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Infectous Disease > Dr. Cluck Clinical Anti-Infective Pens and Cephs > Flashcards

Dr. Cluck Clinical Anti-Infective Pens and Cephs Flashcards

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1
Q

What are antibiotics divided into based on PK/PD parameters?

A

-Time-dependent killing
-concentration-dependent killing

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2
Q

What is the Post antibiotic effect (PAE)

A

-The drug continues to affect organisms’ growth after concentration has fallen below MIC
(Antibiotics are usually not picked based on PAE)

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3
Q

What is the MIC?

A

-Minimum inhibitory concentration

-the lowest concentration of antibiotics needed to stop visible bacterial growth under standard conditions

-each antibiotics has its own MIC

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4
Q

What is the clinical approach to using Time-dependent antibiotics?

A

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

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5
Q

What is the classic Time-dependent-Killer (Time-above-MIC-Killer)?

A

ß-Lactams

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6
Q

What does concentration-dependent-Killer require?

A

Requires a high antibiotic peak
-Cmax : MIC - 10:1 or greater overall
-AUC/MIC
-Increased drug concentration results in increased bacterial killing

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7
Q

What are the common concentration-dependent-Killers?

A

Aminoglycosides (Nephrotoxic and ototoxic at high doses), fluoroquinolones, Daptomycin, metronidazole

-CAUTION -> toxicity at high doses

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8
Q

How is efficient dosing of time VS concentration-dependent-Killers explained?

A

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

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9
Q

What are Bacteriocidals and Bacteriostatics?

A

Bacteriocidal: Kills the bacteria

Bacteriostatic: Inhibits growth, and requires intact immune function to kill the bacteria

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10
Q

What are typical Bacteriocidal and Bacteriostatics?

A

Bacteriocidal: ß-Lactams

Bacteriostatic: Tetracyclines, Macrolides

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11
Q

Spectrum of action for Pen G (benzylpenicillin)

A

Neurosyphilis, Decolonization of Group B strep and pregnant

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12
Q

Spectrum of Pen G Procaine and Benzathine

A

Administered IM -> long-acting

Pen G Benzathine (Bycillin L-A): for Syphilis

Pen G Procaine (Wycillin): STIs

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13
Q

The spectrum of Pen V (phenoxy methyl, Pen VK)

A

Dental Work

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14
Q

What are the IV and PO-administered penicillins?

A

IV: Oxacillin, Nafcillin
PO: Doxacillin

(All can be given: IV, IM, PO)

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15
Q

What is the IV equivalent of Augmentin (Amoxicillin-Clavulanate - PO)?

A

Ampicillin-Sulbactam (IV)

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16
Q

Spectrum of Activity for Natural Penicillins G + V

A

-predominantly active against Strep spp.
-Treponema pallidum (Syphilis)

can also be used for Enterococcus faecalis and in vitro for Neisseria meningitis

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17
Q

Spectrum of Penicillin-resistant Penicillins?
Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin

A

MSSA and Strep
(for MRSA - Vancomycin
PO MRSA. doxycycline, clindamycin, and TMP-SMX)

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18
Q

Spectrum of Activity for Aminopenicillins (Amoxicillin and Ampicillin don’t work for ß-lactamase producing bacteria - need ß-lactam inhibitors)

A

-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

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19
Q

What is the DOC for Listeria meningitis?

A

Ampicillin

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20
Q

Spectrum for Extended-Spectrum Penicillins (Antipseudomonal - different from Roane)

A

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

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21
Q

In what ways are ESBLs beneficial?

Piperacillin + Tazobactam

A

-They are broad (gram-positive and susceptible gram-negatives, anaerobic w/ ß-l-inhibitor)

-They are protected from ß-lactamases with ß-l-inhibitors

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22
Q

Examples of ß-lactam inhibitor

A

Older: Clavulanic acid, sulabactam, tazobactam
New: avibactam, relebactam, vaborbactam

-no microbial activity except of subactam

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23
Q

Pharmacokinetics of Penicillins (ADME)

A

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

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24
Q

Which Penicillins don’t require renal adjustment?

Study These Flashcards
A

Penicillinase-resistant Penicillins (Nafcillin, Oxacillin, ..)
-> Therefore often prescribed by physicians

25
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
26
How is Cross-allergenicity mediated?
By similar side chains of drugs
27
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)
28
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
29
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
30
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
31
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
32
What is the only 4th GEN Cephalosporin?
Cefepime it covers PSEUDOMONAS but does not cover anaerobes
33
Name an important 5th GEN Cephalosporin
Ceftaroline covers MRSA
34
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
35
What are the organisms that are NOT covered by Cephalosporins?
-Anaerobs (besides Cefotoxin and Cephamycin) -Enterococcus, Listeria or Legionella
36
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)
37
Why do especially 3rd GEN Cephalosporins do not need ß-lactamase inhibitors?
Because their structure provides stability against ß-lactamases
38
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)
39
Spectrum of Activity 2nd GEN
Cephamycins: Anaerbos + Ecoli Other 2nd Gen: activity against gram-negatives
40
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
41
Spectrum of Activity 4th GEN
Cefepime -Activity against Pseudomonas -good gram-positive coverage + MSSA (better than 3rd)
42
Spectrum of Activity 5th GEN
Ceftaroline, Ceftolozane -Exclusively MRSA - Ceftaroline -Enhanced activity against PRSP (Penicillin-resistant strep pneumo.) - Ceftaroline
43
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
44
Why is Ceftriaxone so often prescribed?
-Dosed once daily, protein-binding drug -No renal adjustment required
45
Does Cefepime require renal adjustment?
Yes, can cause seizure if not adjusted
46
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
47
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
48
Drug Interaction of Cephalosporins
Probenecid blocks tubular secretion -> increased level Ceftriaxone and calcium-containing solutions -> in adults negligible
49
Drugs against anaerobes
-Extended-spectrum Penicillins (antipseudomonal): Piperacillin + Tazobactam -2nd GEN: Cephamycins, Cefmetazole, Cefotoxin, Cefotetan -Metronidazole, Clindamycin, Carbapenem
50
Drugs against Pseudomonas
-Piperacillin + Tazobactam -Ceftazidime (3) -Cefepime (4) -Ceftolozane/tazobactam -Ceftazidime/avibactam -FQ-DOC: Cipro, Delafloxacin, Levofloxacin -Monobactam: aztreonam
51
Drug against KPC
Ceftazidime(4)/avibactam 1st GEN Cephalosporin with some activity
52
Drugs against E. coli
-1st GEN with some activity -Cephamycins (2nd) -Carbapenem (also Klebsiella)
53
Drugs against MRSA
-for MRSA - Vancomycin PO MRSA - doxycycline, clindamycin, and TMP-SMX -Ceftaroline
54
Important side effect of Cefepime
Seizures/Neurotoxicity
55
An important side effect of 2nd/3rd GEN Cephalosporins?
C. diff infection
56
Drug contraindication for Ceftriaxone
-Hyperbilirubinemic neonates Should not be administered with calcium-containing IV solutions in neonates (for adults negligible)
57
Why might PIP-TAZO be a better choice over Cefepime?
-Both cover Pseudomonas -PIP-Tazo also covers anaerobes For intraabdominal surgery choose PIP-tazo
58

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