4.14 - Tropical Disease

A) Adults

Disease / Etiology

Preferred

Alternative

Comments


Melioidosis:
Burkholderia pseudomallei
 
Initial:
Ceftazidime 2 gm (120 mg/kg/day) IV q6H for at least 14 days ;
prolong treatment duration IV (4 - 8 weeks) for deep seated abscess, OM & septic arthritis.


Initial:
Imipenem 1 gm IV q6H
OR
Meropenem 1 gm q8H
for 14 days
 
Modify treatment according to culture & sensitivity.
Abscesses should be surgically drained.

Bactrim Dose Guide :
1 Tablet Bactrim = 80 mg Trimethoprim / 400 mg Sulfamethoxazole
Dose = 5 mg/kg Trimethoprim q12H,
i.e: 
    < 40 kg = 2 tab bd
    40 - 60 kg = 3 tab bd
    > 60 kg = 4 tab bd
 
Maintenance therapy:
TMP-SMX (80 mg/400 mg) 4 tablets q12H
+
Folic acid 5 mg q24H
for at least 3 months
±
Doxycycline 100 mg q12H for at least 3 months


Maintenance therapy:
See left
Patients allergic / resistant to TMP-SMX:
Co-amoxiclav 625 mg PO q12H for 6 weeks
+
Doxycycline 100 mg q12H for 20 weeks
 
Rickettsia:
Scrub, Murine & Endemic Typhus
 
Doxycycline 100 mg q12H for 7 - 10 days

 
Azithromycin 500 mg PO / IV q24H for 4 days
 

Enteric / Typhoid Fever:
S. typhi
S. paratyphi
A / B / C

Ciprofloxacin 400 mg IV q12H for 7 - 10 days (switch to PO 500 mg q12H as soon as possible)
OR
Azithromycin 1 gm IV / PO q24H D1 then 500 mg IV / PO q24H for 5 - 7 days


Ceftriaxone 2 gm IV q24H till improve clinically then convert to oral
 
If septic shock or severely ill use Dexamethasone 3 mg/kg then 1 mg/kg qid x 8 doses a few minutes before antibiotic.

If acquired from indian sub-continent or SE Asia (Indonesia, Thailand, Myanmar), to confirm FQ susceptibility with lab.
 
Non-Typhoid Bacteremia:
Salmonella sp
 
Ciprofloxacin 400 mg IV q12H or 500 mg PO q12H for 14 days
OR
Azithromycin 1 gm IV / PO q24H D1 then 500 mg IV/PO q24H for 5 - 7 days

 
Ceftriaxone 2 gm q24H IV till improve clinically then convert
OR
TMP-SMX (TMP 8 - 10 mg/kg/day) divided q8H

Look for dissemination (mycotic aneurysm, OM etc).

Prolong treatment duration in immunocompromised & disseminated disease.
 
Leptospirosis:
L. icterohaemorrhagiae
L. canicola
 
Severe:
Penicillin 1.5 MU q6H IV for 7 days

 
Severe:
Ceftriaxone 1 gm q12H IV for 7 days
 
Mild diseases are self limiting and does not require treatment.

Jarisch-Herxheimer reaction can occur post penicillin.

Severe: Leptospiral pulmonary syndrome, multiorgan involvement, sepsis.
 
Mild:
Doxycyline 100 mg q12H for 7 days
 
Mild:
Ampicillin 0.5 - 1 gm q6H for 7 days
OR
Azithromycin 1 gm IV / PO q24H D1, then 500 mg IV / PO q24H D2 and D3

 
Brucellosis:
B abortus (cow)
B suis (swine)
B melitensis (goats)
B canis (dogs)

Systemic disease:
Doxycycline 100 mg PO q12H for 6 weeks 
+
Gentamicin 4 - 6 mg/kg IV q24H (monitor TDM) for 1 week

Spondyllitis, Sacroilitis
As above
+ Rifampicin 600 mg q24H for 3 months

Neurobrucelosis
Doxycycline 100 mg PO q12H
+ Rifampicin 600 mg PO q24H
+ TMP-SMX (TMP 5mg/kg) PO q12H in divided dose until CSF normal

Endocarditis
Surgery
+ Doxycycline 100 mg PO q12H
+ Rifampicin 600 mg PO q24H
+ TMP-SMX (TMP 5 mg/kg) PO q12H for 2 - 6 months
+ Gentamicin 4 - 6 mg/kg IV q24H for 2 - 4 weeks

 

Doxycycline 100 mg PO q12H OR TMP-SMX (TMP 5 mg/kg) PO q12H
+
Rifampicin 600 mg PO q24h

OR

Ciprofloxacin 750 mg q12H + Rifampicin 600 - 900 mg q24H for 3months
 
Relapse rate 10% 
Bone involvement 20 - 30% 
Neurobricellosis 1% 

Steroids not recommended.
Endocarditis rare, but highest mortality: needs surgery.
Pregnancy: avoid in last term.

