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Antimicrobials Flashcards

1
Q

Penicillin G (IM/IV), V (oral) mechanism

A

Binds transpeptidases –> blocks cross-linking of peptidoglycans (cell wall)

  • Also activates autolytic enzymes
  • Penicillinase sensitive

**Prototype B-lactam antibiotics

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2
Q

Penicillin G, V use

A

Gram + cocci, rods, gram neg cocci, spirochetes
- Mostly: S. pneumo, S. pyogenes, Actinomyces

Tox: hypersensitivity rxn, hemolytic anemia
Resistant: penicillinase in bacteria (B-lactamase, cleaves B-lactam ring)

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3
Q

Amoxicillin, Ampicillin mechanism

A

Amox (oral), amp (IV)

  • Binds transpeptidase, blocks cross link of peptidoglycans
  • Combines with clavulanic acid to protect from B-lactamase
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4
Q

Amoxicillin, Ampicillin use

A 
Extended-spectrum penicillin
"Amp/amox HELPSS kill enterococci"
- H. influenza
- E. coli
- Listeria
- Proteus
- Salmonella
- Shigella
- Enterococci

Tox: hypersensitivity rxn, rash, C. diff
Resistance: penicillinase in bacteria (B-lactamase, cleaves B-lactam ring)

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5
Q

Oxacillin, nafcillin, dicloxacillin mechanism

A
  • Binds transpeptidase, blocks cross link of peptidoglycans
  • Penicillinase-resistant penicillins (bulky R group blocks B-lactamase from binding B-lactam ring)
  • Narrow spectrum
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6
Q

Oxacillin, nafcillin, dicloxacillin use

A

S. aureus (except MRSA)
- “Naf for staph”

Tox: hypersensitivity rxn, interstitial nephritis

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7
Q

Ticarcillin, piperacillin mechanism

A

Antipseudomonals

- Binds transpeptidase, blocks cross link of peptidoglycans

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8
Q

Ticarcillin, piperacillin use

A

Pseudomonas spp + gram-neg rods
- Susceptible to B-lactamase, use w/ B-lactamase inhibitors

Tox: hypersensitivity rxn

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9
Q

B-lactamase inhibitors

A

CAST

  • Clavulanic Acid
  • Sulbactam
  • Tazobactam

*Add to penicillin abx to protect from destruction from B-lactamase

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10
Q

Cephalosporins (Gen I-V) mechanism

A

B-lactam drugs that inhibit cell wall synthesis
*Less sensitive to penicillinases

Those NOT covered are LAME:

  • Listeria
  • Atypicals (chlamydia/mycoplasma)
  • MRSA (except 5th gen = ceftaroline)
  • Enterococci
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11
Q

1st generation cephalosporins

A

Cefazolin, cephalexin

  • Gram + cocci and PEcK (Proteus, E. coli, Klebsiella)
  • Use prior to surgery to prevent wound infections (S. aureus)
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12
Q

2nd generations cephalosporins

A

Cefoxitin, cefaclor, cefuroxime

- Gram + cocci and HEN PEcKS - (H. influneza, Enterobacter, Neisseria, Proteas, E. coli, Klebsiella, Serratia)

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13
Q

3rd generation cephalosporins

A

Ceftriaxone, cefotaxime, ceftazidime
- Serious gram neg resistant to other B-lactams

  • Ceftriaxone = meningitis/gonorrhea
  • Ceftazidime = pseudomonas
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14
Q

4th generation

A

Cefepime

- Incr activity against pseudomonas + gram pos

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15
Q

5th generation

A

Ceftaroline

  • Broad spectrum gram pos and gram neg organisms
  • Includes MRSA, not pseudomonas
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16
Q

Azotrenam mechanism

A

Monobactam, resistant to B-lactamases

  • Prevents peptidoglycan cross-linking by binding pencillin-binding protein 3
  • Synergistic with aminoglycosides
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17
Q

Azotrenam use

A

Gram neg rods only (none for gram +)
- Good for those w/ penicillin allergy and renal insuffic (can’t tolerate aminoglycosides)

