National Antimicrobial Guideline (NAG), Ministry of Health Malaysia

ADULT

TROPICAL INFECTIONS

In this topic:

1. TYPHOID FEVER

2. CHOLERA

3. RICKETTSIAL DISEASES

1. TYPHOID FEVER

(Salmonella enterica serovar Typhi)

1.1 Mild

Preferred

Ceftriaxone 50-75mg/kg/24h (2-4 g/day) IV q12-24h

Cefotaxime 40-80mg/kg/24h (2-6 g/day) IV q8-12h

Alternative

Ciprofloxacin 500-750 mg PO q12h

Azithromycin 20mg/kg PO q24h (maximum 1 g q24h)

(Refer susceptibility testing result before considering alternative treatment regime)

Comments

Notifiable disease

IV to PO switch is recommended once symptoms improve based on susceptibility testing result. Refer Appendix 6.

Duration: minimum 7-14 days

Notes: longer duration of fever defervescence may be observed in patients treated with cephalosporin.

1.2 Moderate to Severe

Severe sepsis or shock, gastrointestinal bleeding, intestinal perforation, encephalopathy, metastatic infection or other complications.

Preferred

Ceftriaxone 50-75mg/kg/24h (2-4 g/day) IV q12-24h

Cefotaxime 40-80mg/kg/24h (2-6 g/day) IV q8-12h

Alternative

Ciprofloxacin 400mg IV q8-12h

Azithromycin 20mg/kg IV q24h (maximum 1 g q24h)

(Refer susceptibility testing result before considering alternative treatment regime)

Comments

Consult ID Physician for complicated/severe typhoid or drug-resistant typhoid.

Duration: 10-14 days. Once symptoms improve, may consider IV to oral antibiotic switch based on susceptibility testing results. Refer Appendix 6.

In case of persistent fever after 5-7 days of effective antimicrobial therapy, re-evaluate and repeat culture. Longer duration of antimicrobial therapy may be necessary in the presence of metastatic or deep seated infection.

Adjunctive corticosteroid may be considered after consultation with an ID physician in severe typhoid with delirium, obtundation, coma or shock. In such cases, administer IV dexamethasone 3 mg/kg followed by 8 doses of 1 mg/kg every q6h for 48 hours. Monitor patients closely as corticosteroid use is associated with increased risk of gastrointestinal bleeding and perforation.

1.3 Extensively Drug Resistant

Resistant to ceftriaxone, ciprofloxacin, amoxicillin, chloramphenicol and cotrimoxazole.

Preferred

Meropenem IV 1g q8h

Alternative

Comments

Consult ID Physician

1.4 Chronic Carrier

Individual excreting Salmonella Typhi in stool/urine for > 1 year after onset of acute illness.

Preferred

Ciprofloxacin susceptible:

Ciprofloxacin 750mg PO q12h for 4 weeks

Ciprofloxacin resistant:

Trimethoprim/Sulphamethoxazole 160/800mg PO q12h for 6 weeks

Alternative

Comments

Consult ID Physician

2. CHOLERA

Vibrio cholerae

Preferred

Doxycycline 300mg PO single dose

Alternative

Ciprofloxacin 1g PO single dose

*Azithromycin 1g PO single dose

*Erythromycin Ethylsuccinate 800mg PO q12h for 3 days

Comments

Notifiable disease

Indication for antibiotics:

Oral or intravenous hydration is the mainstay of cholera treatment.
Antibiotics are recommended for patients with moderate to severe illness who are hospitalized.

*Azithromycin / Erythromycin is recommended in pregnancy.

3. RICKETTSIAL DISEASES

(Rickettsia species, Orientia tsutsugamushi (rickettsia tsutsugamushi))

3.1 Mild

Preferred

Doxycycline 100mg PO q12h for 5 days

Alternative

*Azithromycin 500mg PO q24h for 3 days

Comments

*Azithromycin is recommended in pregnancy.

3.2 Moderate to Severe

ARDS, septic shock, myocarditis, meningoencephalitis, hepatitis, renal failure.

Preferred

Azithromycin 500mg IV q12h on Day 1 then 500mg q24h for 6 days

PLUS

Doxycycline 200mg PO q12h Day 1 then 100mg q12h for 6 days

Alternative

Comments

IV to PO switch is recommended once symptoms improve.

4. BRUCELLOSIS

(Brucella melitensis, Brucella abortus, Brucella suis and Brucella canis)

4.1 Systemic Disease

In the absence of focal disease due to spondylitis, neurobrucellosis or endocarditis.

