i s t a n c e

R e s i s t a n c e （％）

（％）

（％）

（％）

Resistance in P. aeruginosa ，，，，CHINET 2009 (n=4912)

Wang Fu, etal. CHINET 2009 surveillance of bacterial resistance in China. Chin J Infect Chemo 2010,10:325-334

0

10

20

30

40

50

60

70

80

1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

P r o p o r t i o n

R e s i s t a n t

Amikacin Ceftazidime Imipenem

Antimicrobial Resistance among Acinetobacter sp.,From ICUs 1986-2003*

*Source: NNIS SystemClinical Infectious Diseases 2005; 41:848–54

BSAC bacteraemia surveillance data for A.baumannii , 2002–2005

16

17

Resistance in Acinetobacter sp, Shanghai 1999-2008 (%)

r e s i s t an c e %

5555 5555

4444 3333 33332222

4444 4444

10101010

16161616

21212121

27272727

33333333

40404040 40404040

46464646

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43434343

45454545

5050505048484848

5353535355555555

22225555

66668888 9999

1414141412121212

8888

11111111

19191919

24242424

20202020

27272727

3030303032323232

37373737

4444444446464646 47474747

0000

10101010

20202020

30303030

40404040

50505050

60606060

1995199519951 99 5 1 99 8199819981 99 8 1 99 9199919991 99 9 2 00 0200020002 00 0 2 00 1200120012 00 1 2 00 2200220022 00 2 2 00 3200320032 00 3 2 00 4200420042 00 4 2 00 5200520052 00 5 2 00 6200620062 00 6 2 00 7200720072 00 7 2 00 8200820082008

imipenemimipenemimipenemi m i pe n e m c e f ta z i di m eceftazidimeceftazidimec e f ta z i di m e C P Z/ S U LCPZ/SULCPZ/SULC P Z/ S U L P I P/ T A ZOPIP/TAZOPIP/TAZOPIP/TAZO

Resistance in Acinetobacter sp, CHINET

31.531.531.531.5 30.930.930.930.935.335.335.335.3

48.148.148.148.1 50505050

25252525

11.611.611.611.6

5.35.35.35.3

14.614.614.614.6

23.623.623.623.6

0000

10101010

20202020

30303030

40404040

50505050

60606060

70707070

2005200520052 005 2 006200620062 00 6 20072007200720 07 2008200820082008 2009200920092009

Imipenem

CPZ/SULR

E

S

I

S

T

A

N

C

E

%

18

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19

Resistance in Acinetobacter sp, CHINET 2009(%)

22.5 23.6

49 49.4 50 52.4

56.2 57.7 58.563

0

10

20

30

40

50

60

70

80

90

100

M i n o c y c l i n

M i n o c y c l i n

M i n o c y c l i n

M i n o c y c l i n

C P Z / S U L

C P Z / S U L

C P Z / S U L

C P Z / S U L

A M / S B

A M / S B

A M / S B

A M / S B

A m i k a c i n

A m i k a c i n

A m i k a c i n

A m i k a c i n

I n i p e n e m

I n i p e n e m

I n i p e n e m

I n i p e n e m

M e r o p e n e m

M e r o p e n e m

M e r o p e n e m

M e r o p e n e m

C e f t a z i d i m e




C e f e p i m e

C e f e p i m e

C e f e p i m e

C e f e p i m e

P I P / T A Z

P I P / T A Z

P I P / T A Z

P I P / T A Z





R e s i s t a n c e

R e s i s t a n c

e

R e s i s t a n c

e

R e s i s t a n c e （％）

（％）

（％）

（％）

Wang Fu, etal. CHINET 2009 surveillance of bacterial resistance i n China. Chin J Infect Chemo 2010,10:325-334

Acinetobacter isolatesresistant tocarbapenems MYSTIC 2004

Countries that have reportedan outbreak of carbapenem-resistant Acinetobacterbaumannii. Red signifies

outbreaks reported before 2006, and yellow signifiesoutbreaks reported since 2006.

