Table 1. Characteristics differentiating the medically important species of the genus Nocardiaa

 

 

N. abscessus

N. africana

N. asteroides sensu stricto type VI

N.brasiliensis

N. brevicatena complex

N. carnea

N. farcinica

N. nova

 N. otitidiscaviarum

N. paucivorans

 N. pseudobrasiliensis

N. transvalensis

(N. asteroides type IV)

N. transvalensis

 (sensu stricto)

N. transvalensis

 (new taxon I)

N. transvalensis

(new taxon II)

 N. veterana

Hydrolysis of:

 Acetamide

-

-

V

-

-

NT

+

-

-

-

+

-

-

-

-

-

 Adenine

-

-

-

-

-

-

-

-

-

-

+

-

-

-

-

-

 Casein

-

+

-

+

-

-

-

-

-

-

+

-

-

-

-

-

 Esculin  

-

-

-

+

+

+

+

-

+

V

+

-

-

-

-

-

 Hypoxanthine

-

-

-

+

-

-

-

-

+

-

+

+

+

+

+

-

 Tyrosine

-

-

-

+

-

-

-

-

-

-

+

-

-

-

-

-

 Xanthine

-

-

-

-

-

-

-

+

-

-

-

-

-

-

-

Growth at or in:

 45°C

V

+

V

-

V

-

+

-

V

NT

-

NT

NT

NT

NT

NT

 Lysozyme broth

+

+

+

+

V

+

+

+

+

+

+

+

+

+

+

+

Production of arylsulfatase

-

-

-

-

-

-

-

+

-

-

-

-

-

-

-

-

Acid production or utilization of L-rhamnose

V

-

V

-

V

-

+

-

-

-

-

-

-

-

-

-

Resistance to:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Amikacin (MIC, >16 μg/ml)

-

-

-

-

-

NT

-

-

-

-

-

+

+

V

V

NT

Gentamicinb (zone, <10 mm)

-

+

-

NT

V

NT

+

V

NT

NT

NT

+

+

+

+

NT

Kanamycin (MIC, >16 μg/ml)

-

+

V

NT

-

NT

+

V

NT

NT

NT

+

+

+

+

NT

 Tobramycin b (zone, <20 mm)

-

NT

-

NT

+

NT

+

V

NT

NT

-

+

+

+

+

NT

Ciprofloxacin (MIC, >4 μg/ml)

+

NT

-

+

-

NT

-

+

NT

NT

-

NT

NT

NT

NT

NT

Ampicillin (MIC, >4 μg/ml)

I

-

+

V

V

NT

+

-

+

NT

V

NT

NT

NT

NT

NT

Amox-clav (MIC, ≥64/32 μg/ml)

NT

NT

NT

-

V

NT

-

+

+

NT

V

V

+

V

-

NT

Cefamandoleb (zone, <20 mm)

-

NT

-

V

V

NT

+

-

NT

NT

NT

NT

NT

NT

NT

NT

Cefotaxime (MIC, ≥64 μg/ml)

-

NT

-

V

-

NT

+

-

V

NT

NT

NT

NT

NT

NT

NT

Ceftriaxone (MIC, ≥64 μg/ml)

-

NT

-

V

-

NT

+

-

V

NT

NT

NT

NT

NT

NT

NT

Erythromycinb (zone, <30 mm)

+

-

I

-

+

NT

+

-

+

NT

-

+

+

+

+

NT

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

a Data were derived from 12, 46, 49, 88, 108, 112, 116, 119, and 120. 

Abbreviations and symbols: -, 90% or more of the strains are negative; +, 90% or more of the strains are positive; V, 11 to 89% of the strains are positive; NT, not tested; I, intermediate; amox-clav, amoxicillin-clavulanate.

b Disk content (µg) was as follows:  gentamicin, 10 µg; tobramycin, 10 µg; cefamandole, 30 µg; and erythromycin, 30 µg.  Methodology adapted from Wallace et al. (111).  Briefly, the inoculum was adjusted to a turbidity equivalent to that of a 0.5 McFarland barium sulfate standard and was streaked onto a Mueller-Hinton agar plate, the plate was inoculated at 35°C, and the zone of inhibition was read at 48 h.

