Antimicrobial drugs

In short

Antimicrobial drugs are agents that kill (microbicidal) or inhibit (microbiostatic) bacteria, fungi, viruses, protozoa and helminths with reasonable selectivity for the pathogen over human cells. They are the largest single block in the B.Pharm Pharmacology syllabus (PCI/AICTE-aligned Pharmacology III) and dominate university long questions, GPAT and NIPER entrance papers, and technical rounds for medical-representative, pharmacovigilance, medical-affairs and clinical-research roles at Cipla, Sun Pharma, Dr Reddy's, Alkem, Macleods and Abbott India. Practical relevance is high: India carries a large tuberculosis and resistant-Gram-negative burden, antimicrobials are sold under Schedule H/H1 of the Drugs and Cosmetics Rules, 1945, and dispensing pharmacists are front-line to antimicrobial stewardship. Examiners test mechanism, spectrum, resistance mechanisms, adverse effects, drug interactions and the national programme regimens.

Explained

Core principles of antimicrobial chemotherapy

• Selective toxicity (Ehrlich): the drug exploits a target absent or different in humans - bacterial cell wall (peptidoglycan), 70S ribosome, folate synthesis de novo, DNA gyrase.
• Bacteriostatic (sulfonamides, tetracyclines, chloramphenicol, macrolides, ethambutol, clindamycin, linezolid) vs bactericidal (beta-lactams, aminoglycosides, fluoroquinolones, vancomycin, rifampicin, isoniazid, metronidazole, cotrimoxazole combination). Static drugs need an intact host immune system; cidal drugs are mandatory in endocarditis, meningitis, neutropenia.
• MIC - lowest concentration preventing visible growth; MBC - lowest concentration killing 99.9% of inoculum. MBC/MIC ≤ 4 means cidal; a large ratio indicates tolerance.
• Killing kinetics: *concentration-dependent* (aminoglycosides, fluoroquinolones, metronidazole) - maximise Cmax/MIC and AUC/MIC, give once-daily large doses; *time-dependent* (beta-lactams, vancomycin, macrolides, linezolid) - maximise the time above MIC, give frequent or extended infusions.
• Post-antibiotic effect (PAE): persistent suppression after the drug falls below MIC - long for aminoglycosides and fluoroquinolones, which justifies once-daily aminoglycoside dosing (also less nephrotoxic because uptake into tubular cells is saturable).
• Spectrum: narrow (penicillin G, isoniazid), broad (tetracyclines, chloramphenicol, third-generation cephalosporins, carbapenems). Broad-spectrum use risks superinfection - oral/vaginal candidiasis, *Clostridioides difficile* pseudomembranous colitis (clindamycin, cephalosporins, fluoroquinolones).
• Why combine: mixed infections (intra-abdominal sepsis), to prevent resistance (TB, HIV, *H. pylori*), synergy (beta-lactam + aminoglycoside in enterococcal endocarditis; sulfamethoxazole + trimethoprim sequential blockade; amoxicillin + clavulanic acid - inhibitor protection), empirical therapy in life-threatening sepsis, and to reduce dose-related toxicity.
• Antagonism: a static drug that stops growth blunts a cidal drug needing active growth (classic example - tetracycline or chloramphenicol with penicillin).
• Chemoprophylaxis: rheumatic fever (benzathine penicillin), surgical prophylaxis (single IV cefazolin/cefuroxime 30-60 min before incision), meningococcal contacts (rifampicin/ciprofloxacin), malaria travel prophylaxis, PCP prophylaxis with cotrimoxazole.

Cell-wall inhibitors (beta-lactams and others)