21

Antimicrobial resistance in S.maltophilia , CHINET(%)

19.1

10.6

20.1

2.9

16.3

12.9

11.4

1.5

17.8

12.111.7

2

15.1

12.413.2

1.8

0

5

10

15

20

25

CPZ/SB LEVO SMZ/TMP MINO

2 00 5 20 072 00 8 20 09

2005 n=877, 2007 n=1180, 2008 n=1310, 2009 n=1656

Antimicrobial resistance in S.maltophilia , CHINET 2009(%)

Antimicrobial agentsAntimicrobial agentsAntimicrobial agentsAntimicrobial agentsS.maltophiliaS.maltophiliaS.maltophiliaS.maltophilia（（（（n=1656n=1656n=1656n=1656））））

resistantresistantresistantresistant suceptiblesuceptiblesuceptiblesuceptible

CefoperazoneCefoperazoneCefoperazoneCefoperazone////sulbactamsulbactamsulbactamsulbactam 15.115.115.115.1 62.262.262.262.2

LevofloxacinLevofloxacinLevofloxacinLevofloxacin 12.412.412.412.4 83.183.183.183.1

SMX/TMPSMX/TMPSMX/TMPSMX/TMP 13.213.213.213.2 83.083.083.083.0

MinocyclineMinocyclineMinocyclineMinocycline 1.81.81.81.8 83.583.583.583.5


Antimicrobial resistance in Burkholderia spp(n=304) , CHINET 2009(%)

23

4.4

11.113.6 14.7

22.7

92.2

80.8

84.3

79.3

68.8

0

10

20

30

40

50

60

70

80

90

100

Minocycline TMP/SMZ Meropenem Ceftazidime Piperacillin/taz

R

S

Wang Fu, etal. CHINET 2009 surveillance of bacterial resistance in China. Chin J Infect Chemo 2010,10:325-334 24

0

10

20

30

40

50

60

20.5

36.4 37.6

41.3

36.3

4039

44.4

58.3 57.6

54.5 56

59.8

53

55.9

52.9

R S

Resistance and susceptibility rates in 12823 strains of

non-fermentative organisms(%)，，，， 2009200920092009 ，，，，CHINETCHINETCHINETCHINET


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Antibiotics commonly used in the treatment ofP. aeruginosa infections

25Drug Resistance Updates (2000) 3, 247–255

26

Core antipseudomonalbeta beta-lactam antibiotics

Cefoperazone/sulbactam

Piperacillin/tazobactam Cefepime

Ceftazidime

Aztreonam

Imipenem

Meropenem

Doripenem

Selection of antibiotics

A therapeutic selection based on

The severity of the infection,

Awareness of underlying risk factors and co-morbid diseases,

Recognition of the epidemiology and resistancephenotypes in individual settings, and

Knowledge of pharmacokinetic–pharmacodynamicparameters

27

Monotherapy versus combination coverage

The potential clinical significance ofcombination therapy over monotherapy for P.aeruginosa pneumonia has been acontroversial subject for many years.

The use of combination therapy is thought to

minimize the emergence of resistance andto increase the likelihood of therapeuticsuccess through antimicrobial synergy

28

29

Pneumonia guidelines

2005 ATS/IDSA guidelines recommend

use of two anti-pseudomonaldrugs An antipseudomonal beta-lactam

PLUS

Either an aminoglycoside or a quinolone

Correlation Between AntibioticCorrelation Between AntibioticCorrelation Between AntibioticCorrelation Between AntibioticConsumption and Resistance inConsumption and Resistance inConsumption and Resistance inConsumption and Resistance in P. aeruginosa P. aeruginosa P. aeruginosa P. aeruginosa

Antibiotic class Hazard ratio

Ceftazidime 0.8

Piperacillin 5.2

Ciprofloxacin 9.2

Imipenem 44

Antimicrobial Agents Chemother. 1999;43:1379-1382

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31

Treatmwnt of P.aeroginosa resistant to

carbapenem

TherapeuticTherapeuticTherapeuticTherapeutic optionsoptionsoptionsoptions

Cefoperozone/sulbactamCefoperozone/sulbactamCefoperozone/sulbactamCefoperozone/sulbactam （（（（checkcheckcheckchecksusceptibilitysusceptibilitysusceptibilitysusceptibility

ciprofloxacinciprofloxacinciprofloxacinciprofloxacin（（（（checkcheckcheckcheck susceptibilitysusceptibilitysusceptibilitysusceptibility））））

aminoglycosideaminoglycosideaminoglycosideaminoglycoside （（（（checkcheckcheckcheck susceptibilitysusceptibilitysusceptibilitysusceptibility

colistncolistncolistncolistn

NoteNoteNoteNote

Many strains remain susceptible toMany strains remain susceptible toMany strains remain susceptible toMany strains remain susceptible toaztreonam, ceftazidime or AP Pensaztreonam, ceftazidime or AP Pensaztreonam, ceftazidime or AP Pensaztreonam, ceftazidime or AP Pens

Combination of (AP Pen & APAG) or (APCombination of (AP Pen & APAG) or (APCombination of (AP Pen & APAG) or (APCombination of (AP Pen & APAG) or (AP----3GC & APAG) may show in vitro activities3GC & APAG) may show in vitro activities3GC & APAG) may show in vitro activities3GC & APAG) may show in vitro activities

New antipseudomonalantibiotics

Doripenem

Biapenem Tomopenem

Ceftobiprole

Sitafloxacin

32Journal of Antimicrobial Chemotherapy (2009) 64, 229–238

Doripenem Doripenem is a new carbapenem with potent in vitro

activity against various aerobic and anaerobic Gram-positive

and Gram-negative bacteria.