 

Table 2.  Characteristics of some antimicrobial agents used clinically* [Download PDF]

Class and microbial agent (s)       

Route of administration

Drug concentration Intracellular/        extracellular  ratio

 Mechanism of action

 Drug interactions

 Side effects

Aminoglycoside

   Amikacin

Parenteral

 

 

 

 

<1 (105) 

2 to 4 after 72 h of incubation (103)

Bactericidal activity results from action on 30S ribosomal subunit to produce faulty protein synthesis

Calcium, sodium bicarbonates, β-lactams, and heparin

Nephro- and ototoxicity

β-Lactams

 

 

 

 

 

Penicillins

       Ampicillin

Oral/ Parenteral

<1 in PMNs and macrophages after prolonged incubation (105)

 

 

 

 

 

 

Bactericidal activity results from interference with construction of bacterial cell wall by inhibition of transpeptidases responsible for catalysis of peptidoglycan cross-linking

Allopurinol, bacteriostatic antibiotics (chloramphenicol,  sulfonamides, or tetracyclines) may interfere with bactericidal effect of ampicillin and probenecid

Aminoglycosides

 

 

Nephro-and ototoxicity

Carbapenem

       Imipenem

Parenteral 

 

Cephalosporins

 

      Cefotaxime

Parenteral

      Ceftriaxone

Parenteral

      Cefixime

Oral

      Cefuroxime  

Oral/Parenteral

b-Lactam-b-lactamase inhibitor

     Amoxicillin-        clavulanic acid

 

Oral

 

 

 

 

 

 

Bactericidal activity  results from the ability of clavulanic acid to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes and thus protects amoxicillin from degradation

Probenecid, allopurinol, antabuse,

and ampicillin

Gastrointestinal and hypersensitivity reactions

Macrolides

     Erythromycin

 

Oral/Parenteral 

 

 

16 to 32 in alveolar

macrophages (55)

2 to 10 in PMNs (15)

Bactericidal activity results from inhibition of protein synthesis by binding 50S ribosomal subunit

Theophylline, digoxin, oral anticoagulants, ergotamine 

 

Gastrointestinal irritation, transient CNS reactions, and cardiac arrhymias  

Quinolones

     Ciprofloxacin

 

 

Oral/Parenteral

2 to 8 in macrophages and fibroblasts (15)

Bactericidal activity results from gyrase inhibition required to fold DNA strands

Theophylline, magnesium -aluminum antacids, and other cations (calcium, zinc, and iron)  

Gastrointestinal, CNS,  and skin/allergic

reactions

 

Sulfonamides

 

 

 

 

 

 Sulfamethoxazole

Oral

1.7 in PMNs (34) 4.1 in PMNs (34) and 9 at 37°C and 13 at 25°C (50)

Bacteriostatic results from the inhibition of folate pathway

Thiazides, warfarin, phenytoin, cyclosporine,and cyclosporin

 

Hepatotoxicity, myelosuppression, and gastrointestinal, allergic skin, hematologic, neurologic, and psychiatric reactions

 Trimethoprim

Oral

TMP-SMX

Oral/Parenteral

Tetracyclines

 

 

 

 

 

 Doxycycline

Oral/Parenteral

7.1 in PMNs (34)

Bacteriostatic activity results from inhibition of protein synthesis

 

Antacids and anticoagulant therapy 

Bacteriostatic drugs may interfere with bactericidal action of penicillin

Gastrointestinal reactions and renal toxicity 

Hypersensitivity reactions and IV minocycline may cause thrombophlebitis

 Minocyline

Oral/Parenteral

*Adapted from Physicians’ Desk Reference (84) except where referenced.