Tox: GI upset, non-toxic
*No cross-allergenicity w/ penicillins

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18
Q

Carbapenems mechanism

A

Imipenem, meropenem, ertapenem, doripenem

  • Broad spectrum, B-lactamase resistant
  • Give with cilastatin (inhib renal dehydropeptidase I) - decr inactivation in renal tubules
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19
Q

Carbapenem use

A

Gram + cocci, gram neg rods, anaerobes (wide spectrum)
- Significant side effects –> only use for life threatening infections

Tox: GI distress, skin rash, CNS tox (sz) at high plasma levels
*Mirapenem = decr sz risk, stable to dehydropeptidase I

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20
Q

Vancomycin mechanism

A

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

  • This is the main component of gram + cell wall!
  • pay back 2 D-alas (dollars) for vandalizing (vanc)*
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21
Q

Vancomycin use

A

Gram pos only!
- Serious, multi-drug resistant organisms: MRSA, enteroccic, C. diff (oral)

Tox - well tolerated but NOT Really trouble free (Nephrotoxicity, Ototoxicity, Thrombophlebitis), diffuse flushing (Red man syndrome; pre-tx with antihistamine/slow infusion)

Resist: bacteria with D-ala D-ala –> D-ala D-lac modification

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22
Q

Inhibitors of cell wall synthesis

A
  • Penicillin-sensitive penicillins: Pen G/V, amox, ampicillin
  • Penicillin-resistant penicillins: oxacillin, nafcillin, dicloxacillin
  • Antipseudomonas: ticarcillin, piperacillin
  • Cephalosporins: 1 (cephazolin, cephelexin), 2 (cefoxitin), 3 (ceftriaxone), 4 (cefepime), 5 (ceftaroline)
  • Carbapenems: imipenem, meripenem, (ertapenem/doripenem = new)
  • Bind transpeptidase (needed to cross-link peptidoglycans)
  • Azotreonam
  • Binding pencillin-binding protein 3
  • Glycopeptides (vancomycin, bacitracin)
  • Binding precursor D-ala D-ala
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23
Q

Inhibitors of protein synthesis

A

Target smaller bacterial ribosome (70S made of 30S and 50S subunits) –> leaves human ribosome unaffected (80S)

30S inhibitors:

  • A = aminoglycosides
  • T = tetracyclines (bacteriostatic) –> block A-site tRNA binding (block aminoacyl-tRNA attachment)

50S inhibitors:

  • C = chloramphenicol, clindamycin (bacteriostatic) –> peptidyl transferase
  • E = erythromycin (macrolides); (bacteriostatic) –> translocation
  • L = Linezolid (variable) –> block 50S

**“buy AT 30, CCEL (sell) at 50”

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24
Q

Aminoglycosides mechanism

A

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin (GNATs)

