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Antibiotics > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Amphotericin B

A

Antifungal (polyene)

cryptococcus meningitis w/ 5-FC; zygomycosis

IV-inpatient

binds to ergosterol and forms channels in fungal cell membrane, oxidative damage

Yeast and filamentous fungi:

Toxicity: nephrotoxicity and infusion related toxicity

Hepatic and renal excretion

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2
Q

Nystatin

A

Antifungal (polyene)

Topical candidiasis

Topical: oral, cutaneous, vaginal

binds to ergosterol and forms channels in fungal cell membrane, oxidative damage

*not systemically absorbed

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3
Q

Clotrimazole/Miconazole

A

Antifungal (azole)

topical - dermatophyte, candidiasis

inhibits lanosterol C-14 demethylase and ergosterol synthesis

*not systemically absorbed

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4
Q

Ketoconazole

A

Antifungal (azole)

shampoo for tinea capitis/tinea versicolor

topical; PO

inhibits lanosterol C-14 demethylase and ergosterol synthesis

Toxicity: hepatotoxic

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5
Q

Fluconazole

A

Antifungal (azole)

candidiasis; cryptococcus maintenance

PO, IV

inhibits lanosterol C-14 demethylase and ergosterol synthesis

Excretion: mostly renal and some hepatic

Toxicity: hepatotoxic

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6
Q

Itraconazole

A

Antifungal (azole)

endemic mycoses: Histo, Blasto, Cocci

PO

inhibits lanosterol C-14 demethylase and ergosterol synthesis

spectrum: yeasts and filamentous fungi

Toxicity: hepatotoxic

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7
Q

Voriconazole

A

Antifungal (azole)

Aspergillosis

PO/IV

inhibits lanosterol C-14 demethylase and ergosterol synthesis

spectrum: yeasts and filamentous fungi

Toxicity: hepatotoxic, hallucinations, rash

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8
Q

Posaconazole

A

Antifungal (azole)

2nd for aspergillosis; prophylaxis

PO

inhibits lanosterol C-14 demethylase and ergosterol synthesis

spectrum: yeasts and filamentous fungi

Toxicity: hepatotoxic

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9
Q

5-Flurocytosine

A

Antifungal (pyrimidine analog)

Cryptococcus w/ Amphotericin B

PO

inhibits thymidylate synthase and DNA/RNA synthesis

spectrum: yeasts

RENAL excretion

Toxicity: myelosuppression (pancytopenia), diarrhea, check AST and ALT

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10
Q

Terbinafine

A

Antifungal (allylamine)

Dermatophytes

PO, topical

inhibits squalene epoxidase and ergosterol synthesis

Toxicity: hepatotoxic

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11
Q

Caspofungin

Micafungin

Anidulafungin

A

Antifungal (echinocandin)

Candidemia, Aspergillus

IV

inhibits cell wall synthesis (1,3 beta glucan formation)

Toxicity: hepatotoxic

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12
Q

Trimethoprim-Sulfamethoxazole

TMP-SMX

A

Folic Acid Anti-Metabolites

Uses: UTI, respiratory, GI (sinusitis, otitis media)

trimethoprim: dihydrofolate reductase (50,000x more senstitive for bacterial enzyme)
sulfamethoxazole: mimic PABA- dihydropteroate synthetase (not in mammals)

*synergistic effects

PO-outpatient/IV - 2/3 daily doses

Spectrum: Broad: Gram negative, some protozoa and fungi,

more use against S. aureus

Excellent tissue penetration: urine, prostate, CSF

Resistance:

TMP: plasmid dhfr gene, transposons, integrons

SMX: plasmid, chromosomal mutation

Adverse Effects:

rash, nausea, vomiting, headache

hyperkalemia, hepatitis, pancreatitis

Stevens-Johnson syndrome, Toxic epidermal necrolysis, aplastic anemia, thrombocytopenia, hemolytic anemia

Pregnancy- kernicterus, displaces bilirubin from albumin

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13
Q

Ciprofloxacin

A

DNA Inhibitors- Fluroquinolone

Uses: UTI

DNA gyrase (topo II) creates supercoils; drug stabilizes enzyme-DNA complex with double stranded breaks-> chromosome fragmentation “bacteriocidal” genes gyr A and gyrB

