USMLE antibiotics

USMLE antibioticsPhlostonProtein synthesis inhibitorsProtein synthesis inhibitors30S and 50S inhibitorsProtein synthesis inhibitors30S and 50S inhibitors30S = aminoglycosides + tetracyclinesProtein synthesis inhibitors30S and 50S inhibitors30S = aminoglycosides + tetracyclines50S = chloramphenicol + clindamycin + macrolides (and linezolid = lower-yield, but in FA)Protein synthesis inhibitors30S and 50S inhibitors30S = aminoglycosides + tetracyclines50S = chloramphenicol + clindamycin + macrolides (and linezolid = lower-yield, but in FA)Knowing the above classifications is mandatory.Protein synthesis inhibitors30S and 50S inhibitors30S = aminoglycosides + tetracyclines50S = chloramphenicol + clindamycin + macrolides (and linezolid = lower-yield, but in FA)Knowing the above classifications is mandatory.However the USMLE is going to throw buzz words at you for these, so you need to know their individual MOAs.Protein synthesis inhibitorsBefore I get into the specifics of each drug, here are the buzz words you need to associate with the 50S drugs:Protein synthesis inhibitorsBefore I get into the specifics of each drug, here are the buzz words you need to associate with the 50S drugs:Macrolides = BLOCK TRANSLOCATION STEP via binding to the 23S rRNA of the 50S subunit.Protein synthesis inhibitorsBefore I get into the specifics of each drug, here are the buzz words you need to associate with the 50S drugs:Macrolides = BLOCK TRANSLOCATION STEP via binding to the 23S rRNA of the 50S subunit.FA says chloramphenicol and clindamycin both block peptide bond formation, but in terms of the USMLE, theyre going to want you to know that chloramphenicol more specifically blocks peptidyl transferase. For clindamycin, it blocks peptide bond formation. Thats how its seen in questions.Protein synthesis inhibitorsFor the 30S buzzwords:Protein synthesis inhibitorsFor the 30S buzzwords:Aminoglycosides = disrupt initiation complex and cause misreading of mRNA.Protein synthesis inhibitorsFor the 30S buzzwords:Aminoglycosides = disrupt initiation complex and cause misreading of mRNA.Tetracyclines = prevent attachment of aminoacyl-tRNA to the A-site on the 30S. Aminoglycosides vs macrolides (names)Gentamycin, neomycin, amikacin, tobramycin, steptomycin (highest-yield ones) = AMINOGLYCOSIDESAminoglycosides vs macrolides (names)Gentamycin, neomycin, amikacin, tobramycin, steptomycin (highest-yield ones) = AMINOGLYCOSIDESErythromycin, azithromycin, clarithromycin = MACROLIDESAminoglycosides vs macrolides (names)Gentamycin, neomycin, amikacin, tobramycin, steptomycin (highest-yield ones) = AMINOGLYCOSIDESErythromycin, azithromycin, clarithromycin = MACROLIDESWhen you see these drug names enough through doing lots of practice questions, you soon wont have to think twice about their classifications, but at the very minimum, dont screw these up. I had an easy question my real deal where I had to pick out the aminoglycoside, and they had also listed a macrolide.Bactericidal vs bacteristaticYouve gotta know which protein synthesis inhibitors are bactericidal vs static.Bactericidal vs bacteristaticYouve gotta know which protein synthesis inhibitors are bactericidal vs static.The 50S ones alone are BACTERISTATIC. That means the macrolides and chloramphenicol + clindamycin are BACTERISTATIC.Bactericidal vs bacteristaticYouve gotta know which protein synthesis inhibitors are bactericidal vs static.The 50S ones alone are BACTERISTATIC. That means the macrolides and chloramphenicol + clindamycin are BACTERISTATIC.Of the 30S, tetracyclines are BACTERISTATIC, but aminoglycosides are BACTERICIDAL.Bactericidal vs bacteristaticYouve gotta know which protein synthesis inhibitors are bactericidal vs static.The 50S ones alone are BACTERISTATIC. That means the macrolides and chloramphenicol + clindamycin are BACTERISTATIC.Of the 30S, tetracyclines are BACTERISTATIC, but aminoglycosides are BACTERICIDAL.Tangential: TMP and SMX, individually, are bacteristatic. But TOGETHER THEY ARE BACTERICIDAL. AminoglycosidesAs said before, these inhibit formation of the initiation complex and cause misreading of the mRNA.

AminoglycosidesAs said before, these inhibit formation of the initiation complex and cause misreading of the mRNA.Target AEROBIC GRAM-NEGATIVE RODS.

AminoglycosidesAs said before, these inhibit formation of the initiation complex and cause misreading of the mRNA.Target AEROBIC GRAM-NEGATIVE RODS.Therefore require O2 for uptake.

