Case Based Learning:

Antimicrobials
07/12/2023
Case 1a
Rajiv, a 23 year-old man, presented to the emergency department
with acute onset of seizures and fever. He was diagnosed with
meningitis and culture/sensitivity revealed Pneumococcus.
The physician prescribed a combination of penicillin-G and
tetracycline.
Comment on this antibiotic regimen
Case 1a
1. Is this a rational combination? Why not?
◦ Pencillin-G is cidal and tetracycline a static antibiotic AND
Pneumococcus is highly sensitive to pencillin-G.

2. Give another example of a similar interaction.

◦ Pencillin-G and erythromycin for Group A streptococcus.
◦ Nalidixic acid and nitrofurantoin for E. coli.
Case 1a
Bacteriostatic Bactericidal
antimicrobials antimicrobials
Tetracyclines Aminoglycosides
Chloramphenicol β lactam antibiotics
Macrolides Rifampin
Sulfonamides Quinolones
Clindamycin Glycopeptide antibiotics
Case 1b
A 50-year-old woman, Sushma, presented in the emergency
department with high grade fever, burning micturition since 3-4 days
and altered sensorium. After laboratory work-up, she is diagnosed
with complicated urinary tract infection.
Patient was started on parenteral imipenem cilastatin with
paracetamol.
Case 1b
What is the rationale of imipenem-cilastatin combination?
o Imipenem has excellent activity against common UTI causing
pathogen like E Coli, Kleibsiella, Pseudomonas, Enterobacter etc.
o Cilastatin inhibits renal tubular dehydropeptidase 1, thereby
decreasing degradation of imipenem
Other similar alternatives:
Piperacillin-tazobactam
Ceftolazone-tazobactam
Ceftazidime-avibactam
 Case 1b
Synergistic combinations:
 Inhibition of enzymatic inactivation
 Blocking sequential steps in metabolic pathway: cotrimoxazole
 Enhancement of uptake: penicillins with aminoglycosides, AmB
with flucytosine

Antagonistic combinations:
Cidal+Static: beta lactam with tetracycline/chloramphenicol
Case 2
Mr Prakash, a 56-year farmer from Bihar, presented to the healthcare
centre with history of recurrent fever, progressive weakness and
abdominal discomfort associated with loss of appetite for past 6
months followed by petechial hemorrhages over body. On
examination there was hepato-splenomegaly. Rapid diagnostic test kit
was positive for Kala-azar. The patient was started on Inj. Sodium
Stibogluconate (20 mg/kg, i.m.) for 30 days.
1. What are the other treatment options for visceral Leishmaniasis?
2. Which option will you prefer for this case?
Case 2
Diagnosis: Kala-azar or visceral Leishmaniasis (VL)
Management: Options available-
a) Tab. Miltefosine 50 mg BD po for 28 days;
b) Inj. L-AMB 10 mg/kg single dose iv infusion
For this case, according to NVBDCP, DOC: Miltefosine for 28 days
(drug resistance to SSG is seen in India)
Case 3a
A 40-year old patient, Mr. Mahesh, had c/o lower abdominal
discomfort, flatulence, and occasional diarrhea. He went to the
chemist and took ORS and Tab Loperamide for his symptoms. The
symptoms temporarily improved, but 3 weeks later, he presented to
the OPD with severe dysentery, right upper quadrant pain, weight
loss, fever. O/E patient had hepatomegaly and tenderness in the right
upper abdominal quadrant.
USG revealed a round hypoechoic lesion with well defined margins
suggestive of amoebic liver abscess
Write a suitable prescription for this patient.
 Dr ABC, MD Medicine
AIIMS, New Delhi. Ph: 9087654321
Registration No.:123456
Date: 30/07/2020
Name: Mr. Mahesh Age: 40 years Sex: Male Address: New Delhi
Diagnosis: Amoebic liver abscess
R x:
1. Tablet METRONIDAZOLE (800 mg) three times daily for 10 days (Taken orally after
food) followed by
2. Tablet DILOXANIDE FUROATE (500mg) three times daily for 10 days (Taken orally after
food)
Advice:
• Maintain food hygiene and personal hygiene
• Stool examination after 20 days
Review with reports after 20 days Signature
and Stamp
Case 3a

