Penicillins and Carbapenems

Question 1

Penicillins Mechanism of Action

Answer 1

Bind to Penicillin binding proteins (Transpeptidase), Defects in cell wall synthesis, Inhibit cross linking
Induce holing-like proteins in bacterial membrane - Cause lesions and collapse of membrane potential
Bacteriocidal

Question 2

Chemistry of Penicillin

Answer 2

5 member ring attached to 4 member ring
Thiazolidine ring
Beta-Lactam ring

Question 3

Penicillin G

Answer 3

Benzylpenicillin

Acid Labile - Destroyed in stomach acid - Administered IM or IV

Question 4

Penicillin V

Answer 4

Phenoxymethylpenicillin

Better oral absorption (Less sensitive to food) - Gram positive organisms - Oral anaerobes or Spirochetes; q6h

Question 5

Ampicillin

Answer 5

Amino group added on, Gram negative antibacterial spectrum, Reduce efficacy on Gram positive, Oral admin

Question 6

Amoxicillin

Answer 6

Better oral absorption - More used in dentistry - Gram negative; q8h; No adjustment in compensated cirrhosis but avoid in decompensated; Used in patients with liver/kidney disease but adjust;

Question 7

Natural Penicillins

Answer 7

Pen G
Pen VK
Procaine
Benzathine penicillin

Question 8

Penicillin Spectrum

Answer 8

Narrow Spectrum
Gram+ve cocci and bacilli (Bacillus anthraces); Spirochetes - ANUG (Anaerobes and Spirochetes cause) - Treponema pallidum (syphilis); Oral anaerobes - Actinomyces (Actinomycosis - Lumpy tumors of jaw and tongue, Loss of wt. strength); Costridial infection - Gas gangrene (C. perfringens), Tetanus (C. tetani - eradicate vegetative forms of bacteria that persist, Use tetanus immune globulin); Anthrax - Pen G (Ciprofloxacin - Drug of choice); Streptococcal infections - Pen V or G - S. Pyogenes (Pharyngitis, otitis media, pneumonia, bacteremia, scarlet fever - chills, scarlet rash, sore throat, nephritis), Endocarditis (Enterococcal endocarditis - Pen G + Aminoglycoside); Penicillin G and Penicillin V (Natural) - Rat bite fever (Spirilum minor, Streptobacillus monliformis) - Pen G choice, Diptheria (Pen G for carrier state - antitoxin), Neisseria Meningitides (Meningitis - Pen G);

Question 9

Aminopenicillins Spectrum

Answer 9

Amoxicillin or Ampicillin
Not penicillinase resistant;
Extended Spectrum (More Gram -);
Gram positive cocci and some Gram negative - ex. P.mirabilis, Salmonella, Shigella, E.Coli; Not active against Pseudomonas, Sensitive to Beta-lactamase, Combine with Beta-lactamase inhibitor clavulanic acid, sulbactam or tazobactam; Amoxicillin + Clavulanic Acid = Augmentin; Prevotella intermedia/nigrescens, F. nucleatum, other Prevotella species. P. gingival is found in periodontal pockets and all produce beta lactamase, treat with Amoxicillin + Clavulanic acid or Amoxicillin + Metronidazole; Prophylaxis prior to dental treatment; Spectrum includes more Gram neg organism, Efficacy got Gram pos degraded

Question 10

Penicillinase-Resistant Penicillins

Answer 10

Methicillin (Injection), Nafcillin (Injection), Cloxacillin (Oral), Dicloxacillin (Best oral absorption), Oxacillin (Parenteral)
Flucloxacillin (Not in US)

Question 11

Penicillinase-Resistant Penicillins Spectrum

Answer 11

Only used to treat infections caused by Beta-lactamase producing Staph Aureus (Bacteremia, Endocarditis, Pneumonia, Osteomyelitis)

Question 12

MRSA Treatment

Answer 12

Vancomycin, Linezolid, Quinupristin-Dalfopristin

Question 13

Anti-Pseudomonal Penicillin

Answer 13

Carboxypenicillins: Ticarcillin (and Carbenicillin) active against P. aeruginosa and Proteus
Ureidopenicillins: Piperacillin(-Tazobactam w/broadest spectrum of penicillins) (and Mezlocillin) extends spectrum of Ampicillin to include Pseudomonas, Enterobacteriaceae, Bacteroides
Sensitive to Beta-lactamase so use inhibitor
Mainly used for serious infections caused by Gram neg organisms [bacteremias, pneumonias, infections following burns, UTI resistant to Pen G, ampicillin - (P. aeruginosa, indole + proteus, enterobacter)]
Mezlocillin, Piperacillin, Ticarcillin - Inactivated by acid, Give IM or IV

Question 14

Procaine and Benzathine Admin

Answer 14

IM Slow Release forms

Question 15

Penicillin Distribution

Answer 15

Most 20-50% Plasma bound, Some beta lactamase resistant genes 90-95% bound; Cross placenta are distributed into breast milk as weak acids; Well distributed, Do not enter CSF unless inflamed meninges