AminoglycosidesAs said before, these inhibit formation of the initiation complex and cause misreading of the mRNA.Target AEROBIC GRAM-NEGATIVE RODS.Therefore require O2 for uptake.Synergistic with beta-lactams (beta-lactams permit the aminoglycoside to enter the cell)

AminoglycosidesAs said before, these inhibit formation of the initiation complex and cause misreading of the mRNA.Target AEROBIC GRAM-NEGATIVE RODS.Therefore require O2 for uptake.Synergistic with beta-lactams (beta-lactams permit the aminoglycoside to enter the cell)Neomycin is used for bowel surgery

AminoglycosidesNephrotoxic with cephalosporins and ototoxic with loop diuretics. I remembered this through ALOe. I thought of aloe vera Aminoglycosides, Loops, Ototoxicity; so that leaves nephrotoxicity for cephs + aminos.AminoglycosidesNephrotoxic with cephalosporins and ototoxic with loop diuretics. I remembered this through ALOe. I thought of aloe vera Aminoglycosides, Loops, Ototoxicity; so that leaves nephrotoxicity for cephs + aminos.FA also mentions that its a teratogen. USMLE wants you to know that aminoglycosides can cause congenital deafness. FA (in the embryo chapter) mentions CNVIII toxicity for aminoglycosides.AminoglycosidesResistance is via acetylation, phosphorylation, adenylation. Sounds low-yield, but its in FA, and Ive seen it in two practice questions (perfect example of a 260+ question bc most people wont make the effort to remember that).Aminoglycosides (beyond FA)All of the following has rocked up in questions:Aminoglycosides (beyond FA)All of the following has rocked up in questions:Can only be given PARENTERALLYAminoglycosides (beyond FA)All of the following has rocked up in questions:Can only be given PARENTERALLYCan also be given with nafcillin for MRSA endocarditis (remember beta-lactam synergy?)Aminoglycosides (beyond FA)All of the following has rocked up in questions:Can only be given PARENTERALLYCan also be given with nafcillin for MRSA endocarditis (remember beta-lactam synergy?)Neomycin for bowel surgery, right? Well it also kills urease(+) organisms decreased NH3 production decreased NH3 absorption = Tx for hyperammonaemia. FA mentions lactulose for NH3 and the gut, but they dont mention neomycin.Aminoglycosides (beyond FA)Contraindicated in myasthenia gravis because it can cause excessive neuromuscular blockade when used with curariform drugs (curare is a neuromuscular blocking agent at nAChR).Aminoglycosides (beyond FA)Contraindicated in myasthenia gravis because it can cause excessive neuromuscular blockade when used with curariform drugs (curare is a neuromuscular blocking agent at nAChR).Any kidney damage via aminoglycosides, in terms of USMLE questions, is ATN. They might try to trick you with tubulointerstitial nephritis, but its always ATN.Aminoglycosides (beyond FA)Contraindicated in myasthenia gravis because it can cause excessive neuromuscular blockade when used with curariform drugs (curare is a neuromuscular blocking agent at nAChR).Any kidney damage via aminoglycosides, in terms of USMLE questions, is ATN. They might try to trick you with tubulointerstitial nephritis, but its always ATN.Ampicillin + gentamycin = 1st-line Tx for severe pyelonephritis.TetracyclinesLike aminoglycosides, 30S, and as said before, they prevent aminoacyl-tRNA binding to the A-site.TetracyclinesLike aminoglycosides, 30S, and as said before, they prevent aminoacyl-tRNA binding to the A-site.Doxycycline is eliminated through feces. Good in pts with renal insufficiency. Theyll ask you that. They also want you to know that its ideal Tx for Lyme disease.TetracyclinesLike aminoglycosides, 30S, and as said before, they prevent aminoacyl-tRNA binding to the A-site.Doxycycline is eliminated through feces. Good in pts with renal insufficiency. Theyll ask you that. They also want you to know that its ideal Tx for Lyme disease.Cant take tetracyclines with antacids. The same thing goes for fluoroquinolones. Ive seen both in questions.TetracyclinesCauses teeth discoloration IN CHILDREN and photosensitivity IN ADULTS. guy gets sunburn while on vacation, which drug.. or girl gets sunburn/blisters while being treated for STD (gotta know Chlamydia)

TetracyclinesCauses teeth discoloration IN CHILDREN and photosensitivity IN ADULTS. guy gets sunburn while on vacation, which drug.. or girl gets sunburn/blisters while being treated for STD (gotta know Chlamydia)VACUUM THe BedRoom vibrio, acne, chlamydia, ureaplasma urealyticum, mycoplasma, tularaemia, H. pylori, Borellia (Lyme disease), Rickettsia rickettsii.

TetracyclinesCauses teeth discoloration IN CHILDREN and photosensitivity IN ADULTS. guy gets sunburn while on vacation, which drug.. or girl gets sunburn/blisters while being treated for STD (gotta know Chlamydia)VACUUM THe BedRoom vibrio, acne, chlamydia, ureaplasma urealyticum, mycoplasma, tularaemia, H. pylori, Borellia (Lyme disease), Rickettsia rickettsii.Resistance mechanism is increased efflux or reduced influx. Contrast with aminoglycosides.