Ciprofloxacin: active in vitro but clinical response not good.
Clinical response to Cetriaxone is variable.
 
Cat scratch disease & other bartonella infections
 
Extensive Lmphadenopathy / Systemic Disease
Azithromycin 500 mg PO D1 then 250 mg PO q24H for 4 days

Endocarditis
Surgery
+ Doxycycline 100 mg PO q12H for 6 weeks
+
Gentamicin 1 mg/kg IV q8H for 2 weeks (monitor TDM)
OR Rifampicin 300 mg q12H for 2 weeks.

 
Doxycycline 100mg q12H for 14 days
 
 
Cholera

HYDRATION is primary therapy
*Doxycycline 300mg PO single dose
 
**EES 500 mg PO q6H for 3 days
OR
Azithromycin 1 gm PO single dose

 
*Non Tetracycline resistance
**Tetracycline resistance and pregnancy: EES or azithromycin only options
 
Tetanus Clostridium Tetani
 
Metronidazole 1000 mg IV q12H for 7 - 10 days
+ Human Tetanus Immunoglobulin 3000 iu to 6000 iu IM

 
Doxycycline 100 mg PO q12H OR Benzylpenicillin 3 MU IV q4H
OR Erythromycin 1 gm IV q6H OR Clindamycin 600 mg IV q6H for 7 - 10 days

 
Penicillin, a GABA antagonist, may aggravate the spasms.
Initiate a full course of tetanus vaccination.

Malaria (Falciparum, Vivax, Ovale, Knowlesi, Malariae)

 
Complicated Malaria
 
D1: Artesunate 2.4 mg/kg IV stat then 2.4 mg/kg at 12 hours
D2 till oral conversion:
Artesunate 2.4 mg/kg IV q24H
+
Doxycycline 100 mg PO q12H from D1 till convert to Riamet
®## 
+
Primaquine# 30 mg PO single dose

Switch to oral 
Riamet®## when possible

 
WHO recommended combination therapy.

#Primaquine: check G6PD status before use.
45 mg/week x 8 weeks for G6PD deficient patients. #Primaquine 15 mg q24H for 14 days if treating for P vivax.

##Riamet®: Artemether 20 mg / Lumefantrine 120 mg

Adult (> 35 kg)

D1: 4 tablets stat then 4 tablets at 8 hours
D2 to D3: 4 tablets q12H

Total: 24 tablets

Adult (< 35 kg)

D1: 3 tablets stat then 3 tablets at 8 hours
D2 to D3: 3 tablets q12H

Total: 18 tablets

Pregnancy: Avoid Doxycycline and Primaquine. Relative contraindication of Artemisinin in 1st trimester.
Seek expert advice.

 
Plasmodium Falciparum - Uncomplicated
 
Riamet®## 
+
Primaquine# 30 mg PO single dose

 
Plasmodium Vivax or Ovale - Uncomplicated
 
Chloroquine-Sensitive
Chloroquine base 10 mg/kg (max 600 mg) PO stat, 

then 5 mg/kg (max 300 mg) PO 6 hours later and on D2 & D3

Chloroquine-Resistant
Riamet®## 
+
Primaquine# 30 mg PO q24H for 14 days

 

Available as Chloroquine phosphate:
1 tab of 250 mg phosphate = 155 mg Chloroquine base
i.e. 
600 mg base of Chloroquine = 4 tabs of Chloroquine phosphate 250 mg
 
Plasmodium Knowlesi - Uncomplicated
 
Riamet®##

 
Chloroquine 10 mg/kg (max 600 mg) PO stat,
then 5 mg/kg (max 300 mg) PO 6 hours later,
then q24H on D2 & D3
OR
Quinine + Doxycycline

 
 
Plasmodium Malariae - Uncomplicated
 
Chloroquine base 10 mg/kg (max 600 mg) PO stat,
then 5 mg/kg (max 300 mg) PO 6 hours later,
then q24H on D2 & D3


Riamet®##
OR
Quinine with Doxycycline
 
Monitor patient’s blood glucose & ECG while on IV quinine.
 
