3.14 - Tropical Disease [updated]

A) Adults

Disease / Etiology

Preferred

Alternative

Comments

Melioidosis:
Burkholderia pseudomallei		  
Initial:
Without Complication
Ceftazidime 2 gm IV q6H 
±
* Co-trimoxazole 480 mg tablets / 480 mg ampoules;

>60 kg
4 tablets PO q12H
/ 4 amps IV q12H

40 - 60 kg
3 tablets PO q12H
/ 3 amps IV q12H

<40 kg
2 tablets PO q12H
/ 2 amps IV q12H

Neuromelioidosis or Persistent Bacteraemia or In ICU or Treatment Failure
Meropenem 1 gm IV q8H
±
* Co-trimoxazole 480 mg tablets / 480 mg ampoules;

>60 kg
4 tablets PO q12H 
/ 4 amps IV q12H

40 - 60 kg
3 tablets PO q12H
/ 3 amps IV q12H

<40 kg
2 tablets PO q12H
/ 2 amps IV q12H

 


Modify treatment according to culture & sensitivity.
  
Abscesses should be surgically drained.

Ceftazidime 6 gm / day can be given by continuous infusion after a 2 gm bolus.


After loading dose of 2g, Ceftazidime 8 gm / day can be given by continuous infusion.

Duration: 10 - 14 days.
4 - 8 weeks IV needed if severe disease (i.e. septic shock, deep seated abscess or organ abscesses, extensive lung disease, osteomyelitis, septic arthritis or neurological Melioidosis)

 

4 weeks:

Septic joint, deep seated abscess or organ abscesses, extensive lung disease

6 weeks:

Osteomyelitis

8 weeks:

Neurological melioidosis

* Consider adding Co-trimoxazole for patients with severe infection involving the brain, prostate or other privileged site- brain, eyes, testicular, articulart cartilage (same dosing as described for eradication therapy).
Co-trimoxazole may be given IVI over 30 minutes 12 hourly, or nasogastric, or oral suspension.

 

**Meropenem 2gm IV q8H for infection with Central nervous system disease
 
Oral Eradication Phase Therapy:
Co-trimoxazole 480 mg tablets
 
>60 kg
4 tablets PO q12H 

40 - 60 kg
3 tablets PO q12H

<40 kg
2 tablets PO q12H


** Co-amoxiclav 625 mg tablets

>60 kg
3 tablets PO q8H 

< 60 kg
2 tablets PO q8H


Duration: Minimum 12 weeks

OM and neurological 6 months.

** Only use if resistant or allergic to Co-Trimoxazole
 
Rickettsia:
Scrub, Murine & Endemic Typhus


Uncomplicated

 

 

 

 Complicated 

  




Doxycycline 100 mg PO q12H for 7 - 10 days

 



Azithromycin 500 mg PO / IV q24H for 5 days		  





Azithromycin 500mg PO/IV x 1 dose 		  




*To use Azithromycin in pregnancy 

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

Ceftriaxone 2gm IV q24H until improve clinically then convert to oral

Once culture available, to target antibiotics according to sensitivities

If sensitive, for Ciprofloxacin 400 mg IV q12H for 7 - 14 days (switch to PO 500 mg q12H as soon as possible)

 
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 Fluoroquinolone susceptibility with lab.
 
Non-Typhoid Bacteremia:
Salmonella sp		  

Ceftriaxone 2 gm IV q24H till improve clinically then convert to oral

 

Once culture available, to target antibiotics according to sensitivities

If sensitive, for Ciprofloxacin 400 mg IV q12H for 7 - 14 days* (switch to PO 500 mg q12H as soon as possible)s
 
Co-trimoxazole (Trimethoprim component) 8 - 10 mg/kg/day divided q8H  (Once sensitivities available and if patient allergic to beta lactams)

Look for dissemination (mycotic aneurysm, OM etc). 


 

 

*Duration:

No extra-intestinal infection: 14 days

Extra-intestinal infection (Mycotic aneurysm, osteomyelitis, or immunosuppressed): 4 – 6 weeks
 
Leptospirosis:
L. icterohaemorrhagiae
L. canicola		  
Mild/ Outpatient:
Doxycyline 100 mg PO q12H for 5-7 days		  

Mild:
Amoxicillin 500mg PO q8H for 7 days


OR

Azithromycin 1 gm IV / PO q24H D1, then 500 mg IV / PO q24H D2 and D3		  
Mild diseases are self limiting and does not require treatment. 

Jarisch-Herxheimer reaction can occur post penicillin. 

