Beta Lactams Flashcards
Narrow Spectrum, penicillinase-susceptible penicillins
Penicillin G, Penicillin V
Narrow spectrum penicillin resistant organisms
- Most Staph aureus strains
- Many Neisseria gonorrhoeae strains
Very narrow spectrum (anti-staphylococcal), penicillinase-resistant penicillins
Methicillin
Oxacillin
Nafcillin
Very narrow spectrum penicillin resistant organisms
MRSA
PRSP
Wider spectrum, penicillinase-susceptible penicillins
Piperacilin Ampicillin Ticarcillin Amoxicillin (fat pata) -use with beta-lactamase inhibitors -synergistic w/ aminoglycosides
Enterococcal & listerial infection treatments
Ampicillin/aminoglycosides
PCN + Beta-lactamase inhibitors
Amox + Clavulanic acid (Augmentin)
Ampi + Sulbactam (Unasyn)
Piper+ Tazobactam (Zosyn)
Ticar + Clavulanic acid (Timentin)
AC, AS, PT, TC
PCN mechanisms of resistance
1) Beta lactamase (staph, gram-)
2) PBP modification (MRSA, MRSE, PRSP, eterococci)
3) Changes in Porin (gram-…P. aeruginosa)
4) Efflux pump (salmonella typhimurium)
Cephalosporin mechanisms of resistance
1) beta lactamases (less susceptible to staph penicillnases than PCN)
2) PBP modification (MRSA, PRSP)
3) Decrease in drug permeability
1st Generation Cephalosporins
Cefazolin
Cephalexin
Cefadroxil
2nd Generation Cephalosporins
Cefaclor Cefotetan Cefamandole Cefoxitin Cefuroximea Cefuroxime Axetil Cefproxil Loracarbef
3rd Generation Cephalosporins
Cefotaxime Cefixime Cefoperazone Ceftriaxone Ceftazidime Cefpodoxime Cefdinir
4th Generation Cephalosporin
Cefepime
Gram + and Gram - coverage
Patterns of cephalosporins from 1st to 3rd generations
- Decrease Gram+ coverage
- Increase Gram - coverage
- Increase CNS penetration
- Increase resistance to B-lactamase
Monobactam
Aztreonam
Monobactam coverage
- certain Gram - rods (resistant to B-lactamases produced by rods) including Pseudomonas
- NO activity against gram + or anaerobes
- Synergistic w/ aminoglycosides
Carbapenems
Imipenem
Meropenem
Ertapenem
Doripenem
Carbapenem coverage
-Broadest spectrum of all antibiotics!
> G+ cocci (staph/strep), G- rods (pseudomonas), anaerobes
> resistant to most B-lactamases, but susceptible to METALLO-B-LACTAMASE
-No coverage against:
MRSA, Listeria Monocytogenes, some enterococci, few hospital-strain Gram-
-Ertapenem: low Pseudomonas activity!
B-lactamase Inhibitors
Clavulanic acid (w/ Amox & Ticar)
Sulbactam (w/ Ampi)
Tazobactam (w/ Pipera)
MRSA & PRSP Treatment
Vancomycin: no B-lactam ring, no binding to PBP
|»_space;PRSP: Vanco + 3G Ceph
Vancomycin coverage
- Active against Gram (+)…MRSR, PRSP
- No coverage against Gram (-), can’t penetrate cell membrane
PCN, Cephalosporin Mechanism of Action
- Bind to PBP b/c they are D-Ala-D-Ala analogs
- Inhibit transpeptidase (comp. inhibitor)–> inhibit cell wall synth
- Activate autolysins (bac enzyme that cause lesions in cell memb and wall)
Monobactam, Carbapenem Mechanism of Action
-Binds to PBP (PBP3 for monobactam)
Vancomycin Mechanism of Action
- Binds to D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide
- Inhibits transglycosylase, sterically hinders ELONGATION of peptido & cross-linking
- Damages cytoplasmic memb
- CIDAL for dividing orgs
- can’t penetrate complex Gram - cell walls
Vancomycin Mechanism of Resistance
- D-Ala-D-Ala modification (VRE, VRSA)
- Change in drug permeability
Daptomycin coverage
VRE
VRSA
>CIDAL for Gram+….act on cell memb
> INACTIVE against Gram -
Daptomycin considerations
-Renal elimination >monitor Creatine phosphokinase activity to watch out for myopathy, esp w/ statins -Long 1/2 life (9hrs) -->once a day -predominantly cleared by kidney -long post-antibiotic effect -concentration-dependent killing
Fosfomycin Mechanism of Action
-Antimetabolite inhibitor of cytosolic enolpyruvate transferase
> prevent N-acetylmuramic acid formation–> block peptido chain formation
Fosfomycin Mechanism of Resistance
-Decreased intracellular accumulation
Fosfomycin Indication
-UTI: excreted by kidney & urinary levels exceed MICs for many UTI pathogens
Parenteral Cephalosporins
1: Cefazolin
2: Cefoxitin, Cefotetan, Cefuroxine
3: Cefaperozone, Ceftriaxone, Ceftazidime, Cefotaxime
4: Cefepime
5: Ceftaroline
Oral Cephalosporins
1: Cefalexin, Cefadroxil
2: Cefuroxime Axetil, Cefaclor, Cefprozil, Loracarbef
3: Cefpodoxime, Cefdinir, Cefixime
Cephalosporin clearance
All renal, except for three 3rd gens
Cefotaxime, Cefoperazone (hepatic + renal)
Cefotriaxone (hepatic)
Cephalosporins w/ CNS coverage
2: Cefuroxine
3: Cefotaxime, Ceftriaxone, Ceftazidime
4: Cefepime
Cephalosporins with long half-lives
Ceftriaxone (8hours), Cefotetan (3.5)
All others are ~1-2 hrs mostly
Ceftaroline Coverage
-MRSA, Enterococci!!
