Antibacterial Agents Flashcards
Penicillins mechanism of action
Cell wall synthesis inhibitor (bactericidal)
- inhibit cross-linking of peptidoglycan polymers at cell wall
- Covalently binds penicillin binding proteins (PBPs)
- Promotes lysis of bacteria
- Effect persists due to covalent binding to bacterial proteins
Resistance to penicillins?
What resistance does MRSA vs. MSSA have?
1) B-lactamase: enzyme that hydrolyze B-lactams (penicillins, cephalosporins)
- MSSA → not broken down by B-lactamase
2) Alteration in PBPs (MRSA)
Penicillins have ______ excretion
renal
Types of Penicillins
Penicillin G Penicillin V Penicillinase-resistant Extended spectrum Antipseudomonal
Penicillin V is administered _____ for ________
orally for mild-to-moderate infections
Dicloaxillin is a ….
penicillinase resistant penicillin
Amoxicillin and ampicillin are…
extended spectrum penicillins
Piperacillin is a _______ and typically administered _______ with _________
antipseudomonal penicillin
administered IV witha B-lactamase inhibitor
B-lactamase inhibitors
Clavulanate or tazobactam
used with amoxicillin/ampicillin and piperacillin
Adverse reactions associated with Penicillins (2)
1) Anaphylaxis, type I, RARE
2) rashes (common)
Ampicillin/Amoxicillin side effects and explain why
1) Extended spectrum but not effective against C.diff and others –> superinfections possible
2) diarrhea
Penicillin spectrum/uses (2)
1) Gram + cocci (staph, strep, entero - NOT MRSA or MSSA)
2) anaerobes (NOT c. dif or b. fragilis)
Dicloxacillin spectrum/uses (1)
Penicillinase resistant
1) Gram + cocci (MSSA, NOT MRSA)
Amoxicillin/Ampicillin spectrum/uses (3)
Amox/Clav spectrum / uses
Extended spectrum
1) Gram + cocci (NOT MRSA or MSSA)
2) Gram - rods (E.coli)
3) some anaerobes (NOT c.diff or bacteriodes)
- ——————————————
* *add B-lactamase inhibitor (clav)**
1) Gram + cocci including MSSA** (NOT MRSA)
2) Gram - rods (E.coli)
3) some anaerobes including B. fragilis** (NOT c.diff)
-more hydrophobic –> can penetrate gram-
Pipercillin + Tazo spectrum/uses
Antipseudomonal + B-lactamase inhibitor
1) Gram - rods (E.coli) AND Pseudomonas**
2) Gram + cocci (MSSA, NOT MRSA)
3) Anaerobes including B. Fragilis
Vancomycin mechanism of action
cell wall synthesis inhibitor
inhibits linear polymerization of subunits at cell membrane
-Binds directly to D-ala-D-ala
stage 2 inhibitor - other CW synthesis inhibitors are stage 3
–> NOT inactivated by B-lactamase****
Administration of Vancomycin
IV usually
poor oral absorption - only use oral for C.diff GI infection
Excretion of vancomycin
renal excretion
Possible renal toxicity
Adverse reactions of Vancomycin (3)
1) ototoxicity
2) renal toxicity - MONITOR CP LEVELS!
3) infusion related side effects (chills, fever, rash)
Spectrum/Uses of Vancomycin (2)
Narrow spectrum
1) Anaerobes - CDIFF
2) Gram + cocci - MRSA**
NOT EFFECTIVE AGAINST GRAM -
Cephalosporins mechanism of action
cell wall synthesis inhibition (bactericidal)
B-lactam antibiotic
- stage 3 - inhibit cross-linking of peptidoglycan polymers at cell wall
- NOT susceptible to penicillinase
If your patient has an immediate sensitivity to penicillin you definitely should NOT…
give them a cephalosporin
Cephalexin is a…
1st Generation Cephalosporin
Ceftriaxone is a ….
