Anti-Microbials Flashcards
Penicillin G, V–form and type of antibiotic
- Penicillin G–IV and IM form
- Penicillin V–oral form
- prototype beta lactam antibiotics
penicillin G, V–mechanism
- D-Ala-D-Ala structural analog
- bind penicillin binding proteins (transpeptidases)
- block transpeptidase cross linking of peptidoglycan in cell wall
- activate autolytic enzymes
penicillin G, V–use
- mostly used for gram + organisms–S. pneumoniae, S. pyogenes, Actinomyces
- also used for gram - organisms–mainly N. meningitidis
- also used for spirochetes–T. pallidum
- bactericidal for gram + cocci, gram + rods, gram - cocci, and spirochetes
- penicillinase sensitive
penicillin G, V–toxicity
- hypersensitivity reactions
- direct Coombs + hemolytic anemia
penicillin G, V–resistance
- penicillinase in bacteria (a type of beta lactamase) cleaves beta lactam ring
name the penicillinase sensitive penicillins
- amoxicillin
- ampicillin
- aminopenicillins
penicillinase sensitive penicillin–mechanism
- same as penicillin
- wider spectrum
- “AMinoPenicillins are AMPed up penicillin”
- penicillinase sensitive
- also combine with clavulanic acid to protect against destruction by beta lactamase
penicillinase sensitive penicillins–oral bioavailability
- “AmOxicillin has greater Oral bioavailability than ampicillin”
penicillinase sensitive penicillins–use
- extended spectrum penicillin
- H. influenzae
- H. pylori
- E. coli
- Listeria monocytogenes
- Proteus mirabilis
- Salmonella
- Shigella
- enterococci
- coverage:
- ampicillin amoxicillin HHELPSS kill entercocci
penicillinase sensitive penicillins–toxicity
- hypersensitivity reactions
- rash
- pseudomembranous colitis
penicillinase sensitive penicillins–mechanism of resistance
- penicillinase in bacteria (a type of beta lactamase) cleaves beta-lactam ring
name the penicillinase-resistant penicillins
- dicloxacillin
- nafcillin
- oxacillin
penicillinase-resistant penicillins–mechanism
- same as penicillin
- narrow spectrum
- penicillinase resistant b/c bulky R group blocks access of beta-lactamase to beta-lactam ring
penicillinase-resistant penicillins–use
-
S. aureus–except MRSA: resistant b/c of altered penicillin binding protein target site
- “use naf (nafcillin) for staph”
penicillinase-resistant penicillins–toxicity
- hypersensitivity rxns
- interstitial nephritis
name the antipseudomonal penicillins
- piperacillin
- ticarcillin
antipseudomonal penicillins–use
- Pseudomonas spp. and gram - rods
- susceptible to penicillinase
- use with beta lactamase inhibitors
antipseudomonal penicillins–toxicity
- hypersensitivity rxns
name the beta lactamase inhibitors
- Clavulanic Acid
- Sulbactam
-
Tazobactam
- CAST
what are beta lactamase inhibitors often taken with? Why?
- often added to penicillin to antibiotics
- to protect the antibiotic from destruction by beta-lactamase (penicillinase)
cephalosporins (gen I-IV)–mechanism
- beta lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
- bactericidal
what are the organisms not covered by 1st-4th generation cephalosporins? what is the exception?
-
LAME
- Listeria
- Atypicals–Chlamydia, Mycoplasma
- MRSA
- Enterococci
- exception: ceftaroline–5th generation cephalosporin which covers MRSA
1st gen cephalosporins:
name 2
what organisms do they cover?
- cefazolin
- cephalexin
- gram + cocci
- Proteus mirabilis
- E. coli
-
Klebsiella pneumoniae
- “PEcK”
why would cefazolin be used prior to surgery?
- to prevent S. aureus wound infections
2nd gen cephalosporins:
name 3
what organisms do they cover?