Tetracyclines (beyond FA)MINOCYCLINE, like doxycycline, is also fecally eliminated. Minocycline, like HIPP, can cause SLE-like syndrome.Tetracyclines (beyond FA)MINOCYCLINE, like doxycycline, is also fecally eliminated. Minocycline, like HIPP, can cause SLE-like syndrome.Tetracyclines can cause pill-induced esophagitis.Tetracyclines (beyond FA)MINOCYCLINE, like doxycycline, is also fecally eliminated. Minocycline, like HIPP, can cause SLE-like syndrome.Tetracyclines can cause pill-induced esophagitis.Not good for meningitis because they dont cross the BBB (FA vaguely mentions limited CNS penetration)Tetracyclines (beyond FA)MINOCYCLINE, like doxycycline, is also fecally eliminated. Minocycline, like HIPP, can cause SLE-like syndrome.Tetracyclines can cause pill-induced esophagitis.Not good for meningitis because they dont cross the BBB (FA vaguely mentions limited CNS penetration)Demeclocycline causes diabetes insipidus (FA says it probably in the renal chapter but not in the micro chapter, although its ridiculously high-yield)

MacrolidesOnce again, they block translocation via binding to the 23S rRNA. (elaborate)MacrolidesOnce again, they block translocation via binding to the 23S rRNA. (elaborate)Ultra-high-yield: Tx for ATYPICAL PNEUMONIAS.MacrolidesOnce again, they block translocation via binding to the 23S rRNA. (elaborate)Ultra-high-yield: Tx for ATYPICAL PNEUMONIAS.Prolongs the QT-interval (FA says erythromycin)MacrolidesOnce again, they block translocation via binding to the 23S rRNA. (elaborate)Ultra-high-yield: Tx for ATYPICAL PNEUMONIAS.Prolongs the QT-interval (FA says erythromycin)DOC for pneumonia in penicillin-allergenic pts keep in mind we have aztreonam, so why use a macrolide?

MacrolidesOnce again, they block translocation via binding to the 23S rRNA. (elaborate)Ultra-high-yield: Tx for ATYPICAL PNEUMONIAS.Prolongs the QT-interval (FA says erythromycin)DOC for pneumonia in penicillin-allergenic pts keep in mind we have aztreonam, so why use a macrolide?GI-discomfort, cholestatic hepatitis, eosinophilia/rash; inhibits P-450. bleeding diathesis in heart valve pt.

MacrolidesResistance is alteration of the 23S rRNA binding siteMacrolides (beyond FA)The reason erythromycin causes acute cholestatic hepatitis is because its the only macrolide eliminated through bile (USMLE would simply ask you for the mechanism of elimination, but if you remember it causes cholestatic hepatitis, it would be easy).Macrolides (beyond FA)The reason erythromycin causes acute cholestatic hepatitis is because its the only macrolide eliminated through bile (USMLE would simply ask you for the mechanism of elimination, but if you remember it causes cholestatic hepatitis, it would be easy).Because erythromycin is eliminated through bile, it also is the only macrolide that doesnt require dosage adjustment in renal failure pts.

Macrolides (beyond FA)The reason erythromycin causes acute cholestatic hepatitis is because its the only macrolide eliminated through bile (USMLE would simply ask you for the mechanism of elimination, but if you remember it causes cholestatic hepatitis, it would be easy).Because erythromycin is eliminated through bile, it also is the only macrolide that doesnt require dosage adjustment in renal failure pts.Macrolides are DOC if pt also has post-operative ileus because they are agonists at the motilin receptor (MMCs).

