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USMLE - Micro AntiMicrobials

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These antibiotics — Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, and Imipenem — prevent bacterial cell wall formation by inhibiting peptidoglycan cross-linking, leading to cell lysis and death.

Blocks cell wall synthesis by inhibiting peptidoglycan cross-linking

Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem

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Key Terms

Term
Definition

Blocks cell wall synthesis by inhibiting peptidoglycan cross-linking

Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem

Blocks peptidoglycan synthesis

Bacitracin, Vancomycin

Inhibits Folic Acid Synthesis (involved in methylation)

Sulfonamides, Trimethoprim

Blocks DNA topoisomerase

Fluoroquinolones

Blocks mRNA synthesis

Rifampin

Damages DNA

Metronidazole

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TermDefinition

Blocks cell wall synthesis by inhibiting peptidoglycan cross-linking

Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem

Blocks peptidoglycan synthesis

Bacitracin, Vancomycin

Inhibits Folic Acid Synthesis (involved in methylation)

Sulfonamides, Trimethoprim

Blocks DNA topoisomerase

Fluoroquinolones

Blocks mRNA synthesis

Rifampin

Damages DNA

Metronidazole

Blocks protein synthesis at 50S ribosome

Chloramphenicol, Macrolides, Clindamycin, Streptogamins (Quinupristin, dalfopristin), Linezolid

Blocks protein synthesis at 30S ribosome

Aminoglycosides, Tetracycline

Penicillin

Names? Class?

MoA

Use? Bactericidal for...

Tox

Resistance

G (IV and IM), V (oral). β-lactam Antibiotic

Binds PBP (transpeptidiases) and blocks its cross-linking of peptidoglycan

Gram+, N meningitidis, T pallidum, Syphilis

Bactericidal for Gram+ cocci, Gram+ rods, Gram- cocci, Spirochetes

Hypersensitivity rxn, Hemolytic anemia

β-lactamase cleaves β-lactam ring

Penicillinase-Resistent Penicillins

Names

Spectrum

MoA

Use

Tox

Oxacillin, Nafcillin, Dicloxacillin

Narrow spectrum

Same as penicillin but bulk R group blocks β-lactamase access

S aureus (except MRSA)

Hypersensitivity reaction. Interstitial nephritis

Aminopenicillins

Names? Spectrum?

MoA

Availability

Use

Tox

Resistance

Ampicillin and Amoxicillin. Wide spectrum

Same as penicillin.

AmOxicillin has greater Oral availability

“HELPSS kill Enterococci “

H influenzae, E coli, Listeria, Proteus, Salmonella, Shigella, Enterococci

Hypersensitivity rxn, Ampicillin rash, Pseudomembranous colitis

Penicillinase sensitive. Combine w/ Clavulanic acid to protect against β-lactamase

Antipseudomonals

Names

MoA? Spectrum?

Use

Tox

Resistance

Ticarcillin and Peperacillin

Same as penicillin. Extended spectrum

Pseudomonas and Gram- rods

Hypersensitivity rxn

Penicillinase. Use with Clavulanic acid

β-lactamase Inhibitors

“CAST”

Clavulanic Acid, Sulbactam, Tazobactam

Cephalosporins

MoA

Resistance

What does it do to bacteria

What bacteria can in kill?

Tox

β-lactam

Less susceptible to penicillinase

Does not kill “LAME” bugs

Listeria, Atypicals (chlamydia, Mycoplasma, MRSA, Enterococci

Ceftaroline covers MRSA

Hypersensitivity, VitK deficiency. ↑ nephrotoxicity of aminoglycosides

1st gen Cephalosporins

Names

Uses

Cefazolin, Cephalexin

Gram+ cocci, Proteus, E coli, Klebsiella

“PEcK”

Cefazolin used prior to surgery to prevent S aureus wound infection

2nd gen Cephalosporins

Names

Uses

Cefoxitin, Cefaclor, Cefuroxime

Gram+ cocci, Haemophilus, Enterobacter aerogenes, Neisseria, Proteus, E coli, Klebsiella, Serratia

“HEN PEcKS”

3rd gen Cephalosporins

Names

Uses

Ceftriaxone, Cefotaxime, Ceftazidime

Serous Gram- infections resistant to other β-lactam

Ceftriazone: Meningitis and Gonorrhea

Ceftazidime: Pseudomonas

4th gen Cephalosporins

Names

Uses

Cefepime

Pseudomonas and Gram+

Aztreonam

MoA

Resistance

Use

Tox

Monobactam. Prevents peptidoglycan cross-linking by binding PBP3

Resistant to β-lactamase

Gram- rods only. No activity against Gram+ or anaerobes (pseudomonas)

Used for penicillin allergy pts and those with renal insufficiency who cannot tolerate aminoglycosides

Generally nontoxic. Possible GI upset.

