Dr. Cluck Clinical Anti-Infective Pens and Cephs Flashcards
What are antibiotics divided into based on PK/PD parameters?
-Time-dependent killing
-concentration-dependent killing
What is the Post antibiotic effect (PAE)
-The drug continues to affect organisms’ growth after concentration has fallen below MIC
(Antibiotics are usually not picked based on PAE)
What is the MIC?
-Minimum inhibitory concentration
-the lowest concentration of antibiotics needed to stop visible bacterial growth under standard conditions
-each antibiotics has its own MIC
What is the clinical approach to using Time-dependent antibiotics?
They are dosed in a way to keep the concentration above the MIC for 40-50% of the dosing interval
-ß-lactams, glycopeptides, macrolides, clindamycin, linezolid
What is the classic Time-dependent-Killer (Time-above-MIC-Killer)?
ß-Lactams
What does concentration-dependent-Killer require?
Requires a high antibiotic peak
-Cmax : MIC - 10:1 or greater overall
-AUC/MIC
-Increased drug concentration results in increased bacterial killing
What are the common concentration-dependent-Killers?
Aminoglycosides (Nephrotoxic and ototoxic at high doses), fluoroquinolones, Daptomycin, metronidazole
-CAUTION -> toxicity at high doses
How is efficient dosing of time VS concentration-dependent-Killers explained?
Time-dependent-Killer: The frequency of the dose determines the outcome
->Ticarcilin
Concentration-dependent-Killer: The higher the dose, the better the outcome
-> Tobramycin, Ciprofloxacin
What are Bacteriocidals and Bacteriostatics?
Bacteriocidal: Kills the bacteria
Bacteriostatic: Inhibits growth, and requires intact immune function to kill the bacteria
What are typical Bacteriocidal and Bacteriostatics?
Bacteriocidal: ß-Lactams
Bacteriostatic: Tetracyclines, Macrolides
Spectrum of action for Pen G (benzylpenicillin)
Neurosyphilis, Decolonization of Group B strep and pregnant
Spectrum of Pen G Procaine and Benzathine
Administered IM -> long-acting
Pen G Benzathine (Bycillin L-A): for Syphilis
Pen G Procaine (Wycillin): STIs
The spectrum of Pen V (phenoxy methyl, Pen VK)
Dental Work
What are the IV and PO-administered penicillins?
IV: Oxacillin, Nafcillin
PO: Doxacillin
(All can be given: IV, IM, PO)
What is the IV equivalent of Augmentin (Amoxicillin-Clavulanate - PO)?
Ampicillin-Sulbactam (IV)
Spectrum of Activity for Natural Penicillins G + V
-predominantly active against Strep spp.
-Treponema pallidum (Syphilis)
can also be used for Enterococcus faecalis and in vitro for Neisseria meningitis
Spectrum of Penicillin-resistant Penicillins?
Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin
MSSA and Strep
(for MRSA - Vancomycin
PO MRSA. doxycycline, clindamycin, and TMP-SMX)
Spectrum of Activity for Aminopenicillins (Amoxicillin and Ampicillin don’t work for ß-lactamase producing bacteria - need ß-lactam inhibitors)
-Pen G spectra: Strep, Syphilis
-Some gram negatives
-Ampicillin is the DOC for Listeria meningitis or Enterococcus faecalis
POOR for Enterobacterales
-> So if a patient comes to the ER with sepsis Aminopenicillin is not the best choice bc the pt probably has some gram-negative ß-lactam producing infection; also not Nafcilin bc it narrows to MSSA
-> These are drugs for definitive therapies
What is the DOC for Listeria meningitis?
Ampicillin
Spectrum for Extended-Spectrum Penicillins (Antipseudomonal - different from Roane)
Piperacillin + Tazobactam
-against gram positives
- EXCELLENT against gram-negative susceptible organisms (Enterobacterales)
-Good against anaerobic organisms (when given with ß-lactamase inhibitor)
-Against Pseudomonas: Piperacillin + Tazobactam
In what ways are ESBLs beneficial?
Piperacillin + Tazobactam
-They are broad (gram-positive and susceptible gram-negatives, anaerobic w/ ß-l-inhibitor)
-They are protected from ß-lactamases with ß-l-inhibitors
Examples of ß-lactam inhibitor
Older: Clavulanic acid, sulabactam, tazobactam
New: avibactam, relebactam, vaborbactam
-no microbial activity except of subactam
Pharmacokinetics of Penicillins (ADME)
Absorption: poor oral absorption due to acid-labile structure
Distribution: well distributed, except for CFS, eye, and prostate
Metabolism: negligible
Excretion: almost exclusively renally excreted
Which Penicillins don’t require renal adjustment?
Penicillinase-resistant Penicillins (Nafcillin, Oxacillin, ..)
-> Therefore often prescribed by physicians
What are the Contraindications of Penicillins
-Hypersensitivity to penicillins
-Cross-allergenicity with related antibiotics
-Don’t treat severe disease (pneumonia, meningitis, pericarditis) with an ORAL penicillin during the acute stage
How is Cross-allergenicity mediated?
By similar side chains of drugs
Adverse effects of penicillins
-Hypersensitivity
-Seizures/neurotoxicity -> most likely IV Penicillin (lowers seizure threshold)
-GI upset, diarrhea -> Augmentin (but could be for any drug)
-C. diff infection (Clindamycin, Amphenicole)
-Blood dyscrasias (imbalance of body fluids, decreased number of white blood cells)
Drug interactions of penicillins
-Probenecid blocks tubular secretion -> decreased clearance of antibiotics - increased levels
-competing with drugs for tubular secretion (methotrexate)
-could decrease the efficacy of oral contraceptives
-Nafcillin lowers the concentration of warfarin/cyclosporine
What is Cefazolin used for and what is its oral equivalent?