What may be the

reason for amoebic
liver abscess?
Case 3a
How do you decide the treatment in such cases?
ANTIAMOEBIC DRUGS Luminal
Tissue amoebicides amoebicides

INTESTINAL + EXTRAINTESTINAL • Diloxanide

EXTRAINTESTINAL: only: furoate
• Metronidazole • Chloroquine • Tetracycline
• Tinidazole
• Secnidazole
Case 3a
AMOEBIC TISSUE AMOEBICIDE LUMINAL ALTERNATIVE
INFECTION AMOEBICIDE AGENTS
1. Acute Metronidazole (800 mg) po three Diloxanide furoate Ornidazole,
Amoebic times daily X 7-10 days OR (500mg) three times Secnidazole
Dysentery Tinidazole (2g) po once daily X 3- daily 5-10 days
6 days Quiniodochlor,
Paromomycin
2. Mild intestinal Metronidazole (400 mg) po three Same as above Ornidazole,
ameobiasis times daily X 5-7 days OR Secnidazole
Tinidazole (2g) po once daily X 2-
3 days Quiniodochlor,
Paromomycin
Case 3a
AMOEBIC TISSUE AMOEBICIDE LUMINAL ALTERNATIVE
INFECTION AMOEBICIDE AGENTS
3. Amoebic liver Metronidazole (800 mg) po three Same as above Emetine/
abscess times daily X 7-10 days OR Dihydroemetine,
Tinidazole (2g) po once daily X 3- Chloroquine
6 days
Case 3b
A 25-year-old male presented in emergency with c/o flushing ,
burning sensation, tightness in chest, dizziness, vomiting, visual
disturbances and mental confusion after consumption of alcohol. On
history taking, it was found that he was taking Tab Metronidazole
400 mg TDS for amoebiasis since the last three days.
What could be the possible explanation for these symptoms?
Case 3b
Case 3b
“Disulfiram like reaction”
o Results from interaction of alcohol with metronidazole
o Disulfiram inhibits aldehyde dehydrogenase in alcohol metabolism
in liver : causes accumulation of acetaldehyde
o Distressing symptoms are due to accumulation of acetaldehyde
Case 4a
Mr. Manish 35-year-old gentleman, presents to the outpatient clinic
with complaints of productive cough and evening rise fever for last 20
days.
One and half months back he was diagnosed as a new case of
pulmonary tuberculosis and was started on anti-tubercular medications
which he took for 25 days and discontinued because of relief of
symptoms.
On investigation his sputum smear was found to be positive for tubercle
bacilli. What would be the likely course of treatment for him?
 Presumptive TB All notified TB patients Non responder to treatment

NAAT#

NO RESISTANCE R resistance detected R resistance not detected

Shorter MDR TB
regimen LPA$

LPA and
DST for Mfx(1.0), H resistance detected H resistance not detected
Lzd*, Cfz*, Z*, Bdq*,
Dlm*
RESISTANCE
H mono/poly DR TB
regimen DS TB treatment
longer MDR TB
regimen
 DS TB Treatment