• Mechanism: beta-lactams acylate the serine site of transpeptidases (penicillin-binding proteins), blocking peptidoglycan cross-linking; autolysins then lyse the cell. Hence cidal and effective only on growing cells; ineffective against mycoplasma (no cell wall) and intracellular/dormant organisms.
• Penicillins: natural (penicillin G - IV/IM, acid-labile; penicillin V - oral; benzathine/procaine depot forms) for streptococci, meningococci, syphilis, diphtheria carriers; penicillinase-resistant (methicillin - now only a laboratory marker, cloxacillin, dicloxacillin, nafcillin) for staphylococci; extended-spectrum aminopenicillins (ampicillin, amoxicillin - better oral absorption) adding *E. coli*, *H. influenzae*, enterococci, *Listeria*; antipseudomonal (piperacillin, ticarcillin, carbenicillin), used as piperacillin-tazobactam.
• Beta-lactamase inhibitors: clavulanic acid, sulbactam, tazobactam (suicide inhibitors); newer avibactam and relebactam (diazabicyclooctanes) cover KPC and OXA-48. Ceftazidime-avibactam and the Indian-developed ceftriaxone-sulbactam-EDTA and cefepime-zidebactam are marketed for resistant Gram-negatives.
• Cephalosporins by generation: 1st (cefazolin, cephalexin) - Gram-positive, surgical prophylaxis; 2nd (cefuroxime, cefaclor; cefoxitin covers anaerobes) - more Gram-negative; 3rd (ceftriaxone, cefotaxime, ceftazidime, oral cefixime, cefpodoxime) - high Gram-negative activity, CSF penetration, ceftazidime covers *Pseudomonas*; 4th (cefepime) - stable to many beta-lactamases, covers both; 5th (ceftaroline) - MRSA-active. Trend across generations: Gram-positive cover falls, Gram-negative cover and beta-lactamase stability rise.
• Carbapenems (imipenem-cilastatin, meropenem, ertapenem, doripenem): widest spectrum - Gram-positive, Gram-negative, anaerobes, ESBL producers; not MRSA or *Stenotrophomonas*; ertapenem spares *Pseudomonas* and *Acinetobacter*. Cilastatin blocks renal dehydropeptidase-I. Imipenem lowers the seizure threshold; carbapenems are reserve/"watch-and-reserve" drugs.
• Monobactam aztreonam: Gram-negative aerobes only; safe in true penicillin anaphylaxis (no cross-reactivity).
• Non-beta-lactam wall inhibitors: vancomycin/teicoplanin bind the D-Ala-D-Ala terminus of the pentapeptide (MRSA, *C. difficile* orally, blind therapy of Gram-positive sepsis) - infusion-related "red man syndrome" from histamine release, nephro/ototoxicity; resistance by D-Ala-D-Lac substitution (VRE, *vanA*). Bacitracin (topical), cycloserine (antitubercular, blocks alanine racemase), fosfomycin (blocks MurA/enolpyruvate transferase; single-dose oral for uncomplicated UTI), daptomycin (lipopeptide - depolarises the membrane; inactivated by pulmonary surfactant so not used in pneumonia; raises CPK).
• Cross-allergy: 1-3% cross-reactivity between penicillins and cephalosporins (highest with first-generation sharing side-chains); penicillin is the commonest cause of drug anaphylaxis.