  • Bactericidal –> binds 30S, inhibits initiation complex formation
  • *Needs O2 for uptake (doesnt work against anerobes)
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25
Aminoglycosides use
Severe gram neg rod infections - Synergistic with B-lactam antibiotics - Give neomycin for bowel surgery Tox: NNOT - nephrotocixity (w/ cephalosporins), neuromusc blockade, ototoxicity (w/ loop diuretics), teratogen **"Mean (aminoglycosides) GNATS caNNOT kill anaerobes" Resist: bacterial transferase enzymes inactivate drug by acetylation, phosphorylation or adenylation
26
Tetracyclines mechanism
Tetracycline, doxycycline, minocycline - Bacteriostatic --> binds 30S, prevent attachment of aminoacyl-tRNA * Doxy elimated fecally (can use in renal pts) * Don't take milk, antacids or iron bc divalent cations inhibit gut absorption of tetracyclines
27
Tetracyclines use
- Borrelia burgforderi, M. pneumoniae, - Rickettsia, chlamydia (good bc drug accum intracellularly, very effective) - Acne Tox: GI distress, discolored teeth/bone in growing kids/fetus (contranind in pregn), photosensitivity Resist: decr uptake/incr efflux out of bacterial cells by plasmid-encoded transport pumps
28
Macrolides mechanism
Azithromycin, clarithromycin, erythromycin | - Block translocation ("macroSlides") bc binding 23S rRNA of 50S
29
Macrolides use
- Atypical pneumonias (mycoplasma, chlamydia, legionella) - STDs (chlamydia) - Gram + cocci (strep infections if allergic to penicillins) Tox: MACRO - gastric Motility issues - Arrhythmia from prolonged QT - acute Cholestatic hepatitis - Rash - eOsinophilia * Incr serum conc of theophyllines, oral anticoags Resist: binding 23S rRNA binding site (drug can't bind)
30
Chloramphenicol mechanism
Blocks peptidyltransferase at 50S --> this blocks transfer from A to P on ribosome
31
Chloramphenicol use
Meningitis (H. flu, Neisseria, S. pneumoniae), Rocky mountain spotted fever (rickettsia) Tox: anemia (dose dependent, reversible), aplastic anemia (dose dep, irreversible), gray baby syndrome (premies bc lack liver UDP-glucuronyl transferase) Resist: plasma-encoded acetyltransferase inactivates drug
32
Clindamycin mechanism
Blocks translocation (peptide transfer) at 50S
33
Clindamycin use
- Anaerobic infections (bacteriodes, clostridium) in aspiration pneumo, lung abscesses, oral infections - Invasive group A strep * *Treats anaerobes ABOVE diaphragm (metronidazole below) Tox: C. diff, fever, diarrhea
34
Inhibitors of folic acid synthesis
- Sulfonamides - block dihydropteroate synthase - Trimethoprim - block dihydrofolate reductase **Need this pathway to make DNA/RNA, proteins**
35
Sulfonamides mechanism
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine | - Inhibit folate syntheis (PABA to DHT): PABA antimetabolites inhibit dihydropteroate synthase
36
Sulfonamides use
Gram +, gram neg, Nocardia, Chlamydia - Simple UTI - triple sulfa or SMX Tox: hypersensitivity rxn, hemolysis if G6DP defic, nephrotoxic (tubulointerstitial nephritis), photosensitive, kernicterus in infants Resist: altered enzyme (dihydropteroate synthase), decr uptake or incr PABA synthesis
37
Trimethoprim mechanism
Inhibits bacterial dihydrofolate reductase (DHT --> THF) | *Use w/ sulfonamides = sequential block of folate synth (TMP-SMX)
38
Trimethoprim use
Combo with sulfas (TMP-SMX = bactrim) for: UTIs, shigella, salmonella, PCP pneumonia tx/ppx, toxo ppx Tox: megaloblastic anemia, leukopenia, granulocytopenia (folinic acid can alleviate) *TMP - Treats Marrow Poorly
39
Fluoroquinolones mechanism
Ciprofloxacin, norfloxacin, levofloxacin, etc. - Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV * Dont take with antiacids
40
Fluoroquinolones use
Gram neg rods for URI/GI tract (incl pseduomonas), neisseria, some gram + Tox: GI upset, superinfect, skin rash, HA, dizziness - Tendonitis, tendon rupture (>60yo, taking prednisone), leg cramps, myalgias - May damage cartilage (dont use in pregn, nursing moms, kids <18) - Prolonged QT * fluoroquinoLones hurt attachments to your bones* Resist: chromosome-encoded DNAgyrase mutation, efflux pumps
