Table 1: Minimum Inhibitory Concentrations (μg /ml) for Selected Antibiotics Against Salmonella typhi

 

 "Sensitive isolates"

"MDR  isolates"

 

MIC50

 MIC90  

MIC50

 MIC90  

Penicillin G

4

 8

 

 

Ampicillin

 0.5

 1.0

 >256

 >256

Amoxicillin-Clavulanic acid

 0.5

 1.0

 8

 8

Piperacillin

 0.5

 1

  

  

Piperacillin-Tazobactam

 0.5

 1

  

  

Ticarcillin

 2

 4

 

  

Azlocillin

 8

 8

  

  

Mezlocillin

 2

 2

  

  

Mecillinam

 0.125

 0.125

 1*

 2*

Cefuroxime

 2

 4

  

  

Cefoperazone

 1

 4

  

  

Cefoxitin

 1

 4

  

  

Ceftriaxone

 0.06

 0.125

 0.06

 0.125

Ceftazidime

 0.25

 0.25

  

  

Cefepime

 0.06

 0.125

  

  

Cefpirome

 0.06

 0.06

 

  

Cefixime

 0.06

 0.06

  

  

Ceftizoxime

 0.06

 0.125

  

  

Aztreonam

 0.125

 0.25

  

  

Imipenem

 0.25

 0.5

  

  

Meropenem

 0.06

 0.06

  

  

Azithromycin

 8

 8

 8

 8

Rifampicin

 8

 16

  

  

Trimethoprim

 0.125

 0.25

 128

 >256

Sulfamethoxazole

 4

 16

 >256

 >256

Chloramphenicol

 4

 8

 >256

 >256

Tetracycline

 1

 1

 >256

 >256

Gentamicin

 0.25

 2.0

  

  

Nalidixic acid

 4

 8

 4

 8

Norfloxacin

 0.06

 0.25

 0.06

 0.25

Ciprofloxacin

 0.015

 0.03

 0.015

 0.03

Ofloxacin

 0.06

 0.125

 0.06

 0.125

Pefloxacin

 0.125

 0.125

 0.125

 0.125

 

Table 2.   Fluoroquinolone Efficacy in Enteric Fever 

Drug

Reference

Dosage

Patients

Clinical cure %

Micro cure %

FCT (days)

Relapse Rate %

Ofloxacin

Morelli et al

1992 132

300 mg tid

15 days

30

100

100

2.6

0

Pefloxacin

Morelli et al

1992 132

400 mg tid

15 days

36

100

100

3.7

0

Ciprofloxacin

Morelli et al

1992 132

500 mg tid

15 days

20

100

100

3.3

0

Enoxacin

Morelli et al

1992 132

300 mg tid

15 days

20

80

80

4.6

0

Norfloxacin

Morelli et al

1992 132

400 mg tid

20

60

60

4.6

0

Norfloxacin

Sarma & Durairaj 1991 162

400mg bd 7 days

20

100

100

3.7 (0.5)

0

Ciprofloxacin

Uwayda et al 1992 193

500mg bd, 7-10 days

34

100

100

4.9 (1.7)

0

Ciprofloxacin

Uwayda et al 1992 193

750mg bd, 7-10 days

28

100

100

5.2 (2.2)

4

Fleroxacin

Arnold et al 1993 13

400mg od, 7 days

28

 83

 96

4

17

Fleroxacin

Arnold et al 1993 13

400mg od, 14 days

35

100

 97

4

0

Ciprofloxacin

Wallace et al 1993 202

500mg bd, 7 days

20

100

100

4

0

Fleroxacin

Hien et al 1994 95

400mg od, 7 days

15

100

100

3.4 (1.7)

0

Ofloxacin

Smith et al 1994 174

200mg bd, 5 days

22

100

100

3.4 (1.0)

0

 

Ciprofloxacin

Alam et al 1995 5

500mg bd, 10 days

35

100

100

4.2 (1.9)

0

Ciprofloxacin

Alam et al 1995 5

500mg bd, 14 days

34

100

100

4.9 (2.6)

0

Ofloxacin

Hien et al 1995 94

15mg/kg/d 3 days

118

100

100

2.5 (0.9)