- cefaclor
- cefoxitin
- cefuroxime
- “Fake fox fur”
- gram + cocci
- H. influenzae
- Enterobacter aerogenes
- Neisseria spp.
- Serratia marcesvens
- Proteus mirabilis
- E. coli
-
Klebsiella pneumoniae
- ”HENS PEcK”
3rd gen cephalosporins:
name 3
what organisms do they cover?
- ceftriaxone
- meningitis
- gonorrhea
- disseminated Lyme dz
- cefotaxime
- ceftazidime
- Pseudomonas
- serious gram - infections resistant to other beta lactams
4th gen cephalosporins:
name 1
what organisms do they cover?
- cefepime
- gram - organisms
- with increased activity against Pseudomonas and gram + organisms
5th gen cephalosporins:
name 1
what organisms do they cover?
- ceftaroline
- broad gram + and gram - organism coverage, including MRSA
- does NOT cover Pseudomonas
cephalosporins–toxicity
- hypersensitivity rxns
- autoimmune hemolytic anemia
- disulfiram like rxn
- vitamin K deficiency
- exhibit cross reactivity with penicillins
- inc nephrotoxicity of aminoglycosides
cephalosporins–mechanism of resistance
- structural change in penicillin binding proteins–transpeptidases
name the carbapenems
- imipenem
- meropenem
- ertapenem
- doripenem
- newer carbapenems include ertapenem (limited Pseudomonas coverage) and doripenem)
imipenem–mechanism
- (carbapenems)
- imipenem is broad spectrum, beta lactamase resistant carbapenem
what is imipenem always administered with? why?
- cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
- with imipenem, “the kill is lastin’ with cilastin”
carbapenems–use
- gram + cocci
- gram - rods
- anaerobes
- wide spectrum but significant side effects limit use to life threatening infections or after other drugs have failed
- meropenem–dec risk of seizures and is stable to dehydropeptidase I
carbapenems–toxicity
- GI distres
- skin rash
- CNS toxicity at high plasma levels
- seizures
name the monobactam
- aztreonam
monobactam (aztreonam)–mechanism
- less susceptible to beta lactamases
- prevents peptidoglycan cross linking by binding to penicillin-binding protein 3
- synergistic with aminoglycoside
- no cross allergenicity with penicillins
monobactam (aztreonam)–use
- gram - rods only
- no activity against gram + rods or anaerobes
- for penicillin allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
monobactams–toxicity
- usually nontoxic
- occasional GI upset
vancomycin–mechanism
- inhibits cell wall peptidoglycan formation by binding D-ala-D-ala portion of cell wall precursors
- bactericidal against most bacteria
- bacteriostatic against C. difficile
- not susceptible to beta lactamases
vancomycin–use
- gram + bugs only
- serious, multidrug-resistant organisms, including MRSA, S. epidermidis, sensitive Enterococcus species, Clostridium difficile
- oral dose for pseudomembranous colitis
- serious, multidrug-resistant organisms, including MRSA, S. epidermidis, sensitive Enterococcus species, Clostridium difficile
vancomycin–toxicity
- well tolerated in general but NOT trouble free
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
- diffuse flusing–red man syndrome
- can largely prevent by pretreatment with antihistamines and slow infusion rate
vancomycin–mechanism of resistance
- occurs in bacteria via amino acid modification of D-ala-D-ala to D-ala-D-lac
- “Pay back 2 D-alas (dollars) for vandalizing (vancomycin)”
protein synthesis inhibitors–mechanism
- specifically, target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected
name the 30S and 50S inhibitors
-
30S inhibitors
- A = Aminoglycosides [bactericidal]
- T = Tetracyclines [bacteriostatic]
-
50S inhibitors
- C = Chloramphenicol, Clindamycin [bacteriostatic]
- E = Erythromycin (macrolides) [bacteriostatic]
-
L = Linezolid [variable]
- “Buy AT 30, CCEL (sell) at 50”
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name the aminoglycosides
- Gentamicin
- Neomycin
- Amikacin
- Tobramycin
-
Streptomycin
- “Mean” (aminoglycoside) GNATS caNNOT kill anaerobes”
aminoglycosides–mechanism
- bactericidal
- irreversible inhibition of initiation complex thru binding of the 30S subunit
- can cause misreadin gof mRNA
- also block translocation
- require O2 for uptake
- therefore ineffective against anaerobes
aminoglycosides–use
- severe gram - rod infections
- synergistic with beta lactam antibiotics
- neomycin for bowel surgery
aminoglycosides–toxicity
- Nephrotoxicity
- Neuromuscular blockage
-
Ototoxicity
- especially when used with loop diuretics
-
Teratogen
- “Mean” (aminoglycoside) GNATS caNNOT kill anaerobes”
aminoglycosides–mechanism of resistance
- bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
name the drug classes that block cell wall synthesis by inhibition of peptidoglycan cross linking?