Preferred

Doxycycline 100mg PO q12h for 6 weeks

PLUS

Gentamicin 5mg/kg/24h IM/IV for the first 7 days

Streptomycin 1g (5mg/kg) IM q24h for 2-3 weeks

Alternative

Doxycycline 100mg PO q12h for 6 weeks

PLUS

Rifampicin 600-900mg (15mg/kg) PO q24h for 6 weeks

Comments

4.2 Pregnancy

Preferred

< 36 weeks gestation:

Rifampicin 600-900mg (15 mg/kg) PO q24h for 6 weeks

PLUS

Trimethoprim/Sulphamethoxazole 160/800mg PO q12h for 6 weeks

> 36 weeks gestation:

*Rifampicin 600-900mg (15mg/kg) PO q24h monotherapy until delivery.

Alternative

Comments

*After delivery, to continue combination therapy as in non-pregnant regime.

4.3 Spondylitis

Preferred

Doxycycline 100mg PO q12h for at least 12 weeks

PLUS

Rifampicin 600-900mg (15mg/kg) PO q24h for at least 12 weeks

PLUS

Gentamicin 5mg/kg/24h IM/IV for the first 7 days

Alternative

Comments

4.4 Neurobrucellosis

Preferred

Ceftriaxone 2g IV q12h for 4-6 weeks

PLUS

Doxycycline 100mg PO q12h for 6 weeks

PLUS

Rifampicin 600-900mg 15mg/kg PO q24h for at least 12 weeks

Alternative

Doxycycline 100mg PO q12h for 12 weeks

PLUS

Rifampicin 600-900mg 15mg/kg PO q24h for at least 12 weeks

PLUS

Trimethoprim/Sulphamethoxazole 160/800mg PO q12h for 12 weeks

Comments

4.4 Endocarditis

Refer to Cardiovascular Infection section for Infective Endocarditis.

4.5 Chemoprophylaxis

For high-risk laboratory exposures to Brucella isolates

Preferred

Doxycycline 100mg PO q12h for 3 weeks

PLUS

Rifampicin 600mg for 3 weeks

Alternative

*Doxycycline 100mg PO q12h for 3 weeks

PLUS

Trimethoprim/Sulphamethoxazole 160/800mg PO q12h for 3 weeks

*In case of exposure to Brucella abortus RB51 strain (which is resistant to rifampicin)

Comments

PEP should be offered as soon as high-risk laboratory exposure to Brucella isolates has been identified and be administered for up to six months following exposure.

PEP may be considered for low risk exposure in pregnant women or immunosuppressed individuals (consult ID physician).

5. LEPTOSPIROSIS

Leptospira interrogans

5.1 Mild

Preferred

Doxycycline 100mg PO q12h for 5-7 days

*Amoxicillin 25-50mg/kg/day PO in 3 divided doses or 500mg PO q8h for 7 days

Alternative

*Azithromycin 500mg PO q24h for 3 days

Comments

Notifiable disease

Early antibiotic therapy is recommended if leptospirosis is clinically suspected following recent high risk exposure (E.g.: flood, recreational activities).

*Amoxicillin or azithromycin is recommended for pregnant women.

5.2 Moderate to Severe

Leptospiral pulmonary syndrome, multiorgan involvement, sepsis.

Preferred

*Benzylpenicillin 1.5MU IV q6h

Alternative

*Ceftriaxone 2g IV q24h

Comments

*IV to PO switch is recommended once symptoms improve. Refer to Appendix 6.

Duration: 7 - 10 days

There is insufficient evidence to support routine use of corticosteroid therapy. However, use of steroids as an adjunct to antibiotic therapy may be considered in severe leptospirosis with pulmonary haemorrhage (consult ID physician).

5.3 Chemoprophylaxis

Consider on a case-by-case basis in short periods of high risk exposure

(E.g.: soldiers, outbreak response personnel involved in occupational/recreational activities (see comments))

Preferred

Doxycycline 200 mg PO weekly starting 1-2 days before exposure and continue during exposure

Alternative

Comments

The mainstay prevention of leptospirosis is avoidance of direct contact with contaminated water or environment.

Evidence on effectiveness of prophylactic antibiotics in prevention of leptospirosis is limited. Routine use of prophylactic antibiotics is not recommended.

In situations of major outbreaks, the use of mass chemoprophylaxis is not recommended.

Notes: Doxycycline is contraindicated in pregnancy and breastfeeding. Gastrointestinal side effects are common.

