Table 10. Revised Interpretive Criteria (Breakpoints) for MIC and Disk Diffusion Testing of Select Cephalosporins

                  against Enterobacteriaceae (Clinical and Laboratory Standards Institute)

 

MIC Testing

Drug (dosage)*

New Breakpoints

Previous Breakpoints

 

S

(µg/ml)

I

(µg/ml)

R

(µg/ml)

S

(µg/ml)

I

(µg/ml)

R

(µg/ml)

Cefazolin

(2 g q8h)

≤ 2

4

≥ 8

≤ 8

16

≥ 32

Cefotaxime

(1 g q8h)

≤ 1

2

≥ 4

≤ 8

16-32

≥ 64

Ceftriaxone

(1 g q24h)

≤ 1

2

≥ 4

≤ 8

16-32

≥ 64

Ceftizoxime

(1 g q12h)

≤ 1

2

≥ 4

≤ 8

16-32

≥ 64

Ceftazidime

(1 g q8h)

≤ 4

8

≥ 16

≤ 8

16

≥ 32

 

 

 

 

 

 

 

Disk Diffusion Testing

Drug (dosage)*

New Breakpoints

Previous Breakpoints

 

S

(mm)

I

(mm)

R

(mm)

S

(mm)

I

(mm)

R

(mm)

Cefazolin

(2 g q8h)

≥ 23

20-22

≤ 19

≥ 18

15-17

≤ 14

Cefotaxime

(1 g q8h)

≥ 26

23-25

≤ 22

≥ 23

15-22

≤ 14

Ceftriaxone

(1 g q24h)

≥ 23

20-22

≤ 19

≥ 21

14-20

≤ 13

Ceftizoxime

(1 g q12h)

≥ 25

22-24

≤ 21

≥ 20

15-19

≤ 14

Ceftazidime

(1 g q8h)

≥ 21

18-20

≤ 17

≥ 18

15-17

≤ 14

* Dosage used to established new breakpoints

S, susceptible; I, intermediate; R, resistant

References 38 and 188

 

 

Table 11. Pharmacokinetics of Oral Cephalosporins after a Single Dose in Healthy Volunteers 

 

 

Drug

 

Dose

(mg)

 

Cmax

(µg/ml)

 

Tmax

(hr)

 

AUC0-∞

(mg*hr/L)

 

T ½

(hr)

Urinary Elimination

(%)

Protein Binding

(%)

 

 

Reference

First-generation

 

 

 

 

 

 

 

Cephalexin

250

500

9.3

20.7

0.9

0.7

14.0

29.0

0.5

0.6

~ 80

~80

18-20

143

Cephradine

500

1,000

17.7

27.7

0.8

1.1

27.5

40.0

0.6

1.1

~ 90

84

10-20

143,164

Cefadroxil

500

1,000

16.2

33.0

1.9

1.7

47.4

108.5

1.3

1.6

~ 80

89.6

18-20

104,143

Second-generation

 

 

 

 

 

 

 

Cefaclor

500

1,000

17.3

34.6

0.7

1.1

17.5

74.5

0.6

0.7

78.9

52.7

25

13,104

Loracarbef

200

400

6.0

15.4

1.0

1.2

10.6

32.0

1.0

1.3

-

94.3

25

167,181

Cefprozil

250

500

1,000

6.2

11.2

17.7

0.9

1.2

1.1

14.2

25.7

52.1

1.1

1.3

1.4

70.1

64.7

56.7

36

12,13

Cefuroxime axetil

250

500

1,000

4.2

7.0

13.6

2.5

3.0

2.5

12.9

27.4

50.0

1.2

1.2

1.3

51

48

43

50

60,78

Third-generation

 

 

 

 

 

 

 

Cefixime

200

400

800

2.5

3.6

4.9

4.3

3.7

4.4

21.7

25.8

37.9

3.9

3.1

3.7

14.4

9.2

8.3

65

57

Cefpodoxime proxetil

200

400

800

2.6

4.5

6.9

2.4

2.5

2.9

14.5

26.5

46.4

2.3

2.4

2.9

39.2

23.8

27.9

22-33

185

Cefdinir

300

600

1.6

2.4

3.2

3.2

6.53

9.84

1.5

1.5

17.7

12.7

60-70

152

Ceftibuten

200

400

800

9.8

17.0

23.3

1.75

2.0

2.0

42.1

79.2

117.6

2.0

2.3

2.3

57-70

65

15

Cefditoren pivoxil

100

200

300

1.7

3.4

4.4

1.4

2.0

2.0

3.7

10.0

13.7

0.8

1.1

1.1

19.9

20.2

21.3

88

100

 

