Antimicrobial Pharmacology

1. Antimicrobial Pharmacology
PROTOZOAL AND HELMINTHIC
INFECTIONS
by
Shivankan Kakkar, MD

2. Green, Frothy,
Foul-Smelling
Diarrhea
Abdominal
Bloating
Burping
3 Stool Samples
NAAT,
Stool Antigen,
or O&P
Fecal-Oral
Incubation: 1–3 Weeks
Diarrhea: 2–6 Weeks
Giardiasis
(Beaver Fever)
A
n
a
e
r
o
b
ic Flagellated
P
r
o
t
o
z
o
a
Giardia lambli
a
E
n
t
a
moeba histoly
t
i
c
a
Ameba
Amebiasis
Granulomatous Mass
(Ameboma)
Dysentery
Flask-shaped
Ulcers
Hematogenous Spread
to Brain/Lungs (Rare)
Incubation: 2–4 Weeks
10% Cases are
Invasive

3. Table - Major Protozoal Infections and the Drugs of Choice
Infection Drug of Choice Comments
Amebiasis Metronidazole Diloxanide for
noninvasiveintestinal
amebiasis
Giardiasis Metronidazole “Backpacker’s diarrhea”
from contaminated water
or food
Trichomoniasis Metronidazole Treat both partners
Toxoplasmosis Pyrimethamine
+ sulfadiazine
—
Leishmaniasis Stibogluconate —
Trypanosomiasis Nifurtimox (Chagas
disease)
Arsenicals (African)
—

4. Nitroimidazoles
This group includes metronidazole and related drugs. These are effective
orally as well as i.v. and eliminated by hepatic metabolism. Nitro group of
these drugs gets bioactivated (by reduction) to form reactive cytotoxic
products that damage DNA.
Metronidazole is the drug of choice for intestinal wall disease and amoebic
liver abscess. It is usually combined with a luminal amoebicide for these
indications. It is NOT a very good drug for luminal amoebiasis because it is
almost completely absorbed in the proximal intestine and very little amount
reaches the colon.
Nausea, metallic taste and abdominal cramps are the most common adverse
effects. It can also cause discoloration of urine, leucopenia and dizziness.
Seizures can occur with the use of high dose. Opportunistic fungal infections
can occur in a patient on metronidazole. It can cause disulfiram like reaction if
used in patients taking alcohol. Metronidazole can potentiate the
anticoagulant effect of coumarins. Tinidazole, secnidazole, ornidazole and
satranidazole have similar potency and efficacy as metronidazole but are long
acting (secnidazole has longest half life). Satranidazole is devoid of metallic
taste, neurological adverse effects as well as disulfiram like reaction.

5. a
*Main Causative Agents
Anopheles spp.
Anopheles spp.
Gametocytes
Incubation: 7–30 Days
Shorter: P. falciparum
Longer: P. malariae
Malaria
Typical Medical
Student Answer!
P
l
asmodium sp
p
.
Prot zoa
P. vivax*
P. falciparum*
P. malariae
P. ovale
Liver Cells
Infected
Hepatic
Schizonts
Hemolysis
Hypnozoites
Late
Trophozoite
Early
Trophozoite
Blood Cell
Schizont
Merozoites
Injects
Sporozoites
P. vivax
P. ovale
Malaria Symptoms
Paroxysmal Fevers/Chills
Tachycardia/Tachypnea
Fatigue/Malaise
Headache/Cough
Nausea/Vomiting/Abdominal Pain
Arthralgia/Myalgia
Splenomegaly
Severe Malaria
AMS/Seizures
ARDS/Shock
Metabolic Acidosis
Hypoglycemia
Renal Failure
Hepatic Failure
Anemia/Coagulopathy

6. Antimalarial Drugs
• Clinical uses:
– Chloroquine-sensitive regions
º Prophylaxis: chloroquine +/– primaquine
º Backup drugs: hydroxychloroquine,
primaquine, pyrimethamine-sulfadoxine