6. TETANUS

Clostridium tetani

Preferred

Metronidazole 500mg IV q6-8h for 7-10 days

PLUS

Human Tetanus Immunoglobulin single dose 500IU IM

PLUS

Anti-tetanus toxoid vaccine IM (initiate age appropriate active immunization at a different site)

Alternative

Benzylpenicillin 100,000-200,000 unit/kg/24h IV q6h for 7-10 days

PLUS

Human Tetanus Immunoglobulin single dose 500IU IM

PLUS

Anti-tetanus toxoid vaccine IM (initiate age appropriate active immunization at a different site)

Comments

Notifiable disease

All patients with tetanus should undergo wound debridement to eradicate spores and necrotic tissue.

*IV to oral switch is recommended once symptoms improve.

7. MELIOIDOSIS

Burkholderia pseudomallei

7.1 Intensive Therapy

Preferred

Mild to Moderate (Non-Neurological):

Ceftazidime 100-120mg/kg/24h IV q6-8h (usual dose: 2g IV q6h)

MAY ADD

*Trimethoprim 80mg/ Sulphamethoxazole 400mg

< 40 kg: 160/800mg PO q12h
40-60kg: 240/1200mg PO q12h
> 60kg: 320/1600 mg PO q12h

Refer to comment section for graded dosing.

Severe (Neuromeliodosis, persistent bacteremia or severe sepsis):

Meropenem 75mg/kg/24h IV q8h

(usual dose: 1g IV q8h; 2g IV q8h for CNS disease)

Imipenem 50mg/kg/24h IV q6h or maximum 4g/day

(usual dose : 500mg IV q6h; 1g q6-8h for severe infection)

MAY ADD

*Trimethoprim 80mg / Sulphamethoxazole 400mg

(Consider de-escalate to ceftazidime once symptoms improve/stable)

Alternative

Comments

*Add on Trimethoprim/Sulphamethoxazole in eye, neurologic, testicular, prostatic, pericardium, bone and joint melioidosis.

To minimise side effects, trimethoprim/sulfamethoxazole should be introduced gradually, except in neurological melioidosis or critically ill patients with multifocal abscess where full dosage is administered as soon as feasible.

The graded dose will take 1-2 weeks to reach full dose, depending on circumstances. Cessation of intravenous therapy and commencement of timed eradication phase is set only once the full planned dose of trimethoprim/sulfamethoxazole is reached. Refer below for graded dosing of trimethoprim/sulfamethoxazole:

Body weight > 60kg with normal renal function

Day 1- Day 2: 40/200mg (½ tab of 80/400mg) q12h
Day 3 - Day 4: 80/400mg (1 tab of 80/400mg) q12h
Day 5 - Day 6: 160/800mg (2 tabs of 80/400mg) q12h
Day 7 - Day 8: 240/1200mg (3 tabs of 80/400mg) q12h
Day 9 onwards: 320/1600mg (4 tabs of 80/400mg) q12h

Body weight <60kg or impaired renal function Consult ID physicians to determine graded dosing schedule.

All patients who undergo intensive therapy and eradication therapy for melioidosis require counselling regarding monitoring for adverse effects of medication

Drainage of abscesses should be attempted wherever appropriate such as prostatic, empyema and pericardium.

Duration of intensive therapy:

Skin and soft tissue infection, mild pneumonia: 2 weeks
Bacteraemia with no foci: 2-4 weeks
Complicated pneumonia, prostatic, deep-seated foci, septic arthritis: 4 - 6 weeks
Osteomyelitis: 6 weeks
Neurologic/CNS: 8 weeks
Arterial infection e.g.: mycotic aneurysm: 8 weeks

Use clinical judgement to guide prolongation of intensive phase in patients with slow clinical improvement or persistent bacteraemia.

Carbapenems are potentially neurotoxic especially at higher doses. Use with caution in patients with renal impairment or CNS disorders.

7.2 Eradication Therapy

Preferred

Trimethoprim 80mg / Sulphamethoxazole 400mg

< 40 kg: 160/800mg PO q12h
40-60kg: 240/1200mg PO q12h
> 60kg: 320/1600 mg PO q12h

Alternative

Amoxicillin/clavulanate

< 60kg: 1250mg (2 tabs of 625 mg) PO q8h
> 60kg: 1875mg (3 tabs of 625 mg) PO q8h

Comments

Duration of eradication therapy:

Osteomyelitis, neurologic/CNS: 24 weeks
Others: minimum 12 weeks

8. MALARIA

Refer to the Ministry of Health's latest Guideline on Management of Malaria and Director General of Health Circular Letter 14/2016.

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