Antimicrobial Agents Practice Questions

Q: Which compound is primarily responsible for the hepatotoxicity associated with Isoniazid (INH)?

INH acetylhydrazine. ***INH acetylhydrazine*** - The hepatotoxicity of Isoniazid (INH) is primarily attributed to **acetylhydrazine**, a toxic metabolite formed during INH metabolism - **Metabolic pathway:** INH is first acetylated by N-acetyltransferase 2 (NAT2) to form acetylisoniazid, which then hydrolyzes to **acetylhydrazine** and isonicotinic acid - Acetylhydrazine is further oxidized by **cytochrome P450 2E1 (CYP2E1)** to form highly reactive intermediates that covalently bind to hepatic macromolecules, causing **hepatocellular injury** - **Risk factors:** Rapid acetylators, concurrent alcohol use, and CYP2E1 inducers increase acetylhydrazine formation and hepatotoxicity risk - This is the well-established mechanism of INH-induced hepatitis in clinical pharmacology *INH sulfhydrazine* - Sulfhydrazine is not a metabolite of isoniazid - INH metabolism involves acetylation and hydrolysis, not sulfonation pathways - This compound is not implicated in INH hepatotoxicity *INH methylhydrazine* - Methylhydrazine is not formed during isoniazid metabolism - The metabolic pathway of INH involves acetylation, not methylation - While hydrazine compounds can be hepatotoxic, methylhydrazine is not relevant to INH toxicity *None of the options* - This is incorrect as acetylhydrazine (listed as "INH acetylhydrazine") is indeed the primary toxic metabolite responsible for hepatotoxicity

Q: What are the active ingredients in Savlon antiseptic?

Cetrimide + Chlorhexidine. ***Cetrimide + Chlorhexidine*** - Savlon antiseptic liquid contains **cetrimide (0.5%)** and **chlorhexidine gluconate (0.1%)** as its active ingredients - This combination provides **broad-spectrum antiseptic activity** with complementary mechanisms - **Cetrimide** acts as a quaternary ammonium compound with surfactant and detergent properties, disrupting bacterial cell membranes - **Chlorhexidine** provides prolonged antimicrobial action by binding to bacterial cell walls and disrupting membrane integrity - This is the **standard formulation** used in Savlon antiseptic liquid *Cetrimide + Chlorhexidine + butyl alcohol* - While cetrimide and chlorhexidine are the active ingredients, **butyl alcohol is not listed as a primary active antiseptic ingredient** in standard Savlon formulation - Butyl alcohol may be present as a **solvent or excipient** but not as an active antiseptic agent *Cetrimide + butyl alcohol* - This combination **omits chlorhexidine**, which is a crucial component for Savlon's antiseptic efficacy - Butyl alcohol is not an active antiseptic ingredient in Savlon *Cetrimide + Cetavlon* - **Cetavlon is a trade name** for preparations containing cetrimide itself, not a separate active ingredient - This option represents a **redundancy** as it essentially lists cetrimide twice under different names

Q: Typhoid is treated by all except

Erythromycin. ***Erythromycin*** - **Erythromycin** is a macrolide antibiotic primarily effective against Gram-positive bacteria and atypical bacteria. - It has **NO role** in the treatment of typhoid fever as it lacks adequate activity against *Salmonella typhi* and does not achieve therapeutic intracellular concentrations. - Unlike azithromycin (another macrolide), erythromycin has poor intracellular penetration and is **never used** for typhoid. *Ceftriaxone* - **Ceftriaxone** is a third-generation cephalosporin that is highly effective against *Salmonella typhi*. - It is a **first-line treatment** for severe typhoid fever and is preferred in regions with fluoroquinolone resistance. - Dosage: 2-4 g IV daily for 10-14 days. *Amikacin* - **Amikacin** is an aminoglycoside with generally poor intracellular penetration, making it suboptimal for treating intracellular pathogens. - While **not a standard agent** for typhoid, it has been used in **rare cases of extensively drug-resistant (XDR) typhoid** as part of combination therapy, particularly in outbreaks where other options have failed. - It is **not a recommended first-line or routine agent** due to limited efficacy, potential toxicity (nephrotoxicity and ototoxicity), and availability of better alternatives. *Ciprofloxacin* - **Ciprofloxacin** is a fluoroquinolone with excellent intracellular penetration and was historically the **first-line oral treatment** for uncomplicated typhoid fever. - Its efficacy against *Salmonella typhi* made it the preferred agent for decades. - However, widespread **fluoroquinolone resistance** has emerged in South Asia, limiting its current use as empirical first-line therapy in many regions.