41
Metronidazole mechanism
Damages DNA | - Forms free radical toxic metabolites in bacterial cell --> damages DNA
42
Metronidazole use
GET GAP on metro with metronidazole - Giardia - Entamoeba - Trichomonas - Gardnerella vaginalis - Anaerobes (Bacterioides, C. diff) - h. Pylori (use metronid + clarithromycin + PPI for triple therapy) Tox: disulfiram-like rxn (severe flushing, tachy, hypotension) w/ alcohol; HA, metallic taste
43
Antimycobacterial drugs
Mycobacterium TB - PPx = isoniazid - Tx = RIPE (rifampin, isoniazid, pyrazinamide, Ethambutol) MAC - more resistance than TB - PPx = azithromycin, rifabutin - Tx = Azithro/clarithro + ethambutol (can add rifabutin or cipro) M. leprae - no ppx - Tx = dapsone + rifampin (tuberculoid form); add clofazimine for lepromatous form
44
Rifamycins mechanism
Rifampin, rifabutin | - Inhibits DNA-dependent RNA polymerase
45
Rifamycins use
Rifampin: - Mycobacterium TB - Leprosy (delays resistance to dapsone) - Meningococcal and HiB ppx (exposure) Tox: - Hepatotoxicity - Orange body fluids (nonhazardous) - Drug interactions (stim p450) - less w/ rifabutin (favored in HIV) * RifAMP RAMPS up cytochrom p450, BUT rifaBUTin doesn't* * 4 R's of rifampin: - RNA polymerase inhib - Ramps up cytochrome p450 - Red/orange body fluids - Rapid resistance if use alone
46
Isoniazid (INH) mechanism
Decreased synthesis of mycolic acids (which make cell wall) | - Need bacterial catalase-peroxidase to convert INH to active metabolite
47
INH use
M. TB tx (RIPE) and as ppx (alone) Tox: INH Injurs Neurons and Hepatocytes - Neurotox, hepatotoxicity * Pyridoxine (B6) can prevent neutrotox/lupus*
48
Pyrazinamide mechanism
Acidify environment by converting to pyrazinoic acid | - Effective in phagolysosomes --> TB engulfed by macrophages found here
49
Pyrazinamide use
TB (RIPE) Tox: hyperuricemia, hepatotoxicity
50
Ethambutol mechanism
Blocks arabinosyltransferas --> decr carb polymerization of mycobacterium cell wall
51
Ethambutol use
TB (RIPE), and MAC (azithro/clarithro + ethambutol) Tox: optic neuropathy (red-green color blindness)
52
PPx for endocarditis w/ surgery/dental procedure
Penicillin
53
Ppx for gonorrhea
Ceftriaxone
54
Ppx for recurrent UTIs
TMP-SMX
55
Ppx for meningococcal infection
Cipro; rifampin for kids (dont give to kids bc fluroquinolones hurt cartilage)
56
PPx for pregn woman w/ GBS
Ampicillin
57
Prevent gonococcal/chlamydia conj in newborn
Erythromycin ointment
58
Prevent post-surgical infection from S. aureus
Cefazolin
59
PPx of strep pharyngitis w/ previous rheumatic fever
Oral penicillin
60
Syphillis
Benzathine penicillin G
61
PPx in HIV pts
CD4 <50 azithro for MAC
62
Treating highly resistant bacteria
MRSA - vanc, daptomycin, linezolid | VRE - linezolid, streptogramins (-"pristins")
63
Antifungal therapy - formation of membrane proteins
- Amphotericin B | - Nystatin
64
Amphotericin B mechanism
``` Binds ergosterol (unique to fungi) --> forms membrane pore --> leakage of electrolytes *AmphoTERicen TEARs hole in fungal membrane (pores) ```
65
Amphotericin use
Serious systemic mycoses - Cryptococcus, blastomyces, coccidioides, histoplasma, candida, mucor - Intrathecally for meningitis * Supplement K+ and Mg2+ bc altered renal tubule permeability Tox: fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrythmias (hypokalemia), anemia, IV phlebitis * Amphoterri-ble* --> liposomal amphotericin has less tox - Hydration reduces nephrotoxicity
66
Nystatin mechanism
``` Binds ergosterol (unique to fungi) --> forms membrane pore --> leakage of electrolytes **To toxic for systemic, use TOPICAL* ```
67
Nystatin use
- "Swish and swallow" for oral candidiasis (thrush) | - Topical for vaginal rash/vaginal candidiasis
68
Antifungal therapy - inhibit ergosterol synthesis
Azoles!
69
Azoles mechanism
Inhibit fungal sterol (ergosterol) synthesis by inhib cytochrom p450 enzyme (1,4 a-demethylase) converting lanosterol to ergosterol
70
Azoles use