Mixed Malaria Infection
 
Treat as Plasmodium Falciparum

   


B) Paediatrics

Disease / Etiology

Preferred

Alternative

Comments

Malaria

 
Plasmodium Falciparum - Uncomplicated

 
Artesunate / Mefloquine (Artequine)

10 - 20 kg
Artesunate 50 mg q24H for 3 days
Mefloquine 125 mg q24H for 3 days
(Artequine pellets)

20 - 40 kg
Artesunate 100 mg q24H for 3 days
Mefloquine 250 mg q24H for 3 days
(Artequine 300 / 750)

> 40 kg
Artesunate 200 mg q24H for 3 days
Mefloquine 500 mg q24H for 3 days
(Artequine 600 / 1500)
 
Artemether / Lumefantrine (Riamet®)

1 tablet = Artemether 20 mg / Lumefantrine 120 mg

5 - 14 kg
Day 1: 1 tablet stat then 1 tablet again after 8 hours
Day 2 & 3: 1 tablet q12H

15 - 24 kg
Day 1: 2 tablets stat then 2 tablets again after 8 hours
Day 2 & 3: 2 tablets q12H

25 - 35 kg
Day 1: 3 tablets stat then 3 tablets again after 8 hours
Day 2 & 3: 3 tablets q12H 

> 35 kg
Day 1: 4 tablets stat then 4 tablets again after 8 hours
Day 2 & 3: 4 tablets q12H

 
Add Primaquine 0.75 mg/kg single dose OD if gametocyte is present at any time during treatment.
Check G6PD status before giving Primaquine.

Avoid Artequine in child with epilepsy or impaired consciousness.

Both Artequine and 
Riamet® are Artemisinin based Combination Treatment (ACT)

Second Line Treatment
  • An alternative ACT is used (if Riamet® was used in first regime, used Artequine instead and vice versa) 
OR
  • Artesunate 4 mg/kg q24H + Clindamycin 10 mg/kg q12H for 7 days 
OR

  • Quinine 10 mg salt/kg q8H + Clindamycin 10 mg/kg q12H for 7 days
 
Plasmodium Falciparum - Severe

 
Day 1: Artesunate 2.4 mg/kg IV stat then at 12H and 24H
Day 2 - 7: Artesunate 2.4 mg/kg IV q24H or switch to oral Artemisinin based combination treatment

 
Day 1: Quinine loading 7 mg salt/kg IV over 1H
followed by Quinine 10 mg salt/kg IV over 4H, then 10 mg salt/kg IV q8H
OR
Loading 20 mg salt/kg over 4H then IV 10 mg salt/kg q8H

Day 2 - 7: Quinine 10 mg salt/kg IV q8H
+
Doxycycline (> 8 years old) 3.5 mg/kg q24H OR
Clindamycin (< 8 years old) 10 mg/kg IV q12H given for 7 days

 
IM Artesunate can be used in those with difficult intravenous access.

Quinine infusion rate should not exceed 5 mg salt/kg/hour.

Monitor patient’s blood glucose & ECG while on IV quinine.
 
Plasmodium Vivax

 
Total Chloroquine 25 mg base/kg divided over 3 days 
Day 1: 10 mg base/kg stat then 5 mg base/kg 6 hours later 
Day 2 & 3: 5 mg base/kg q24H + Primaquine 0.5 mg base/kg q24H for 14 days

   
Severe Plasmodium Vivax, Knowlesi or Malariae should be treated as severe Plasmodium Falciparum.
Chloroquine resistant 
Plasmodium Vivax, Knowlesi or Malariae - please consult ID specialist.
 
Plasmodium Knowlesi or Malariae

 
Total Chloroquine 25 mg base/kg divided over 3 days 
Day 1: 10 mg base/kg stat then 5 mg base/kg 6 hours later 
Day 2 & 3: 5 mg base/kg q24H

   
 
Mixed Malaria Infection

 
Treat as Plasmodium Falciparum

   
 
Congenital Malaria

 
Total Chloroquine 25 mg base/kg orally divided over 3 days
Day 1: 10 mg base/kg stat then 5 mg base/kg 6 hours later
Day 2 & 3: 5 mg base/kg q24H
   
 
Malaria Chemoprophylaxis

 
Atovaquone / Proguanil (Malarone)
1 Paeds tablet =
Atovaquone 62.5 mg and Proquanil 25 mg

1 Adult tablet = Atovaquone 250 mg and Proguanil 100 mg

5-8 kg: 1/2 tablet q24H
> 8-10 kg: 3/4 tablet q24H
> 10-20 kg: 1 tablet q24H
> 20-30 kg: 2 tablets q24H
> 30-40 kg: 3 tablets q24H
> 40 kg : 1 adult tablet q24H


Mefloquine
1 tablet: 250 mg Mefloquine hydrochloride
< 15 kg: 5 mg/kg weekly
15-19 kg: 1/4 tablet weekly
20-30 kg: 1/2 tablet weekly
31-45 kg: 3/4 tablet weekly
> 45kg: 1 tablet weekly

OR

Doxycycline 1.5 mg base/kg q24H (max 100 mg) 
DO NOT USE for those < 8 years old OR < 25 kg.
25 - 35 kg OR 8 - 10 years old: 50 mg
36 - 50 kg OR 11 - 13 years old: 75 mg
> 50 kg OR > 14 years old: 100 mg

 
Malarone:
Start 2 days before, continue daily during exposure and 7 days after.