In vitro antibacterial activity against wildtype P. aeruginosa

is 2–4 fold more potent than meropenem and imipenem

In a study comparing the in vitro activity of doripenem withother antipseudomonal antibiotics (imipenem, levofloxacin,

piperacillin, ceftazidime, aztreonam, tobramycin and

cefepime), the MIC of doripenem was lower than those of

all comparative agents against P. aeruginosa isolates

Doripenem had MIC90s of 2 and 16 mg/L for

ceftazidimesusceptible and -resistant isolates, respectively,

compared with meropenem (8 and 32 mg/L, respectively)and imipenem (16 and 32 mg/L, respectively)


Doripenem

The first randomized, open-label, Phase III study72

of 531 patients compared doripenem 0.5 q8h with

imipenem 0.5 q6h

There was no statistically significant difference in

clinical cure between the two groups (68.3% for

doripenem and 64.8% for imipenem).

In a subgroup analysis, P. aeruginosa was isolated

from 28 patients in the doripenem group and 25 in

the imipenem group.

There was also a statistically non-significant trendtowards higher clinical cure rates with doripenem

[16/20 (80%)] versus imipenem [6/14 (42.9%)].


Doripenem

A second randomized, Phase III, prospective, open-label study of 448 patients with nosocomial

pneumonia or early onset compared doripenem 0.5q8h with piperacillin/tazobactam 4.5 q6h.

Step-down therapy to oral levofloxacin wasallowed after 72 h.

Overall microbiological and the clinical cure rate inthe Clinical evaluated population were 84.5% and81.3% for doripenem and 80.7% and 79.8% forpiperacillin/tazobactam(p=NS) respectively.


Biapenem

Biapenem is a parenteral carbapenem antibacterial

agent that was launched in Japan in 2002 and it is

currently in Phase II trials in the USA.

It has a broad spectrum of in vitro antibacterial

activity against Gram-negative (including b-

lactamase-producing strains and P. aeruginosa),

Gram-positive and anaerobic bacteria.

Biapenem shows a good post-antibiotic effect, similar

to imipenem, and has a high bactericidal activity

against Pseudomonas biofilm-forming strains and

several efflux system mutants.


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Biapenem in vitro activity of biapenem against P. aeruginosa tends to

be similar to that of imipenem in most investigations

In clinical trials, 300 mg biapenem twice daily showed

clinical and bacteriological efficacy similar to that of 500mg imipenem twice in adult patients with various types of

bacteriologically documented lower respiratory tract

infections, including those with P. aeruginosa.

Clinical efficacy rates in the biapenem and imipenem

groups were 94.8% (73/77 patients) and 92.8% (64/69),

respectively.

Bacterial eradication was achieved in 90.9% (20/22) of

biapenem and 93.1% (27/29) of imipenem recipients.


Tomopenem

a novel 1-b-methylcarbapenem that has avery broad-spectrum activity against Gram-

positive and Gram-negative bacteria,including P. aeruginosa, MRSA and PRSP.

In vitro and in vivo murine studies showedthat tomopenem exhibited improved activityagainst P. aeruginosa.


Ceftobiprole

Ceftobiprole is a fifth-generation cephalosporinwith properties similar to those of tomopenem inits strong affinity for penicillin-binding proteins.

The antipseudomonal activity of ceftobiprole issimilar to that of cefepime, displaying identicalMIC50 and MIC90 in vitro studies.

In a study assessing 741 isolates of P. aeruginosa,72% of isolates were inhibited by 4 mg/Lceftobiprole, compared with 68% and 73% ofisolates being inhibited by 4 mg/L cefepime and

ceftazidime, respectively.


Comparative in vitro activity vs P. aeruginosa (n=403)

Antimicrobial

agent

MIC50

(µµµµg/ml)

MIC90

(µµµµg/ml)

MIC Range

(µµµµg/ml)

Ceftobiprole 4 16 0.25->32

Ceftazidime 2 32 0.25->32

Cefepime 4 16 0.12–>32

Piperacillin-

Tazobactam

16 >128 0.5->128

Brown NP et al. Poster E-0112, presented at 46th ICAAC, Sept, 2006; San Francisco,

In vitro activity does not necessarily correlate with clinical results.