- penicillinase sensitive penicillins
- penicillinase resistant penicillins
- antipseudomonals
- cephalosporins
- carbapenems
- monobactams
name the drugs that prevent cell wall synthesis by inhibiting peptidoglycan synthesis
- vancomycin
- bacitracin
name the drugs that block nucleotide synthesis by inhibiting folic acid synthesis (involved in methylation)
- sulfonamides
- trimethoprim
name the drug that damages DNA via free radicals
- metronidazole
name the drug that blocks mRNA synthesis
- rifampin
name the drug classes that block DNA gyrase
- fluoroquinolones
- quinolone
name the drugs that block protein synthesis at the 50S subunit
- chloramphenicol
- clindamycin
- linezolid
- macrolides
- streptogramins
name the drugs that block protein synthesis at the 30S subunit
- aminoglycosides
- tetracyclines
name the tetracyclines
- tetracycline
- doxycycline
- minocycline
tetracyclines–mechanism
- bacteriostatic
- bind to 30S and prevent attachment of aminoacyl tRNA
- limited CNS penetration
how is doxycycline eliminated, and in which patients can it be used?
- fecally eliminated
- can be used in patients with renal failure
what should you avoid when taking tetracyclines, and why?
- milk (Ca2+), antacids (Ca2+ or Mg2+), or iron containing preparations
- b/c divalent cations inhibit drugs’ absorption in the gut
tetracyclines–use
- Borrelia burgforferi
- M. pneumoniae
- drugs ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia
- used to treat acne
tetracyclines–toxicity
- GI distress
- discoloration of teeth and inhibition of bone growth in children
- photosensitivity
what is a contraindication for taking tetracyclines?
- pregnancy
tetracyclines–mechanism of resistance
- dec uptake or inc efflux out of bacterial cells by plasmid encoded transport groups
chloramphenicol–mechanism
- blocks peptidyltransferase at 50S ribosomal subunit
- bacteriostatic
chloramphenicol–use
- meningitis (Haemophilus influenzae, Neisseria meningitidis, Stretococcus pneuomoniae) and Rocky Mountain Spotted Fever (RIckettsia rickettsii)
- limited use owing to toxicities but often still used in developing countries b/c of low cost
chloramphenicol–toxicity
- anemia–dose dependent
- aplastic anemia–dose independent
- gray baby syndrome–in premature infants b/c they lack liver UDP glucuronyl transferase
chloramphenicol–mechanism of resistance
- plasmid encoded acetyltransferase inactivates the drug
clindamycin–mechanism
- blocks peptide transfer (translocation) at 50S ribosomal subunit
- bacteriostatic
clindamycin–use
- anaerobic infections (ie. Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections
- also effective against invasive group A streptococcal infection
clindamycin vs. metronidazole
- clindamycin–treats anaerobic infections above the diaphragm
- metronidazole–treats anaerobic infections below the diaphragm
name the oxalidinones
- linezolid
oxalidinones–mechanism
- inhibit protein synthesis by binding to 50S subunt and preventing formation of the initiation complex
oxalidinones–use
- gram + species including MRSA and VRE
oxalidinones–toxicity
- bone marrow suppression–especially thrombocytopenia
- peripheral neuropathy
- serotonin syndrome
oxalidinones–mechanism of resistance
- point mutation of ribosomal RNA
name the macrolides
- azithromycin
- clarithromycin
- erythromycin