 

Table 12. Pharmacokinetic Parameters of Parenteral Cephalosporins 

 

 

Agent

 

 

Dose

Peak Concentration

(µg/ml)

Protein Binding

(%)

 

T½

(hr)

 

Apparent Vd (L)

 

CLTotal

(ml/min)

 

CLRenal

(ml/min)

Urinary Excretion

(%)

CSF Concentration Range (µg/ml)

First-generation

 

 

 

 

 

 

 

 

 

Cefazolin

1 g

188

88

1.8

10

64

64

80

-

Second-generation

 

 

 

 

 

 

 

 

 

Cefuroxime

0.75g

51.1

33-50

1.7

13

128

123

96

1.1-17

Cefamandole

1 g

139

70

0.8

17

250

257

96

-

Cefonicid

2 g

260

98

4.4

9

-

-

88

-

Cefoxitin

1 g

64

73

0.7

8

268

270

78

-

Cefotetan

1 g

126-158

90

4.5

11

33-46

25-30

61

-

Cefmetazole

2 g

140

85

1-1.5

10

90-165

90-110

75

-

Third-generation

 

 

 

 

 

 

 

 

 

Cefotaxime

1 g

102

30

1.1

14

260-326

154

50

5.6-44

Ceftriaxone

1 g

123-151

83-96

8

10.7

17.6

6

46

1.2-39

Ceftizoxime

1 g

84

30

1.8

28

155

89-110

93

0.5-29

Ceftazidime

1 g

83

17

1.8

13.6

78-144

72-130

84

0.5-30

Cefoperazone

1 g

153

90

2.1

11

80

18

29

-

Fourth-generation

 

 

 

 

 

 

 

 

 

Cefepime

1 g

66-82

20

2-2.3

20.5

122-131

103-110

84

3.3-5.7

Adapted from references 4, 57, 58, 63, 80, 94, 140, 171

 

 

Table 13. Recommended Dosages for Oral and Parenteral Cephalosporins [Download PDF]

Agent

Route

Adult Dose and Interval

Pediatric Dose and Interval

First-generation

 

 

 

Cephalexin

PO

0.25-1 g q6-12h

50-100 mg/kg/d, q6-8h

Cefadroxil

PO

0.5-1 g q12-24h

30 mg/kg/d, q12-24h

Cephradine

PO

0.5-1 g q6-12h

75-100 mg/kg/d, q6-12h

Cefazolin

IV/IM

1-2 g q8h

50-100 mg/kg/d, q6-8h

Second-generation

 

 

 

Cefaclor

PO

250-500 mg q8h

20-40 mg/kg/d, q8h

Cefprozil

PO

250-500 mg q12-24h

15-30 mg/kg/d, q12h

Loracarbef

PO

200-400 q12h

15-30 mg/kg/d, q12h

Cefuroxime

PO

IV/IM

250-500 mg q12h

0.75-1.5 g q8h

30 mg/kg/d, q12h

50-100 mg/kg/d, q6-8h

Cefamandole

IV/IM

0.5-1 g q4-8h

50-150 mg/kg/d, q4-8h

Cefoxitin

IV/IM

1-2 g q6-8h

80-160 mg/kg/d, q4-6h

Cefotetan

IV/IM

1-2 g q12h

40-60 mg/kg/d, q12h

Cefmetazole

IV

2 g q6-12h

Not recommended

Third-generation

 

 

 

Cefpodoxime proxetil

PO

100-400 mg q12h

10 mg/kg/d, q12h

Cefditoren pivoxil

PO

200-400 mg q12h

Not recommended

Ceftibuten

PO

400 mg q24h

9 mg/kg/d, q24h

Cefdinir

PO

300-600 mg q12-24h

7-14 mg/kg/d, q12-24h

Cefotaxime

IV/IM

1-2 g q4-8h

100-150 mg/kg/d, q4-6h

Ceftizoxime

IV/IM

1-2 g q8-12h

100-200 mg/kg/d, q6-8h

Ceftriaxone

IV/IM

1-2 g q12-24h

50-100 mg/kg/d, q12-24h

Cefoperazone

IV/IM

1-2 g q12h

100-150 mg/kg/d, q8-12h

Ceftazidime

IV/IM

1-2 g q8h

75-150 mg/kg/d, q8h

Fourth-generation

 

 

 

Cefepime

IV/IM

1-2 g q8-12h

100-150 mg/kg/d, q8-12h