PMN, polymorphonuclear leukocytes; CNS, central nervous system; and IV, intravenous. 

 

Table 3  Antimicrobial susceptibility of N. farcinica, N. nova, and N. asteroides sensu stricto isolates*

MIC (µg/mL) in broth 

 

50%

90%

Geometric mean

Range

Breakpoint (µg/mL) ╪

% Resistant

isolates

 

Nf

  Nn

Na

Nf

Nn

Na

Nf

Nn

Na

Nf

Nn

Na

Nf

Nn

Na

Nf

Nn

Na

Ampicillin

>32

4

8

>32

8

   >32

49

2

6

32->32

≤0.25-16

≤0.25-16

≥4

≥4

≥4

100

56

73

Amoxicillin/ clavulanic acid

16/8

64/32

   8/4

32/16

64/32

64/32

  12/6

   48/24

    8/4

2/1-64/32

2/1-64/32

≤0.5/0.25->64/32

≥32/16

≥32/16

≥32/16

29

94

33

Cefuroxime

32

1

    <1

64

4

8

30

1

2

4->64

≤1-16

≤1-32

≥32

≥32

≥32

64

0

6

Cefotaxime

64

4

2

 >64

16

16

66

4

2

32->64

≤0.5-64

<0.5-64

≥64

≥64

≥64

82

6

2

Ceftriaxone

>64

4

2

 >64

16

8

45

5

2

8->64

≤1-64

≤1-64

≥64

≥64

≥64

86

11

2

Cefixime

>64

64

16

 >64

>64

  >64

111

49

26

64->64

8->64

≤1->64

≥4

≥4

$4

100

100

87

Imipenem

8

   <0.25

2

 >32

0.5

32

7

0.3

2

0.5-32

≤0.25-2

≤0.25->32

≥16

≥16

$16

36

0

23

Amikacin

1

   <0.25

   <0.25

1

 >0.25

1

1

0.25

0.4

≤0.25-2

≤0.25

≤0.25-4

≥64

≥64

≥64

0

0

0

Erythromycin

16

0.25

4

 >16

0.5

  >16

14

0.3

3

1->16

≤0.13-0.3

≤0.13->16

≥8

≥8

≥8

86

0

40

Minocycline

2

1

1

8

4

8

2

1.6

1

0.5-16

0.25-8

≤0.13->16

≥16

≥16

≥16

4

0

6

Doxycycline

4

4

2

8

8

16

4

4

2

1-16

1->16

≤0.13->16

≥16

≥16

≥16

14

6

12

Ciprofloxacin

1

8

8

8

  >8

     >8

1

8

3

0.25->8

4->8

≤0.06->8

≥4

≥4

≥4

32

100

62

Rifampin

 >32

2

32

  >32

>32

   >32

42

8

3

≤0.25->32

≤0.5->32

≤0.5->32

≥4

≥4

≥4

93

50

73

Sulfamethoxazole

8

32

4

32

8

16

7

2.3

4

≤1-128

≤1->128

≤1-32

>32

>32

>32

11

11

0

Dapsone

8

4

2

  >32

8

32

8

3.5

5

1->32

≤0.5->32

≤0.5->32

>32

>32

>32

14

6

8

PS-15

4

2

2

4

4

4

2

1.8

2

≤0.063->4

0.5-4

0.5->4

 

 

 

 

 

 

WR99210

≤0.063

≤0.063

≤0.063

0.5

0.125

2

0.2

0.08

0.2

≤0.063-2

≤0.063-0.5

≤0.063-4

 

 

 

 

 

 

Cycloguanil

512

64

256

>512

128

 >512

512

60

194

128->512

16-256

≤8->512

 

 

 

 

 

 

Proguanil

128

32

64

512

64

 >512

132

37

60

32->512

16-128

≤8->512

 

 

 

 

 

 