Ceftobiprole

Ceftobiprole has completed one Phase III

investigation for the treatment of hospital-acquired

pneumonia (HAP) including a subgroup of patientswith VAP.

Participants were randomized to receive 500 mg

ceftobiprole intravenously every 8 h as a 2 h infusion

or ceftazidime plus linezolid for a total of 7–14 days.

Seventy patients had P. aeruginosa pneumonia.

In the CE patient population excluding VAP, clinical

cure rates were 77% for ceftobiprole and 76% forcombination therapy


Sitafloxacin

Sitafloxacin has activity comparable to that of

ciprofloxacin towards wild-type strains of P. aeruginosa,

but shows lower MICs for gyrA or parC mutants, due to abetter affinity for the mutated targets.

A Phase II, randomized, open-label, multicentre studydemonstrated that sitafloxacin (400 mg once daily) was

as safe and as well tolerated as imipenem (500 mg three

times a day) for the treatment of pneumonia, including

two cases of P. aeruginosa pneumonia, one in each group


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Antimicrobial Agents for the Treatment of Acinetobacter Infections

43Clinical Infectious Diseases 2010; 51(1):79–84

44

The antibiotic armamentarium fortreatment of Acinetobacter

the most active agents are

Sulbactam containing regimen,

carbapenems,

colistin,

polymyxin

Carbapenem Use and MDRCarbapenem Use and MDRCarbapenem Use and MDRCarbapenem Use and MDR Acinetobacter Acinetobacter Acinetobacter Acinetobacter

Variable OR (95 % CI)

Age 1.03 (1.01-1.05)

Time at risk 1.02 (1.002 -1.03)

ICU stay 21.54 (10.73-43.23)

Imipenem 9.18 (3.99-21.13)

3-GC 2.11 (1.13-3.95)

Risk factors for imipenem –resistant A. baumannii

Antimicrob Agents Chemother. 2004;48:224- 228

Abx Associated with MDRAbx Associated with MDRAbx Associated with MDRAbx Associated with MDRA. baumannii and P. aeruginosaA. baumannii and P. aeruginosaA. baumannii and P. aeruginosaA. baumannii and P. aeruginosa

A.A.A.A. baumannii baumannii baumannii baumannii CarbapenemsCarbapenemsCarbapenemsCarbapenems

ThirdThirdThirdThird----generationgenerationgenerationgeneration

cephalosporinscephalosporinscephalosporinscephalosporins

P. aeruginosa P. aeruginosa P. aeruginosa P. aeruginosa CarbapenemsCarbapenemsCarbapenemsCarbapenems

FluorquinolonesFluorquinolonesFluorquinolonesFluorquinolones

Based on review of 55Based on review of 55Based on review of 55Based on review of 55 A.A.A.A. baumannii baumannii baumannii baumannii studies and 42studies and 42studies and 42studies and 42 P.P.P.P.aeruginosa aeruginosa aeruginosa aeruginosa studies that met prestudies that met prestudies that met prestudies that met pre----defined criteriadefined criteriadefined criteriadefined criteria

The multiThe multiThe multiThe multi----drug nature of efflux pump spectra means thatdrug nature of efflux pump spectra means thatdrug nature of efflux pump spectra means thatdrug nature of efflux pump spectra means that

virtually any antibiotic can select for resistance tovirtually any antibiotic can select for resistance tovirtually any antibiotic can select for resistance tovirtually any antibiotic can select for resistance toany otherany otherany otherany other

J. Hosp. Infect. 2006;64: 7-15.

Avoid using carbapenems if

possible…

- May decrease the frequency of imipenemresistance

- Decrease cost

The role of sulbactam

Sulbactam-containing regimen should be

considered as a therapeutic option formild to severe A. baumannii infectionscaused by sulbactam-susceptibleorganisms

48CLINICAL MICROBIOLOGY REVIEWS, July 2008, p. 538–582

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Acinetobacter spp . – Antimicrobial therapy

Acinetobacter spp . – Antimicrobial therapy

51

Treatment of Acinetobacter baumanni

resistant to carbapenem

Therapeutic options

Cefoperozone/sulbactam ,ampicillin/sulbactam (sulbactam alone is active againstsome A. baumanni)

colistn

Sulbactam: Two studies have shownsuperior outcome compared to colistin （J

Infect. 2008;56:432；J Antimicrob Chemother. 2008;61:1369）

We identified 22 microbiological studies reporting data for 2384 Acinetobacter spp. (1906 Acinetobacter baumannii).Susceptibility of atleast 90% of the Acinetobacter isolates to tigecycline (with an MIC

breakpoint of susceptibility 2 mg/L) was noted in 9/18 studies reportingdata on MDR Acinetobacter and in 7/15 studies reporting specific dataon carbapenem-resistant Acinetobacter.