Macrolides (beyond FA)Ive seen in a practice question where they wanted to know which drug was most injurious to myocytes. Macrolides was the answer (although protein synthesis inhibitors in general would also be correct). The rationale is that although eukaryotes have 40S/60S (80S) ribosomes, because mitochondria are derived from prokaryotes, they have 30S/50S (70S) ribosomal systems, so muscle, which is heavily mitochondria-dependent, can theoretically be injured by protein synthesis inhibitors. Macrolides vs tetracyclinesI had seen in a practice question that a pt had an atypical pneumonia and then developed severe sunburn on vacation. They had asked which drug was used. Youve gotta know that atypical pneumonias are classically mycoplasma, chlamydia or legionella. And youve gotta remember that despite macrolides serving as the 1st-line Tx for atypical pneumonias, tetracyclines treat chlamydia, so in this case, the guy had had an atypical chlamydial pneumonia treated with a tetracycline, and he developed photosensitivity.ChloramphenicolBlocks peptide bond formation, but if you see it in a question, they want you to know that it knocks out peptidyl transferase.ChloramphenicolBlocks peptide bond formation, but if you see it in a question, they want you to know that it knocks out peptidyl transferase.In turn, resistance is via a plasmid-encoded acetyltransferase that inactivates the drug (FA says this, but on the USMLE, theyll reword it as bacterial enzymatic acetylation to see if you actually know what acetyltransferase means).ChloramphenicolBlocks peptide bond formation, but if you see it in a question, they want you to know that it knocks out peptidyl transferase.In turn, resistance is via a plasmid-encoded acetyltransferase that inactivates the drug (FA says this, but on the USMLE, theyll reword it as bacterial enzymatic acetylation to see if you actually know what acetyltransferase means).Causes aplastic anaemia and grey baby syndromeChloramphenicolUsed commonly to treat meningitis in the third-world because of its cheap costChloramphenicol (beyond FA)Kaplan liked chloramphenicol as Tx for Lyme disease in early pregnancy > doxycycline. However, if near term, doxy is > chloramphenicol. Both drugs carry fetal risks.Chloramphenicol (beyond FA)Kaplan liked chloramphenicol as Tx for Lyme disease in early pregnancy > doxycycline. However, if near term, doxy is > chloramphenicol. Both drugs carry fetal risks.USMLE will ask you to pick out the most lipophilic drug of the bunch. Chloramphenicol, bc its great for meningitis due to its BBB penetration, is heavily lipophilic.ClindamycinBlocks peptide bond formationClindamycinBlocks peptide bond formationAnaerobic infections ABOVE the diaphragm (metronidazole is below)ClindamycinBlocks peptide bond formationAnaerobic infections ABOVE the diaphragm (metronidazole is below)Good for lung abscesses or aspiration pneumoniaClindamycinBlocks peptide bond formationAnaerobic infections ABOVE the diaphragm (metronidazole is below)Good for lung abscesses or aspiration pneumoniaCauses pseudomembranous colitis bc it allows for C. difficile overgrowthClindamycinOnly real thing Ive found outside FA for this drug is that it can also treat MRSA. Or theyll make pseudomembranous colitis apparent then ask you for the AB-toxin test or MOA of C. difficile-mediated necrosis.LinezolidFor this drug, you only need to remember two things:

LinezolidFor this drug, you only need to remember two things:1) it acts on the 50S subunit (binds to 23S of 50S subunit - same as macrolides/clindamycin)

LinezolidFor this drug, you only need to remember two things:1) it acts on the 50S subunit (binds to 23S of 50S subunit - same as macrolides/clindamycin)2) Side-effects are HOT:

LinezolidFor this drug, you only need to remember two things:1) it acts on the 50S subunit (binds to 23S of 50S subunit - same as macrolides/clindamycin)2) Side-effects are HOT:H = High risk of serotonin syndrome

LinezolidFor this drug, you only need to remember two things:1) it acts on the 50S subunit (binds to 23S of 50S subunit - same as macrolides/clindamycin)2) Side-effects are HOT:H = High risk of serotonin syndromeO = optic neuritis

LinezolidFor this drug, you only need to remember two things:1) it acts on the 50S subunit (binds to 23S of 50S subunit - same as macrolides/clindamycin)2) Side-effects are HOT:H = High risk of serotonin syndromeO = optic neuritisT = thrombocytopenia

LinezolidFor this drug, you only need to remember two things:1) it acts on the 50S subunit (binds to 23S of 50S subunit - same as macrolides/clindamycin)2) Side-effects are HOT:H = High risk of serotonin syndromeO = optic neuritisT = thrombocytopenia

LinezolidI had only ever encountered one question on this drug, and it was a vignette of someone with serotonin syndrome (flushing, diarrhea, sweating, hyperthermia, agitation, etc.) and blurry vision, and then they wanted to know the drug that caused the Sx.Sulfonamides vs trimethoprim

Sulfonamides vs trimethoprimSulfadiazine + pyrimethamine used to Tx toxoplasmosis are analogous. So if they ask you for the MOA of pyrimethamine, you know its like trimethoprim.SulfonamidesDihydropteroate synthase inhibitors (PABA analogues)SulfonamidesDihydropteroate synthase inhibitors (PABA analogues)Simple UTIsSulfonamidesDihydropteroate synthase inhibitors (PABA analogues)Simple UTIsCan treat Nocardia (SNAP)SulfonamidesDihydropteroate synthase inhibitors (PABA analogues)Simple UTIsCan treat Nocardia (SNAP)Can treat Chlamydia, as per FA, but Ive never seen this in a practice question

