Batch A (18/03/26)

1) Explain antimicrobial resistance with examples

1. Intrinsic (natural) resistance
   • Inherent property of organism.
   • Example: Mycoplasma is resistant to beta lactams (no cell wall).
2. Acquired resistance
   • Develops by mutation or gene transfer (plasmids, transposons, integrons).
   • Example: MRSA acquiring mecA gene.
3. Cross resistance
   • Resistance to related drugs in same class.
   • Example: macrolide resistance causing reduced response to erythromycin, azithromycin.
4. Multidrug resistance (MDR)
   • Resistance to multiple antimicrobial classes.
   • Example: MDR-TB.

• Enzymatic inactivation: beta-lactamases (ESBL, carbapenemases) destroy beta-lactam drugs.
• Altered target site: PBP2a in MRSA; altered ribosome for macrolides.
• Reduced permeability: porin loss in gram-negative bacilli.
• Efflux pumps: tetracycline resistance.
• Bypass pathways: altered folate pathway reducing sulfonamide/trimethoprim effect.
• Biofilm formation: protects bacteria from antibiotics and host defenses.

• MRSA resistant to methicillin/most beta lactams.
• VRE (Enterococcus faecium) resistant to vancomycin.
• ESBL-producing E. coli/Klebsiella resistant to 3rd generation cephalosporins.
• Carbapenem-resistant Enterobacterales (CRE).
• MDR/XDR-TB resistant to isoniazid + rifampicin (and more drugs in XDR).

• Inappropriate prescriptions, wrong dose/duration, poor adherence.
• OTC/self-medication, use in livestock, poor infection control.
• Substandard drugs and inadequate diagnostics.

• Antimicrobial stewardship, culture-guided therapy, narrow spectrum use.
• Vaccination, hand hygiene, infection control, surveillance.

2) Write a note on 3rd generation cephalosporins

• Parenteral: cefotaxime, ceftriaxone, ceftazidime, cefoperazone.
• Oral: cefixime, cefpodoxime proxetil, ceftibuten, cefdinir.

• Good against Enterobacteriaceae, H. influenzae, Neisseria.
• Less gram-positive coverage than 1st generation.
• Ceftazidime active against Pseudomonas aeruginosa.
• Not active against MRSA, Enterococcus, Listeria.

• Good tissue penetration; many cross BBB when meninges inflamed (ceftriaxone, cefotaxime, ceftazidime).
• Mostly renal excretion; ceftriaxone has significant biliary excretion and long half-life (once daily possible).

• Community and hospital-acquired severe infections.
• Meningitis (ceftriaxone/cefotaxime ± vancomycin).
• Gonorrhea (ceftriaxone is drug of choice).
• Enteric fever, complicated UTI, sepsis, pneumonia.
• Pseudomonas infections (ceftazidime, cefoperazone).

• Hypersensitivity reactions, diarrhea, C. difficile colitis.
• Biliary sludging/pseudolithiasis with ceftriaxone.
• Bleeding tendency and disulfiram-like reaction with cefoperazone (NMTT side chain related).
• Superinfection with prolonged use.

3) Write a note on cotrimoxazole: composition, mechanism, uses

• Fixed-dose combination of sulfamethoxazole + trimethoprim in 5:1 ratio.
• This gives plasma ratio around 20:1, optimal for synergy.

1. Sulfamethoxazole inhibits dihydropteroate synthase (blocks folic acid synthesis).
2. Trimethoprim inhibits dihydrofolate reductase.

• Combined action is usually bactericidal (each alone mostly bacteriostatic).

• Many gram-positive and gram-negative bacteria, Nocardia, Stenotrophomonas maltophilia, Pneumocystis jirovecii.
• Resistance common in some regions/pathogens.

• UTI and prostatitis (if susceptible).
• Respiratory infections (selected cases).
• Pneumocystis jirovecii pneumonia treatment and prophylaxis (HIV/immunocompromised).
• Nocardiosis.
• Shigellosis, some GI infections.
• Community-acquired MRSA skin infections (where local susceptibility supports use).