0

Ofloxacin

Hien et al 1995 94

10mg/kg/d5 days

110

100

100

3.0 (0.9)

1

Fleroxacin

Duong et al

1995 62

400mg od, 5 days

41

97.5

100

3.4(1.5)

4

Fleroxacin

Duong et al 1995 62

400mg od, 3 days

22

100

100

3.7 (1.2)

0

Ofloxacin

Vinh et al 1996 197

15mg/kg/d 3 days

47

 96

100

4.5 (2.5)

0

Ofloxacin

Vinh et al 1996 197

15mg/kg/d 2 days

53

 89

 98

4.5 (2.7)

2

Pefloxacin

Unal et al 1996 192

400mg bd 7 days

24

100

100

3.4 (1.0)

4

Pefloxacin

Unal et al 1996 192

400mg bd 5 days

22

100

 96

3.1 (1.0)

0

 

Ofloxacin

Chinh et al 1997 48

15mg/kg/d 3 days

53

 89

100

4.0 (1.4)

2

Ofloxacin

Chinh et al 199748

15mg/kg/d 2 days

47

 98

 98

4.0 (1.8)

0

Ofloxacin

Secmeer et al

1997167

40mg/kg/d

24

100

100

3.3 (    )

0

Ciprofloxacin

Girgis et al

199978

500mg b.d.

7 days

28

100

100

3.3 (1.0)

0

Ofloxacin

Phuong et al

1999158

10mg/kg/d

5 days

38

97

100

4.4 (1.0)

0

Ofloxacin*

Chinh et al

200049

8mg/kg/d

5 days

44

86

95.5

5.6 (1.0)

5

* 48% of the infections were quinolone resistant

 

Table 3. Third Generation Cephalosporin Efficacy In Enteric Fever 

Drug

Reference

Dosage

No of patients

Clinical Cure (%)

Micro Cure

(%)

mean (SD) FCT(days)

or range

Relapse Rate(%)

Cefotaxime

Soe et al 1987175

200mg/kg    /day 6-14 d

61

  82

 

 

 6

Ceftriaxone

Islam et al 1988 104

3-4g/day,

 7 d

32

  91

100

4->14

 6

Ceftriaxone

Lasserre et al 1991 113

3g/day,3 d

19

  95

100

3-13

11

Ceftriaxone

Lasserre et al 1991 113

4g/day, 3 d

20

100

100

4-11

 0

Ceftriaxone

Wallace et al 1993 202

3g/day, 7 d

22

  73

100

5.2

 5

Ceftriaxone

Islam et al 1993 104

4g/day, 5 d

28

  79

100

 

 4

Ceftriaxone

Hien et al 1994 95

2g/day, 5 d

15

  87

 93

6.7 (3.1)

 0

Ceftriaxone

Smith et al 1994 174

3g/day, 3 d

25

  72

  92

8.2 (3.6)

 4

Ceftriaxone

Bhutta et al 1994 20

65mg/kg

 /day, 14 d

25

  88

  88

8.0 (4.1)

14

Cefixime

Bhutta et al 1994 20

20mg/kg

/day, 12+ d

50

100

100

5.3 (1.5)

 4

Cefixime

Girgis et al 1994 80

10mg/kg

/day, 14 d

25

  88

 96

8.3 (3.7)

 4

Cefixime

Girgis et al 1995 79

7.5mg/kg

bd, 14 d

50

100

100

5.3

 6

 

Ceftriaxone

Girgis et al 1995 79

50-70mg/kg

daily, 5 d

43

100

100

3.9

 5

 

Cefixime

Rabbani et al 1998 146a

10mg/kg/d

14d

20

90

90

 

  6

 

Cefixime

Phuong et al 1999 158

20mg/kg/d

7d

44

75

90

8.5

(8.5-15)

  2

 

Ceftriaxone

French et al 2000 72

75mg/kg/d

7d

30

97

97

3.9 (1.0)

 13

 

Ceftriaxone

Bhutta et al 2000 19

6mg/kg/d

7d

29

93

100

5.4 (3.2)

  4

 

Ceftriaxone

Bhutta et al 2000 19

65mg/kg/d

14d

28

96

100

5.2 (3.2)

  0

 

FCT = Fever clearance time

 