1st GEN
Cefazolin is one of the most commonly used antibiotics -> often used as prophylaxis
-MSSA in the blood or in a wound
PO equivalent: Cephalexin
What are the Cephalosporins that cover anaerobes?
2nd GEN
2nd GEN:
-Cephamycins
-Cefmetazole
-Cefoxitin (often used as prophylaxis for surgery of intrabdominal surgery bc the gut contains anaerobes)
-Cefotetan
What are the most commonly used 3rd GEN Cephalosporins?
-Ceftriaxone !!!
-Ceftazidime - better PK profile but expensive, covers PSEUDOMONAS; but doesn’t cover gram-positive bacteria
-Cefdinir - is cheaper, but PK profile is worse
-Cefpodoxime
What is the only 4th GEN Cephalosporin?
Cefepime
it covers PSEUDOMONAS but does not cover anaerobes
Name an important 5th GEN Cephalosporin
Ceftaroline
covers MRSA
New Cepahlosporins
Cephalosporin Combinations
-Ceftolozane/tazobactam - covers Pseudomonas
-Ceftazidime/avibactam - avibactam restores activity agianst KPC, also cover Pseudomonas
-Cefiderocol - gram negative drug with activiry aginst MDR organism
What are the organisms that are NOT covered by Cephalosporins?
-Anaerobs (besides Cefotoxin and Cephamycin)
-Enterococcus, Listeria or Legionella
How does cephalosporin generation evolve in terms of spectra?
-Gram-negative coverage increases with generations, although there is still gram-positive coverage in higher generations
-Structural differences provide stability against ß-lactamases in higher generations (especially 3rd GEN)
Why do especially 3rd GEN Cephalosporins do not need ß-lactamase inhibitors?
Because their structure provides stability against ß-lactamases
Spectrum of Activity 1st GEN
-Activity against gram-positive also E.coli and Klebsiella (gram-negative)
-Cephazolin is DOC for MSSA in the blood or in a wound (for infections anywhere else use Cephalexin)
Spectrum of Activity 2nd GEN
Cephamycins: Anaerbos + Ecoli
Other 2nd Gen: activity against gram-negatives
Spectrum of Activity 3rd GEN
-predominantly gram-negatives, but also partial gram-positive activity + MSSA
-Ceftazidime with activity against Pseudomonas
-ESBL due to overuse of 3rd GEN
Spectrum of Activity 4th GEN
Cefepime
-Activity against Pseudomonas
-good gram-positive coverage + MSSA (better than 3rd)
Spectrum of Activity 5th GEN
Ceftaroline, Ceftolozane
-Exclusively MRSA - Ceftaroline
-Enhanced activity against PRSP (Penicillin-resistant strep pneumo.) - Ceftaroline
The difference in Cephalosporins Pharmacokinetics compared to Penicillins
-Absorption: well absorbed orally, better bioavailability when pro-drugs are given with food
-Distribution: well through the body, 3rd/4th penetrate CSF the best -> Ceftriaxone or Cefepime are good for meningitis
-Metabolism/Excretion: predominantly excreted in the urine
Why is Ceftriaxone so often prescribed?
-Dosed once daily, protein-binding drug
-No renal adjustment required
Does Cefepime require renal adjustment?
Yes, can cause seizure if not adjusted
Which Cephalosporin has a Contraindication for neonates?
Ceftriaxone
-Hyperbilirubinemic neonates - displacement of bilirubin from albumin
-Caution in use with calcium-containing IV solutions and TPN agents due to precipitation
Adverse Effects of Cephalosporins
-Serum sickness (2nd GEN)
-Seizures/neurotoxicity - especially Cefepime, especially when not renal adjusted
-C. difficile infection - 2nd/3rd GEN
-Cholelithiasis (gallstones) - Ceftriaxone tends to concentrate in the gallbladder -> chelates with Ca2+ -> biliary sludging
Drug Interaction of Cephalosporins
Probenecid blocks tubular secretion -> increased level
Ceftriaxone and calcium-containing solutions -> in adults negligible
Drugs against anaerobes
-Extended-spectrum Penicillins (antipseudomonal): Piperacillin + Tazobactam
-2nd GEN: Cephamycins, Cefmetazole, Cefotoxin, Cefotetan
-Metronidazole, Clindamycin, Carbapenem
Drugs against Pseudomonas
-Piperacillin + Tazobactam
-Ceftazidime (3)
-Cefepime (4)
-Ceftolozane/tazobactam
-Ceftazidime/avibactam
-FQ-DOC: Cipro, Delafloxacin, Levofloxacin
-Monobactam: aztreonam
Drug against KPC
Ceftazidime(4)/avibactam
1st GEN Cephalosporin with some activity
Drugs against E. coli
-1st GEN with some activity
-Cephamycins (2nd)
-Carbapenem (also Klebsiella)
Drugs against MRSA
-for MRSA - Vancomycin
PO MRSA - doxycycline, clindamycin, and TMP-SMX
-Ceftaroline
Important side effect of Cefepime
Seizures/Neurotoxicity
An important side effect of 2nd/3rd GEN Cephalosporins?
C. diff infection
Drug contraindication for Ceftriaxone
-Hyperbilirubinemic neonates
Should not be administered with calcium-containing IV solutions in neonates (for adults negligible)
Why might PIP-TAZO be a better choice over Cefepime?
-Both cover Pseudomonas
-PIP-Tazo also covers anaerobes
For intraabdominal surgery choose PIP-tazo