7. Chloroquine is the drug possessing largest volume of distribution (>1300
L).
It accumulates in the food vacuole of the plasmodium. Thus, it is
selectively concentrated in the parasitized erythrocytes. It prevents
polymerization of heme to hemozoin resulting in accumulation of heme
that is toxic for the parasite.
It is the drug of choice for treatment and prophylaxis of non-falciparum
malaria and chloroquine sensitive P. falciparum malaria.
Adverse effects of chloroquine include skin rashes (lichenoid eruptions),
peripheral neuropathy, hypotension, myocardial depression (T wave changes
in ECG), auditory impairment and toxic psychosis. Prolonged use of high
doses can result in blindness due to retinal damage (Bull’s eye maculopathy).
It can also precipitate porphyria and cause discolouration of nails and
mucous membranes.
Chloroquine is the drug of choice for treatment of malaria in pregnant
women.

8. • Specific treatment:
Table - Treatment of Chloroquine-Sensitive Malaria
P. falciparum Chloroquine
P. malariae Chloroquine
P. vivax Chloroquine + primaquine
P. ovale Chloroquine + primaquine

9. – Chloroquine-resistant regions
º
º
Prophylaxis: doxycycline, mefloquine, atovaquone-proguanil
Treatment: ACT, quinine +/– either doxycycline or
clindamycin or pyrimethamine
• Side effects:
– Hemolytic anemia in G6PD deficiency (primaquine,
quinine)
– Cinchonism (quinine)

10. TREATMENT AND PROPHYLAXIS OF MALARIA
(NATIONAL GUIDELINES ACCORDING TO
NVBDCP)
Treatment of Uncomplicated malaria
Parasite
Males and Non-
pregnant females
Pregnancy (1st
trimester)
Pregnancy (2nd and
3rd trimester)
P. vivax (or P. ovale)
Chloroquine
+
Primaquinea,b
Chloroquine Chloroquine
P. falciparum(or P. malariae)
ACTc
+
Primaquined
Quinine ACTc
Mixed
ACTc
+
Primaquined
Quinine ACTc
a
Primaquine is contraindicated in pregnancy, infants and G-6–PD deficiency b
For P. vivax, primaquine is given for 14
days
c
ACT is artemisinin-based combination therapy. Preferred ACT is
– North-Eastern states: Artemether + Lumefantrine
– Rest of India: Artesunate + Sulfadoxine/Pyrimethamine
d
For P. falciparum, Primaquine is given as a single dose to kill gametes

11. Treatment of severe/complicated malaria
P. falciparum Artesunatee
followed by
oral ACT
Artesunatee
followed
by oral ACT
Artesunatee
followed
by oral ACT
ACT is artemisinin-based combination therapy. Preferred ACT is
– North-Eastern states: Artemether + Lumefantrine
– Rest of India: Artesunate + Sulfadoxine/Pyrimethamine
e
Artesunate is given by IV or IM route. It is continued for minimum 48 hours.

12. Artemisinin, dihydroartemisinin, artesunate, artemether and arteether are
the compounds obtained from a Chinese herb Artemisia annua.
Artemisinin is a prodrug and is activated in the body to
dihydroartemisinin.
These drugs generate highly active free radicals that damage parasite
membranes.
These drugs are the fastest acting drugs against malaria.
Artesunate has a very short half life and can be given i.v. These can be
used for the treatment of multidrug resistant malaria as well as serious
forms like cerebral malaria.
Artemisinin derivatives are not indicated for chemoprophylaxis of malaria.
It can rarely cause QT prolongation.

13. CHEMOPROPHYLAXIS OF MALARIA
Short-term (< 6 weeks):
Doxycyclinea,b
Long-term (> 6 weeks):
Mefloquinec,d
a
Doxycycline is started 2 days before travel and continued for 4 weeks after leaving the endemic area b
Doxycycline is contraindicated in pregnancy and children < 8 years.
c
Mefloquine is started 2 weeks before travel and continued for 4 weeks after leaving the endemic area
d
Mefloquine is contraindicated in patients with history of convulsions or neuropsychiatric conditions.