PO-outpatient/IV BID

Spectrum: Gram negative, Atypicals, Mycobacteria

Good oral bioavailability

**Resistance: **

mutations in target enzyme gyrA, efflux pumps, plasmids

Adverse Effects:

safe, nausea, vomiting, abdominal pain

serious: prolongs QT interval in combination with other medications, tendon rupture, arthropathy??in children

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14
Q

Moxifloxacin

A

DNA Inhibitors- Fluroquinolone

Uses: pneumonia, mycobacterial

topo IV deconcatenates intertwined supercoils genes parC and parE

PO-outpatient/IV BID

Spectrum: Gram positive, Gram negative, Atypicals, Mycobacteria, Anaerobes

Good oral bioavailability; poor urinary penetration

NOT FOR UTIs

**Resistance: **

mutations in target enzyme parC, efflux pumps, plasmids

Adverse Effects:

safe, nausea, vomiting, abdominal pain

serious: prolongs QT interval in combination with other medications, tendon rupture, arthropathy??in children

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15
Q

Nitrofurantoin

A

DNA Inhibitors

UTIs FIRST LINE

relevant mechanism unclear

PO ONLY qID good urine levels

Spectrum: Gram negative, Gram positive uropathogens NOT pseudomonas, proteus, serratia, marcescens

Resistance rare but can develop with repeated use

Adverse effects: nausea, pulmonary fibrosis rare but can have acute pulmonary reactions

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16
Q

Rifampin

A

RNA Inhibitors

bind B subunit of RNA polymerase and block transcription, bacteriostatic

PO/IV qD-BID

Resistance due to mutations in binding pocket at 10-8, rapid due to mutations in target enzyme, frequenty pre-existing in population

Metabolism: potent inducer of P450 3A4

Spectrum: prophylaxis, N. meningitites, S. aureus, w/other antimicrobials for Mycobacterium infections

Adverse effects: turns secretions orange, GI- pain, nausea, vomiting, diarrhea, Heme- mild thrombocytopenia, Hepatits

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17
Q

Rifabutin

A

RNA Inhibitors

bind B subunit of RNA polymerase and block transcription, bacteriostatic

PO

Metabolism: less inducer of P450 3A4 but be aware

Spectrum: prophylaxis, N. meningitites, S. aureus, w/other antimicrobials for Mycobacterium infections

Adverse effects: turns secretions orange, GI- pain, nausea, vomiting, diarrhea, Heme- mild thrombocytopenia, Hepatits

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18
Q

Rifaximin

A

RNA Inhibitors

bind B subunit of RNA polymerase and block transcription, bacteriostatic

PO

*Not absorbed

Spectrum: GI: travelers’ diarrhea, C. difficile

Adverse effects: turns secretions orange, GI- pain, nausea, vomiting, diarrhea, Heme- mild thrombocytopenia, Hepatits

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19
Q

Fidaxomicin

A

RNA Inhibitors

blocks RNA polymerase, prevents formation of open DNA complex

*Not absorbed- PO

Spectrum: C. difficile

No serious side effects, very expensive, no resistance described

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20
Q

** Penicillin G**

A

Penicillin

Uses: syphilis, strep A, B, pneumo, dental abscesses

IM/IV q4h IV, q12h IM w/procain, qweek w/ benzathine

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Resistance: penicillinase (B-lactamase)

Adverse: hypersensitivity, seizures in high doses

21
Q

** Ampicillin**

A

Aminopenicillin

CAQ: HEENT, UTI

IV/PO q4-6h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas

Spectrum: gram positive, more gram negative, some anaerobes

Resistance: penicillinase (B-lactamase)

Adverse: hypersensitivity, seizures in high doses

22
Q

** Amoxicilin**

A

Aminopenicillin

CAQ: HEENT, UTI

NOT for mono-> maculopapular rash

PO TID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas

Spectrum: gram positive, more gram negative (see above), some anaerobes

Resistance: penicillinase (B-lactamase)

Adverse: hypersensitivity, seizures in high doses

23
Q

** Nafcillin/Dicloxacillin**

A

Semisynthetic penicillin

Uses: MSSA

nafcillin- IV q4-6hr dicloxacillin PO QID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

bulky R group cant fit into many B-lactamases

Spectrum: GRAM POSITIVE ONLY, can’t penetrate Gram negative cell wall

Resistance: altered PBP, PBP2a encoded by mecA gene- MRSA

Adverse: hypersensitivity, seizures in high doses

24
Q

Piperacillin

A

Antipseudomonal penicillin

Uses: Pseudomonas coverage

IV q4h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, gram-negative, Pseudomonas