Carbapenems

Names

MoA

Co-administration w/...

Resistance

Use

Tox

Imipenem, Meropenem, Ertapenem, Doripenem

Broad spectrum β-lactam.

I is coadministered w/ Cilastatin (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules. M resistent to inactivation

Resistent to β-lactamase

Gram+ cocci, Gram- rods, and anaerobes

Only used when all else fails or life threatening

GI distress, Skin rash, CNS tox (seizures)

Vancomycin

MoA

What does it do to bacteria?

Use

Tox

Resistance

Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors

Bactericidal

Gram+ only. Multi-drug resistant organisms: MRSA, enterococci, C diff

“NOT so bad”

Nephrotoxic, Ototoxic, Thrombophlebitis (inflammation of a vein caused by a blood clot), Diffuse flushing - Red Man Syndrome (prevented by pretreatment with antihistamines and slow infusion rate)

Mutation of 2nd D-ala to D-lac

Protein Synthesis inhibitors

“Buy AT 30, CCEL (sell) at 50”

30S inhibitors:

Aminoglycosides (bactericidal), Tetracyclines (bacteristatic)

50S inhibitors (bacteristatic):

Chloramphenicol, Clindamycin, Erythromycin (macrolides), Linezolid (variable)

Aminoglycosides

Names

What does it do to bacteria?

MoA

Uptake

“Mean GNATS caNNOT kill Anaerobes”

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

Bactericidal

Inhibits formation of initiation complex and causes misreading. Blocks translocation

Needs O2 for uptake thus ineffective against anaerobes

Aminoglycosides

Use

Tox

Resistance

“Mean GNATS caNNOT kill Anaerobes”

Severe Gram- rods. Synergistic w/ β-lactams. N for bowel surgery

Nephrotoxic (esp w/ cephalosporins), Neuromuscular blockade, Ototoxic (esp w/ loops diuretics), Teratogen

Transferase enzyme that inactivates the drug by acetylation, phosphorylation or adenylation

Tetracylcines

Names

What does it do to bacteria?

MoA

Elimination

Do not take w/

Tetracycline, Doxycycline, Demeclocycline, Minocycline
Bacteriostatic
Binds 30S and prevents attachment of aminoacyl-tRNA
Demeclocycline is an ADH antagonist used to treat SIADH
Doxycycline fecally eliminated so it can be given to pts with renal failure
Do not take with milk, antaacids, iron b. divalent cations inhibit gut absorption

Tetracylcines

Use

Tox

Contraindications

Resistance

Borrelia burgdorferi, M pneumoniae, Rickettsia, and Chlamydia (accumulates in cells so good at killing last 2)
GI distress, discoloration of teeth and inhibition of bone growth in children. Photosensitivity
Pregnancy
↓ Uptake or ↑ efflux by plasmid encoded pump

Macrolides

Names

What does it do to bacteria

MoA

Use

Azithromycin, Clarithromycin, Erythromycin

Bacteriostatic

Blocks translocation ("macroSLIDES"). Binds 23S rRNA of 50S ribosome

Atypical pneumonia (Mycoplasma, Chlamydia, Legionella), STDs (Chlamydia), Gram+ cocci (strep in pts allergic to penicillin)

Macrolides

Tox

Resistance

"MACRO"
Motility issues, Arrhythmia (long QT), acute Cholestatic hepatitis, Rash, eOsinophilia. Increased serum concentration of theophyllines and oral anticoagulants
Methylation of 23S rRNA binding site

Chloramphenicol

What does it do to bacteria?

MoA

Use

Tox

Resistance

Bacteriostatic. Blocks peptidyltransferase at 50S
Meningitis (Haemophilus, N meningitidis, Strep pneumoniae)
Anemia, Aplastic anemia, Gray baby syndrome (in premies b/c lack of UDP glucuronyl transferase)
Plasmid encoded acetyltransferase inactivates drug

Clindamycin

What does it do to bacteria?