• Nausea, vomiting, rash, photosensitivity.
• Severe hypersensitivity: SJS/TEN.
• Bone marrow suppression: megaloblastic anemia, leukopenia, thrombocytopenia.
• Hemolysis in G6PD deficiency.
• Hyperkalemia (trimethoprim), crystalluria/interstitial nephritis (rare).

• Pregnancy near term, neonates (risk of kernicterus due to sulfonamide component).
• Folate deficiency, severe liver disease, severe renal impairment (dose adjustment required).

4) Classify antitubercular drugs and describe first-line drugs

1. Isoniazid (H)
2. Rifampicin (R)
3. Pyrazinamide (Z)
4. Ethambutol (E)
5. Streptomycin (S) (now less commonly first choice in many regimens)

• Fluoroquinolones: levofloxacin, moxifloxacin.
• Injectable agents: amikacin, kanamycin, capreomycin.
• Oral second-line: ethionamide/prothionamide, cycloserine, PAS.
• Newer: bedaquiline, delamanid, pretomanid, linezolid, clofazimine.

First-line drugs (brief)

• MOA: inhibits mycolic acid synthesis (cell wall), prodrug activated by KatG.
• Action: bactericidal against rapidly dividing bacilli.
• ADR: hepatitis, peripheral neuropathy (prevent with pyridoxine), lupus-like syndrome, seizures (overdose).
• Note: monitor LFTs.

• MOA: inhibits DNA-dependent RNA polymerase.
• Action: bactericidal, active intra- and extracellularly.
• ADR: hepatotoxicity, orange discoloration of body fluids, flu-like syndrome.
• Important: potent CYP inducer causing many drug interactions (e.g., OCPs, warfarin, ART).

• MOA: prodrug; active in acidic pH, disrupts membrane energetics and transport.
• Role: sterilizing action in macrophages/caseous lesions; shortens therapy.
• ADR: hepatotoxicity, hyperuricemia, arthralgia.

• MOA: inhibits arabinosyl transferase, impairing cell wall arabinogalactan synthesis.
• Action: bacteriostatic.
• ADR: optic neuritis (decreased visual acuity, red-green color blindness), hyperuricemia.
• Note: monitor vision regularly.

• MOA: aminoglycoside; inhibits 30S ribosomal function.
• Use: now limited; used in specific situations.
• ADR: ototoxicity, nephrotoxicity, neuromuscular blockade; parenteral use only.

• Intensive phase: 2 months HRZE
• Continuation phase: 4 months HR
  (Program and country guidelines may vary)

Batch B (19/03/26)

1) Discuss chemoprophylaxis for surgical site infection: principles and examples

1. Indication based on wound class/risk
   • Clean surgery usually no prophylaxis, except prosthesis/implant/cardiac/neurosurgery.
   • Clean-contaminated and contaminated procedures usually need prophylaxis.
2. Choose drug by expected flora
   • Skin flora: Staphylococcus aureus, streptococci.
   • GI/gynecologic: gram negatives + anaerobes.
3. Correct timing
   • Give IV antibiotic within 60 min before incision.
   • Vancomycin/fluoroquinolones: start within 120 min (long infusion time).
4. Adequate dose and redosing
   • Weight-based dosing when needed.
   • Redose if long surgery (>2 half-lives) or major blood loss.
5. Shortest duration
   • Usually single pre-op dose or <24 hours post-op.
   • Prolonged postoperative use gives no extra benefit and increases resistance/C. difficile.
6. Source control and asepsis remain essential
   • Hair clipping, skin antisepsis, glycemic control, normothermia, oxygenation.

• Cefazolin: first choice for many clean procedures (orthopedic, cardiac, general surgery).
• Colorectal surgery: cefazolin + metronidazole, or cefoxitin/cefotetan, or ampicillin-sulbactam.
• Cesarean section: cefazolin before skin incision.
• Beta-lactam allergy: clindamycin or vancomycin ± gentamicin/aztreonam/metronidazole depending on site.
• MRSA colonization/high risk: add vancomycin (not routine monotherapy for all).