Protein-synthesis and nucleic-acid inhibitors

• Aminoglycosides (streptomycin, gentamicin, amikacin, tobramycin, netilmicin, neomycin topical/oral): bind 30S, cause misreading and block translocation; cidal, concentration-dependent, need oxygen-dependent uptake so inactive against anaerobes and in abscesses; not absorbed orally. Toxicities - ototoxicity (cochlear with amikacin/neomycin, vestibular with streptomycin/gentamicin), nephrotoxicity (reversible tubular), neuromuscular blockade (avoid with curare, caution in myasthenia). Resistance mainly by plasmid-coded acetyl/phospho/adenylyl transferases; amikacin resists most.
• Tetracyclines (tetracycline, doxycycline, minocycline; glycylcycline tigecycline): bind 30S A-site, static, broad - rickettsia, chlamydia, *Mycoplasma*, cholera, brucellosis, plague, scrub typhus, acne, *H. pylori* regimens. Chelate calcium - teeth staining and enamel hypoplasia, so avoided under 8 years and in pregnancy; photosensitivity; dose-related hepatic/renal effects (doxycycline is safest in renal failure as it is eliminated in faeces); absorption reduced by milk, antacids, iron.
• Chloramphenicol: 50S peptidyl transferase inhibitor; reserved because of dose-dependent reversible marrow suppression and idiosyncratic irreversible aplastic anaemia, plus grey baby syndrome in neonates (immature glucuronidation); CYP inhibitor.
• Macrolides (erythromycin, azithromycin, clarithromycin, roxithromycin): bind 50S, block translocation; used for atypical pneumonia, pertussis, diphtheria, *Campylobacter*, chlamydia (single-dose azithromycin 1 g), and as penicillin substitutes. Erythromycin and clarithromycin are CYP3A4 inhibitors (raise statins, warfarin, theophylline, carbamazepine); all can prolong QT. Azithromycin has a very long tissue half-life, allowing 3-5 day courses.
• Lincosamide clindamycin: anaerobes, Gram-positive, osteomyelitis, toxin suppression in necrotising fasciitis; notorious for *C. difficile* colitis.
• Oxazolidinones (linezolid, newer tedizolid): bind the 50S 23S rRNA and block initiation - MRSA, VRE, and MDR-TB; thrombocytopenia, peripheral/optic neuropathy, serotonin syndrome risk with SSRIs (weak MAO inhibition). Streptogramins, mupirocin (topical, inhibits isoleucyl-tRNA synthetase for nasal MRSA decolonisation).
• Fluoroquinolones: inhibit DNA gyrase (topoisomerase II) in Gram-negatives and topoisomerase IV in Gram-positives. Generations: norfloxacin (urinary/GI), ciprofloxacin (best antipseudomonal of the class), ofloxacin/levofloxacin and moxifloxacin ("respiratory" quinolones covering pneumococcus and atypicals; moxifloxacin lacks urinary activity and is a second-line antitubercular). Adverse effects - tendinitis and Achilles rupture, arthropathy in the young (so avoided in children and pregnancy except for specific indications), QT prolongation, dysglycaemia, aortic aneurysm risk, CNS effects, phototoxicity; absorption cut by antacids, iron, calcium, zinc.
• Antifolates: sulfonamides compete with PABA for dihydropteroate synthase; trimethoprim inhibits bacterial dihydrofolate reductase - sequential blockade gives the synergistic cidal cotrimoxazole, used for PCP (treatment and prophylaxis), nocardiosis, *Stenotrophomonas*, UTI. Adverse - hypersensitivity and Stevens-Johnson syndrome, crystalluria, kernicterus in neonates, hyperkalaemia, marrow suppression, haemolysis in G6PD deficiency.
• Nitroimidazoles (metronidazole, tinidazole, ornidazole, secnidazole): reduced by ferredoxin in anaerobes/protozoa to reactive nitro radicals that fragment DNA - amoebiasis, giardiasis, trichomoniasis, anaerobic sepsis, *H. pylori*, *C. difficile*. Metallic taste, disulfiram-like reaction with alcohol, peripheral neuropathy on long use.
• Nitrofurantoin: concentrates in urine, for uncomplicated lower UTI; avoid in renal failure and G6PD deficiency.

Antitubercular, antileprotic and antifungal drugs

• First-line antitubercular (HRZE): Isoniazid - inhibits InhA/mycolic acid synthesis via KatG activation; peripheral neuropathy prevented by pyridoxine 10-25 mg; hepatitis, acetylator polymorphism, SLE-like syndrome. Rifampicin - inhibits DNA-dependent RNA polymerase (rpoB); orange-red urine/secretions, hepatitis, and a powerful CYP enzyme inducer that fails oral contraceptives, warfarin, protease inhibitors and antiepileptics. Pyrazinamide - active in acidic intracellular pH; hyperuricaemia and hepatotoxicity. Ethambutol - inhibits arabinosyl transferase; dose-related optic neuritis with loss of red-green discrimination.
• Second-line/MDR drugs: levofloxacin, moxifloxacin, bedaquiline (ATP synthase inhibitor; QT prolongation), delamanid/pretomanid (nitroimidazoles), linezolid, clofazimine, cycloserine, amikacin, para-aminosalicylic acid, ethionamide.
• Indian practice: the National TB Elimination Programme (NTEP), renamed from RNTCP in 2020, supplies daily fixed-dose combinations by weight band - intensive phase 2 months HRZE then continuation 4 months HRE, with Ni-kshay for notification and Ni-kshay Poshan Yojana nutrition support. Shorter all-oral regimens (BPaLM-type) for drug-resistant TB are being rolled out; exact regimen and duration follow current NTEP guidelines, which are revised periodically.
• Antileprosy: WHO/NLEP multidrug therapy - rifampicin + dapsone (paucibacillary, 6 months) with clofazimine added for multibacillary (12 months); dapsone is a folate antagonist causing haemolysis in G6PD deficiency and methaemoglobinaemia; clofazimine discolours skin reddish-black.
• Antifungals: polyenes amphotericin B (binds ergosterol, forms pores; infusion reaction, dose-limiting nephrotoxicity and hypokalaemia - liposomal forms are less toxic) and nystatin (topical/oral thrush); azoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole; topical clotrimazole, ketoconazole) inhibit fungal CYP450 14-alpha-demethylase, blocking ergosterol synthesis - many drug interactions and QT effects; echinocandins (caspofungin, micafungin, anidulafungin) inhibit beta-1,3-glucan synthase - "penicillin of antifungals", for candidaemia; griseofulvin (disrupts microtubules, for dermatophytes of hair/nail), terbinafine (squalene epoxidase inhibitor), flucytosine (converted to 5-FU, with amphotericin in cryptococcal meningitis). India's 2021 COVID-associated mucormycosis surge was treated with amphotericin B and posaconazole.
• Anthelmintics in brief: albendazole/mebendazole (bind beta-tubulin; national deworming day), ivermectin (glutamate-gated chloride channels), praziquantel, diethylcarbamazine for filariasis.