Trimethoprim

4

8

4

 >32

32

  >32

5

7

5

≤0.5->32

1->32

≤0.5-

>32

≥16

≥16

≥16

82

39

2

TMP-SMX

0.5/

9.55

0.06/

1.19

 0.25/

4.8

 2/

38

0.5/

9.5

 1/

19

0.5/

9.5

0.17/

3.2

0.22/

4.18

≤0.06/

1.19-4/76

≤0.06/1.19->8/152

≤0.06/

1.19-1/19

>2/

38

>2/

38

>2/

38

7

11

0

 

 

 

 

 

 

 

Zone of inhibition (mm) on disk

 

 

 

 

 

 

 

Arithmetic mean

Range

Breakpoint (mm)

% Resistant

isolates

 

 

 

 

 

 

 

Nf

Nn

Na

Nf

Nn

Na

Nf

Nn

Na

Nf

Nn

Na

Cefamandole

(30 µg)

 

 

 

 

 

 

12

 

53

38

6-46

6-90

6-50

≤14

≤14

≤14

70

17

29

Tobramycin

(10 µg)

 

 

 

 

 

 

7

24

37

6-22

6-46

6-40

≤14

≤14

≤14

96

33

25

Note. Nf, N. farcinica (23 clinical isolates, five reference strains); Nn, N. nova (16 clinical isolates, two reference strains); Na, N. asteroides sensu stricto (49 clinical isolates, three reference strains).

* Modified from reference 72.

Estimated value (next highest twofold value was used when calculating geometric mean of values that were greater than the highest concentration tested). 

‡  Breakpoint for resistance from National Committee for Clinical Laboratory Standards (79).

 

Table 4.  Antimicrobial susceptibility of Nocardia abscessus and Nocardia asteroides sensu stricto type VI

 MIC (ug/mL) in broth

 

 

 50%

 90%

 Geometric mean*

Range

 Breakpoint (ug/mL)                                % Resistant  isolates

Antimicrobial agent

Na

Na (VI)

Na

Na (VI)

Na

Na (VI)

Na

Na (VI)

Na

Na (VI)

Na

Na (VI)

Ampicillin

 4

 32

 8

 >32

 4

 16->32

 1-8

 16->32

 >4

 >4

 86

 100

Amoxicillin/

   clavulanic acid

 4/2

 32/16

 16/8

 64/32

 3.2/1.6

 20/10

 <0.5/0.25-16/8

 1/0.5->64/32

≥32/16

 ≥32/16

 0

 61

Cefuroxime

 2

 1

 4

 16

 2

 2

 <1-4

 <1-32

 ≥32

 ≥32

 0

 11

Cefotaxime

 2

 2

 4

 8

 2

 3

 0.5-16

 1-64

 ≥64

 ≥64

 0

 6

Ceftriaxone

 <1

 2

 4

 8

 3

3

 <1-16

 <1-64

 ≥64

 ≥64

 0

 6

Cefixime

 64

 >64

 >64

 >64

 32

 45

 0.5->64

 0.5->64

 ≥64

 ≥64

71

 61

Imipenem

 1

 4

 4

 16

 1

 5

 <0.25->32

 <0.25>32

 ≥16

 ≥16

14

 11

Amikacin

 0.5

 0.5

 2

 1

 1

 0.5

 <0.25-4

 <0.25-1

 ≥16

 ≥16

 0

 0

Erythromycin

 >16

 16

 > 16

 >16

 24

 12

 8->16

 2->16

 ≥8

 ≥8

100

 72

Minocycline

 1

 2

 8

8

 3

 2

 1-16

 <0.13->16

 ≥16

 ≥16

 14

 6

Doxycycline

 8

 2

 16

 8

 7

 2

 0.25->8

 0.13->16

 ≥16

 ≥16

 43

 6

Ciprofloxacin

 8

 8

 8

 >8

 4

 2

 0.25->8

 0.13->8

 ≥4

 ≥4

 71

 83

Rifampin

 >32

 32

 >32

 >32

 24

 24

 4->32

 0.5->32

 ≥4

 ≥4

 100

 94

Sulfamethoxazole

 8

 4

 32

 16

 32

 5

 2->32

 <1-16

 >32

 >32

 0

 0

Dapsone

 4

 4

 8

 32

 4

 4

 2-16

 1->32

 ≥32

 ≥32

 0

17

PS-15

2

2

 2

 4

 2

 2

 1-4

 1->4

  

