Pseudomonas

aeruginosa
Wild Phenotype

6.4 The Non Fermenters

6.4 The Non Fermenters

•  β-lactams
•  Produc'on of a Cephalosporinase and Efflux mechanisms

Resistance Mechanisms of the
Non-Enterobacteriaceae

•  Resistance to aminopenicillin, Cephalosporine1st and 2nd genera'on, and some Cephalosporin
3rd genera'on (latamoxef, cefotaxim)

•  Quinolone
•  Natural resistance to 1st genera'on

•  Cotrimoxazole
•  Natural resistant

•  Aminosides
•  Sensi've to all aminoglycosides

•  Polymixines
•  Natural suscep'bility

Pseudomonas
aeruginosa

Pseudomonas
aeruginosa

6.4 The Non Fermenters

6.4 The Non Fermenters

Wild
type

•  β lactams Known Mechanisms of Resistance
•  Impermeability
•  Efflux
•  β-lactamase produc'on
• 
• 
• 
• 

Penicillinase
Extended Spectrum β lactamase (ESβL)
High Level Cephalosporinase
Carbapenemase

•  Target Modifica'on (rare)

Pase

HLCase

ESβL

Carba

OXA

PER

OprM

Loss
OprD2

Efflux

Aminopenicillin

R

R

R

R

R

R

R

R

Aminopenicillin + Clav. ac

R

R

R

R

R

R

R

R

Carboxypenicillin

S

R

R

R

R

R

R

S

Carboxypenicillin + Clav. AC

S

V

R

R

V

R

R

S

Ureidopenicillin

S

R

R

R

R

V

S

S

Ureidopenicillin + Tazobactam

S

V

R

R

S

V

(s)

S

Cephalosporin 1st Gen

R

R

R

R

R

R

R

R

Cefoperazone (C3G)

S

S

R

R

R

R

(s)

S

Cefepim (C3G)

S

S

(s)/R

R

R

R

(s)

Aztreonam

S

S

R

R

R

V

(s)

S

Imipenem

S

S

S

S

S

R

S

R

+

+

ä

+

+

Frequency

S

(s) Reduced sensitivity

Pseudomonas
aeruginosa

6.4 The Non Fermenters

Pseudomonas
aeruginosa

6.4 The Non Fermenters

Aminoglycosides
•  Aminoglycosides Known Mechanisms of Resistance
• 
• 
• 
• 

Impermeability
Efflux
Enzymes produc'on
Respiratory muta'on

Enzym
AAC(3) I
AAC(3)
ANT(2’’) I
AAC(6’) II
AAC(6’)
AAC(6’)+ ANT(2’’) I
Efflux (30% to 40% of all resistance)

Phenotype

GEN

TOB

NET

AKN

G

R

S

S

S

GNt

R

S

R

S

GT

R

R

S

S

GTN

R

R

R

S

TNtA

S

R

R

R

GTNA

R

R

R

R

R

S

R

R

•  Impermeability is the most common mechanism (74 permutaEons
involving 11 enzymes)

Pseudomonas
aeruginosa

6.4 The Non Fermenters

6.4 The Non Fermenters

Acinetobacter spp
Wild Phenotype

•  β-lactams

•  Before 70’s resistance to Peni G only (!), s'll the case today for « non baumanii » acinetobacter
•  Now Resistance to aminopenicillin, aminopenicillin + Clav. Ac, Cephalosporin 1st and 2nd
genera'on => call « suscep'ble » bacteria

•  Quinolones Known Mechanisms of Resistance
•  Impermeability
•  Efflux
•  Target modifica'on

•  Aminosides

•  Sensi've to all aminoglycosides

•  Trimethoprim

•  N atural resistance

6.4 The Non Fermenters

6.4 The Non Fermenters

Acinetobacter spp

Acinetobacter spp
β - lactams

•  β lactams Known Mechanisms of Resistance
•  β-lactamase produc'on
•  Penicillinase
•  Oxacillinase
•  Cephalosporinase

