Antibiotics Flashcards
What are the 4 MOA’s of antibacterials?
- inhibitors of cell wall synthesis
- inhibitors of translation and transcription
- inhibition of DNA synthesis
- inhibitors of folate synthesis and function
What are some abx that act as inhibitors of cell wall synthesis?
Beta-lactams penicillins
Cephalosporins
glycopeptides: Vanco
TB meds
What are some abx that act as inhibitors of translation and transcription?
Tetracyclines Macrolides Clindamycin Oxazolidinones Aminoglycosides Spectinomycin TB meds
What abx act as inhibitors of DNA syntheses/integrity as well as folate synthesis and function?
sulfonamides, Trimethoprim
Quinolones
MOA for bactericidal abx’s
generally inhibition of cell wall synthesis
- time-dependent killing: serum level above MIC (i.e. beta-lactams and vanco)
- concentration-dependent killing: higher drug concentration determines rate and extent of killing (aminoglycosides and quinolones)
MOA of bacteriostatic abx’s
generally inhibition of protein synthesis
- i.e. Tetracyclines, macrolides, sulfonamides
What is the post-antibiotic effect?
Persistent suppression of bacterial growth after limited exposure to an antimicrobial agent
Which drugs need a dosage adjustment for renal impairment?
aminoglycosides carbapenems cephalosporins penicillins trimethoprim-sulfamethoxazole vancomycin
What drugs are contraindicated in renal impairment?
Nitrofurantoin, sulfonamides (long-acting), tetracyclines
What drugs need a dosage adjustment in hepatic impairment?
Chloramphenicol, clindamycin, erythromycin (Z-pack), metronidazole
Which Penicillins are considered narrow spectrum?
Peniciilinase-susceptible –> Penicillin G and Penicillin VK
Penicillinase-resistant –> Nafcillin and Oxacillin
Which Penicillins are considered wider spectrum?
\+/- penicillinase inhibitor: Ampicillin Amoxicillin Piperacillin Ticarcillin
What additional microorganisms are covered by amoxicillin but not by penicillin?
H. influenza
PK of Penicillin
rapid renal elimination
Biliary clearance - ampicillin, nafacillin
What are the ADE’s of Penicillin?
Hypersensitivity reactions (~5-6% incidence)
Maculopapular rash - ampicillin
What are the clinical uses for narrow and wider spectrum penicillins?
Narrow: strept, staph, meningococcal, syphilis
Wider: greater activity vs. gram-neg bacteria
List examples of medications in the 5 generations of Cephalosporins.
1st -- Cephalexin 2nd -- Cefuroxime 3rd -- Ceftriaxone and Cefixime 4th -- Cefipime 5th -- Ceftaroline
[1st narrow —-> 5th broader]
PK of Cephalosporins
3rd generation drugs enter the CNS
renal elimination (aka dosage adjustment)
What are the ADE’s of Cephalosporins?
- assume complete cross-reactivity b/t cephalosporins
- 1st generation partial cross-reactivity w/penicillins
- Hypersensitivity rxn’s
What cephalosporin is NOT given to newborns and why?
Ceftriaxone (Rocephin) bc it is cleared by the biliary tract –> elevated bilirubin
What are the clinical applications for each generation of Cephalosporins?
1st – skin, soft tissue, UTI
2nd – S. pneumo, H. influenza, B. fragilis (cefotetan)
3rd – pneumonia, meningitis, gonorrhea, broad activity, beta-lactamase stable
4th – psuedomonas coverage
5th – skin, soft tissue, CAP
Which generation of cephalosporins cross react w/ Penicillins?
1st generation
- may be linked to side chain in common
Which generations of cephalosporins can usu. be given safely to Penicillin allergic patients?
2nd, 3rd, 4th, maybe 5th
What are examples and ADE’s of Carbapenems?
Imipenem-cilastatin (Primaxin)
- also Doripenem, Meropenem, Ertapenem
ADE’s: CNS effects include confusion and seizures
Clinical application of Carbapenems?
Broad spectrum activity: Penicillin-resistant Strep pneumo, gram-neg rods, pseudomonas
Which beta-Lactam does not have a cross allergenicity w/other beta-lactams, and is only active against 3 gram negative bacteria? Name these bacteria.
Monobactams - active against Klebsiella, Pseudomonas, serratia
ADE’s for Monobactams
CNS - headache and vertigo
Glycoproteins include which drugs?
Vancomycin
Dalbavancin
Oritavancin
Telavancin (HA- bacterial pneumo)
What are the clinical applications for Vancomycin?
Gram-positive activity covers MRSA and PRSP (penicillin-resist strep pneumo) strains
PK for glycopeptides (Vanco)?
- parental for systemic infections
- Oral vancomycin for C. diff colitis (an IV dose will NOT work!)
- renal elimination
What are toxicities of glycopeptides?
- Red-neck or red man syndrome –> erythematous rash on face and upper body
- infusion rate related
- rare nephrotoxicity
____ is a Lipopeptide w/activity against MSSA & MRSA w/ ____ as a unique toxicity.
Daptomycin
Myopathy - monitor CPK weekly
Clinical applications of Lipopeptides
Gram positive activity
- Endocarditis and sepsis
- Off-labeled uses: Osteomyelitis, prosthetic joint infections
- MSSA and MRSA coverage
What are Tetracyclines agents and what’s included on its activity spectrum?