Q: Which antifungal can be used orally but not intravenously?

Griseofulvin. ***Griseofulvin*** - **Griseofulvin** is an oral antifungal agent primarily used for dermatophyte infections [2], and it is **not available** or administered intravenously. - Its mechanism involves binding to **keratin** in newly forming skin, hair, and nails, preventing fungal invasion. *Voriconazole* - **Voriconazole** is a broad-spectrum triazole antifungal that is available in both **oral and intravenous** formulations [1]. - It is often used for invasive aspergillosis and other serious fungal infections [2]. *Amphotericin B* - **Amphotericin B** is a potent antifungal agent administered **intravenously** for severe systemic fungal infections [2]. - It has **poor oral bioavailability** and is not absorbed from the gastrointestinal tract, making it unsuitable for oral systemic therapy. - Oral formulations exist only for **local treatment** of GI candidiasis, not for systemic infections. *None of the options* - This option is incorrect because **griseofulvin** fits the description of being an antifungal that can be used orally but not intravenously.

Q: Which of the following cephalosporins is most commonly associated with drug-induced thrombocytopenia?

Cefoperazone. ***Cefoperazone*** - **Cefoperazone** is most commonly associated with drug-induced thrombocytopenia among the listed cephalosporins. - It contains the **N-methylthiotetrazole (NMTT) side chain**, which is associated with two major hematological complications: - **Hypoprothrombinemia** due to interference with vitamin K metabolism (leading to bleeding) - **Immune-mediated thrombocytopenia** where the drug acts as a hapten, inducing antibody formation against platelets - Other cephalosporins with NMTT side chains (cefamandole, cefotetan, moxalactam) share similar risks. - The dual mechanism of both coagulation factor depletion and platelet destruction makes cefoperazone particularly notable for hematological adverse effects. *Ceftazidime* - **Ceftazidime** is a third-generation cephalosporin that can rarely cause thrombocytopenia through immune-mediated mechanisms. - However, the incidence is **lower compared to cefoperazone** and it lacks the NMTT side chain. - Reports exist but it is not the "most commonly associated" among cephalosporins. *Cefixime* - **Cefixime** is an oral third-generation cephalosporin with a **very low risk** of hematological side effects. - Reports of cefixime-induced thrombocytopenia are **exceedingly rare** and not commonly cited in pharmacology literature. *Cefdinir* - **Cefdinir** is an oral third-generation cephalosporin used for common bacterial infections. - Like cefixime, reports of **cefdinir-induced thrombocytopenia** are extremely rare and not a recognized common adverse effect.

Q: What is the drug of choice for MRSA infection?

Vancomycin. ***Vancomycin*** - **Vancomycin** is the **drug of choice** for **methicillin-resistant Staphylococcus aureus (MRSA)** infections due to its activity against the resistant strain. - It works by inhibiting cell wall synthesis, targeting the **D-Ala-D-Ala** precursor in peptidoglycan. *Ciprofloxacin* - **Ciprofloxacin** is a **fluoroquinolone antibiotic** that is generally ineffective against **MRSA**. - MRSA strains are typically **resistant to ciprofloxacin** and other fluoroquinolones. *Oxacillin* - **Oxacillin** is a **beta-lactam antibiotic** in the penicillin family, specifically used for **methicillin-sensitive Staphylococcus aureus (MSSA)** infections. - It is **ineffective against MRSA** because MRSA possesses the *mecA* gene, encoding an altered penicillin-binding protein (PBP2a) that renders beta-lactams inactive. *Clindamycin* - **Clindamycin** can be used for **MRSA infections**, but it is generally reserved for **milder localized infections** or in specific cases based on susceptibility testing. - Its use often requires **D-test** to rule out **inducible clindamycin resistance**, which can lead to treatment failure.

