Antibiotics Flashcards
Gram + Antibiotics
Beta lactams
- Penicillines
- Cephas
- Carbapenems
Macrolides
- Erythromycin
- Azithromycin
Glycopeptides
- Vancomycin
**Gram+ but may vary
Gram Negative antibiotics
Aminoglycosides
Fluoroquinolones
2-4th cephalosporins
Gram - and Fx2-4
Broad spectrum antibiotics
Tetracyclines
TMS
Chloramphenicol
vanc
linazolid
2nd-4th gen cephas
carbapenems
**Tries to look very casual clocking 2-4
Anaerobic coverage
Azithromycin
Chloramphenicols
Metronidazole
Lincosamides –> clindamycin
Beta Lactams
- Pens: clostridium, peptostreptococci, actinomyces, fusobacterium
-Aminopen-clav against bacterioides
-cephas
** Anaerobes are clearly more like Bitches
Bacteriostatic antibiotics
Interferes with protein production, DNA replocation or cellular metabolism
- Stops reproduction but depends on immune system to kill bacteria
Tetracyclines
Chloramphenicol
Lincosamides (clindamycin)
Macrolides
3 types of resistance
- intrinsic: inherent feature of microbes to be resistant to drug (ex: pseudomonas is intrinsically resistant to beta lactams)
- Circumstantial: susceptible in vitro, but resistant in vivo (ex: inactivated by platelets or cant reach site like CSF)
- Acquired: change in phenotypic characteristic
Inhibitory quotient
Cmax/MIC
High inhibitory quotient must be achieved to reliably kill offending organism with concentration dependent antibiotics
MRS
MC Staph pseudointermedium then aureus
-MOA: acquired mecA gene –> alters PBP
- Also resistent to clinda, fluoroquinolones, macrolides & TMS
Escalation protocols:
- Aminoglycosides - will not act in puss or cellular debris
- Vancomycin drug of choice ((linesolid indicated if resistant or oral therapy needed))
-Tetracyclines, chloramphenicol, rifampin
*Staph be calling man fucking tyrant
MDR Enterococcus
E. Faecalis & E. Faecium
INtrinsic resistance to cephas, clinda, aminoglycosides & fluoroquinolones
Acquired MOA: aminoglycoside-modifying enzymes (AME) or alterations on PBP5
Fluoroquinolone + Cepha use assd with development of vanc resistent MDRE!!!
Treatment options:
-Gentamicin + amp –> synergistic ( no other Aminos synergistic)
- Vancomycin (linesolid indicated if resistant or oral therapy needed)
**Often nosocomial
Pseudomonas aeroginosa
Intrinsic resistance: majority beta lactams (exc ticarcillin, pipercarcillin ceftazadime & carbapenems), quinolones & aminoglycosides
Acquired 3 MOAs:
- Decreased intracellular drug due to efflux pumps or altered membrane structure
-Enzymes modify/destroy antibiotics
-Modify target of antibiotics (DNA gyrase mutation)
Treatment often requires amikacin or carbapenem
RNA synthase inhibitors
- Inhibits RNA polymerase
- lipohilic
- Hepatic clearance
- ABX: Rifampin
Side effects: discolored urine, GI, hepatotoxicity, hypersensitivity
Protein Synthesis Inhibitors
- Inhibit 30s & 50s ribosome units –> prevent mRNA translation
30s inhib: aminoglycosides, tetracyclines
50s inhib: macrolides, chloramphenicol, clindamycin
DNA synthesis inhibitors
-INhibits DNA gyrase & topisomerase IV
- lipophilic
-Renal/hepatic clearance
- ABX: fluoroquinolones, metronidazole
Side Effects: GI, nephrotoxicity, cartilage damage, hepatotox, hypersensitivity
Cephalosporins
- Inhibit cell wwall synthesis
- Bacteriocidal
- Hydrophilic–> renal clearance
- Time dependent
- Aerobic bacteria
- 1st gen> Gram + coverage
- 3 & 4 gen > gram+ & Gram -
*3rd gen ideal for CNS
Ceftazadime –> labeled for pseudomonas
Carbapenems
- Cell wall synthesis inhibition
- Hydrophilic – renal clearance
- Time dept
- Bacteriocidal
- 4 quad coverage
-Withstand beta lactamases (even ESBL)
Imipenem: inc Gram + for E. Faecalis –> neuro signs poss
Meropenem: inc gram - including pseudomonas
Etrapenem: no activity against enterococci
Macrolides
Inhibit ribosomal 50s subunit
-Lipophilic –> hepatic clearance
- Concentration dependent- azithromycin
- Time dep + conc enhanced– erythromycin
-Aerobic Gram + & - & atypical bacteria
-bacteriostatic
- Concentrated in macs–> get to infection
Side effects: GI upset, hypersensitivity–> products of streptomyxces species
Vancomycin
- Cell wall synthesis inhibition
- Hydrophilic - renal clearance
- Time Dept
- Gram + coverage, MRSA, & enterococcus sp
- Bacteriocidal
Augmented renal clearance
- In critically ill: increased renal clearance due to increase CO with decrease SVR
- Human Study: antibiotic clearance 3x with normal Crea
**MC in trauma, sepsis, blood malignancies & pancreatitis
TMS combos
- Inhibit enzymes in folic acid synthesis pathway
- Sulfas–> static
- trimethoprim - cidal
- Sulfa+ trimetho = cidal
- Gram +/- & protozoa
- Renal excretion, metabolism by liver