•  Impermeability
•  Target Modifica'on

Phenotype

I

II

III

IV

V

Enzyme

« Susceptible »
*

Pase

Case

Pase
+Case

Multiple
Mechanisms

Aminopenicillin

R

R

R

R

R

Aminopenicillin + Clav. ac

R

R

R

R

R

Carboxypenicillin

S

R

S

R

R

Cephalosporin 1st gen

R

R

R

R

R

Cephalosporin 2nd gen

R

R

R

R

R

Cephalosporin 3rd gen

S

S

R

R

R

Aztreonam

S

S

R

R

R

Carbapenems

S

S

S

S

R

* Chromosomal Cephalosporinase

6.4 The Non Fermenters

6.4 The Non Fermenters

Acinetobacter spp

•  Aminoglycosides Known Mechanisms of
Resistance
•  Enzymes produc'on

Acinetobacter spp

•  Acinetobacter baumanii is naturally suscepEble to:
•  Rifampicin,
•  ColisEn
•  Fluoroquinolones

•  But
•  70 % of strains are now resistant to fluoroquinolones (target
modifica'on)

Stenotrophomonas
malthophilia

Stenotrophomonas
malthophilia

6.4 The Non Fermenters

6.4 The Non Fermenters

Hyper
sensible

Wild Phenotype
•  Naturally resistant to high number of resistance
• 
• 
• 
• 
• 

Sensible

Imi S

Others

CAZ S CAZ R

β-lactams (aminopenicillin, cephalosporin, carbapenems)
Aminoglycoside (Kana, Tobra, Genta, Ne'l, Amika)
Cyclin
Quinolones (1st genera'on, 2nd genera'on)
Fosfomycin

6.4 The Non Fermenters

Amoxicillin

R

R

R

R

R

Amoxicillin + Clav. Ac

R

R

R

S

R

Ticarcillin

S

R

R

S

R

Ticarcillin + Clav. Ac

S

S

S

S

V

Ceftazidim

S

S

R

S

I/R
R

Aztreonam

S

S

S

S

Imipenem

R

R

R

S

R

Frequency

5-10%

< 1%

15-20%

20-30% 40-50%

6.4 The Non Fermenters

Chapter 6.4
The non Fermenters

For Pseudomonas and other non-fermenters
•  AnEbioEcs and breakpoints adapted to:
•  the natural resistance of these bacteria
•  their high MIC
•  Example Pseudomonas aeruginosa:

Susceptibility testing of NonEnterobacteriaceae

•  Natural Resistance to Cotrimoxazole
•  Low level Cephalosporinase
•  Natural suscepEbility to ColisEn

•  Also for:

- Stenotrophomonas maltophilia



6.4 The Non Fermenters

6.4 The Non Fermenters

ANTIBIOTICS

mg/l

Code

ANTIBIOTICS

mg/l

FAM

Ampi + Sulbactam

8-16

AKN

Amikacin

16-32

TIC

Ticarcillin

16

GEN

Gentamicin

4-8

TICP

Ticarcillin Pyo

64

TOB

Tobramycin

4-8

TCC

Ticar + Ac .Clav

16

COL

Colistin

TCCP

Ticar + Ac. Clav Pyo

64

CIP

Ciprofloxacin

1-2

PIC

Piperacillin

16

TSU

Cotrimoxazol

2

PICP

Piperacillin Pyo

16

TZP

Piper + Tazo

16

TZPP

Piper + Tazo Pyo

CAZ

Ceftazidime

8-16

FEP

Cefepim

8-16

IMI

Imipenem

4-8

MERO

Meropenem

4-8

64

The Non fermenters

ATB PSE 5: characteristics

Code

- Pseudomonas fluorescens
- Acinetobacter baumanii
- Brevundimonas diminuta
- Burkholderia cepacia ...

4