MULTI-DRUG RESISTANT GRAM NEGATIVE RODS

Acinetobacter spp., Stenotrophomonas maltophilia, Burkholderia cepacia 

  1. Acinetobater species:
  • Gram negative coccobacilli that are non-motile and oxidase negative
  • They oxidize sugars, but do not ferment, and do not reduce nitrate
  • Identification to species level is unnecessary for clinical isolate
  • Nosocomial strains may be multi-drug resistant. Carbapenem resistant strains can occur.

 

  1. Stenotrophomonas maltophilia
  • Motile, late oxidase positive gram negative rods
  • They oxidize, but do not ferment sugars
  • They are DNAse positive
  • Inherently resistant to carbapenems, which may aid in presumptive identification

 

  1. Burkholderia cepacia
    • Motile, oxidase variable gram negative rods
    • They oxidize, but do not ferment sugars
    • Isolates are characteristically resistant to polymyxins

 

  1. SENSITIVITY TESTING AND REPORTING

MIC testing is preferable to disk diffusion testing for non-fermenters. However, disk diffusion is more convenient for most clinical laboratories.

QC strains must be tested daily to ensure the validity of test results. The following QC strains must be tested:

  • coli ATCC® 29522
  • aeruginosa ATCC® 27853
  • coli ATCC® 35218 (for β-lactam/β-lactamase inhibitor combinations); with disk diffusion and MIC results within the ranges proposed by the CLSI.

 

  1. Acinetobacter spp.
  2. Ceftazidime and Imipenem should always be tested and reported.
  3. Other agents may be reported as alternative therapeutic options e.g. Fluoroquinolones, tetracyclines, trimethoprim/sulfamethoxazole, aminoglycosides, etc.
  4. Polymyxins may be tested  by measuring MICs (by broth microdilution or agar dilution) for multi-drug resistant isolates.

 

  • Alternative antimicrobials in each group are not cross-reportable.
  • Isolates sensitive to tetracycline are usually sensitive to doxycycline and minocycline; however, some tetracycline resistant isolates may be sensitive to either doxycycline and/or minocycline.

 

Preference Agent

( +disk content where applicable)

Breakpoints

Disk diffusion Zone diameters

Interpretive standards

MIC (µg/ml)

S I R S I R
1st line CEFTAZIDIME (30 µg) < 14 15-17 > 18 < 8 16 > 32
1st line IMIPENEM (10 µg) < 13 14-15 > 16 < 4 8 > 16
2nd line PENICILLINS*:

-Piperacillin (100 µg)

 

< 17

 

18-20

 

> 21

 

< 16

 

32-64

 

> 128

2nd line CEPHALOSPORINS*:

-Cefotaxime (30 µg)

-Ceftriaxone (30 µg)

-Cefepime (30 µg)

 

< 14

< 13

< 14

 

15-22

14-20

15-17

 

> 23

> 21

> 18

 

< 8

< 8

< 8

 

16-32

16-32

16

 

> 64

> 64

> 32

2nd line Trimethoprim/ sulfamethoxazole (1.25/23.75)  

< 10

 

11-15

 

> 16

 

< 2/38

 

 

> 4/76

2nd line TETRACYLINES**:

-Tetracycline (30 µg)

-Doxycycline (30 µg)

-Minocycline (30 µg)

 

< 11

< 9

< 12

 

12-14

10-12

13-15

 

> 15

> 13

> 16

 

< 4

< 4

< 4

 

8

8

8

 

> 16

> 16

> 16

2nd line AMINOGLYCOSIDES*:

-Gentamicin (10 µg)

-Amikacin (30 µg)

-Tobramycin (10 µg)

 

< 12

< 14

< 12

 

13-14

15-16

13-14

 

> 15

> 17

> 15

 

< 4

< 16

< 4

 

8

32

8

 

> 16

> 64

> 16

2nd line FLUOROQUINOLONES:*

-Ciprofloxacin (5 µg)

-Levofloxacin (5 µg)

 

< 15

< 13

 

16-20

14-16

 

> 21

> 17

 

< 1

< 2

 

2

4

 

> 4

> 8

2nd line β-LACTAM/ β-LACTAMASE INHIBITOR COMBINATIONS*:

-Ampicillin/sulbactam (10/10 µg)

-Piperacillin/tazobactam (100/10 µg)

-Ticarcillin/ clavulanate (75/10 µg)

 

 

< 11

< 17

< 14

 

 

12-14

18-20

15-19

 

 

> 15

> 21

> 20

 

 

< 8/4

< 16/4

< 16/2

 

 

16/8

32/4-64/4

32/2-64/2

 

 

> 32/16

> 128/4

> 128/2

3rd line Polymyxin-B/ Colistin <2 >4

 

  1. Stenotrophomonas maltophilia
  1. Trimethoprim/sulfamethoxazole is the therapeutic agent of choice and must always be reported.
  2. Carbapenems should not be tested/ reported.
  3. Other agents may be reported as alternatives e.g., fluoroquinolones, tetracyclines.
  4. Cephems (cephalosporins including ceftazidime), chloramphenicol, and ticarcillin/clavulanate may be reported based on MIC results.
  5. Minocycline is the preferable than tetracycline to test against Stenotrophomonas maltophilia strains.

 

Preference Agent

( +disk content where applicable)

Breakpoints

Disk diffusion Zone diameteres

Interpretive standards

MIC (µg/ml)

S I R S I R
1st line Trimethoprim-Sulfamethoxazole

(1.25/23.75 µg)

 

< 10

 

11-15

 

> 16

 

< 2/38

 

 

> 4/76

2nd line Levofloxacin < 13 14-16 > 17 < 2 4 > 8
2nd line Minocycline (30 µg)* < 14 15-18 > 19 < 4 8 > 16
2nd line Ticarcillin/clavulanate < 16/2 32/2-64/2 > 128/2
2nd line CEPHEMS/ Ceftazidime

(30 µg)

 

< 8

 

16

 

> 32

2nd line Chloramphenicol < 8 16 > 32

 

  1. Burkholderia cepacia
  2. Trimethoprim/sulfamethoxazole is the therapeutic agent of choice and must always be reported.
  3. Polymyxins should not be tested/ reported.
  4. Other agents may be reported as alternatives e.g. cephems, carbapenems, tetracyclines.
  5. Fluoroquinolones, chloramphenicol, and ticarcillin/clavulanate may be reported based on MIC results.

 

Preference Agent

( +disk content where applicable)

Breakpoints

Disk diffusion Zone diameters

Interpretive standards

MIC (µg/ml)

S I R S I R
1st line Trimethoprim-Sulfamethoxazole

(1.25/23.75 µg)

 

< 10

 

11-15

 

> 16

 

< 2/38

 

 

> 4/76

2nd line CEPHEMS/ Ceftazidime

(30 µg)

 

< 17

 

18-20

 

> 21

 

< 8

 

16

 

> 32

2nd line Meropenem (10 µg) < 15 16-19 > 20 < 4 8 > 16
2nd line Minocycline (30 µg)* < 14 15-18 > 19 < 4 8 > 16
2nd line Ticarcillin/clavulanate < 16/2 32/2-64/2 > 128/2
2nd line Levofloxacin < 2 4 > 8
2nd line Chloramphenicol < 8 16 > 32

Updated July 2018

Dr.Fizza Faroqui

Year V Resident

Department of pathology and laboratory medicince

Aga Khan University Hospital, Karachi