Antifungals Flashcards
Amphotericin B
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
Nystatin
Antifungal (polyene)
Topical candidiasis
Topical: oral, cutaneous, vaginal
binds to ergosterol and forms channels in fungal cell membrane, oxidative damage
*not systemically absorbed
Clotrimazole/Miconazole
Antifungal (azole)
topical - dermatophyte, candidiasis
inhibits lanosterol C-14 demethylase and ergosterol synthesis
*not systemically absorbed
Ketoconazole
Antifungal (azole)
shampoo for tinea capitis/tinea versicolor
topical; PO
inhibits lanosterol C-14 demethylase and ergosterol synthesis
Toxicity: hepatotoxic
Fluconazole
Antifungal (azole)
candidiasis; cryptococcus maintenance
PO, IV
inhibits lanosterol C-14 demethylase and ergosterol synthesis
Excretion: mostly renal and some hepatic
Toxicity: hepatotoxic
Itraconazole
Antifungal (azole)
endemic mycoses: Histo, Blasto, Cocci
PO
inhibits lanosterol C-14 demethylase and ergosterol synthesis
spectrum: yeasts and filamentous fungi
Toxicity: hepatotoxic
Voriconazole
Antifungal (azole)
Aspergillosis
PO/IV
inhibits lanosterol C-14 demethylase and ergosterol synthesis
spectrum: yeasts and filamentous fungi
Toxicity: hepatotoxic, hallucinations, rash
Posaconazole
Antifungal (azole)
2nd for aspergillosis; prophylaxis
PO
inhibits lanosterol C-14 demethylase and ergosterol synthesis
spectrum: yeasts and filamentous fungi
Toxicity: hepatotoxic
5-Flurocytosine
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
Terbinafine
Antifungal (allylamine)
Dermatophytes
PO, topical
inhibits squalene epoxidase and ergosterol synthesis
Toxicity: hepatotoxic
Caspofungin
Micafungin
Anidulafungin
Antifungal (echinocandin)
Candidemia, Aspergillus
IV
inhibits cell wall synthesis (1,3 beta glucan formation)
Toxicity: hepatotoxic
Trimethoprim-Sulfamethoxazole
TMP-SMX
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
Ciprofloxacin
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
Moxifloxacin
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
Nitrofurantoin
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
Rifampin
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
Rifabutin
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
Rifaximin
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
Fidaxomicin
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
** Penicillin G**
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
** Ampicillin**
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
** Amoxicilin**
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
** Nafcillin/Dicloxacillin**
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
Piperacillin
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
** Ampicilin-Sulbactam**
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
** Amoxicilin-Clavulanic Acid**
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
Piperacillin-Tazobactam
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
Cefazolin
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
Cephalexin
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
Cefoxitin
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
Ceftriaxone
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
Ceftazidime
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
Ceftazidime
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
Ceftaroline
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
Aztreonam
Monobactam
Uses: B-lactam allergy, limited
IV q8h
Spectrum: GRAM NEG ONLY
covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal
Imipenem
Doripenem
Ertapenem
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
Vancomycin
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
Daptomycin
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)
Polymyxin B
Other
Uses: serious- GN , inhaled resistant GN pneumonia
IV q12hr
Spectrum: GRAM NEGATIVE ONLY
Adverse Effects: significant toxicities (nephrotoxicity, neurotoxic, inhaled ->bronchospasm)
Bacitracin
Other
topical GRAM POSITIVE only Strep pyogenes, Staph
Fosfomycin
Other: UTI
oral powder 1 dose
GRAM POS AND GRAM NEG
Amikacin / Gentamicin
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
Doxycycline
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
Tigecycline
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
Azithromycin Clarithromycin Erythromycin
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
Clindamycin
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
Linezolid
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
Mupirocin
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