Antivirals, antimalarials and antiprotozoals

• Anti-herpes: acyclovir (valacyclovir) - activated by viral thymidine kinase to a triphosphate that inhibits viral DNA polymerase and chain-terminates; ganciclovir/valganciclovir for CMV (marrow suppression); foscarnet, cidofovir for resistant strains.
• Anti-influenza: oseltamivir and zanamivir are neuraminidase inhibitors blocking release of virions; baloxavir inhibits cap-dependent endonuclease.
• Antiretrovirals by class: NRTIs (tenofovir, lamivudine, zidovudine, abacavir - chain termination after phosphorylation), NNRTIs (efavirenz, nevirapine - direct allosteric reverse transcriptase binding), protease inhibitors (lopinavir, atazanavir, ritonavir as a pharmacokinetic booster), integrase strand-transfer inhibitors (dolutegravir, raltegravir), entry inhibitor maraviroc. India's NACO first-line adult regimen is TLD - tenofovir + lamivudine + dolutegravir, single-pill daily; adherence must exceed about 95% to avoid resistance.
• Hepatitis: direct-acting antivirals sofosbuvir + daclatasvir/velpatasvir cure most hepatitis C (India is a major generic source and runs the National Viral Hepatitis Control Programme); tenofovir and entecavir suppress hepatitis B.
• Antimalarials: artemisinins (artesunate, artemether - iron-mediated free radical damage; parenteral artesunate is first-line for severe malaria), 4-aminoquinoline chloroquine (blocks haem polymerisation in the food vacuole; retinopathy on long use), primaquine/tafenoquine (hypnozoites and gametocytes; haemolysis in G6PD deficiency), mefloquine, lumefantrine, atovaquone-proguanil, quinine (cinchonism). India's NVBDCP/NCVBDC policy: ACT-SP (artesunate + sulfadoxine-pyrimethamine) for *P. falciparum* in most of the country with ACT-AL (artemether-lumefantrine) in the north-eastern states, where SP resistance is established, chloroquine plus 14-day primaquine for *P. vivax*; single low-dose primaquine as a gametocytocide.
• Antiamoebic/antikala-azar: metronidazole plus a luminal amoebicide (diloxanide furoate, paromomycin); liposomal amphotericin B single dose and miltefosine for visceral leishmaniasis under the national kala-azar elimination effort.

