What are the 5 main mechanisms of antibiotic action? π¦
1οΈβ£ Inhibition of Cell Wall Synthesis π§± (e.g. beta-lactams, glycopeptides)
2οΈβ£ Inhibition of Protein Synthesis π (e.g. aminoglycosides, tetracyclines)
3οΈβ£ Inhibition of Nucleic Acid Synthesis 𧬠(e.g. fluoroquinolones, rifamycins)
4οΈβ£ Inhibition of Metabolic Pathways π¦ (e.g. sulfonamides, trimethoprim)
5οΈβ£ Disruption of Cell Membrane Integrity βοΈβπ₯ (e.g. polymyxins, daptomycin)
Give examples of antibiotics that inhibit cell wall synthesis π§±
πΉ Beta-lactams: penicillin, ceftriaxone, meropenem (bind PBPs)
πΉ Glycopeptides: vancomycin, teicoplanin (bind D-Ala-D-Ala)
πΉ Monobactams: aztreonam (Gram-negative only)
Which antibiotics act on the 30S ribosomal subunit? π
πΉ Aminoglycosides (gentamicin, amikacin) β bactericidal
πΉ Tetracyclines (doxycycline, tigecycline) β usually bacteriostatic
Which antibiotics act on the 50S ribosomal subunit? π
πΉ Macrolides (azithromycin, clarithromycin)
πΉ Lincosamides (clindamycin)
πΉ Oxazolidinones (linezolid)
Give examples of antibiotics that inhibit nucleic acid synthesis π§¬
πΉ Fluoroquinolones (ciprofloxacin, levofloxacin) β inhibit DNA gyrase/topoisomerase IV
πΉ Rifamycins (rifampicin) β inhibit RNA polymerase
πΉ Nitroimidazoles (metronidazole) β DNA strand breakage
Give examples of antibiotics that inhibit metabolic pathways π¦
πΉ Sulfonamides β inhibit dihydropteroate synthase
πΉ Trimethoprim β inhibits dihydrofolate reductase
π‘ Often combined as co-trimoxazole for synergy
Give examples of antibiotics that disrupt cell membrane integrity βοΈβπ₯
πΉ Polymyxins (colistin, polymyxin B) β Gram-negative MDR, nephro/neurotoxic
πΉ Daptomycin β Gram-positive resistant, inactivated by lung surfactant
What is MIC and why is it important?
π‘ Minimum Inhibitory Concentration: lowest antibiotic concentration that prevents visible bacterial growth.
π Determines dosing strategies to keep drug above MIC for effective bacterial kill.
What are time-dependent antibiotics? β³
π§± Aim: Keep concentration above MIC for as long as possible in dosing interval
π Examples: beta-lactams, vancomycin
π‘ ICU: prolonged/continuous infusions improve efficacy
What are concentration-dependent antibiotics? π
π Aim: High peak:Cmax ratio for best kill
π Examples: aminoglycosides
β
Dose once daily to maximise peak and reduce toxicity
What are AUC-dependent antibiotics? π
π Aim: Optimise total exposure (AUC:MIC)
π Examples: fluoroquinolones, vancomycin, linezolid
π‘ TDM needed for vancomycin (AUC:MIC >400)
What are the 4 major mechanisms of antimicrobial resistance? π§¬
1οΈβ£ Enzymatic degradation/modification (e.g. beta-lactamases)
2οΈβ£ Altered target site (e.g. MRSA altered PBP2a)
3οΈβ£ Efflux pumps (e.g. Pseudomonas)
4οΈβ£ Reduced permeability (e.g. porin loss in Gram-negatives)
Give examples of common resistant organisms in ICU π₯
πΉ MRSA β mecA gene β altered PBP2a
πΉ VRE β altered peptidoglycan terminus
πΉ ESBL Enterobacteriaceae β hydrolyse beta-lactams
πΉ CRE β carbapenemases
πΉ MDR Pseudomonas & Acinetobacter
πΉ Azole-resistant Candida (C. auris)
What are the main challenges of fungal infection in ICU? π
π§ Non-specific presentation
β³ Delayed/difficult diagnosis
π Rising incidence in immunosuppression, devices, TPN
π Limited antifungal options + resistance
β οΈ High mortality
What are the 5 main mechanisms of antibiotic action? π¦
1οΈβ£ Inhibition of Cell Wall Synthesis π§± (beta-lactams, glycopeptides, monobactams)
2οΈβ£ Inhibition of Protein Synthesis π (aminoglycosides, tetracyclines, macrolides, clindamycin, linezolid)
3οΈβ£ Inhibition of Nucleic Acid Synthesis 𧬠(fluoroquinolones, rifampicin, metronidazole)
4οΈβ£ Inhibition of Metabolic Pathways π¦ (sulfonamides, trimethoprim)
5οΈβ£ Disruption of Cell Membrane Integrity βοΈβπ₯ (polymyxins, daptomycin)
Give examples of cell wall synthesis inhibitors π§±
πΉ Beta-lactams: penicillin, ceftriaxone, meropenem (bind PBPs)
πΉ Glycopeptides: vancomycin, teicoplanin (bind D-Ala-D-Ala)
πΉ Monobactams: aztreonam (Gram-negative only)
Which antibiotics act on 30S ribosomal subunit? π
πΉ Aminoglycosides (gentamicin, amikacin) β bactericidal
πΉ Tetracyclines (doxycycline, tigecycline) β bacteriostatic
Which antibiotics act on 50S ribosomal subunit? π
πΉ Macrolides (azithromycin, clarithromycin)
πΉ Lincosamides (clindamycin)
πΉ Oxazolidinones (linezolid)
Give examples of nucleic acid synthesis inhibitors π§¬
πΉ Fluoroquinolones (ciprofloxacin, levofloxacin) β inhibit DNA gyrase/topoisomerase IV
πΉ Rifamycins (rifampicin) β inhibit RNA polymerase
πΉ Nitroimidazoles (metronidazole) β DNA strand breakage
Give examples of antibiotics that inhibit folate synthesis π¦
πΉ Sulfonamides β inhibit dihydropteroate synthase
πΉ Trimethoprim β inhibits dihydrofolate reductase
π‘ Often combined as co-trimoxazole
Give examples of antibiotics that disrupt cell membrane integrity βοΈβπ₯
πΉ Polymyxins (colistin, polymyxin B) β MDR Gram-negative, nephro/neurotoxic
πΉ Daptomycin β Gram-positive resistant, inactivated by lung surfactant
What is MIC?
Minimum Inhibitory Concentration = lowest antibiotic concentration preventing visible growth. Guides dosing to ensure drug stays above MIC for efficacy.
Time-dependent antibiotics β³ β definition and examples
Efficacy depends on time above MIC. Use prolonged/continuous infusions in ICU.
Examples: beta-lactams, vancomycin.