(but still NO LISTERIA!)
-Other Strep, Staph
-H.Flu
Cefepime Coverage
-Strep, Staph
-H.Flu
-Pseudomonas
-Other Gram-
Very broad spectrum: almost everything except ANAEROBES, ENTEROCCI, LISTERIA, and MRSA
Cefazolin Coverage
Notable for non-MRSA Staph, Strep
> DOC for surgical prophylaxis
Cefuroxime Coverage
- Notable for non-MRSA Staph, strep
- Other Gram - (non pseudomonas)
Cefoxitin/Cefotetan Coverage
Notable for Bacteroides
Cefotaxime, Cefitriaxone Coverage
Notable for Other Gram -
Ceftazidime Coverage
Notable for Pseudomonas
Cephalosporins that cover Pseudomonas
3: Cefoperazone, Ceftazidime
4: Cefepime
Cephalosporins that cover Bacteroides
2: Cefoxitin, Cefotetan
3: Cefotaxime, Ceftriaxone, Cefoperazone, Ceftazidime
4: Cefepime
Tx for Serious Adult Bacterial Pneumonia (except pseudomonas, hospital strains)
Cefuroxime
Tx for Serious Pediatric Bacterial Pneumonia
Cefuroxime
|»_space;CSF penetration protects against meningitis
Tx for infections due to combo of anaerobes and community aerobic orgs
Cefoxitin and Cefotetan
> Cefotetan has longer half-life
Tx for respiratory infections where H. flu and Moraxella suspected (outpatient)
Oral 2nd generation cephalosporins
Tx for hospital-acquired Gram - (except Pseudomonas)
3rd Gen cephalosporins
May need to use w/ clindamycin or metroidazole (effective against anaerobes)
DOC for Menigitis (and pneumonia w/ same orgs)
Ceftriaxone and Cefotaxime
Tx for “hospital-acquired” Gram - INCLUDING pseudomonas
Ceftazidime–should be combined w/ aminoglycosides
Back-up drugs for respiratory infections and UTI
Oral 3rd Gen cephalosporins
Tx for skin & soft tissue infections
Ceftaroline
Tx for community onset pneumonia
Ceftaroline: covers strep pneumo and common Gram -, but NOT pseudomonas
Monobactam/Carbanepem administration and clearance
All given IV and cleared renally
This drug combination blocks action of dipeptidase in renal tubule and allows for reasonable urinary concentration in active drug
Imipenem-Cilastatin
Carbapenem with longest half-life
Ertapenem: 4 hours (good for outpatient IV)
Other Carbapenems are 1hr
Aztreoname (monobactam): 1.7hr
Aztreonam traits
- Used to treat serious Gram - infections
- LIttle cross allergenecity with penicillins and cephalosporins
- Avoids risk of nephrotoxicity from aminoglycosides
Carbapenem traits
- May have cross-allergenicity w/ penicillins and cephalosporins
- “Shotgun” use, but should be replaced with narrow spectrum when possible
Toxicities common to cephalosporins, aztreonams, and carbapenems
- GI: Nausea, diarrhea, colitis
- Allergic
- Hematologic: neutropenia, hemolytic anemia (rare)
- Renal: interstitial nephritis (rare)
- SUPERINFECTION
Cefotetan and Cefoperazone unique toxicities
Antabuse-like reactions to alcohol
Imipenem unique toxicity
Occationally precipitates seizures in elderly or those w/ impaired renal function
Ceftriaxone unique toxicity
More frequent diarrhea and can cause biliary “sludge”… avoid in infants!
Vancomycin pharmacokinetics
- Low oral absorption
- Painful IM, but given IV
- T 1/2=6 hrs; 9 hrs w/ renal failure
- Excreted renally–glom filtration
- wide distribution, except CNS, EYE, and PROSTATE
Vancomycin coverage
- All Gram + (except VRE)
- No activity against Gram -
Tx for pseudomembranous colitis
ORAL Vancomycin
Vancomycin Toxicity
Dose-related toxicities:
- Mild nephrotoxicity (bad if combined w/ aminoglycosides)
- Ototoxicity–Cochlear
- *Must measure peak & trough blood levels and renal fxn during therapy
-Hypersensitivity
>”RED NECK” Syndrome (from Histamine)–> give slowly to avoid
Televancin differences to Vancomycin
- Greater activity against resistant S. aureus
- Longer 1/2 life (8 hours)
- More nephrotoxic
- Contraindicated in preg
- Freq nausea and tasts perversion
Daptomycin inactivation
In lung by surfactant
|»_space; can’t use for pneumonia!