The effectiveness of tigecycline for MDR Acinetobacter infections wasevaluated in eight identified clinical studies, reporting retrospective dataregarding 42 severely ill patients, among whom 31 had respiratory tractinfection (in 4 cases with secondary bacteraemia) and 4 hadbacteraemia.

Tigecycline therapy (in combination with other antibiotics in 28 patients)

was effective in 32/42 cases. In three cases, resistance to tigecycline developed during treatment.

52

53

CRAB的联合治疗的联合治疗的联合治疗的联合治疗

AAC, 2007，，，，51

舒普深舒普深舒普深舒普深3g,q8h,疗程疗程疗程疗程14天治疗鲍曼不动杆菌天治疗鲍曼不动杆菌天治疗鲍曼不动杆菌天治疗鲍曼不动杆菌HAP患患患患者者者者PK/PD参数与临床疗效关系的研究参数与临床疗效关系的研究参数与临床疗效关系的研究参数与临床疗效关系的研究（（（（n=12)

患者号患者号患者号患者号 MICs(µg/mL) %T>MIC 临床临床临床临床疗效疗效疗效疗效

细菌学细菌学细菌学细菌学疗效疗效疗效疗效

综合综合综合综合疗效疗效疗效疗效CPZ SUL CPZ SUL

10 1.5 0.75 304 128 治愈治愈治愈治愈清除清除清除清除治愈治愈治愈治愈

26 4 2 268 73 治愈治愈治愈治愈清除清除清除清除治愈治愈治愈治愈



8 4 2 123 60 治愈治愈治愈治愈菌交替菌交替菌交替菌交替治愈治愈治愈治愈



5 32 16 63 14 失败失败失败失败未清除未清除未清除未清除失败失败失败失败





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55

Treatment of S. maltophiliaTreatment of S. maltophiliaTreatment of S. maltophiliaTreatment of S. maltophilia RecommendedRecommendedRecommendedRecommended：：：：TMPTMPTMPTMP----SMZSMZSMZSMZ

AlternativeAlternativeAlternativeAlternative：：：：TC/CLTC/CLTC/CLTC/CL或或或或（（（（AztreonamAztreonamAztreonamAztreonam＋＋＋＋TCTCTCTC----CLCLCLCL））））

Minocyclin, doxycycline, ceftazidimeMinocyclin, doxycycline, ceftazidimeMinocyclin, doxycycline, ceftazidimeMinocyclin, doxycycline, ceftazidime

may also effectivemay also effectivemay also effectivemay also effective

Combination show in vitro synergyCombination show in vitro synergyCombination show in vitro synergyCombination show in vitro synergy

TC/CL+TMP/SMZ, TC/CL+CiprofloxacinTC/CL+TMP/SMZ, TC/CL+CiprofloxacinTC/CL+TMP/SMZ, TC/CL+CiprofloxacinTC/CL+TMP/SMZ, TC/CL+Ciprofloxacin

Data in mainland ChinaData in mainland ChinaData in mainland ChinaData in mainland China

Highly susceptible toHighly susceptible toHighly susceptible toHighly susceptible tocefoperazone/sulbactamcefoperazone/sulbactamcefoperazone/sulbactamcefoperazone/sulbactam

Sanford guideline 2010

Potency of tigecycline against non-fermentative Gram-negative bacteria

Organism MIC(mg/L) %S %R

Range MIC50 MIC90

P. aeruginosa (n = 1121) 0.12 to >32 8 16 5.1 77.2

Acinetobacter spp. (n = 326) 0.06-8 0.5 2 94.5 0.9

B. cepacia (n = 21) 0.25-32 1 16 67.0 29.0

S. maltophilia (n = 203) 0.12-8 1 2 93.1 3.0

56

Conclusion Pseudomonas aeruginosa, A. baumannii, S. maltophilia and

members of the B. cepacia complex are an increasingly

recognised cause of infection and are increasingly difficult

to treat.

There are currently no much more new drugs for the

treatment of multidrug resistant non-fermenters.

Therefore, currently available antibiotics require judicious

and prudent use, following evidence based trial data

whenever possible.

The role of combining these antibiotics in combating thedevelopment of further antibiotic resistance and delivering

superior clinical efficacy requires more rigorous evaluationthan in the past.

57Thank you for your attention ! Thank you for your attention ! Thank you for your attention ! Thank you for your attention !

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