MoA

Use

Tox

Bacteriostatic. Blocks peptide transfer (transpeptidation) at 50S ribosomal subunit
Anaerobes (Bacteroides fragilis, C perfringens) in aspiration pneumonia or lung abscesses. Oral infections with mouth anaerobes
"Anaerobes above the diaphragm"
Pseudomembranous colitis (C diff overgrowth), Fever, Diarrhea

Sulfonamides

Names

What does it do to bacteria?

MoA

Use

Tox

Resistance

Sulfamethoxazole (SMX), Sulfisoxazole, Sulfadiazine
Bacteriostatic
PABA antimetabolite inhibits dihydropteroate syntahse
Gram+, Gram-, Nocardia, Chlamydia, UTIs
Hypersensitivity, Hemolysis (G6PD deficiency), Nephrotoxic (tubulointerstitial nephritis), Photosensitivity, Kernicterus (infants), Displace other drugs from albumin (warfarin)
Altered dihydropteronate synthase, ↓ uptake, ↑ PABA synthesis

Bacterial DNA, RNA, and Protein Synthesis

PABA + Pteridine --> [Dihydropteroate Synthase] --> Dihydropteroic acid --> Dihydrofolic acid --> [Dihydrofolate reductase] --> THF --> N methylene THF --> Purines (DNA and RNA), Thymidine (DNA), and Methionine (proteins)

Trimethoprim

What does it do to bacteria?

MoA

Used w/

Use

Tox

Bacteriostatic
Inhibits bacterial DHF reductase
Combined with SMX
UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia (treatment and prophylaxis)
"TMP: Treats Marrow Poorly"
Megaloblastic anemia, Leukopenia, Granulocytopenia. May alleviate w/ supplemental folic acid (Leucovorin rescue)

Fluoroquinolones

Names

What does it do to bacteria

Co-administration

MoA

Resistance

Ciprofloxacin, Norfloxacin, Levofloxacin, Olfoxacin, Sparfloxacin, Moxifloxacin, Gatifloxacin, Enoxacin. Nalidixic acid (quinolone)
Bactericidal. Do not take with antacids
Inhibits DNA gyrase (topoisomerase II) and topoisomerase IV
Chromosome-encoded mutation in DNA gyrase, Plasmid-mediated resistance, efflux pumps

Fluoroquinolones
Use
Tox
Contraindications

Gram- rods of Urinary and GI tracts (including Pseudomonas), Neisseria, Some Gram+ organisms
"LONES hurt your BONE attachments"
GI upset, Super-infections, Skin rashes, Headache, Dizziness. Tendonitis, Tendon rupture, Leg cramps, Myalgias, Long QT
Pregnant women, Children (damage to cartilage)

Metronidazole

What does it do to pathogens?

MoA

Use

Tox

Bactericidal. Antiprotozoal
Free radicals
"GET GAP on the METRO"
Giardia, Entamoeba, Trichomanas, Gardnerella vaginalis, Anaerobes below the diaphragm (Bacteroides, C diff), H pylori (w/ PPI and Clarithromycin)
Disulfiram-like reaction w/ EtOH, Headache, Metallic taste

Antimycobacterial Drugs

Tuberculosis
Prophylaxis: Isoniazid. Treatment: "RIPE" Rifampin, Isoniazid, Pyrazinamide, Ethambutol
M avium-intracellulare
Prophylaxis: Azithromycin. Treatment: Azithromycin, Rifampin, Ethambutol, Streptomycin
Leprae
Treatment: Tuberculoid form w/ Dapsone and Rifampin. Add Clofazimine for Lepromatous form

Isoniazid

Activation

MoA

Use

Tox

Bacterial catalase-peroxidase (KatG) converts INH into active metabolite

↓ synthesis of mycolic acids

TB

Neurotoxicity and Hepatotoxicity. Lupus

VitB6 prevents neurotoxicity

Rifampin

MoA

Use

Tox

"4Rs" RNA pol, Revs up P450, Red/Orange fluid, Rapid resistance if used alone

Inhibits DNA-dependent RNA pol

TB. Delays resistance to dapsone in leprosy. Meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B

Hepatotoxic. Drug interactions (↑ P450). Orange body fluid

Pyrazinamide

MoA

Use

Tox

Acidifies intracellular environment

TB

Hyperuricemia, Hepatotoxic

Ethambutol

MoA

Use

Tox

↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltranferase
TB
Optic neuropathy (Red-Green Color Blindess)