Local/less serious systemic mycoses - Fluconazole - chronic suppression of candidal infect and cryptococcal meningitis in AIDS pts - Itraconazole for blastomyces, coccidioides, histoplasma - Clotrimazole/miconazole - topical fungal infections Tox: - Inhibits testosteron synthesis (gynecomastic) esp ketoconazole - Liver dysfxn (inhib cytochrom p450)
71
Antifungal therapy - inhibit nucleic acid synthesis
Flucytosine
72
Flucytosine mechanism
Inhibits DNA/RNA synthesis by converting U to 5-flurouracyl (cytosine deaminase)
73
Flucytosine use
Systemic fungal infections (esp meningitis from cryptococcus) in combo with amphotericin B Tox: bone marrow suppression
74
Antifungal therapy - inhibit cell wall synthesis
Echinocandins ('fungins) = caspofungin, micafungin, anidulafungin
75
Echinocandins mechanism
'fungins | - Inhibit cell wall synthesis by inhibiting synth of B-glucan (B-D-glucan)
76
Echinocandins use
Invasive aspergillosis, candida Tox: GI upset, flushing (histamine release)
77
Antifungal therapy - inhibit lanosterol synthesis
Terbinafine
78
Terbinafine mechanism
Inhibits fingal enzyme squalene epoxidase (lanosterol synthesis)
79
Terbinafine use
Fermatophytoses (esp onychomycosis - fungal infection of finger/toe nails) Tox: GI upset, HA, hepatotox, taste disturbance
80
Griseofulvin mechanism
Interferes with microtubule formation --> disrupts mitosis | - Deposit in keratin-containing tissues (nails)
81
Griseofulvin use
Oral tx of superficial infections; inhibits growth of dermatophytes (tinea, ringworm) Tox: teratogenic, carcinogenic, confusion, HA, incr p450 and warfarin metab
82
Antiprotozoan therapy - Toxo - Trypanosoma brucei - T. cruzi - Leishmaniasis - Plasmodium (except falciparum) - P. falciparum
- Toxoplasmosis - pyrimethamine - Trypanosoma brucei - suramin/melarsoprol - T. cruzi - nifurtimox - Leishmaniasis - sodium stibogluconate - Plasmodium - chloroquine (except P. falciparum) - P. falciparum - artemether/lumefantrine or atovaquone/proguanil
83
Chloroquine mechanism
Blocks detox of heme into hemozoin --> heme accumulates, toxic to plasmodia
84
Chloroquine use
Plasmodia (except P. falciparum bc resistant) - Resist: membrane pump that decr intracellular concentration of drug - If life-threatening use quinidine (US) or quinine (elsewhere) Tox: retinopathy, pruritis (esp in dark-skinned people)
85
Antihelminthic therapy
Mebendazole, pyrantel pamoate, ivermectin, diethycarbamazine, praziquantel - Immobilizes helminths **Use praziquantel against flukes (trematodes) like schistosoma
86
Zanamivir, oseltamivir
Inhibit influenza neuraminidase, decreases release of progeny virus - Tx/prevention of influenza A/B
87
Ribavarin
Inhibits guanine nucelosides by inhibiting inosine monophosphage dehydrogenase - Tx RSV/chronic HCV Tox = hemolytic anemia, severe teratogen
88
Acyclovir/famciclovir, valacyclovir
Monophosphorlayed by HSV/VZV thymidine kinase (not phosphorylated by uninfected cells = few SEs) - Inhibits viral DNA polymerase by chain termination - Use for: HSV/VZV, weak activity for EBV, none for CMV - HSV lesions/encephalitis (valacyclovir = better oral bioavailability) - Tox = obstructive crystalline nephropathy/acute renal failure (w/o hydration) - Resist: mutated thymidine kinase
89
Ganciclovir
Phosphorylated to monophosphate, then to triphosphate (more in infected cells than uninfected) - Guanosine analog - Inhibits viral DNA polymerase - Tx - CMV (esp immunocompromised) - Tox - leukopenia, neutropenia, thrombocytopenia, renal tox * More toxic than acyclovir - Resistance: mutated CMV DNA polymerase or lack of viral kinase
90
Foscarnet and Cidofovir
Viral DNA polymerase inhibitor, binds pyrophosphate binding site of enzyme *Doesnt need to be activated by viral kinase - Tx - CMV retinitis (when ganclyclovir fails) or acyclovir-resistant HSV - Tox = nephropathy (+ electrolyte imbalance) - Resist: mutated DNA polymerase
91
HIV therapy
HAART - give when CD4 3 drugs | - 2NRTIs + 1NNRT/protease inhib/integrase inhibitor

Microbiology (7 decks)

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