 Intensive Phase - 4 FDC  Continuation Phase -3 FDC

 One tab has HRE-
 One tab has HRZE-
75/150/275
75/150/400/275
 For 4 months
 For 2 months
H mono/poly DR TB regimen
All oral H mono/poly DR TB regimen is of 6 months with no separate IP/CP
Shorter MDR TB regimen
Shorter MDR TB regimen is of 9-11 months with 4-6 months of IP containing
injectables and 5 months of CP
 longer MDR TB regimen
All oral longer
MDR TB
regimen is of
18-20 months
with no
separate IP/CP.
Case 4b
A 30-year-old male, Mr. Ram Manohar, weight 55 kg, was recently
diagnosed with MDR tuberculosis (In Liquid Culture Drug
Susceptibility Testing, resistance was found against isoniazid,
rifampicin and fluoroquinolones) at the National Institute of
Tuberculosis and Respiratory Diseases in Delhi. He was started on tab
Bedaquiline, 400 mg once daily for 2 weeks at the same institute on
20/09/2017. Baseline ECG was normal.
Case 4b
1. What is the mechanism of action of Bedaquiline?
a) Inhibition of mycolic acid synthesis
b) Inhibition of ATP synthase on cell wall of mycobacterium
c) Inhibition of cell wall synthesis
d) Inhibition of RNA synthesis
Case 4b
1. What is the mechanism of action of Bedaquiline?
a) Inhibition of mycolic acid synthesis
b) Inhibition of ATP synthase on cell wall of mycobacterium
c) Inhibition of cell wall synthesis
d) Inhibition of RNA synthesis
2. What is the importance of base line ECG in this patient?
o QT prolongation is the known side effect
Case 4c
A 35-year-old female patient on combined oral contraceptives was
recently diagnosed with pulmonary tuberculosis. She was prescribed
isoniazid, rifampicin, pyrazinamide and ethambutol.
1. What drug interaction do you expect in this patient?
2. What is the mechanism of this drug interaction?
3. How can you prevent this interaction?
Case 4c
1. What drug interaction do you expect in this patient?
◦ Patient may develop contraceptive failure.
◦ Estrogens in combined pills are metabolized by hydroxylation by
CYP3A4.
2. What is the mechanism of this drug interaction?
◦ Rifampicin is known to induce CYP3A4. This will lead to increased
metabolism of estrogens which may lead to contraceptive failure.

3. How can you prevent this interaction?

◦ To prevent an unwanted pregnancy, an alternative method of
contraception such as barrier contraceptives should be used.
Case 5
A 45-year-old male was diagnosed with pulmonary tuberculosis. On
further evaluation, he was found to be HIV positive and his CD4
counts are 350 cells/mm3.
Patient was started on regimen (2 HRZE + 4 HRE).
1. Consideration for management of HIV –TB co- infection.
2. When to start first line ART in patients with active TB?
3. What is the ART regimen recommended for patients on ATT?
Case 5
1. Consideration for management of HIV –TB co- infection.
oDrug interactions between rifampicin and NNRTIs and Protease
inhibitors
o IRIS (Immune Reconstitution Inflammatory Syndrome)
o Pill burden
o Adherence
o Drug toxicity
Case 5
2. When to start first line ART in patients with active TB?
◦ The first priority is to start TB treatment
◦ ART may need to be started later (between 2 weeks to 2 months)
 Case 5
3. What is the ART regimen recommended for patients on ATT?
Triple Drug Combination from
The first-line ART essentially comprises of
◦ NRTI backbone, preferably Non-Thymidine(Tenofovir plus Lamivudine)

◦ And one INSTI, preferably DTG.

◦ Age >10 years and weight >30kg

Tenofovir (TDF 300 mg) + Lamivudine (3TC 300 mg) + DOLUTEGRAVIR (DTG 50 mg) regimen

“TLD” ) as FDC in a single pill once a day (at a fixed time every day as per patient’s convenience)

Rifampicin-containing ATT regimen

◦ Tenofovir (300 mg) + Lamivudine (300 mg) + Dolutegravir(50 mg) – FDC one tablet once daily

◦ Additional dose of DTG 50 mg to be provided (12 hours after taking their regular dose) until 2 weeks after completion of ATT
Case 6
A 35-year-old woman was recently tested positive for both HIV &
HBsAg. She also has a history of smoking & heroin addiction. She is
currently receiving methadone for same. Based on her WBC count and
CD4 count, She is prescribed following drugs: Tenofovir, Emtricitabine &
Efavirenz
1. Which class of drugs do these medications belong to?
2. Comment on the rationality of using these drugs in this patient.
3. What other investigations should be done before starting this
regimen?
4. What other advice you will give to the patient?
 Case 6
1. Which class of drugs do these medications belong to?
Nucleoside RTI, Nucleotide RTI & NNRTI respectively.
Nucleoside reverse transcriptase inhibitors (NsRTI): Zidovudine (AZT), Lamivudine (3TC),
Emtricitabine,