SulfonamidesDihydropteroate synthase inhibitors (PABA analogues)Simple UTIsCan treat Nocardia (SNAP)Can treat Chlamydia, as per FA, but Ive never seen this in a practice questionCan cause hypersensitivity rxns (tubulointersititial nephritis; in contrast to aminoglycosides ATN)SulfonamidesDihydropteroate synthase inhibitors (PABA analogues)Simple UTIsCan treat Nocardia (SNAP)Can treat Chlamydia, as per FA, but Ive never seen this in a practice questionCan cause hypersensitivity rxns (tubulointersititial nephritis; in contrast to aminoglycosides ATN)Haemolysis in G6PD-deficiency (ISPAIN)SulfonamidesDihydropteroate synthase inhibitors (PABA analogues)Simple UTIsCan treat Nocardia (SNAP)Can treat Chlamydia, as per FA, but Ive never seen this in a practice questionCan cause hypersensitivity rxns (tubulointersititial nephritis; in contrast to aminoglycosides ATN)Haemolysis in G6PD-deficiency (ISPAIN)Displaces drugs from albumin kernicterusSulfonamides (beyond FA)So if a pregnant woman takes a drug and the baby has jaundice kernicterus sulfonamide.Sulfonamides (beyond FA)So if a pregnant woman takes a drug and the baby has jaundice kernicterus sulfonamide.Because the bilirubin is displaced from albumin, it can cross the BBB kernicterusTrimethoprimInhibits dihydrofolate reductaseTrimethoprimInhibits dihydrofolate reductaseOnce again, sulfonamides and trimethoprim are both BACTERISTATIC, but if combined (TMP-SMX), they are BACTERICIDAL.TrimethoprimInhibits dihydrofolate reductaseOnce again, sulfonamides and trimethoprim are both BACTERISTATIC, but if combined (TMP-SMX), they are BACTERICIDAL.Highest-yield for TMP-SMX is Pneumocystis jiroveci pneumonia. If high-yield were diarrhea, it would be explosive here.TrimethoprimInhibits dihydrofolate reductaseOnce again, sulfonamides and trimethoprim are both BACTERISTATIC, but if combined (TMP-SMX), they are BACTERICIDAL.Highest-yield for TMP-SMX is Pneumocystis jiroveci pneumonia. If high-yield were diarrhea, it would be explosive here.Can Tx SALMONELLA and SHIGELLATrimethoprimInhibits dihydrofolate reductaseOnce again, sulfonamides and trimethoprim are both BACTERISTATIC, but if combined (TMP-SMX), they are BACTERICIDAL.Highest-yield for TMP-SMX is Pneumocystis jiroveci pneumonia. If high-yield were diarrhea, it would be explosive here.Can Tx SALMONELLA and SHIGELLAMay cause megaloblastic anaemia or (or any penia).TrimethoprimMay alleviate TMP-induced megaloblastic anaemia with leucovorin rescue folinic acidTrimethoprimMay alleviate TMP-induced megaloblastic anaemia with leucovorin rescue folinic acidAs stated before, remember the pyrimethamine for toxoplasmosis has same MOAFluoroquinolones-floxacin drugs; inhibit bacterial topoisomerase II (aka DNA gyrase) very very high-yieldFluoroquinolones-floxacin drugs; inhibit bacterial topoisomerase II (aka DNA gyrase) very very high-yieldLike tetracyclines, cannot be taken with antacidsFluoroquinolones-floxacin drugs; inhibit bacterial topoisomerase II (aka DNA gyrase) very very high-yieldLike tetracyclines, cannot be taken with antacidsCan treat a range of organisms (mostly gram(-) rods)Fluoroquinolones-floxacin drugs; inhibit bacterial topoisomerase II (aka DNA gyrase) very very high-yieldLike tetracyclines, cannot be taken with antacidsCan treat a range of organisms (mostly gram(-) rods)Can cause cartilage damage or tendon ruptureFluoroquinolones-floxacin drugs; inhibit bacterial topoisomerase II (aka DNA gyrase) very very high-yieldLike tetracyclines, cannot be taken with antacidsCan treat a range of organisms (mostly gram(-) rods)Can cause cartilage damage or tendon ruptureLeg cramps + myalgias in kids (as per FA, but Ive never seen this in a practice question)