Table 4.   Azithromycin Efficacy In Enteric Fever 

Reference

Dosage

Patients

Clinical cure %

Micro cure %

FCT (days)

Relapse Rate %

Butler et al

1999 35

9.6 mg/kg/d

7 days

42

88

100

4.1 (2.4)

0

Girgis et al

1999 78

16 mg/kg followed by 8 mg/kg total

7 days

36

100

100

3.8

0

Chinh et al

2000 49

20 mg/kg/d

5 days

44

96

98

5.5 (1.5)

0

Frenck et al

2000 72

10 mg/kg/d

7 days

34

91

97

4.1 (1.1)

0

 

Table 5:  Antibiotics of Choice [Download PDF]

 

Endemic area

 Non-immune

 Uncomplicated enteric fever

Ofloxacin or ciprofloxacin orally 7.5mg/kg b.i.d for 3-5 days*

Ofloxacin or ciprofloxacin orally 7.5mg/kg b.i.d for 5-7 days*

Severe typhoid**

Ofloxacin or ciprofloxacin 7.5mg/kg infused  over 30-60 minutes every 12 hours until oral treatment can be substituted. Continue same dose for 10-14 days.

Ofloxacin or ciprofloxacin 7.5mg/kg infused  over 30-60 minutes every 12 hours until oral treatment can be substituted. Continue same dose for 10-14 days. Immunocompromised patients should receive at least three weeks treatment.

Carriers

Adults: Ofloxacin or Ciprofloxacin 7.5 mg/kg b.i.d. for 4 weeks.

Children: Amoxicillin 10mg/kg/day for 6-8 weeks plus probenecid

 

 

*Pefloxacin or fleroxacin have both proved very effective as well (Table 2). The three days course is particularly useful in epidemic containment.

**Dexamethasone 3mg/kg i.v.stat followed by 1mg/kg six hourly for 48 hours should be given to patients with encephalopathy or shock unrelated to perforation or hemorrhage. For quinolone resistant infections substitute ceftriaxone.

Alternative Treatments

  

Uncomplicated enteric fever

 Severe typhoid

 Chloramphenicol

75mg/kg/day in 4 divided oral doses for 14 days

Chloramphenicol succinate 75mg/kg/day i.v. or i.m. in 4 divided doses until oral treatment can be substituted. Then 50mg/kg/day orally for 14-21 days

Ampicillin/ amoxicillin

Amoxicillin 75-100mg/kg/day in 3-4 divided oral doses for 14 days

Ampicillin 15mg/kg/day i.v. in 4 divided doses for 14-21 days

Trimethoprim/ sulfamethoxazole

8/40 mg/kg/day in 2 divided oral doses (corresponding in adults to 2-3 tablets b.i.d.) 14 days.

Intravenous dose regimen similar to the oral regimen

 

Cefixime/ ceftriaxone

 

Cefixime 20mg/kg/day in 4 divided oral doses for 7-10 days

 

Ceftriaxone 60 mg/kg/day  i.v. or i.m. for at least 5 days, then if possible switch to oral therapy to complete 14-21 days treatment

 

Table 6: Typhoid Vaccines [Download PDF]

Vaccine

Dose

Adverse effects

Comments

 

Vi capsular polysaccharide vaccine

 

Single dose 0.5mL of 50 g/mL vaccine by i.m. or deep s.c. injection

 

Local pain, erythema and fever may occur 1-3 days after administration.

 

Children < 18 months may show sub-optimal response. Repeat every 3 years

 

Ty 21a oral live attenuated vaccine

 

1 capsule to be swallowed with cold or lukewarm drink on days 1, 3, and 5

 

Usually none.Nausea, vomiting, abdominal cramps, headache, fever, allergic reactions.

Rarely: anaphylaxis.

 

Contraindicated in patients who are immunosuppressed either by disease or drugs

Inactivated by antibiotics

Capsules must be refridgerated.

Not recommended for children <6 years. Provides protection 7-10 days after last dose, and in endemic areas this lasts for 3 years in most cases, but for travellers who are not repeatedly exposed, protection may last for only one year.

Do not give mefloquine until 3 days after last dose, and administration of oral polio vaccine should be separated by at least three weeks