3rd Generation Cephalosporin
Cephalosporins vs. Penicillins (3 differences)
1) Broader spectrum of action vs. gram-neg bacteria
2) Less susceptible to penicillinase (cephalosporinases are emerging)
3) Less cross-reactivity in penicillin sensitive patients
3rd generation cephalosporins (ceftriaxone) can penetrate…
THE CNS
Adverse reactions associated with 3rd gen cephalosporin (ceftriaxone)
superinfection possible
-not effective against C.diff
Spectrum/uses for Cephalexin (3)
1) Gram + cocci (MSSA, not MRSA)
2) Gram - rods (E.coli)
3) some anaerobes (not c.diff or b. fragilis)
Spectrum/uses for Ceftriaxone (5)
1) Gram + cocci (MSSA, not MRSA)
2) Gram - rods (E.coli)
3) Gram - cocci (N. Gonorrhoeae)
4) moderate anti-pseusomonal
5) some anaerobes (not c.diff or b. fragilis)
Carbapenems mechanism of action
cell wall synthesis inhibition (bactericidal)
- B-lactamase resistant
- interact with PBPs responsible for cell wall elongation
Carbapenems are administered…
IV/IM only
Carbapenems are excreted…
renally
Spectrum of carbapenems
WIDE spectrum
-reserve for multidrug resistant organisms
Strep. pneumoniae, strep viridans, N. gonorrhoeae all carry __________ that cause resistance to penicillins
Altered penicillin binding proteins (PBPs)
Oral formulations of Vancomycin will work for _______ because IV formulations _________
C. diff
will not get into the gut
Macrolides mechanism of action
protein synthesis inhibition
50S
bacteriostatic
Macrolides include ______, _________, and ________
Erythromycin
Azithromycin
Clarithromycin
Macrolides are all excreted…
NON-RENALLY
Erythromycin –> liver metabolism
Azithromycin –> Biliary
Clarithromycin –> metabolized to active metabolite
Resistance to macrolides can occur via…
methylation of 50S subunit
altered target –> resistance
Macrolides are administered…
orally (also IV)
Adverse reactions associated with Macrolides (2)
1) GI disturbances (N/V/D)
2) Inhibits CYP450** –> drug-drug interactions
Spectrum/Uses of Macrolides (Erythromycin, Azithromycin, Clarithromycin) (3)
Extended spectrum
1) Gram + cocci (MSSA, NOT MRSA)
2) Gram - diplococci (N. Gonorrhoeae)
3) Atypical (Chlamydia, Mycoplasma)
NOT gram - rods or anaerobes (NO ecoli, pseudomonas, c diff)
Mechanism of action of tetracyclines
protein synthesis inhibitor
30S
Bacteriostatic
Tetracyclines include ________ and ________
Doxycycline and Minocycline
Resistance can occur to tetracyclines via…
changes in drug transport out of the cell
Doxycycline is excreted _________ and tetracycline is excreted _________
non-renally (biliary)
renally
Administration of doxy and tetracycline
oral
Adverse effects of tetracycline and doxy (4)
- Abnormal bone/tooth development
- Fungal superinfection
- Drug-Drug interaction with metal cations (antacids, iron supplements, milk)
- GI
Spectrum/uses for tetracyclines (5)
BROAD spectrum (lots of resistance now though)
1) Gram + cocci - MRSA!
2) Gram - diplococci (N. Gonorrhoeae)
3) Gram - rods (E. coli)
4) Atypical - Chlamydia, Mycoplasma
5) Anaerobes - B. Fragilis (NOT c.diff)
NOT pseudomonas, NOT c diff
Clindamycin mechanism of action
protein synthesis inhibition
50S
bacteriostatic
Clindamycin is administered…
orally
Clindamycin is excreted…
non-renally
Hepatobiliary elimination
Clindamycin can penetrate…
BONE
Adverse reactions to Clindamycin
1) severe diarrhea
2) Pseudomembranous colitis (C.diff)
Spectrum/Uses of Clindamycin (2)
NARROW spectrum
1) Gram + cocci (MRSA!)
2) Anaerobes - B. Fragilis (NOT c.diff)
NOT gram- rods, Gonorrhea, c.diff, chlamydia, or mycoplasma
Aminoglycoside mechanism of action
Protein synthesis inhibition
30S
BACTERICIDAL** - binds irreversible
Administration of aminoglycoside
Dose once a day
IV/IM - poor oral absorption
Aminoglycosides includes _______, ________, ________, and ________
Tobramycin
Gentamicin
Neomycin
Streptomycin
Aminoglycosides are excreted…
renally
Aminoglycosides preferentially accumulate where?