Non-nucleoside reverse transcriptase inhibitors (NNRTI): Efavirenz (EFV), Nevirapine (NVP)

Nucleotide reverse transcriptase inhibitors (NtRTI) : Tenofovir Disoproxil Fumarate (TDF)

Protease inhibitor: Ritonavir (RTV), Lopinavir (LPV), Darunavir (DRV), Atazanavir (ATV)

Integrase Inhibitors :Dolutegravir (DTG), Raltegravir (RGV)

Fusion inhibitors: Enfuvirtide (T-20)

CCR5 entry inhibitor: Maraviroc (MVC)

Case 6
2. Comment on the rationality of using these drugs in this patient.
o Activity against both HIV & HBV.
o Tenofovir and Emtricitabine do not interact with methadone.
Efavirenz is an inducer CYP3A4. May lower methadone levels, so
patient should be monitored for signs of opioid withdrawal,
may require an increased dose of methadone.
Case 6
3. What other investigations should be done before starting this
regimen?
Renal function test, Bone mineral density, Pregnancy test ( S/E of
tenofovir)
4. What other advice you will give to the patient?
Avoid alcohol
Abrupt cessation of treatment may precipitate an acute flare of
hepatitis.
Case 7a
A 23-year-old lady comes to the medicine OPD with complains of
fever, rigor and chills, headache, body-ache, anorexia, nausea and
fatigue for the last four days. A diagnosis of uncomplicated P.
falciparum malaria is made based on microscopic examination of
blood smear. She informs that she is 10 weeks pregnant.
1. How will you manage this case?
2. What is the treatment of uncomplicated falciparum malaria in
second and third trimester of pregnancy?
3. What treatment would you give if the lady was not pregnant in
the above-mentioned case?
Case 7a
1. How will you manage this case?
2. What is the treatment of uncomplicated Falciparum malaria in
second and third trimester of pregnancy?
1st trimester*- Quinine 10mg/kg, 3 times for 7 days
2nd and 3rd trimester- ACT-SP in all states except NE (ACT-AL)

o ACT-SP: artesunate 4mg/kg for 3 days+sulfadoxine 25mg/kg-pyrimethamine

1.25mg/kg on first day
o ACT-AL: artemether 80mg+lumefantrine 480mg twice daily for 3 days
*In addition primaquine 0.75mg/kg on day 2
Case 7a
3. What treatment would you give if the lady was not pregnant in
the above-mentioned case?
Dose schedule for treatment of uncomplicated P. falciparum cases:
Artemisinin based Combination Therapy (ACT-SP)*
o Artesunate 4 mg/kg body weight daily for 3 days PLUS
o Sulfadoxine (25 mg/kg body weight) – Pyrimethamine (1.25 mg/kg
body weight) on first day
*ACT is not to be given in 1st trimester of pregnancy.
Primaquine: 0.75 mg/kg body weight on day 2
Case 7a
Dose schedule for treatment of uncomplicated P. falciparum cases:
Age group 0-1 1-4 5-8 9-14 >15
Pink Blister Yellow Blister Green Blister Red Blister White Blister
AS 25 mg 50 mg 100 mg 150 mg 200 mg
1st Day
SP 250 + 500 + 750 + 1000 + 1500 +
12.5 mg 25 mg 37.5 mg 50 mg 75 mg
AS 25 mg 50 mg 100 mg 150 mg 200 mg
2nd Day
PQ Nil 7.5 mg base 15 mg base 30 mg base 45 mg base