Resistance, stewardship and Indian regulation

• Genetic basis: chromosomal mutation (vertical) or acquired/transferable (horizontal) by conjugation (plasmids, R-factors), transduction, transformation, with transposons and integrons carrying cassettes.
• Biochemical mechanisms: (i) enzymatic inactivation - beta-lactamases, ESBL, carbapenemases (NDM-1, first reported from New Delhi isolates, KPC, OXA-48), aminoglycoside-modifying enzymes, chloramphenicol acetyltransferase; (ii) reduced permeability/porin loss; (iii) efflux pumps (tetracyclines, macrolides, quinolones); (iv) altered target - PBP2a encoded by mecA in MRSA, rpoB in rifampicin resistance, gyrA mutations, ribosomal methylation (erm); (v) alternative pathway - preformed folate use; (vi) biofilm and persister tolerance.
• Drivers in India: over-the-counter sales, incomplete courses, irrational fixed-dose combinations, antibiotic use in poultry and aquaculture, hospital-acquired infection, and pharmaceutical effluent.
• Stewardship and policy: National Programme on AMR Containment and the National Action Plan on AMR with state action plans; ICMR's annual AMR surveillance network report; NCDC National Treatment Guidelines for Antimicrobial Use; WHO AWaRe classification - Access, Watch, Reserve - used to steer prescribing; infection control and hand hygiene remain the cheapest controls.
• Legal framework: antimicrobials are prescription drugs under Schedule H, and specified ones (most third-generation cephalosporins, carbapenems, newer fluoroquinolones, antitubercular drugs) under Schedule H1 of the Drugs and Cosmetics Rules, 1945 - the retailer must keep a separate H1 register with prescriber and patient details for three years, and the label carries the red "Rx" box warning. Colistin in animal feed was banned in 2019, and the Red Line campaign marks prescription-only antimicrobials. Prices of many antibiotics are capped under the DPCO 2013 ceiling prices notified by NPPA; GST on medicines is 5% after the 22 September 2025 rate revision (some lifesaving formulations are nil-rated).

Key points

• Selective toxicity - therapeutic action depends on a target absent or different in human cells.
• MIC and MBC - MIC inhibits visible growth, MBC kills 99.9%; MBC/MIC ≤ 4 means bactericidal.
• Beta-lactams - inhibit PBP transpeptidases, blocking peptidoglycan cross-linking; cidal, time-dependent, need growing cells.
• Cephalosporin trend - Gram-positive cover decreases and Gram-negative cover plus beta-lactamase stability increase from 1st to 4th generation; 5th generation covers MRSA.
• Carbapenems - broadest spectrum, reserve class; do not cover MRSA; imipenem needs cilastatin and lowers seizure threshold.
• Vancomycin - binds D-Ala-D-Ala, for MRSA; red man syndrome on fast infusion; VRE arises by D-Ala-D-Lac change.
• Aminoglycosides - 30S misreading, oxygen-dependent uptake (useless in anaerobes/abscesses), once-daily dosing exploits concentration-dependent killing and long PAE; oto- and nephrotoxic.
• Tetracyclines - 30S static, broad; chelate calcium so contraindicated under 8 years and in pregnancy; doxycycline is safe in renal failure.
• Macrolides - 50S translocation block; erythromycin/clarithromycin inhibit CYP3A4; class prolongs QT.
• Fluoroquinolones - inhibit DNA gyrase and topoisomerase IV; tendon rupture, arthropathy, QT and glycaemic effects; chelated by antacids and iron.
• Cotrimoxazole - sequential blockade of folate synthesis makes a static pair cidal; drug of choice for *Pneumocystis jirovecii*.
• Metronidazole - activated only in anaerobes/protozoa; disulfiram-like reaction with alcohol.
• HRZE - isoniazid (mycolic acid), rifampicin (RNA polymerase, CYP inducer), pyrazinamide (acidic pH, hyperuricaemia), ethambutol (arabinosyl transferase, optic neuritis); NTEP gives daily FDCs by weight band, 2 months intensive + 4 months continuation in drug-sensitive TB.
• MDT for leprosy - rifampicin + dapsone, plus clofazimine in multibacillary disease.
• Antifungal targets - polyenes bind ergosterol, azoles block 14-alpha-demethylase, echinocandins block beta-1,3-glucan synthase, terbinafine blocks squalene epoxidase.
• Antiviral principle - most need activation by a viral or host kinase and inhibit a viral polymerase, protease, neuraminidase or integrase; India's first-line HIV regimen is TLD.
• Resistance mechanisms - enzyme inactivation, permeability loss, efflux, target alteration, bypass pathway; transferred by plasmids, transduction and transformation.
• Indian control - Schedule H1 register kept for three years, AWaRe-based stewardship, NCDC treatment guidelines, National Action Plan on AMR, DPCO price ceilings.