Severe: Leptospiral pulmonary syndrome, multiorgan involvement, sepsis
 
Severe:
Penicillin 1.5 MU q6H IV for 7 days

  
Severe:
Ceftriaxone 2 gm q24H IV for 7 days
 
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
Doxycycline 100 mg PO q12H for 3 months
+
Gentamicin 5 mg/kg IV q24H (monitor TDM) for 1 week 
+
Rifampicin 600 - 900 mg PO q24H for 3 months

Neurobrucelosis
Doxycycline 100 mg PO q12H
+
Rifampicin 600 - 900 mg PO q24H
+
Ceftriaxone 2 gm IV q12H until CSF normal




Endocarditis
Surgery
+
Doxycycline 100 mg PO q12H for 6 weeks to 6 months
+
Rifampicin 600 mg PO q24H for 6 weeks to 6 months
+
Co-trimoxazole (Trimethoprim component) 5 mg/kg PO q12H for 6 weeks to 6 months 
+
Gentamicin 5 mg/kg IV q24H for 2 - 4 weeks

  

Doxycycline 100 mg PO q12H
OR Co-trimoxazole (Trimethoprim component) 5 mg/kg PO q12H
+
Rifampicin 600 mg PO q24h

For 6 weeks 



Ciprofloxacin 750 mg PO q12H
+
Rifampicin 600 - 900 mg q24H

For 3 months




Doxycycline 100 mg PO q12H
+
Rifampicin 600 - 900 mg PO q24H
+
Co-trimoxazole (Trimethoprim component) 5 mg/kg PO q12H in divided dose until CSF normal		  

Relapse rate 10% 
Bone involvement 20 - 30% 
Neurobricellosis 1% 

Steroids not recommended. 


Endocarditis rare, but highest mortality: needs surgery

 

Pregnancy:

Rifampicin  600-900mg (15mg/kg) PO q24H for 6 weeks

+


Co-trimoxazole 480mg tab (2 tabs) q12H for 6 weeks


Ciprofloxacin: active in vitro but clinical response not good. 





Clinical response to Cetriaxone is variable.

Duration: Until CSF clears
 
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



Surgery
+
Azithromycin 500 mg PO q24H for 3 months
+
Gentamicin 1 mg/kg IV q8H for 2 weeks (monitor TDM)
OR Rifampicin 300 mg q12H for 2 weeks

  
Duration:
If valve not removed,
Regimen with Doxycycline is to be continued for 3 months.
Regimen with Azithromycin is to be continued for 6 months.
 
Cholera
HYDRATION is primary therapy
* Doxycycline 300mg PO single dose 		 
** Erythromycin Ethyl Succinate 400 mg PO q8H for 3 days
  
OR
  
Azithromycin 1 gm PO single dose

  
* Non Tetracycline resistance. 
** Tetracycline resistance and pregnancy: Erythromycin Ethyl Succinate or Azithromycin.
 
Tetanus Clostridium Tetani		  
Surgical debridement of infected source tissue

Metronidazole 1000 mg IV q12H
OR

Benzylpenicillin 3 MU IV q4H

+
  
Human Tetanus Immunoglobulin 3000 iu to 6000 IU IM single dose

  
Doxycycline 100 mg PO q12H 

OR

Clindamycin 600 mg IV q6H

  
Duration: 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: Artesunate 2.4 mg/kg IV q24H till oral conversion

(* Parenteral Artesunate should be given for a minimum of 24 hours)


+
Primaquine# 30 mg PO single dose (for P. falciparum), 15 - 30 mg q24H for  14 days (for P. vivax / ovale)

Switch to oral Riamet®## when possible
  
























Artesunate 200mg/Mefloquine* 440mg q24H for 3 days

Or

 

Oral Quinine* (10mg/kg) q8H for 7 days

+

 

Doxycycline 100mg q12H for 7 days
WHO recommended combination therapy.

#Primaquine (dosed as base): check G6PD status before use.
45 mg/week x 8 weeks for G6PD deficient patients.

Contraindicated in pregnant women, children aged < 6 months, women BF child < 6 months.

##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.


*Artesunate 200mg/Mefloquine 440mg and oral Quinine are not available at UMMC
 
Plasmodium Falciparum - Uncomplicated		  
Riamet®## 
+
Primaquine# 30 mg PO single dose
 
Plasmodium Vivax or Ovale - Uncomplicated		  
Riamet®## 
+
Primaquine# 15 - 30 mg PO q24H for 14 days

  

 
Plasmodium Knowlesi - Uncomplicated		  
Riamet®##

  


  
 
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

  

  
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
Plasmodium Knowlesi or Malariae		  
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

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


  
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 (Trimethoprim component) 4 mg/kg PO q12H for 12 - 24 weeks
+
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