Q: Which of the following can prolong QT interval?

Gatifloxacin. ***Gatifloxacin*** - This **fluoroquinolone antibiotic** is known to cause **significant QT prolongation**, which can lead to serious cardiac arrhythmias like **Torsades de Pointes** [1]. - Among fluoroquinolones, gatifloxacin carries the **highest risk** of QT interval prolongation. - Its use has been **withdrawn or restricted** in many countries due to these **serious cardiac side effects** and dysglycemia, especially in patients with pre-existing cardiac conditions. - This is the **best answer** as it has the most clinically significant association with QT prolongation. *Nalidixic acid* - This is a **first-generation quinolone** primarily used for **urinary tract infections**. - While it can theoretically prolong QT interval, the **clinical significance is much lower** compared to fluoroquinolones. - It is **rarely implicated** in clinically significant QT prolongation in practice. *Ofloxacin* - Ofloxacin is a **second-generation fluoroquinolone** with a **moderate risk** of QT prolongation. - All fluoroquinolones carry a **class warning** for QT effects, but ofloxacin has **significantly lower risk** compared to gatifloxacin, moxifloxacin, and sparfloxacin. - It is considered **relatively safer** within the fluoroquinolone class for cardiac effects. *Pefloxacin* - Pefloxacin is another **second-generation fluoroquinolone** with **moderate QT prolongation potential**. - Like ofloxacin, it has a **comparatively lower risk** than gatifloxacin. - The **clinical incidence** of significant QT prolongation is **much less** than with newer fluoroquinolones.

Q: Colistin is obtained from ?

Bacteria. ***Bacteria*** - Colistin, also known as **polymyxin E**, is an antibiotic derived from the bacterium **Bacillus polymyxa subspecies colistinus** (now reclassified as *Paenibacillus polymyxa*). - It works by disrupting the **outer membrane** of Gram-negative bacteria, making it effective against multi-drug resistant strains. - While actinomycetes are also bacteria, in pharmacology, antibiotics from **Bacillus species** are categorized separately from actinomycete-derived drugs. *Fungi* - Many common antibiotics, such as **penicillin** and **cephalosporins**, are derived from fungi (e.g., *Penicillium*, *Cephalosporium*), but colistin is not one of them. - Fungal-derived antibiotics typically target bacterial **cell wall synthesis** or **protein synthesis**. *Actinomycetes* - **Actinomycetes**, particularly from the *Streptomyces* genus, are a rich source of antibiotics, including **streptomycin**, **tetracyclines**, and **erythromycin**. - While actinomycetes are technically bacteria, they are classified separately in pharmacology due to their unique characteristics and prolific antibiotic production. - Colistin is specifically produced by **Bacillus species**, not actinomycetes. *Herbs* - Herbs are used for traditional medicine and can have various therapeutic properties, but they do **not produce antibiotics** like colistin. - While some plant-derived compounds have antimicrobial activity, colistin is a product of **microbial fermentation**.

Q: Which of the following drugs is not recommended for the treatment of P. falciparum malaria?

Ciprofloxacin. ***Ciprofloxacin*** - **Ciprofloxacin** is an antibiotic that is not effective against **Plasmodium falciparum** and is therefore not used in the treatment of malaria. - While it targets bacterial infections, it lacks the necessary antimalarial activity to clear the parasitic infection. *Quinine* - **Quinine** is an **oral antimalarial drug** that is effective against **P. falciparum**, especially in cases of multidrug resistance. - It works by inhibiting the parasite's ability to detoxify heme, leading to oxidative stress. *Artemether* - **Artemether** is an **artemisinin derivative**, a class of drugs that are highly effective and are the **first-line agents** for treating uncomplicated **P. falciparum malaria**. - It rapidly reduces parasite biomass, particularly in combination with drugs like lumefantrine. *Doxycycline* - **Doxycycline** is a **tetracycline antibiotic** that can be used as an alternative or adjunctive treatment for **P. falciparum malaria**, particularly in areas with resistance to other antimalarials. - It functions by inhibiting protein synthesis in the parasite and is commonly used for both treatment and prophylaxis.