Mefloquine:
Start 2 - 3 weeks before, continue weekly during exposure and 4 weeks after.

Doxycycline:
Start 2 days before, continue daily during exposure and 4 weeks after.

Tuberculosis (TB)

 
Isoniazid (H)
10 - 15 mg/kg/day PO
(max 300 mg)
and
Rifampicin (R)
10 - 20 mg/kg/day PO
(max 600 mg)
and
Pyrazinamide (Z)
20 - 40 mg/kg/day PO
(max 2000 mg)
±
Ethambutol (E)
15 - 25 mg/kg/day PO
(max 1000 mg)
±
Streptomycin (S)
20 - 30 mg/kg/day IM
(max 1000 mg)

 
2nd line treatment / resistant M TB – please consult ID specialist
 
Decision duration of treatment depends on whether pulmonary or extrapulmonary TB

Intensive phase requires at least three drugs and 
maintenance two drugs regime.

Melioidosis

 
Burkholderia pseudomallei

 
Induction 
Ceftazidime 50 mg/kg IV q8H for at least 14 days 

Deep seated abscess: 
4 to 8 weeks 

Maintenance
Co-amoxiclav 20 mg/kg/dose (Amoxicillin component) PO q8H for total 20 weeks 
 
Induction
Imipenem 25 mg/kg IV q6H
OR Meropenem 20 - 30 mg/kg q8H for at least 14 days (may be considered in life threatening case)

Maintenance
> 8 years old:
Co-trimaxazole (TMP component) 4 mg/kg PO q12H for 12 - 24 weeks
PLUS
Doxycycline 2 mg/kg PO q12H for total 20 weeks

 
Localised meliodosis abscess should be drained.

Leptospirosis: 
L. icterohaemorrhagiae
L. canicola
 

Benzylpenicillin 100,000 units/kg IV q6H for 7 days
 
Ceftriaxone 50 mg/kg IV q12H for 7 days

OR
> 8 years old: 
Doxycycline 4 mg/kg PO q12H for 7 days
< 8 years old:
Ampicillin 75 - 100 mg/kg PO / IV q6H for 7 days

OR
Amoxycillin 50 mg/kg/dose PO q6 - 8H for 7 days

 
Penicillin is drug of choice for moderate to severe disease.

Doxycycline for mild disease, can cause permanent discoloration of teeth.

Amoxicillin / Ampicillin is second line drug for children < 8 years old.

Role of prophylaxis for paediatric patients not yet adequately studied.
 
Enteric / Typhoid Fever: 
S. typhi
S. paratyphi
 A / B / C

 
Ceftriaxone 50 mg/kg IV q12H for 10 - 14 days

Cefotaxime 50 mg/kg IV q6 - 8H for 7 - 14 days

Co-trimoxazole 4 mg/kg (Trimethoprim component) PO / IV q12H for 14 days

 
Meningitis / abscess / OM – at least 4 weeks

Avoid Quinolones as it can induced arthropathy in children.
 
Scrub Typhus:
Ricketsia tsutsugamushi

 
Chloramphenicol 50 - 75 mg/kg/day PO in 4 divided dosage for 5 - 7 days

 
> 8 years old:
Doxycycline 2 - 4 mg/kg/day in 1 - 2 divided dosage for 5 - 7 days

 
Avoid Doxycycline in younger ones as they can cause staining of teeth.


Bibliography
1. Antibiotic Expert Groups, Respiratory Infections Expert Group, Infective Endocarditis Prophylaxis Expert Group. Therapeutic guidelines: Antibiotic. Version 14. Melbourne: Therapeutic Guidelines Limited; 2010.
2. Gilbert DN, Moellering RC, Eliopoulos GM, Chambers HF, Saag MS et al. The Sanford Guide to Antimicrobial Therapy 2014, 44th edition. Antimicrobial Therapy Inc.; 2014.
3. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG et al. Clinical Practice Guidelines for antimicrobial prophylaxisin surgery. Am J Health-Syst Pharm,Vol 70 Feb 2013;195-283;2013.
4. Cunha BA. Antibiotic Essentials 2013. Jones & Bartlett Learning; 2013.
5. Malaysian National Antibiotic Guideline 2008