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 µg/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