Q: Anti-HIV drug used for prevention of vertical transmission?

Nevirapine. ***Nevirapine*** - **Nevirapine** is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was historically used in resource-limited settings for the prevention of **mother-to-child transmission (MTCT)** of HIV. - A single dose of **nevirapine** given to the mother during labor and to the neonate within 72 hours of birth was shown to significantly reduce the risk of **vertical transmission** (HIVNET 012 trial) [1]. - **Historical significance**: This was a landmark approach in the early 2000s when resources were limited. - **Current practice note**: Modern guidelines (WHO, 2023+) now recommend **combination antiretroviral therapy (cART)** for all pregnant women with HIV, rather than single-dose nevirapine, due to superior efficacy and reduced resistance risk [1]. *Lamivudine* - **Lamivudine** is a nucleoside reverse transcriptase inhibitor (NRTI) that is **part of current combination therapy regimens** for prevention of mother-to-child transmission. - It is not used alone but is a component of **cART regimens** recommended in modern PMTCT protocols. - In the historical context of this question, it was not the single-agent answer being sought. *Efavirenz* - **Efavirenz** is an NNRTI now used in HIV treatment regimens for pregnant women in current PMTCT protocols. - Previous concerns about first-trimester teratogenicity have been re-evaluated, and it is included in WHO-recommended regimens [1]. - However, in the context of single-drug prophylaxis (historical approach), nevirapine was preferred. *Tenofovir* - **Tenofovir** is a nucleotide reverse transcriptase inhibitor (NtRTI) and is the **backbone of current first-line cART regimens** for pregnant women with HIV. - It is highly effective as part of combination therapy for PMTCT. - It was not used as a single-dose prophylactic agent in the historical context of this question.

Question 1

Which compound is primarily responsible for the hepatotoxicity associated with Isoniazid (INH)?

Accepted Answer

INH acetylhydrazine

Answer

INH sulfhydrazine

Answer

INH methylhydrazine

Answer

None of the options

Question 2

What are the active ingredients in Savlon antiseptic?

Accepted Answer

Cetrimide + Chlorhexidine

Answer

Cetrimide + Chlorhexidine + butyl alcohol

Answer

Cetrimide + butyl alcohol

Answer

Cetrimide + Cetavlon

Question 3

Typhoid is treated by all except

Accepted Answer

Erythromycin

Answer

Amikacin

Answer

Ciprofloxacin

Answer

Ceftriaxone

Question 4

Which antifungal can be used orally but not intravenously?

Accepted Answer

Griseofulvin

Answer

Voriconazole

Answer

Amphotericin B

Answer

None of the options

Question 5

Which of the following cephalosporins is most commonly associated with drug-induced thrombocytopenia?

Accepted Answer

Cefoperazone

Answer

Cefixime

Answer

Ceftazidime

Answer

Cefdinir

Question 6

What is the drug of choice for MRSA infection?

Accepted Answer

Vancomycin

Answer

Ciprofloxacin

Answer

Oxacillin

Answer

Clindamycin

Question 7

Which of the following can prolong QT interval?

Accepted Answer

Gatifloxacin

Answer

Nalidixic acid

Answer

Pefloxacin

Answer

Ofloxacin

Question 8

Colistin is obtained from ?

Accepted Answer

Bacteria

Answer

Fungi

Answer

Herbs

Answer

Actinomycetes

Question 9

Which of the following drugs is not recommended for the treatment of P. falciparum malaria?

Accepted Answer

Ciprofloxacin

Answer

Artemether

Answer

Doxycycline

Answer

Quinine

Question 10

Anti-HIV drug used for prevention of vertical transmission?

Accepted Answer

Nevirapine

Answer

Lamivudine

Answer

Efavirenz

Answer

Tenofovir

Antimicrobial Agents — MCQs

Antimicrobial Agents — MCQs

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