Resistance limits use

Adverse: hypersensitivity, seizures in high doses

25
Q

** Ampicilin-Sulbactam**

A

Aminopenicillin

CAQ: HEENT, UTI

IV q6h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas

Spectrum: gram positive, more gram negative (see above), some anaerobes

ADDED STAPHYLOCOCCUS and B-lactamase anaerobes

Adverse: hypersensitivity, seizures in high doses

26
Q

** Amoxicilin-Clavulanic Acid**

A

Aminopenicillin

CAQ: HEENT, UTI

PO TID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas

Spectrum: gram positive, more gram negative (see above), some anaerobes

ADDED Staphylococcus and B-lactamase anaerobes

Adverse: hypersensitivity, seizures in high doses

27
Q

Piperacillin-Tazobactam

A

Antipseudomonal penicillin

Uses: Pseudomonas coverage

IV q6h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, gram-negative, Pseudomonas

ADDED STAPHYLOCOCCUS and B-lactamase producing anaerobes

Adverse: hypersensitivity, seizures in high doses

28
Q

Cefazolin

A

1st Gen Cephalosporin

Uses: Surgical prophylaxis; skin. soft tissue infections

IV q8h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, limited Gram negative

Pseudomonas and Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

29
Q

Cephalexin

A

1st Gen Cephalosporin

Uses: Surgical prophylaxis; skin. soft tissue infections

PO QID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, limited Gram negative

Pseudomonas and Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

30
Q

Cefoxitin

A

2nd Gen Cephalosporin

Uses: intraabdominal surgery prophylaxis

PO QID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, increasing Gram negative, excellent anaerobe

Pseudomonas and Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

31
Q

Ceftriaxone

A

3rd Gen Cephalosporin

Uses: serious infections; CAQ pneumonia, meningitis

IV qD good tissue penentration, long half life

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, excellent Gram negative

Pseudomonas and Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

32
Q

Ceftazidime

A

3rd Gen Cephalosporin

Uses: Activity against PSEUDOMONAS

IV qD good tissue penentration, long half life

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, excellent Gram negative

Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

33
Q

Ceftazidime

A

4th Gen Cephalosporin

Uses: serious infections

IV q12h good tissue penentration, long half life

Spectrum: broad: gram positive, excellent Gram negative INCLUDING PSEUDOMONAS

Very resistant to B-lactamases, Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

34
Q

Ceftaroline

A

5th Gen Cephalosporin

Uses: serious infections

IV good tissue penentration, long half life

Spectrum: broad: gram positive INCLUDING MRSA, Gram negative W/O pseudomonas

BInds PBP2a, very resistant to B-lactamases, Enterococci intrinsically resistant

Generally well tolerated

Some cross-reactivity with Penicillin allergy

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

35
Q

Aztreonam

A

Monobactam

Uses: B-lactam allergy, limited

IV q8h

Spectrum: GRAM NEG ONLY

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

36
Q

Imipenem

Doripenem

Ertapenem

A

Carbapenems

Uses: empiric treatment for serious infections, resistant infections

IV q8h

Spectrum: BROAD Gram positive, Gram negative including pseudomonas, anaerobes

Resistance: typically resistant to B-lactamases, emergence of carbapenem-hydrolyzing B-lactamases

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

**ertapenem- doesn’t have activity against pseudomonas or acinetobacter

37
Q

Vancomycin

A

Glycopeptides

Uses: inferior to B-lactams, empiric treatment for serious infections, resistant Gram positive Oral C. Diff infection

IV q12h (*renally excreted, dose adjustment)

binds to terminal D-ala, D-ala inhibits cell wall synthesis transglycosylase and transpeptidase, bactericidal

Spectrum: GRAM POSITIVE ONLY: MRSA, enterococci, GP anaerobes, streptococcus

Resistance:vanA-E changes NAM terminal peptide VISA- thickened cell wall, dec penetration

Adverse Effects: Red Man Syndrome- infusion reaction, nephrotoxic, dose-dependent ototoxicity

38
Q

Daptomycin

A

Cyclic Lipopeptide

Uses: complicated GP infections, skin/soft tissue infections, bacteremia/endocarditis

IV q24hr

lipid tail inserts into cell mbr, mem depol./K efflux, cessation of vital processes, cell death w/o lysis; bactericidial