macrolides–mechanism
- inhibit protein synthesis by blocking translocation (“macroslides”)
- bind to the 23S rRNA of the 50S ribosomal subunit
- bacteriostatic
macrolides–use
- atypical pneumonias–Mycoplasma, Chlamydia, Legionella
- STIs–Chlamydia
- gram + cocci–streptococcal infections in patients allergic to penicllin
- B pertussis
macrolides–toxicity
-
MACRO
- gastrointestinal Motility issues
- Arrhythmia caused by prolonged QT interval
- acure Cholestatic hepatitis
- Rash
- eOsinophilia
- increases serum concentration of theophylline, oral anticoagulants
- clarithromycin and erythromycin inhibit cytochrome P-450
macrolides–mechanism of resistance
- methylation of 23S rRNA -binding site prevents binding of drug
name the sulfonamides
- sulfamethoxazole (SMX)
- sulfisoxazole
- sulfadiazine
sulfonamides–mechanism
- inhibit dihydropteroate synthase, thus inhibiting folate synthesis
- bacteriostatic
- bacteriocidal when combined with trimethoprim
sulfonamides–use
- gram +
- gram -
- Nocardia
- Chlamydia
- SMX for simple UTI
sulfonamides–toxicity
- hypersensitivity rxns
- hemolysis if G6PD deficient
- nephrotoxicity–tubulointerstitial nephritis
- photosensitivity
- kernicterus in infants
- displace other drugs from albumin (ie. warfarin)
sulfonamides–mechanism of resistance
- altered enzyme (bacterial dihydropteroate)
- decrease uptake
- increase PABA synthesis
dapsone–mechanism
- similar to sulfonamides
- but structurally distinct agent
dapsone–use
- leprosy (lepromatous and tuberculoid)
- Pneumocystis jirovecii prophylaxis
dapsone–toxicity
- hemolysis if G6PD deficient
trimethoprim–mechanism
- inhibits bacterial dihydrofolate reductase
- bacteriostatic
trimethoprim–use
- used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX])
- causes sequential block of folate synthesis
- combination used for UTIs, shigella, Salmonella, Pneuomocystis jirovecii pneuomonia treatment and prophylaxis, toxoplasmosis prophylaxis
trimethoprim–toxicity
- megaloblastic anemia
- leukopenia
- granulocytopenia
- may alleviate with supplemental folinic acid
- “TMP Treats Marrow Poorly”
- may alleviate with supplemental folinic acid
name the fluoroquinolones
- ciprofloxacin
- norfloxacin
- levofloxacin
- ofloxacin
- moxifloxacin
- gemifloxacin
- enoxacin
fluoroquinolones–mechanism
- inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
- bactericidal
- must not be taken with antacids
fluoroquinolones–use
- gram - rods of urinary and GI tracts (including Pseudomonas)
- Neisseria
- some gram + organisms
fluoroquinolones–toxicity
- GI upset
- superinfections
- skin rashes
- headache
- dizziness
- less commonly, can cause leg cramps and myalgias
- may prolong QT interval
- may cause tendonitis or tendon rupture in people > 60 years old and in patients taking prednisone
- “fluoroquinolones hurt attachments to your bones”
what are contraindications for fluoroquinolones?
- pregnant women
- nursing mothers
- children < 18 yo due to possible damage to cartilage
fluoroquinolones–mechanism of resistance
- chromosome encoded mutation in DNA gyrase
- plasmid mediated resistance
- efflux pumps
daptomycin–mechanism
- lipopeptide that disrupts cell membrane of gram + cocci
daptomycin–use
- S. aureus skin infections (especially MRSA)
- bacteremia
- endocarditis
- VRE
why is daptomycin not used for pneumonia?