Formulas and examples

Example 1 - Amikacin peak and Cmax/MIC. A 60 kg adult is given amikacin 15 mg/kg = 900 mg once daily IV. Vd = 0.25 L/kg = 15 L.

• Peak concentration ≈ dose/Vd = 900/15 = 60 mg/L.
• For an isolate with MIC 4 mg/L, Cmax/MIC = 60/4 = 15 - above the target of 8-10, so a once-daily regimen is adequate.
• If a second isolate has MIC 16 mg/L, Cmax/MIC = 60/16 = 3.75 - inadequate; a different agent (for example meropenem) is needed rather than a higher, toxic dose.

Example 2 - Renal dose adjustment. Female, 68 years, 55 kg, serum creatinine 1.8 mg/dL.

• CL_cr = [(140 − 68) × 55 × 0.85] / (72 × 1.8) = (72 × 55 × 0.85)/129.6 = 3366/129.6 ≈ 26 mL/min.
• Severe renal impairment: aminoglycosides are best avoided; if essential, extend the interval (for example 48-72 hourly) with level monitoring. Doxycycline needs no adjustment (faecal elimination); nitrofurantoin is contraindicated below about 30-45 mL/min as urinary levels become subtherapeutic.

Example 3 - Maintenance dose from clearance. Target steady-state vancomycin trough-based average Css = 15 mg/L, CL = 4 L/h, IV so F = 1.

• Dose rate = 15 × 4 / 1 = 60 mg/h → 1,440 mg/day, given as 750 mg IV 12-hourly (practically 1 g 12-hourly, then adjusted by AUC/MIC monitoring).
• If AUC₀₋₂₄ = dose/CL = 1,440/4 = 360 mg·h/L and MIC = 1 mg/L, AUC/MIC = 360 - just below the ≥ 400 target, so the dose would be raised to about 1,600 mg/day.

Example 4 - NTEP weight-band FDC. An adult of 54 kg with new drug-sensitive pulmonary TB falls in the 46-55 kg band: 3 tablets daily of the four-drug FDC in the intensive phase (each tablet H 75 + R 150 + Z 400 + E 275 mg), i.e. H 225, R 450, Z 1,200, E 825 mg daily for 2 months, then 3 tablets of the three-drug HRE FDC for 4 months. Total 6 months, 168 daily doses; pyridoxine 10 mg daily accompanies isoniazid. (Bands and the role of newer shorter regimens follow the current NTEP guideline.)

Example 5 - Course cost comparison (indicative Indian retail, generic).

Carbapenem cost is roughly 20-100 times an oral course - a concrete argument for stewardship beyond resistance.

Where it is used

• Hospital pharmacy and clinical pharmacy: dose individualisation by creatinine clearance, therapeutic drug monitoring of vancomycin and amikacin, IV-to-oral switch, antibiotic policy and antimicrobial stewardship committees in AIIMS, PGIMER, CMC Vellore, Tata Memorial and large corporate chains.
• Community pharmacy and retail: Schedule H1 register upkeep, counselling on completing the course, food-drug interactions (tetracycline with milk, quinolone with antacids), refusing OTC antibiotic sales.
• Formulation and manufacturing: India is the world's largest generic antibiotic producer - penicillin and cephalosporin intermediates, dry-syrup suspensions, sterile injectables under Schedule M revised GMP (with dedicated beta-lactam blocks and cross-contamination control) and WHO-GMP/USFDA plants at Aurangabad, Baddi, Hyderabad and Goa.
• Medical representative and medical-affairs roles: mechanism, spectrum, dosing, interactions and comparative data for antibiotic, antifungal and antiretroviral brands are the standard technical interview content at Cipla, Alkem, Macleods, Mankind and Abbott India.
• Regulatory affairs, pharmacovigilance and clinical research: ADR reporting of SJS, anaphylaxis, tendon rupture and hepatotoxicity to PvPI at IPC Ghaziabad; bioequivalence studies and clinical trials under the New Drugs and Clinical Trials Rules, 2019.
• Public health programmes: NTEP TB centres and Ni-kshay reporting, NACO ART centres, the national kala-azar and malaria programmes, National Deworming Day, and ICMR AMR surveillance laboratories.