3rd Day AS 25 mg 50 mg 100 mg 150 mg 200 mg

Case 7a
3. What treatment would you give if the lady was not pregnant in
the above-mentioned case?
In NE states: ACT (artemether) – AL (lumefantrine)
Co-formulated 5–14 kg
15–24 kg 25–34 kg > 34 kg
tablet ( > 5 months to
(≥ 3 to 8 years) (≥ 9 to14 years) (> 14 years)
ACT-AL < 3 years)
20 mg/ 120mg 40 mg/ 240mg 60 mg/ 80 mg/
Total Dose of twice daily for 3 twice daily for 3 360mg 480mg
ACT-AL days days twice daily for 3 twice daily for 3
days days
Case 7b
Ramu, a 30-year-old man is brought to the emergency with complains
of confusion, drowsiness and passage of red colored urine. History
reveals that he is having high fever, chills and rigor, headache, body-
ache and fatigue since last one day. Urine examination shows
macroscopic hemoglobinuria. RDT is positive for P falciparum. A
diagnosis of complicated P. falciparum is made.
What antimalarial will you prescribe in this case?
What precautions shall you take if you are prescribing Quinine to the
patient?
 Case 7b
Chemotherapy of complicated and severe P. falciparum malaria
Initial parenteral treatment for Follow-up treatment, when patient can take
at least 48 hours: oral medication following parenteral
CHOOSE ONE of following four options treatment
1. Quinine: 20mg quinine salt/kg body weight Quinine 10 mg/kg three times a day with:
on admission (IV infusion or divided IM doxycycline 100 mg once a day or clindamycin
injection) followed by maintenance dose of in pregnant women and children under 8 years
10 mg/kg 8 hourly; infusion rate should not of age,
exceed 5 mg/kg per hour. Loading dose of - to complete 7 days of treatment.
20mg/kg should not be given, if the patient
has already received quinine.
Case 7b
Chemotherapy of complicated and severe P. falciparum malaria
Initial parenteral treatment for Follow-up treatment, when patient can take
at least 48 hours: oral medication following parenteral
CHOOSE ONE of following four options treatment
2. Artesunate: 2.4 mg/kg i.v. or i.m. given on Full oral course of Area-specific ACT:
admission (time=0), then at 12 h and 24 h, In North-Eastern states: Age-specific ACT-AL for
then once a day. 3 days + PQ Single dose on second day
or
3. Artemether: 3.2 mg/kg i.m. given on In other states: Treat with: ACT-SP for 3 days +
admission then 1.6 mg/kg per day. PQ Single dose on second day
or
4. Arteether: 150 mg daily i.m for 3 days in
adults only (not recommended for children).
Case 8a
A 18-year boy, Naveen, presented to the
dermatology department with pain in great
toe for the past month. He also noticed a
discoloration in the nail which he thought
was probably a blood clot resulting from
tight footwear. On further questioning, he
revealed that he had been playing soccer in
the rain.
The discoloration was observed on
examination and toenail scrapings
confirmed onychomycosis.
Case 8a
How will you manage this case?
◦ Diagnosis: Onychomycosis
◦ Treatment options:
1. Azole anti-fungal agents:
a) Tab. Fluconazole 150 mg weekly/bi-weekly for 10-12 months
b) Tab. Griseofulvin: 125 mg QID for 10-12 months
2. Topical: Ciclopirox olamine 8% nail lacquer solution
*Reason for long duration of Rx: most drugs are fungistatic and not
fungicidal, removed as the nail grows
Case 8b
Ms Jaspreet, a 39-year woman, k/c/o epilepsy which was well
controlled with monotherapy of Phenytoin (300 mg/day, po)
presented to the emergency with c/o impaired speech, confusion,
altered gait and vertigo. On further questioning, patient attenders
gave h/o treatment for white lesions on tongue and cheek with Tab
Fluconazole 100 mg daily for past 5 days. Patient’s phenytoin
concentrations were found to be 67 μg/mL (Therapeutic range: 10-20
μg/mL).
1. What is the cause for this interaction?
2. How will you manage this patient?
Case 8b
1. What is the cause for this interaction?
◦ Interaction between phenytoin (enzyme inducer metabolized by
CYP450 enzymes) and fluconazole (enzyme inhibitor): reduced
metabolism of phenytoin led to increased serum levels manifesting
as toxicity
2. How will you manage this patient?
◦ Discontinue fluconazole; consider triazole anti-fungal agents that
have lesser effect on CYP enzymes (such as itraconazole and
voriconazole) for treating oral thrush
Thank You