Question 16

Penicillin Metabolism and Excretion

Answer 16

Primarily eliminated by renal route, Rapidly excreted by kidney through filtration and tubular secretion, Pen V 50% metabolized by liver
Biliary excretion - Particularly nafcillin, oxacillin - Piperacillin partly biliary
Renal compromised - Total daily dose reduction or interval reduction or use Clindamycin or Azithromycin (Min urinary excretion)
Take Penicillin 1hr before/2hr after meal
Antibiotics - Prolong Warfarin (EXCEPT Dicloxacillin)

Question 17

Probenacid

Answer 17

Inhibits tubular secretion, Used to elevate penicillin blood levels

Question 18

Penicillin Adverse Effects

Answer 18

Allergic Rxns - Hypersensitivity; Skin rashes of various types (High with Ampicillin), Public health problem
Acute Anaphylactic rxns - Rare, But fatal; Treat w/Epi, Skin test with Penicilloyl Polylysine helpful but not always conclusive (May need diphenhydramine &/ glucocorticoid anti-inflammatories)
Superinfection by Resistant organisms - ex. Pseudomembranous colitis (C. difficile), More likely with extended spectrum agents
Electrolyte disorder - Rapid IV infusion of Potassium Salt of Penicillin G produces hyperkalemia leading to arrhythmias and cardiac arrest
Very high doses lower seizure threshold

Question 19

Metabolite of Penicillin

Answer 19

D-Benzylpenicillenic acid

Question 20

Mechanism of Resistance to Penicillin

Answer 20

Change in Penicillin Binding Protein - Important in gram-positive cocci ex. S. aureus resistance to methicillin and pneumococcus
Increased production of Beta-Lactamase enzymes - Main mechanism of resistance
Development of tolerance by loss of autolysis mechanism (Agents become bacteriostatic)

Question 21

Penicillin Uses in Dentistry

Answer 21

Treat post extraction infections, post surgical infections, pericoronitis, dentoalveolar abscesses, osteomyelitis, cellulites, ulcerative gingivitis, periodontitis, prophylaxis

Question 22

Amoxicillin + Metronidazole

Answer 22

Treat Aggregatibacter (Actinobacillus) Actinomycetemcomitans associated periodontitis and aggressive/and or advanced forms of chronic periodontitis

Question 23

Oral Regimens for Dental Procedure

Answer 23

Amoxicillin
Adult: 2g
Children: 5mg/kg

Question 24

Unable to Take Oral Meds Regimens for Dental Procedure

Answer 24

Ampicillin
Adults: 2g IM or IV
Children: 50mg/kg IM or IV
Cefazolin or Ceftriaxone
Adults: 1g IM or IV
Children: 50mg/kg IM or IV

Question 25

Allergic to Penicillin/Ampicillin Oral Regimens for Dental Procedure

Answer 25

Cephalexin
Adults: 2g
Children: 50mg/kg
Clindamycin
Adults: 600mg
Children: 20mg/kg
Azithromycin or Clarithromycin
Adults: 500mg
Children: 15mg/kg

Question 26

Allergic to Penicillins/Ampicillins and Unable to Take Oral Regimens for Dental Procedure

Answer 26

Cefazolin or Ceftriaxone 
Adults: 1g IM or IV
Children: 50mg/kg IM or IV
Clindamycin
Adults: 500mg IM or IV
Children: 20mg/kg IM or IV

Question 27

Carbapenems Chemistry

Answer 27

Imipenem/Cilastatin
Meropenem
Contains C instead of S in 5member ring

Question 28

Carbapenems Spectrum of Action

Answer 28

Broad Spectrum
Active VS Gram - and Gram + organisms
NOT Active VS MRSA (Altered PBP), VRE, Choice for Enterobacter infections, Useful for treatment of pulmonary, intra-abdominal and soft tissue infections caused by mix of bacteria

Question 29

Carbapenems Mechanism of Action

Answer 29

Bind to PBPs 1 and 2 rather than PBP 3 to which Aminopenicillins bind, Small size allows easy penetration of Gram - envelope through Porins

Question 30

Carbapenems Pharmacokinetics

Answer 30

Not absorbed from GI tract so IV or IM, Hydrolyzed rapidly by dehydropeptidase 1 present in brush border of proximal renal tubule; Must be administered with Cilastatin - a competitive inhibitor of dehydropeptidase 1 - Cilastatin prevents destruction of Imipenem ring; Meropenem is resistant to degradation by dehydropeptidase 1

Question 31

Carbapenems Adverse Effects

Answer 31

Imipenem at high doses causes seizures, less with Meropenem; GI complaints of N, V, D, skin rash and rare neutropenia

Question 32

Carbapenems Resistance

Answer 32

Alteration of porins so drug can’t access periplasmic space