FluoroquinolonesBacterial resistance is via chromosome-mediated mutation in DNA gyrase. FA mentions this, but its not minutiae. Ive seen in a couple questions where they want you to know that bacterial resistance is ALMOST ALWAYS plasmid-mediated, but fluoros are the exception because theyre chromosomal.Fluoroquinolones (beyond FA)First-line Tx for diarrhea due to Shigella + travelers diarrheaFluoroquinolones (beyond FA)First-line Tx for diarrhea due to Shigella + travelers diarrheaCiprofloxacin is DOC for UTIs in pts with sulfa allergy. If pt has sulfa allergy and has GERD nitrofurantoinFluoroquinolones (beyond FA)First-line Tx for diarrhea due to Shigella + travelers diarrheaCiprofloxacin is DOC for UTIs in pts with sulfa allergy. If pt has sulfa allergy and has GERD nitrofurantoinKaplan liked that H. influenzae can also be treated by fluoros.Fluoroquinolones (beyond FA)First-line Tx for diarrhea due to Shigella + travelers diarrheaCiprofloxacin is DOC for UTIs in pts with sulfa allergy. If pt has sulfa allergy and has GERD nitrofurantoinKaplan liked that H. influenzae can also be treated by fluoros.GOOD ORAL BIOAVAILABILITY. That rocked up on an NBME exam (Gd knows why), which means it was once (or still is) floating around on the real deal.Fluoroquinolones (beyond FA)Gatifloxacin causes dysglycaemia (rocked up in GT)Fluoroquinolones (beyond FA)Gatifloxacin causes dysglycaemia (rocked up in GT)Moxifloxacin causes heart conduction abnormalitiesFluoroquinolones (beyond FA)Gatifloxacin causes dysglycaemia (rocked up in GT)Moxifloxacin causes heart conduction abnormalitiesUSMLE might try to re-word the MOA as that which affects the DNA nicking processMetronidazoleForms toxic metabolites that damage DNAMetronidazoleForms toxic metabolites that damage DNAGET GAP Tx for Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes, H. pyloriMetronidazoleForms toxic metabolites that damage DNAGET GAP Tx for Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes, H. pyloriUSMLE will literally give you a classic vignette / presentation of one of the above organisms, then ask for the Tx. They might tell you clue cells, for instance, then ask for the Tx, or theyll tell you a guy went swimming in a lake and now has steatorrhoea, then ask for the Tx, etc.MetronidazoleDisulfiram-like rxn with EtOH headache / metallic taste in the mouthMetronidazoleDisulfiram-like rxn with EtOH headache / metallic taste in the mouthOnce again, clindamycin = anaerobes ABOVE diaphragm; metronidazole = BELOWMetronidazole (beyond FA)FA doesnt say it for metro at the end of the micro chapter, although it does under C. difficile, but metronidazole is a TREATMENT FOR pseudomembranous colitis. Vancomycin and metro are both Txs for it, but if a question has both as answer choices, metro is always correct > vancomycin because of the scare of vancomycin-resistant organisms. Another thing: vanco is always given IV (poor oral bioavailability), but for pseudomembranous colitis, ITS GIVEN ORALLY (makes sense bc it stays confined to the gut).Metronidazole (beyond FA)Ive also seen it in a practice question: USMLE likes metronidazole CREAM as Tx for acne rosacea. But erythromycin CREAM is Tx for acne vulgaris.PolymyxinsUSMLE for some reason likes you to know the structures/MOA of these drugs really well. Know that they have a long hydrophobic tail and that they are cationic and basic. They act as detergents on the cell membrane and DISRUPT ITS OSMOTIC PROPERTIES. PolymyxinsUSMLE for some reason likes you to know the structures/MOA of these drugs really well. Know that they have a long hydrophobic tail and that they are cationic and basic. They act as detergents on the cell membrane and DISRUPT ITS OSMOTIC PROPERTIES. Theyre used only when a pt is resistant to practically all other Txs very high neuro- and nephrotoxicityPolymyxinsYoull find them in the THAYER-MARTIN medium used to culture N. gonorrhea. TM medium = VPN client = vancomycin (hits gram+), Polymyxin = colistin (hits other gram-), nystatin (hits fungi)DaptomycinDont be fooled by the name. Its not an aminoglycoside, nor is it a macrolide.DaptomycinDont be fooled by the name. Its not an aminoglycoside, nor is it a macrolide.Youve gotta know that it creates membrane channels that result in depolarization and **disruption of the membrane potential.**DaptomycinDont be fooled by the name. Its not an aminoglycoside, nor is it a macrolide.Youve gotta know that it creates membrane channels that result in depolarization and **disruption of the membrane potential.**Its notable side-effect is myopathy with increased CPK (so contraindicated with statins/fibrates)DaptomycinDont be fooled by the name. Its not an aminoglycoside, nor is it a macrolide.Youve gotta know that it creates membrane channels that result in depolarization and **disruption of the membrane potential.**Its notable side-effect is myopathy with increased CPK (so contraindicated with statins/fibrates)It is only effective against gram(+)s.DaptomycinDont be fooled by the name. Its not an aminoglycoside, nor is it a macrolide.Youve gotta know that it creates membrane channels that result in depolarization and **disruption of the membrane potential.