Side effects: KCS (reversible), hepatitis, hemolytic anemia, leukopenia, GI
Hypersensitivities in Dobies
Chloramphenicol
- Inhibits ribosomal 50s subunit
- Bacteriostatic
- Time dependent
- 4 quadrant coverage, rickettsial, mycoplasma, chlamydia
- EXTENSIVE liver metabolism
- Gram neg resistance via acetylation & inactivated by bascterial enzymes
Side effects: GI upset, hypersensitivity
Nitromidazoles
- ie metronidazole
- Disrupt DNA by forming reactive intermediates
- Bacteriocidal
- Concentration dept
- ONly active in anaerobic conditions
Excellent distribution –> including CNS & abscess
Lincosamides
- Inhibit protein synthesis via binding 50s ribosomeal subunit
- bacteriostatic
- Gram + aerobes, most anaerobes, intracellular bacteria
- Reach high concentrations in abscesses
Ex: clindamycin, lincomycin (less active against anaerobes)
Antibiotics for resistant infections
- Carbapenems
- Glycopeptides –> vancomycin
- Oxazolidinones –> linazolid
Oxazolidinones
MOA: inhibit protein synthesis by binding to bacterial 23s rRNA of 50s subunit
-Static against most bacteria, maybe cidal in vivo
- Resistant Gram + bacteria (streptococci, enterococci)
Ex: linezolid $$$
Clindamycin
- Inhibit ribosomal 50s subunit
- lipophilic
- hepatic clearance
- Time Dept + concentration enhanced (PAE)
- Gram + - aerobic & anaerobic
- Gram - anaerobic
Side effects: GI, hypersensitivity
Bacteriocidal
Kill bacteria via inhibition of wall synthesis, bacterial enzyme inhibition or protein translation
Rifampin
- Inhibits RNA polymerase
- lipophilic
- kepatic clearance
Side effects: discoloer urine, GI, hepatotoxicity, hypersensitivity
Antiobiotics with MOA cell wall synthesis inhibition
- Block cross linking of peptidoglycans –> cell lysis
- Hydrophilic
- renal clearance
- Abx classes: penicillins, cephas, vancomycin, monobactams, carbapenems, bacitracin
Side effects: GI, hypersensitivity, neurotoxicity
Monobactems
- Cell wall synthesis inhibition
- Hydrophilic
- Renal clearance
- Bacteriocidal
- Time dependent
- Not used in vet med
Time Dept vs Concentration Dept
TIme: amount of time antibiotic agent is above MIC of infecting organism
* ideally above this for 100% of time
Concentration: Max antibiotic effect when peak drug concentration exceeds MIC several times (>8-10x MIC)
Cmax above MIC –> area under curve
Bacitracin
Cell wall synthesis inhibition
Hydrophilic
Renal clearance
Tetracyclines
- Inhibit ribosomal 30s subunit
- Lipophilic
- renal & hepatic clearance
- time dependent + PAE (conc enhanced)
- Bacteriostatic
- Aerobic gram- & +
Atypicals: rickettsia, mycobacteria, treponema, chlamydia, mycoplasma
**Delayed bone growth, esophageal stricture
Penicillins
- Cell wall synthesis inhibition
- Renal Clearance
- Hydrophilic
- Time dependent
- bacteriocidal
- Gram + bacteria
- Aerobic>anaerobic
– PenG –> strep!! (necrotizing fasciitis (not against staph)
–Aminopenicillins – susecpt beta lactamases –> increased effect against gram -
– Ticarcillin/piperacillin –> active against pseudomonas & proteus (none against ecoli)
Post antibiotic effect
- occurs because bacteria need to make new proteins
- Drugs with prolonged PAE:
Clindamycin
Erythromycin
Linezolid
Tetracycline
Fluoroquinolones
- Inhibit DNA gyrase (gram -) & topoisomerase IV (gram +)
- lipophilic
- Hepatic/renal clearance
- Concentration dependent
- bacteriocidal, marked PAE
- Intracellular pathogens: mycoplasma, chlamydia, brucella
- Decreased absorbtion with polyvalen cations (calcium, magnesium, aluminum, iron, zinc)
Side Effects: GI, neurotoxicity, cartilage damage, hepatoxic hypersensitivity, inhibit P450
4 Quad coverage:
- Ciproflox –> inc gram -
- levoflox –> inc gram +
Aminoglycosides
- 30s subunit inhibition
- Gram - & select gram + coverage (staph sp)
- Synergistic with beta lactams
- Long PAE
- Adaptive resistance: after first exposure, decreased uptake –> give once daily to avoid this!
- Distribute well in ECF
- NMJ blockade: inhibit presynthesis calcium –> reverse with calcium or neostigmine
** Quinolones can also do this!
Side effects: ototoxicity, nephrotox
Ex: amikacin, gentamicin, neomycin
Metronidazole
- Inhibits DNA gyrase & topoisomerase IV
- lipophilic
- hepatic/renal clearance
- concentration dependent
- Anaerobic - gram - & gram +
Side effects: GI, neurotoxicity, hepatotoxicity, hypersensitivity
Definition MDROs
Organism not susceptible to at least one agent in 3 or more classes of antimicrobials to which they are susceptible
ESBL
Extended spectrum B lactamases
- hydrolyze third generation cepha’s beta lactam ring, but carbapenems still stable against these abx (not true for XDR)
Primary infections: E. Coli, Klebsiella pneumoniae, & enterobacter specieas