Meningococcal infection prophylaxis

Ciprofloxacin or Rifampin (for children)

Gonorrhea prophylaxis

Ceftriaxone

Syphilis prophylaxis

Benzathine Penicillin G

History of recurrent UTI prophylaxis

TMP-SMX

Endocarditis with surgical or dental procedures prophylaxis

Penicillins

Pregnant woman carrying GBS prophylaxis

Ampicillin

Strep Pharyngitis in child with prior RF prophylaxis

Oral penicillin

Post-surgical infection due to S aureus prophylaxis

Cefazolin

Gonococcal or Chlamydial conjunctivitis in newborns prophylaxis

Erythromycin ointment

HIV prophylaxis for CD4 less than 200

TMP-SMX for Pneumocystis pneumonia

| Aerosolized pentamidine used if pt cannot tolerate TMP-SMX but this may not prevent toxoplasmosis

HIV prophylaxis for CD4 less than 100

TMP-SMX for Pneumocystis pneumonia and Toxoplasmosis

| Aerosolized pentamidine used if pt cannot tolerate TMP-SMX but this may not prevent toxoplasmosis

HIV prophylaxis for CD4 less than 50

Azithromycin for Mycobacterium avium complex

Treatment of MRSA and VRE (enterococci)?

MRSA: Vancomycin
VRE: Linezolid and Streptogramins (quinupristin/dafopristin)

Amphotericin B

MoA

Use

Route

Supplement

Tox

How to reduce tox?

Binds ergosterol forming pores in membrane
Cryptococcus (w/ or w/o Flucytosine), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
Intrathecally for fungal meningitis
K and Mg to change renal tubule permeability
Fever/Chills ("shake and bake"), Hypotension, Nephrotoxic, Arrhythmias, Anemia, IV phlebitis
Hydration (for kidneys) and Liposomal form reduces tox

Nystatin
MoA
Use

Binds ergosterol forming pores in membrane

| "Swish and swallow" for oral candidiasis (thrush). Topical for diaper rash or vaginal candidiasis

Azoles

Names

MoA

Use

Tox

Fluconazole, Ketoconazole, Clotimazole, Miconazole, Itraconazole, Voriconazole
Inhibits fungal sterol (ergosterol) synthesis by inhibiting P450 that converts Lanosterol to Ergosterol
F for chronic suppression of Crytococcal meningitis in AIDS and Candidal infection of all types
I for Blastomyces, Coccidioides, Histoplasma
C and M for topical fungal infections
Inhibits Testosterone synthesis (gynecomastia), Liver dysfunction

Flucytosine
MoA
Use
Tox

Inhibits DNA and RNA synthesis by conversion to 5FU by cytosine daminase
Systemic fungal infections (esp miningitis by Cryptococcus) w/ Amphotericin B
Bone marrow suppression

Caspofungin, Micafungin
MoA
Use
Tox

Inhibits cell wall synthesis by inhibiting β-glucan
Invasive aspergillosis, Candida
GI upset, Flushing (by histamine release)

Terbinafine
MoA
Use
Tox

Inhibits fungal enzyme Squalene Epoxide
Dermatophytoses (onychomycosis)
LFTs, visual disturbances

Griseofulvin

MoA

Where does it accumulate?

Use

Tox

Interferes to MT function disrupting mitosis
Oral treatment for superficial infection.
Deposits in keratin containing tissues (nails)
Inhibits growth of dermatophytes (tinea, ringworm)
Teratogenic, Carcinogenic, Confusion, Headaches, ↑ P450 (warfarin metabolism)

Antiprotozoan Therapy

Pyrimethamine (toxoplasmosis), Suramin and Melarsoprol (Trypanosoma brucei), Nifurtimox (T cruzi), Sodium Stibogluconate (Leishmaniasis)

Chloroquine

MoA

Resistance

Use

Tox

Blocks detoxification of Heme into Hemozoin. Heme accumulates and is toxic to Plasmodia
Plasmodial species other than P falciparum
Membrane pump that ↓ intracellular concentration
Retinopathy

Treatment for Plasmodia falciparum

Artemether/lumifantrine or Atovaquone/Proguanil

Treatment for life-threatenting malaria

Quinidine (in US), Quinine (Elsewhere), Artisunate

Anti-Helminthic Therapy
Names
MoA

Mebendazole, Pyrantel Pamoate, Ivermectin, Diethylcarbamazine, Praziquantel (for flukes like Schistosoma)
Imobilizes helminths

Zanamivir, Oseltamivir
MoA
Use

Inhibits Influenza Neuraminidase decreasing release of progeny
Treatment and Prevention of Influenza A and B

Ribavirin
MoA
Use
Tox

Inhibits synthesis of Guanine by competitively inhibiting IMP dehydrogenase
RSV, HCV (chronic)
Hemolytic anemia, Teratogen

Acyclovir

MoA

Use

Better version?