kidney and inner ear –> ototoxicity, and renal toxicity
Adverse reactions associated with aminoglycosides
1) vestibular and auditory toxicity
2) Nephrotoxicity - MONITOR CP LEVELS
for _______ and _______ you must routinely monitor CP levels due to possible renal toxicity
Aminoglycosides (neomycin, streptomycin)
Vancomycin
Spectrum of aminoglycosides (1)
Narrow Spectrum
1) Gram - aerobes (e.coli, pseudomonas)
NO super infections b/c narrow spectrum
What can be used to treat MRSA (3)
1) Vancomycin
2) Tetracyclines
3) Clindamycin
What can be used to treat N. Gonnorrhoeae? (3)
1) Ceftriaxone
2) Macrolides
3) Tetracyclines
What can be used to treat c. diff? (2)
1) Vancomycin
2) Metronidazole
What can be used to treat chlamydia? (2)
1) Macrolides
2) Tetracyclines
Aminoglycosides will sometimes be used synergystically with _______ or ______ in treatment of _________
penicillin or ampicillin
Enterococcal
By themselves aminoglycosides do NOT have activity against enterococcal isolates
Erythromycin is given ______ x a day
Azithromycin is given ______ x a day
Clarithromycin is given ______ x a day
4x a day
1x a day
2x a day
Fluoroquinolones include ________, _________ and __________
Ciprofloxacin, Levofloxacin, Moxifloxacin
Mechanism of action of fluoroquinolones
inhibit DNA gyrase
BACTERICIDAL
Resistance to Fluoroquinolones due to…
due to point mutations in binding site on DNA gyrase or changes in drug permeability into organism
Administration of fluoroquinolones
oral (or IV)
Adverse reactions associated with fluoroquinolones? (6)
1) N/V/D
2) Superinfections with CDIFF possible
3) Drug-Drug interactions
- CYP450 inhibitor***
4) NOT first choice in children less than 12 yrs (arthralgias possible)
5) QT prolongation
6) rashes
What Drug-Drug interactions occur with fluoroquinolones?
Drug-Drug interactions with theophylline and antacid
Antacids reduce oral absorption of cipro
Spectrum of ciprofloxacin
1) Gram - rods (psuedomonas)
2) Atypical (chlamydia, mycoplasma)
Uncomplicated-complicated UTIs**
Traveler’s diarrhea
Spectrum of Levofloxacin
1) gram - rods (including pseudomonas)
2) atypical (chlamydia, and mycoplasma)
3) AND gram + cocci (streps only)
Good for UTI and respiratory
Spectrum of Moxifloxacin
1) atypical (chlamydia, and mycoplasma)
2) gram + cocci (streps only)
3) some anaerobes
Good for respiratory
Nitrofurantoin mechanism of action
reduced in cell to intermediates that damage bacterial DNA → BACTERICIDAL
-CANNOT be used for treatment of systemic infections - only UTI
Administration and excretion of Nitrofurantoin
Oral admin with RAPID renal excretion –> urinary antiseptic
Adverse reactions of Nitrofurantoin (1)
1) GI side effects
Spectrum of Nitrofurantoin (1)
1st line agent in uncomplicated UTIs
1) ONLY gram- rods (can’t treat atypical)
Metronidazole mechanism of action
- Reduced intracellularly to active form → interfere with DNA function
- Radical formation → target DNA
- Only good against anaerobes
- BACTERICIDAL
Administration and excretion of Metronidazole
Oral therapy
Hepatic metabolism
Spectrum of Metronidazole (2)
1) Anaerobes (C. Diff, B. Fragilis)
2) Protozoa
Adverse drug reactions of Metronidazole
1) Nausea, headache
2) Antabuse-like reaction (drug to tx alcoholism)
3) occasional candidal superinfections
Why does Metronidazole have antabuse-like reactions?
Inhibits aldehyde dehydrogenase → antabuse-like effect if alcohol is consumed within 3 days of metronidazole
Antabuse → GI upset, vomiting, headache - used in alcohol tx
Sulfonamides mechanism of action
Inhibits folate metabolism (dihydropteroate synthetase - only in bacteria) → interfere with DNA synthesis
BACTERIOSTATIC alone and BACTERICIDAL in combo (SMX/TMP)
SMX/TMP
inhibit two sequential enzymatic processes involved in tetrahydrofolic acid biosynthesis
- Trimethoprim - NOT a sulfonamide
- Sulfamethoxazole
Administration and Excretion of Sulfonamides
oral therapy
renal excretion AND hepatic excretion
Adverse reactions of sulfonamides
1) Hypersensitivity skin reactions
2) Kernicterus in neonates**
3) Renal crystalluria (rare) via decrease in water solubility of metabolites
You should NEVER give sulfonamides to who?
neonates!
–> Kernicterus due to bili build up
Spectrum of TMP/SMX (3)
1) Gram + cocci (including MRSA)
2) gram - rods (e. coli)
3) atypical (chlamydia)