Interview questions

• Q: Why are beta-lactams ineffective against *Mycoplasma*? A: *Mycoplasma* has no peptidoglycan cell wall, so there is no transpeptidase target for a beta-lactam to inhibit.
• Q: What is the rationale for once-daily aminoglycoside dosing? A: Killing is concentration-dependent with a long post-antibiotic effect, and tubular uptake is saturable - so a single large dose gives better killing and less nephrotoxicity than divided doses.
• Q: How does MRSA resist methicillin? A: The *mecA* gene codes an altered transpeptidase, PBP2a, with very low affinity for beta-lactams, so cross-linking continues despite the drug.
• Q: Why is cotrimoxazole bactericidal when each component is bacteriostatic? A: Sulfamethoxazole and trimethoprim block two sequential steps of folate synthesis, and this sequential blockade is synergistic and cidal.
• Q: Which antibiotic should not be combined with a penicillin, and why? A: A bacteriostatic drug such as tetracycline or chloramphenicol - penicillin needs actively growing, dividing cells to kill, so growth arrest antagonises it.
• Q: Why is pyridoxine given with isoniazid? A: Isoniazid increases urinary excretion of pyridoxine and interferes with its metabolism, causing peripheral neuropathy that pyridoxine 10-25 mg daily prevents.
• Q: A woman on rifampicin for TB becomes pregnant despite taking an oral contraceptive. Explain. A: Rifampicin is a strong CYP3A4 and P-glycoprotein inducer; it accelerates metabolism of oestrogen and progestin, so a non-hormonal or alternative method is required.
• Q: Why does amphotericin B damage human kidneys if it targets fungal ergosterol? A: Its selectivity is only relative - it also binds human cholesterol in membranes, especially in renal tubular cells, causing nephrotoxicity and potassium wasting; liposomal formulations reduce this.
• Q: Which antimicrobials are contraindicated in children and why? A: Tetracyclines (calcium chelation - teeth staining, enamel hypoplasia), fluoroquinolones in routine use (cartilage/tendon effects), chloramphenicol in neonates (grey baby syndrome), and sulfonamides near term (kernicterus).
• Q: What does the WHO AWaRe classification mean for a dispensing pharmacist? A: It groups antibiotics as Access (first-choice, widely usable), Watch (higher resistance potential, restricted) and Reserve (last-resort); stewardship aims to maximise Access use and tightly control Watch and Reserve agents.
• Q: What extra record must an Indian retailer keep for a Schedule H1 drug? A: A separate bound register with the prescriber's name, patient's name, the drug and quantity supplied, retained for three years and open to inspection.
• Q: Why is azithromycin effective in a 3-day course? A: It concentrates in tissues and phagocytes with a terminal half-life of about 2-4 days, so tissue levels stay above MIC long after dosing stops.

Common mistakes

• Calling methicillin a therapeutic drug - it is now only a laboratory resistance marker; cloxacillin or cefazolin are used clinically.
• Writing that aminoglycosides work on anaerobes - uptake requires an oxygen-dependent transport system, so they fail in anaerobes and abscess cavities.
• Mixing up the knock-on classifications: stating that cephalosporin Gram-positive cover increases with generation, or that carbapenems cover MRSA.
• Confusing targets - saying azoles bind ergosterol (they inhibit its synthesis at 14-alpha-demethylase) while polyenes bind preformed ergosterol.
• Treating MIC as a dose; it is an in-vitro concentration, and clinical success depends on achieving it at the infection site.
• Attributing resistance only to mutation and forgetting plasmid-mediated horizontal transfer by conjugation, which spreads it across species.
• Quoting old programme names and regimens - RNTCP is now NTEP, intermittent thrice-weekly TB therapy has been replaced by daily FDCs, and HIV first-line in India is TLD, not a nevirapine-based regimen.

Related topics

• Pharmacodynamics: how drugs act · Pharmacokinetics and dose calculation · Pharmaceutical microbiology and sterility testing · Anticancer drugs and immunopharmacology · Hospital and clinical pharmacy practice · Pharmacology of inflammation and immunity.