2) Short note on artemisinin-based combination therapy (ACT)

• Artemisinin rapidly reduces parasite biomass.
• Partner drug clears residual parasites and prevents recrudescence.
• Combination delays resistance development.

• Artemether-lumefantrine
• Artesunate-amodiaquine
• Artesunate-mefloquine
• Dihydroartemisinin-piperaquine
• Artesunate-sulfadoxine-pyrimethamine (only where SP still effective)

• Use 3-day regimen with full adherence.
• Confirm diagnosis where possible (smear/RDT).
• Add single low-dose primaquine in many settings to reduce transmission (avoid in contraindications).
• For severe malaria: IV artesunate first, then complete oral ACT.

• High cure rates, rapid fever and parasite clearance.
• Reduces gametocyte carriage and transmission.
• Better resistance control than monotherapy.

• Emerging artemisinin partial resistance in some regions.
• Partner drug resistance can compromise efficacy.
• Must avoid artemisinin monotherapy.

• Usually mild: nausea, dizziness, headache.
• Drug-specific effects: QT prolongation (some regimens), neuropsychiatric effects with mefloquine partner.

3) Classify penicillins and write briefly about extended spectrum penicillin

Classification of penicillins

1. Natural penicillins
   • Penicillin G (aqueous, procaine, benzathine)
   • Penicillin V
2. Penicillinase-resistant (anti-staphylococcal)
   • Cloxacillin, dicloxacillin, nafcillin, oxacillin
3. Aminopenicillins (extended spectrum)
   • Ampicillin, amoxicillin
4. Antipseudomonal penicillins (extended spectrum)
   • Carboxypenicillins: ticarcillin
   • Ureidopenicillins: piperacillin, mezlocillin
5. Beta-lactam/beta-lactamase inhibitor combinations
   • Amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam

Extended-spectrum penicillins (brief)

• Aminopenicillins: ampicillin, amoxicillin
• Antipseudomonal: piperacillin, ticarcillin

• Broader than natural penicillins.
• Better gram-negative coverage (E. coli, H. influenzae, Proteus).
• Piperacillin/ticarcillin active against Pseudomonas.
• Still susceptible to beta-lactamases, so often combined with inhibitors.

• ENT/respiratory/UTI infections (amoxicillin/ampicillin, depending on susceptibility).
• Enterococcal infections (ampicillin often useful).
• Severe hospital infections, intra-abdominal sepsis, febrile neutropenia (piperacillin-tazobactam).

• Hypersensitivity reactions.
• Diarrhea, rash (ampicillin rash more common in EBV).
• Electrolyte load and platelet dysfunction with some antipseudomonal agents.

4) Short note on tetracyclines: uses and adverse effects

• Tetracycline, doxycycline, minocycline (common)
• Tigecycline is related (glycylcycline)

• Bind 30S ribosomal subunit and block aminoacyl-tRNA attachment.
• Bacteriostatic, broad spectrum.

• Rickettsial infections (RMSF, typhus): doxycycline drug of choice.
• Chlamydial infections (urethritis, cervicitis, PID components).
• Atypical pneumonia (Mycoplasma, Chlamydophila).
• Cholera, brucellosis (in combinations), plague.
• Acne vulgaris, rosacea.
• Malaria prophylaxis/treatment adjunct (doxycycline).
• CA-MRSA skin infections in some settings.
• H. pylori regimens (tetracycline-containing bismuth quadruple therapy).

• GI irritation, esophagitis (especially doxycycline if taken without water).
• Photosensitivity.
• Tooth discoloration and enamel hypoplasia in children.
• Inhibition of bone growth in fetus/young child.
• Hepatotoxicity (high doses/pregnancy risk), vestibular toxicity (minocycline).
• Superinfection (Candida, C. difficile).

• Pregnancy, breastfeeding (relative), children <8 years (except specific serious indications like rickettsial disease where benefits outweigh risks).
• Avoid coadministration with milk, iron, antacids (chelation reduces absorption).