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

Dr. Cluck Clinical Anti-Infective Pens and Cephs Flashcards

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?

A

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

25
Q

What are the Contraindications of Penicillins

A

-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
Q

How is Cross-allergenicity mediated?

A

By similar side chains of drugs

27
Q

Adverse effects of penicillins

A

-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
Q

Drug interactions of penicillins

A

-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
Q

What is Cefazolin used for and what is its oral equivalent?

1st GEN

A

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
Q

What are the Cephalosporins that cover anaerobes?

2nd GEN

A

2nd GEN:
-Cephamycins

-Cefmetazole
-Cefoxitin (often used as prophylaxis for surgery of intrabdominal surgery bc the gut contains anaerobes)
-Cefotetan

31
Q

What are the most commonly used 3rd GEN Cephalosporins?

A

-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
Q

What is the only 4th GEN Cephalosporin?

A

Cefepime
it covers PSEUDOMONAS but does not cover anaerobes

33
Q

Name an important 5th GEN Cephalosporin

A

Ceftaroline
covers MRSA

34
Q

New Cepahlosporins
Cephalosporin Combinations

A

-Ceftolozane/tazobactam - covers Pseudomonas

-Ceftazidime/avibactam - avibactam restores activity agianst KPC, also cover Pseudomonas

-Cefiderocol - gram negative drug with activiry aginst MDR organism

35
Q

What are the organisms that are NOT covered by Cephalosporins?

A

-Anaerobs (besides Cefotoxin and Cephamycin)
-Enterococcus, Listeria or Legionella

36
Q

How does cephalosporin generation evolve in terms of spectra?

A

-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
Q

Why do especially 3rd GEN Cephalosporins do not need ß-lactamase inhibitors?

A

Because their structure provides stability against ß-lactamases

38
Q

Spectrum of Activity 1st GEN

A

-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
Q

Spectrum of Activity 2nd GEN

A

Cephamycins: Anaerbos + Ecoli
Other 2nd Gen: activity against gram-negatives

40
Q

Spectrum of Activity 3rd GEN

A

-predominantly gram-negatives, but also partial gram-positive activity + MSSA

-Ceftazidime with activity against Pseudomonas

-ESBL due to overuse of 3rd GEN

41
Q

Spectrum of Activity 4th GEN

A

Cefepime

-Activity against Pseudomonas
-good gram-positive coverage + MSSA (better than 3rd)

42
Q

Spectrum of Activity 5th GEN

A

Ceftaroline, Ceftolozane

-Exclusively MRSA - Ceftaroline
-Enhanced activity against PRSP (Penicillin-resistant strep pneumo.) - Ceftaroline

43
Q

The difference in Cephalosporins Pharmacokinetics compared to Penicillins

A

-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
Q

Why is Ceftriaxone so often prescribed?

A

-Dosed once daily, protein-binding drug
-No renal adjustment required

45
Q

Does Cefepime require renal adjustment?

A

Yes, can cause seizure if not adjusted

46
Q

Which Cephalosporin has a Contraindication for neonates?

A

Ceftriaxone

-Hyperbilirubinemic neonates - displacement of bilirubin from albumin
-Caution in use with calcium-containing IV solutions and TPN agents due to precipitation

47
Q

Adverse Effects of Cephalosporins

A

-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
Q

Drug Interaction of Cephalosporins

A

Probenecid blocks tubular secretion -> increased level

Ceftriaxone and calcium-containing solutions -> in adults negligible

49
Q

Drugs against anaerobes

A

-Extended-spectrum Penicillins (antipseudomonal): Piperacillin + Tazobactam

-2nd GEN: Cephamycins, Cefmetazole, Cefotoxin, Cefotetan

-Metronidazole, Clindamycin, Carbapenem

50
Q

Drugs against Pseudomonas

A

-Piperacillin + Tazobactam
-Ceftazidime (3)
-Cefepime (4)

-Ceftolozane/tazobactam
-Ceftazidime/avibactam

-FQ-DOC: Cipro, Delafloxacin, Levofloxacin
-Monobactam: aztreonam

51
Q

Drug against KPC

A

Ceftazidime(4)/avibactam
1st GEN Cephalosporin with some activity

52
Q

Drugs against E. coli

A

-1st GEN with some activity
-Cephamycins (2nd)
-Carbapenem (also Klebsiella)

53
Q

Drugs against MRSA

A

-for MRSA - Vancomycin
PO MRSA - doxycycline, clindamycin, and TMP-SMX

-Ceftaroline

54
Q

Important side effect of Cefepime

A

Seizures/Neurotoxicity

55
Q

An important side effect of 2nd/3rd GEN Cephalosporins?

A

C. diff infection

56
Q

Drug contraindication for Ceftriaxone

A

-Hyperbilirubinemic neonates
Should not be administered with calcium-containing IV solutions in neonates (for adults negligible)

57
Q

Why might PIP-TAZO be a better choice over Cefepime?

A

-Both cover Pseudomonas
-PIP-Tazo also covers anaerobes

For intraabdominal surgery choose PIP-tazo

58
Q
A

Infectous Disease (29 decks)

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