DOXYCYCLINE, tetracycline, minocycline, tigecycline
anthrax, chlamydial, mycoplasma, rickettsiae
spirochetes, H. pylori
ADE’s for Tetracycline
GI upset, deposition in developing bones and teeth, photosensitivity
What can you treat w/ Tetracycline?
acne, CAP, bronchitis, cellulitis, lyme disease, periodontitis
What are Macrolide agents and ADE’s?
AZITHROMYCIN, erythromycin, clarithromycin
ADE’s: GI upset, hepatic dysfunction, QT elongation, CYP450 inhibition (NOT azithro)
Activity spectrum for Macrolides?
CAP, Pertussis, Corynebacteria (Diphtheria), Chlamydial
Lincosamides: agent, activity spectrum, and ADE’s?
agent: Clindamycin
spectrum: skin, soft tissue infections, anaerobic infections
ADE’s: can cause C. difficile colitis
Chloramphenicol activity spectrum
- treatment of serious infection d/t organisms resistant to less toxic abx
- bacteroides, H. influenza, salmonella, meningitides, rickettsia
- active against many vancomycin-resistant enterococci
ADE’s of Chloramphenicol
dose-related anemia (monitor CBC), gray baby syndrome
risk: serum levels >50mcg, patients w/impaired hepatic or renal function
Oxazolidinone: agent, activity spectrum, and ADE’s?
Linezolid
activity: MRSA, PRSP, VRE strains
ADE’s: dose related anemia, neuropathy, optic neuritis, SSRI’s
Aminoglycoside agents
GENTAMICIN Tobramycin Amikacin Streptomycin Neomycin
Aminoglycoside ADE’s
Nephrotoxicity (reversible)
Ototoxicity (irreversible)
Neuromuscular blockade
Aminoglycoside activity spectrum
aerobic gram negatives, H. influenza, M. catarrhalis, Shigella species
Often used in combo w/ beta-lactams
Anti-folate abx: MOA for sulfonamide and trimethoprim
Blockade of folic acid synthesis
Trimethoprim-sulfamethoxazole (TMP-SMZ) activity spectrum
UTI, resp. infections (bronchitis), ear infections, MSSA or MRSA-skin/soft tissue infections, traveler’s diarrhea, toxiplasmosis,
Combination of Trimethoprim-sulfamethoxazole (TMP-SMZ) is or bacteriostatic or bactericidal? Dosing is based on which component?
bactericidal
Trimethoprim component
ADE’s of TMP-SMZ
rash, bone marrow suppression, hyperkalemia, fever
ADE’s esp. in AIDs pt’s
What stage of pregnancy should TMP-SMZ be avoided?
1st trimester
What is the activity spectrum for Quinolones?
urogenital infections, GI tract infections, bacterial conjunctivitis, activity vs. gonococci rapidly declining
Which 2 quinolones are mainly used for UTI’s?
Ciprofloxacin
ofloxacin
ADE’s of Quinolones
CNS effects (dizzy, HA) tendinitis (Achilles affected most) Peripheral neuropathy Neuromuscular-blocking activity QTc prolongation
Avoid in young children & pregnancy
Quinolones drug interactions
oral absorption impaired by cations - Ca, Mg, Al
caution w/use of class IA and III antiarrhythmic
In what neuromuscular disease should quinolones be avoided?
Mesthenia Gravis
What is synergism?
killing effects or 2 or more antimicrobials used together are significantly greater than expected from their effects when used individually (4X or greater)
What is guided treatment?
effective antimicrobial agent identified by susceptibility testing of infecting microorganism
What factors should be considered before empiric therapy is initiated?
- Age, pregnancy, allergies
- metabolic or genetic variation
- renal and hepatic function
- concomitant drug therapy and disease states
What is an antibiogram?
- report of susceptibility/resistance of pathogens to abx’s
- can be used to determine empiric tx options
- information about local resistance patterns
MOA of Penicillins
inhibit bacterial cell wall synthesis
MOA of Cephalosporins
inhibit cell wall synthesis
MOA of Carbapenems
inhibit cell wall synthesis
MOA of Monobactams
inhibits GRAM NEG bacterial cell wall synthesis
MOA of glycoproteins
inhibit cell wall synthesis
MOA of Lipopeptides
inhibit cell wall synthesis
MOA of Tetracyclines
inhibit bacterial protein syntesis via binding to 30S ribosomal unit
MOA of Macrolides
inhibit bacterial protein synthesis via binding to 50S ribosomal subunit
MOA of Lincosamides
inhibit bacterial protein synthesis via binding to 50S ribosomal subunit
MOA of Chloramphenicol
inhibit bacterial protein synthesis via binding to 50S ribosomal subunit
MOA of Oxazolidinone
inhibit bacterial protein synthesis via binding to 23S RNA of 50S ribosomal subunit
MOA of Aminoglycosides
inhibit bacterial protein synthesis via binding to 30S ribosomal subunit
MOA of anti-folates
blockade of folic acid synthesis
MOA of Quinolones
inhibit DNA replication via binding to DNA gyrase and topoisomerase IV