- daptomycin avidly binds to and is inactivated by surfactant
metronidazole–mechanism
- forms toxic free radical metabolites in the bacterial cell that damage DNA
bactericidal - antiprotozoal
metronidazole–use
- treats:
- Giardia
- Entamoeba
- Trichomonas
- Gardnerella vaginalis
- Anaerobes–Bacteroides, C. difficile
- used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. pylori
- “GET GAP on the Metro with metronidazole”
metronidazole–toxicity
- disulfiram-like rxn (severe flushing, tachycardia, hypotension) with alcohol
- headache
- metallic taste
- M. tuberculosis*
1. prophylaxis
2. treatment
- Isoniazid
-
Rifampin, Isoniazid, Pyrazinamide, Ethambutol
- RIPE for treatment
- M. avium-intracellulare*
1. prophylaxis
2. treatment
- azithromycin, rifabutin
- more drug resistant than M. tuberculosis
- azithromycin or clarithromycin + ethambutol
- can add rifabutin or ciprofloxacin
- M. leprae*
1. prophylaxis
2. treatment
- N/A
- long term treatment with dapsone and rifampin for tuberculoid form
- add clofazimine for lepramatous form
name the rifamycins
- rifampin
- rifabutin
rifamycins–mechanism
- inhibit DNA dependent RNA polymerase
rifamycins–use
-
Mycobacterium tuberculosis
- delay resistance to dapsone when used for leprosy
- used for meningococcal prphylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B
rifamycins–toxicity
- minor hepatotoxicity
- drug reactions–inc cytochrome P-450
- orange body fluids–non hazardous side effect
when is rifabutin favored over rifampin and why?
- RIfabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation
- “Rifampin ramps up cytochrome P-450, but rifabutin does not”
rifamycins–mechanism of resistance
- mutations reduce drug binding to RNA polymerase
- monotherapy rapidly leads to resistance
Rifampin: 4 things to remember
-
4 R’s
- RNA polymerase inhibitor
- Ramps up microsomal cytochrome P-450
- Red/orange body fluids
- Rapid resistance if used alone
name the 4 antimycobacterial drugs
- Rifamycins–rifampin, rifabutin
- Isoniazid
- Pyrazinamide
- Ethambutol
- Streptomycin
Isoniazid–mechanism
- dec synthesis of mycolic acids
- bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite
Isoniazid–use
-
Mycobacterium tuberculosis
- this is the only agent used as solo prophylaxis against TB
- also used as monotherapy for latent TB
isoniazid–toxicity
- hepatotoxicity
- P-450 inhibition
- drug induced SLE
- vitamin B6 deficiency–peripheral neuropathy, sideroblastic anemia
- INH Injures Neurons and Hepatocytes
what should be administered with isoniazid?
- puridoxine (vitamin B6)
isoniazid–mechanism of resistance
- mutations leading to underexpression of KatG
pyrazinamide–mechanism
- mechanism uncertain
- prodrug that is converted to the active compound pyrazinoic acid
- works best at acidic pH (ie. in host phagolysosomes)
pyrazinamide–use
- Mycobacterium tuberculosis
pyrazinamide–toxicity
- hyperuricemia
- hepatotoxicity
ethambutol–mechanism
- dec carbohydrate polymerization of mycobacterium cell wall by blocking arabinocyltransferase
ethambutol–use
- Mycobacterium tuberculosis
ethambutol–toxicity
-
optic neuropathy (red-green color blindness)
- pronouce “eyethambutol”
streptomycin–mechanism
- interferes with 30S component of ribosome
streptomycin–use
- Mycobacterium tuberculosis (2nd line)
streptomycin–toxicity
- tinnitus
- vertigo
- nephrotoxicity