Tox

Resistance

Guanosine analog that inhibits viral DNA pol by chain termination
HSV and VZV. Weak activity against EBV
HSV induced mucocutaneous or genital lesions and encephalitis. Prophylaxis for immunocompromised pts
No effect on latent HSV or VZV
Vanacyclovir has better bioavailability
Few toxicities
Mutated viral Thymidine kinase

Treatment for Herpes Zoster (Shingles)

Famciclovir

Ganciclovir

MoA

Use

Better version?

Tox

Resistance

Guanosine analog that inhibits viral DNA pol

CMV

Valganiciclovir is a prodrug with better bioavailability

Leukopenia, Neutropenia, Thrombocytopenia, Renal toxicity

Mutated CMV DNA pol or lack of viral kinase

Foscarnet

MoA

Use

Tox

Resistance

Pyrophosphate analog. Viral DNA pol inhibitor
CMV retinitis (when ganciclovir fails), HSV (when acyclovir fails)
Nephrotoxic
Mutated DNApol

Cidofovir

MoA

Use

Half life

Tox

Co-administration

Inhibits viral DNA pol
CMV retinitis, HSV (when acyclovir fails)
Long half-life
Nephrtoxic
Probenecid and IV saline to reduce toxicity

HAART
When is it initiated?
Regimen

AIDS-defining illness, low CD4 (below 500), High vial load

| 2 nucleoside RT inhibitors + 1 non-nucleoside RT inhibitor OR Protease inhibitor OR Integrase inhibitor

Protease inhibitors
Names
MoA
Tox

"Navir tease a protease"
-navir (Lopi, Ataza, Daru, Fosampre, Saqui, Rito, Indi)
Protease cleaves products of HIV mRNA into functional parts
Ritonavir can boost other [drug] by inhibiting P450
Hyperglycemia, GI intolerance (nausea, diarrhea), Lipodystrophy
Indinavir: Nephropathy and Hematuria

NRTI

Names

MoA

Activation

Uses

Tox

"Have you DINED with my NUCLEAR family"
Tenofovir (TDF), Emtricitabine (FTC), Abacavir (ABC), Lamivudine (3TC), Zidovudine (ZDV, AZT), Didanosine (ddl), Stavudine (d4T)
Competitive NT that gets used by RT but has not 3' OH --> early chain termination
TDF does not need activation. The rest need to phosphorylated
ZDV used as prophylaxis during pregnancy
Bone marrow suppression (reversible w/ G-CSF and EPO), Peripheral neuropathy, Lactic Acidosis, Anemia (ZDV)

NNRTIs

Names

MoA

Activation

Tox

Nevirapine, Efaverenz, Delavirdine
Inhibits RT
Does not require phosphorylation
Bone marrow suppression (reversible w/ G-CSF and EPO), Peripheral neuropathy, Rash, Anemia (ZDV)

Integrase Inhibitors
Names
MoA
Tox

Raltegravir
Inhibits HIV genome integration into host cell chromosome
Hypercholesterolemia

Interferons

What is it? What produces it?

MoA

Use

Tox

Glycoprotein synthesized by virus-infected cells.
Blocks replication of both RNA and DNA viruses
IFNα: chronic HBV or HCV, Kaposi sarcoma
IFNβ: MS
IFNγ: NADPH oxidase deficiency
Neutropenia, Myopathy

Antibiotics to avoid during pregnancy

"SAFe Children Take Really Good Care"

Sulfonamides (Kernicterus), Aminoglycosides (Ototoxic), Fluoroquinolones (Cartilage damage), Clarithromycin (Embryotoxic), Tetrocycline (Discolored teeth, inhibition of bone growth), Ribavirin (teratogenic), Griseofulvin (Teratogenic), Chloramphenicol (gray baby)

Killed Influenza Vaccine

Generates Abs to H preventing entry of viral particles into the cells