**Its notable side-effect is myopathy with increased CPK (so contraindicated with statins/fibrates)It is only effective against gram(+)s.Cannot be used for pneumonia bc pulmonary surfactant inhibits it.Anti-TB drugsAnti-TB drugsProphylaxis = isoniazid. High-yield.Anti-TB drugsProphylaxis = isoniazid. High-yield.Tx = RIPE = rifampin, isoniazid, pyrazinamide, ethambutolAnti-TB drugsProphylaxis = isoniazid. High-yield.Tx = RIPE = rifampin, isoniazid, pyrazinamide, ethambutolAll are HEPATOTOXIC, except for ethambutol, which causes VISUAL CHANGES. RifampinInhibits DNA-dependent RNA-polymerase. USMLE really likes that. And theyll really nail it. Theyll literally list RNA-dependent DNA-polymerase and other types of similar polymerases to trick you, but you need to remember that rifampin inhibits DNA-dependent RNA-polymerase. That means it prevents RNA synthesis. The way I remembered this was RDR = rifampin-DNA-RNA. Whatever works for you. Just find a way to remember it. RifampinFA says that rifampin delays resistance to dapsone when used for leprosy. Ive never actually seen a question on this though.RifampinFA says that rifampin delays resistance to dapsone when used for leprosy. Ive never actually seen a question on this though.As said prior, isoniazid, NOT rifampin, is the prophylaxis for TB. But you need to remember that rifampin is the prophylaxis for N. meningitidis and H. influenzae type-B.RifampinFA says that rifampin delays resistance to dapsone when used for leprosy. Ive never actually seen a question on this though.As said prior, isoniazid, NOT rifampin, is the prophylaxis for TB. But you need to remember that rifampin is the prophylaxis for N. meningitidis and H. influenzae type-B.Ill summarize that last point bc its so important:TB prophylaxis = isoniazidTB Tx = rifampin, isoniazid, pyrazinamide, ethambutolN. meningitidis / H. influenzae prophylaxis = rifampinN. meningitidis Tx = ceftriaxone (FA says ceftriaxone or penicillin G, but in terms of USMLE questions, Ive only ever seen ceftriaxone)Rifampin (contd)Upregulates P-450 (very high-yield)Rifampin (contd)Upregulates P-450 (very high-yield)Can cause orange tears/sweat/urine (high-yield); harmless side-effect, but pt will be concernedRifampin (beyond FA)Since rifampin upregulates P-450, you dont want to give it to HIV pts on protease inhibitors bc youll increase the rate of the latters degradation, so you instead give rifabutin. USMLE will list both as Txs for TB in the same question, but the answer is rifabutin if the pt is HIV(+) bc you need to assume he/she is on HAART.Rifampin (beyond FA)Since rifampin upregulates P-450, you dont want to give it to HIV pts on protease inhibitors bc youll increase the rate of the latters degradation, so you instead give rifabutin. USMLE will list both as Txs for TB in the same question, but the answer is rifabutin if the pt is HIV(+) bc you need to assume he/she is on HAART.USMLE wants to know WHY rifampin is prophylaxis for N. meningitidis.Rifampin (beyond FA)Since rifampin upregulates P-450, you dont want to give it to HIV pts on protease inhibitors bc youll increase the rate of the latters degradation, so you instead give rifabutin. USMLE will list both as Txs for TB in the same question, but the answer is rifabutin if the pt is HIV(+) bc you need to assume he/she is on HAART.USMLE wants to know WHY rifampin is prophylaxis for N. meningitidis...it penetrates the respiratory tract wall and prevents meningococcal pharyngeal colonization.Rifampin (beyond FA)Rifampin binds the beta-subunit of DNA-dependent RNA-polymerase. Retarded, but it showed up in a question (lord knows why). This is an example of how everyone needs a little luck on the real deal.Rifampin (beyond FA)Rifampin binds the beta-subunit of DNA-dependent RNA-polymerase. Retarded, but it showed up in a question (lord knows why). This is an example of how everyone needs a little luck on the real deal.USMLE might tell you the pts contact lenses were rusty colored as an indirect reference to the orange tears a little trickierRifampin (beyond FA)Rifampin binds the beta-subunit of DNA-dependent RNA-polymerase. Retarded, but it showed up in a question (lord knows why). This is an example of how everyone needs a little luck on the real deal.USMLE might tell you the pts contact lenses were rusty colored as an indirect reference to the orange tears a little trickierWhy is isoniazid used over rifampin for TB prophylaxis?Rifampin (beyond FA)Rifampin binds the beta-subunit of DNA-dependent RNA-polymerase. Retarded, but it showed up in a question (lord knows why). This is an example of how everyone needs a little luck on the real deal.USMLE might tell you the pts contact lenses were rusty colored as an indirect reference to the orange tears a little trickierWhy is isoniazid used over rifampin for TB prophylaxis?..bc rifampin is way more hepatotoxic.Isoniazid (INH)Decreases synthesis of mycolic acids (high-yield)Isoniazid (INH)Decreases synthesis of mycolic acids (high-yield)KatG (catalase-peroxidase) needed to convert INH to active metaboliteIsoniazid (INH)Decreases synthesis of