Spectrum: ONLY GRAM POS, includes MRSA, enterococci VRE, GP anaerobes

Adverse Effects: GI, headache, elevated CPK/rhabdomyolysis (monitor, avoid statins)

39
Q

Polymyxin B

A

Other

Uses: serious- GN , inhaled resistant GN pneumonia

IV q12hr

Spectrum: GRAM NEGATIVE ONLY

Adverse Effects: significant toxicities (nephrotoxicity, neurotoxic, inhaled ->bronchospasm)

40
Q

Bacitracin

A

Other

topical GRAM POSITIVE only Strep pyogenes, Staph

41
Q

Fosfomycin

A

Other: UTI

oral powder 1 dose

GRAM POS AND GRAM NEG

42
Q

Amikacin / Gentamicin

A

Aminogylcosides, IV only

Mech: binds 30S subunit causing misreading/terminates genetic code

Spectrum: primarily GN (includes Pseudomonas) no anaerobes, Other: MB, Yersinia pestis, Francisella tularensis

**synergy with B-lactams, allow aminoglycosides to enter gram positive cell wall

PK/PD: bactericidal or static depending on concentration; inhibited by acidic environment does not work in the lungs

Adverse Effects: ototoxicity, nephrotoxicity, neuromuscular blockade

43
Q

Doxycycline

A

Tetracycline

Mech: binds 30S subunit reversibly blocks access of tRNA to mRNA

Uses: bronchitis, CAQ pneumonia, STDs- chlamydia, lyme, leptospirosis, malaria prophylaxis

Spectrum: GN, GP, anaerobic, atypicals: chlamydia, mycoplasma

Resistance: efflux pumps and ribosomal protection proteins

PK/PD: bacteriostatic; absorption inhibited by Ca **binds to tissues undergoing calcification (bones, teeth) NOT for kids or PG women

Adverse Effects: deposition in bone, teeth, photosensitivity

44
Q

Tigecycline

A

Synthetic derivative tetracycline, IV only

Mech: binds 30S subunit structural modifications overcome a lot of resistance

Uses: complicated skin/soft tissue infections; CAQ pneumonia, intraabdominal infections

Spectrum: GN, GP (MRSA, VRE), anaerobic

Adverse Effects: black box increased mortality risk

45
Q

Azithromycin Clarithromycin Erythromycin

A

Macrolides

Mech: binds 50S subunit, blocks translocation

Uses: ** azithro- CAQ pneumonia/bronchitis, chlamydia, travellers diarrhea, MAC prophylaxis **erythro- gut motility, prokinetic **clarithromycin- Mycobacterium avium, H. pylori

Spectrum: GN, GP, some GN anaerobes, Atypicals: mycoplasma, legionella, chlamydia

Resistance: (4) decreased permeability, efflux pumps, target site alteration (erm gene), enzymatic drug inactivation

PK/PD: static, widely distributed in tissues, erythro CYP450

Adverse Effects: N/V/D – prolonged QT

46
Q

Clindamycin

A

Macrolides

Mech: binds 50S subunit, blocks translocation

Uses: CAQ pneumonia, oral HEENT, human bites, abscesses, soft tissue/skin infections

Spectrum: ONLY GP, above diapraghm anaerobes

Resistance: target site alteration (erm gene), S. aureus- worry about erythromycin resistance inducing clinda resistance

PK/PD: cidal, widely distributed in tissues except CNS

Adverse Effects: C. difficile associated disease

47
Q

Linezolid

A

Oxazolidinones

Mech: binds 50S subunit, prevents formation of 70S complex

Uses: VRE, MRSA, complicated skin/soft tissue infections

Spectrum: ONLY GP, other Mycobacteria

Resistance: uncommon, acquire cfr plasmid

PK/PD: static, 100% bioavailable

Adverse Effects: bone marrow suppression, thrombocytopenia, inhibits MOA- serotonin syndrome

48
Q

Mupirocin

A

Mech: unique

Uses: VRE, MRSA, complicated skin/soft tissue infections

Spectrum: ONLY GP, other Mycobacteria

Resistance: uncommon, acquire cfr plasmid

PK/PD: static, 100% bioavailable

Adverse Effects: bone marrow suppression, thrombocytopenia, inhibits MOA- serotonin syndrome

Antibiotics (8 decks)

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