  

  

  

WR99210

0.125

 0.125

 2

 2

 0.26

 0.35

 <0.063-2

 <0.063-4

  

  

  

  

Cycloguanil

 128

 512

 >512

 >512

 388

 338

 128->512

 8->512

 

  

  

 

Proguanil

 64

 64

 128

 >512

 97

 97

 32->512

 8->512

  

  

  

  

Trimethoprim

 8

 4

 16

 32

 9.7

 6.5

 2->32

 2->32

 ≥16

 ≥16

 43

33

TMP-SMX

0.5/9.5

 

0.25/4.80

 0.5/9.5

 0.5/9.5

0.15/2.80

0.2/4.4

<0.06/1.19-1/19

<0.06/1.19-1/19

>2/38

>2/32

0

0

 Zone of inhibition (mm) on disk

 

 

 

 

Arithmetic mean

Range

Breakpoint (mm)

% Resistant isolates

Cefamandole

    (30 μg)

 

 

 

 

 35

 47

 0-50

 0-50

 <14

 <14

 

 57

 89

Tobramycin

    (10 μg)

 

 

 

 

 

 40

 45

 0-34

 0-40

 <14

 <14

 86

 89

Note: Na, N. abscessus  (7 clinical isolates); Na (VI) (18 clinical isolates).

*Estimated value (next highest twofold value was used when calculating geometric mean of values that were greater than the highest  concentration tested).

HBreakpoint for resistance from National Committee for Clinical Laboratory Standards (79).

Table 5. Treatment for Pulmonary Nocardiosis

  

Drugs

 

Dose

Synergistic/Additive with*

References

Trimethoprim/Sulfamethoxazole

(TMP/SMX)          

Parenteral

oral

160mg/800mg q6h

2 tabs DS BID**

Imipenem (S)

Amikacin (S/A) 

Gombert, 1983,

Gombert, 1983

Kanemitsu, 2003

Sulfonamides

Oral

1.5-2 mg BID

 

 

Minocycline

Oral

100 to 200 mg BID

Amikacin (A)

Kanemitsu, 2003

Amoxicillin-clavulanate

Oral

875 BID

 

 

Amikacin

Parenteral

5-7.5 mg/kg 1 12 h

TMP/SMX (S/A)

Cefotaxime (S/A)

Imipenem (S/A)

Minocycline (A)

Gombert 1983

Gombert 1983

Gombert 1983

Cefotaxime

Parenteral

2g q 6h

Imipenem (S)

Amikacin (S/A)

Gombert 1983

Gombert 1983

Kanemitsu, 2003

Ceftriaxone

Parenteral

1 g 2 12 h

 

 

Imipenem

Parenteral

500 mg q 6 h

TMP/SMX (S)

Cefotaxime (S)

Amikacin (S/A)

Gombert 1983

Gombert 1983

Gombert 1983

Kanemitsu, 2003

Meropenem

Parenteral

1 g 8h

 

 

Linezolid

0ral/Parenteral

600mg BID

 

 

Sparfloxacin***

 

 

Amikacin (S)

Kanemitsu, 2003

* Against Nocardia asteroids  (AAC 1983, Tohoku J Exp 2003)    S: Synergistic  A: Additive    BID: Twice a day    q: Every    h: Hour(s)

**TMP 10-20mg/kg   SMX 50-100mg /kg   in two divided doses       

***ZagamŽ no longer available in the United States.