mycolic acids (high-yield)KatG (catalase-peroxidase) needed to convert INH to active metaboliteAlthough hepatotoxic, USMLE loves that INH is a common cause of vitamin B6 deficiency. Quite HY.Isoniazid (INH)Decreases synthesis of mycolic acids (high-yield)KatG (catalase-peroxidase) needed to convert INH to active metaboliteAlthough hepatotoxic, USMLE loves that INH is a common cause of vitamin B6 deficiency. Quite HY.Theyll tell you a person with TB was treated and now has paresthesias (or sometimes seizures) B6 def.Isoniazid (beyond FA)KatG needed to convert INH to active metabolite does so via acyl-carrier and ketoacyl-carrier protein synthesis. So KatG is a catalase-peroxidase enzyme that carries out acyl-carrier and ketoacyl-carrier protein synthesis.Isoniazid (beyond FA)KatG needed to convert INH to active metabolite does so via acyl-carrier and ketoacyl-carrier protein synthesis. So KatG is a catalase-peroxidase enzyme that carries out acyl-carrier and ketoacyl-carrier protein synthesis.USMLE loves to ask about metabolism of INH. If they show you a bimodal curve of INH metabolism, youve gotta know that people demonstrate phenotypic variation regarding fast vs slow acetylation.Isoniazid (beyond FA)Ive seen a practice question where the hepatotoxicity of INH was presented as fever, anorexia and nausea, WITHOUT jaundice. Effects can be acute. If they throw neurotoxicity at you, it will be the paresthesias. If its hepatotoxicity, youll get the former Sx (just think, in paracetamol poisoning, does jaundice develop?)Isoniazid (beyond FA)USMLE wants you to know WHY isoniazid causes B6 deficiency.Isoniazid (beyond FA)USMLE wants you to know WHY isoniazid causes B6 deficiency.Its bc INH inhibits pyridoxal kinase, so B6 cannot get activated (normally pyridoxine pyridoxal phosphate).Isoniazid (beyond FA)USMLE wants you to know WHY isoniazid causes B6 deficiency.Its bc INH inhibits pyridoxal kinase, so B6 cannot get activated (normally pyridoxine pyridoxal phosphate).INH can cause D/NE/E deficiency (secondary to the B6 deficiency)Isoniazid (beyond FA)USMLE wants you to know WHY isoniazid causes B6 deficiency.Its bc INH inhibits pyridoxal kinase, so B6 cannot get activated (normally pyridoxine pyridoxal phosphate).INH can cause D/NE/E deficiency (secondary to the B6 deficiency)Seizures secondary to B6 deficiency and INH occur bc of decreased GABA (bc you need B6 to decarboxylate glutamate to GABA!).PyrazinamideKnocks out mycobacterial fatty acid synthase IPyrazinamideKnocks out mycobacterial fatty acid synthase IEffective in the acidic pH of phagolysosomesPyrazinamideKnocks out mycobacterial fatty acid synthase IEffective in the acidic pH of phagolysosomes Although it causes hepatotoxicity, it also causes gout (hyperuricaemia). On my real deal, I was asked the lower-yield side-effect of a drug (hint hint).Pyrazinamide (beyond FA)Like INH, pyrazinamide requires activation by TBPyrazinamide (beyond FA)Like INH, pyrazinamide requires activation by TBFA mentions that pyrazinamide is most effective in the acidic pH of phagolysosomes, but what this means is that pyrazinamide is the most effective intracellular TB medication thats how theyll ask it. The other drugs still penetrate the cell, but pyrazinamide is simply the best at killing TB that have already been engulfed by macrophages.EthambutolDecreases carbohydrate polymerization of the mycobacterial cell wall by blocking arabinosyltransferase.EthambutolDecreases carbohydrate polymerization of the mycobacterial cell wall by blocking arabinosyltransferase.So they want you to know that ethambutol knocks out carbohydrate synthesis but that pyrazinamide knocks out fatty acid synthesis. Isoniazid hits mycolic acid synthesis directly, and rifampin inhibits nucleic acid synthesis.EthambutolCauses optic neuropathy. FA says red-green color blindness for ethambutol, but Ive seen it in questions as decreased visual acuity and central scotoma.EthambutolCauses optic neuropathy. FA says red-green color blindness for ethambutol, but Ive seen it in questions as decreased visual acuity and central scotoma.Although, of RIPE, RIP are hepatotoxic, ethambutol causes VISUAL PROBLEMS, so if they list hepatotoxicity and central scotoma as two answers, the latter is right, even though FA only says red-green color blindness.EthambutolCauses optic neuropathy. FA says red-green color blindness for ethambutol, but Ive seen it in questions as decreased visual acuity and central scotoma.Although, of RIPE, RIP are hepatotoxic, ethambutol causes VISUAL PROBLEMS, so if they list hepatotoxicity and central scotoma as two answers, the latter is right, even though FA only says red-green color blindness.Tangential: sildenafil instead causes blue-green color blindness.TB drugs in generalRIPES can also be used instead of RIPE. If they ask about an aminoglycoside, streptomycin has shown some use against TB.TB drugs in generalRIPES can also be used instead of RIPE. If they ask about an aminoglycoside, streptomycin has shown some use against TB.Ive seen in a practice question cycloserine as general TB Tx. It is a broad-spectrum TB drug and can cause CNS effects/seizures.