14. Nematode
A
s
c
a
r
is lumbric
o
i
d
e
s
Ascariasis
Ingestion of
Infected Egg
Large Quantity of Worms
Needs Surgical Removal
Loeffler’s Syndrome
(Eosinophilic Pneumonia)
Ectopic Ascariasis
Pancreas
GB
CBD
Appendix
Stomach
Nasal Oropharyngeal
Unfertilized
Egg Dies
Fertilized Eggs
Develop in Soil
MOIST
SOIL WARM
SHADE
Cysticerci
in Brain
Hooks
Scolex
Proglottid
Hermaphrodite
A
u
t
o
in
o
c
u
la
t
io
n
o
r
E
g
g
In
g
e
s
t
io
n
l
C
y
s
t
ic
e
r
c
o
s
is
I’ve got
Dope Hooks!
Cysticerci
in Eyes
Cysticerci
Develops
in Muscle
Cysticerci
in Muscle
(Measly)
Undercooked
Pork
Ovum (Eggs)
in Feces
Pork Tapeworm Taenia solium
2–8 meters
Cestode
produces tapeworm

15. Definative Host
(Humans)
Eggs
Eggs ingested
by snail.
Fluke lives in
gallbladder and
bile ducts.
Causes
Cancer!
Liver Fluke
(Chinese Liver Fluke)
O
p
i
sthorchis felin
e
u
s
O
p
i
sthorchis vive
r
r
i
n
i
C
l
o
n
ochis sin
e
n
s
i
s
Trematode
1st
Intermediate
Host
2nd
Intermediate
Host
Miracidia
mature to
cercariae.
Cercariae
penetrate fish.
Metacercarial
cysts form
in fish.
Human ingests
undercooked fish.

16. Drugs for Helminthic Infections
• Most intestinal nematodes (worms)
– Albendazole (↓ glucose uptake and ↓ microtubular
structure)
– Pyrantel pamoate (NM agonist → spastic paralysis)
• Most cestodes (tapeworms) and trematodes (flukes)
– Praziquantel (↑ Ca2+ influx, ↑ vacuolization)

17. Prescription
Writing
Exercises

18. Problem 1:
A 30 year old woman complaining of colicky lower abdominal pain,
malaise, diarrhea (5 to 6 motions per day), with mucous and blood for last
two days.
Macroscopic examination of stool shows dark coloured faeces mixed
with mucous and blood.
Microscopic examination of stool shows mucous, RBC and trophozoites
of E. histolytica.
Diagnosis is acute amoebia dysentery (acute intestinal amoebiasis).
Write down a prescription for the patient.

19. RX
1. Tab. Metronidazole 400-800 mg 8 hourly orally with food for 10 days.
In children, 15 mg/kg divided in three doses for 7 days.
Or
Tab. Tinidazole (300 mg, 500 mg and 1 g) 2 g orally as single dose with
food.
In children, 50 mg/kg as a single dose.
2. Tab. Diloxanide furoate 500 mg 8 hourly for 10 days.
In children, 20 mg/kg/day in three divided doses for 10 days.

20. Problem 2:
A 25 year old man complains of fever with rigors, headache, nausea,
vomiting and anorexia.
He has past history of malaria with completion of chloroquine treatment 3
weeks ago.
Peripheral blood smear examination shows presence of gametocyte and ring
form of P. falciparum.
Diagnosis: malaria due to P. falciparum resistant to chloroquine.
Write down a prescription for the patient.

21. RX
1. Artemisinin based combination therapy (ACT):
Artesunate 4 mg/kg body weight daily for 3 days
plus
Sulfadoxine (25 mg/kg body weight) Pyrimethamine (1.25 mg/kg body
weight) on first day.
(Caution: ACT is not to be given in 1st trimester of pregnancy).
2. Primaquine: 0.75 mg/kg body weight on day 2.